Douleur (PDQ): Les soins de soutien - information sur la santé professionnelle [NCI]

Cette information est produite et fournie par le National Cancer Institute (NCI). Les informations contenues dans ce sujet peut avoir changé depuis qu'il a été écrit. Pour l'information la plus à jour, contactez l'Institut national du cancer via le site Web Internet à http://cancer.gov ou appelez au 1-800-4-CANCER.

Douleur

L'Association internationale pour l'étude de la douleur définit la douleur comme une expérience sensorielle et émotionnelle désagréable associée à une lésion tissulaire réelle ou potentielle ou décrite en termes d'un tel dommage. La douleur cancéreuse peut être géré efficacement par des moyens relativement simples dans un maximum de 90% des huit millions d'Américains qui ont le cancer ou des antécédents de cancer. Malheureusement, la douleur associée au cancer est fréquemment-traitée. [1]

Bien que la douleur de cancer ou symptômes associés ne peuvent souvent pas être entièrement éliminés, l'utilisation appropriée de thérapies disponibles peut effectivement soulager la douleur dans la plupart des patients. Gestion de la douleur améliore la qualité de vie du patient à tous les stades de la maladie. Les patients atteints de cancer avancé de l'expérience des symptômes multiples simultanées avec la douleur; par conséquent, une gestion optimale de la douleur nécessite une évaluation des symptômes systématique et une gestion appropriée de la qualité de vie optimale. [2] En dépit de la large gamme de thérapies de gestion de la douleur disponibles, les données sont insuffisantes pour guider leur utilisation chez les enfants, les adolescents, les personnes âgées et les populations spéciales . [3]

Les lois des États et locales limitent souvent l'utilisation médicale des opioïdes pour soulager la douleur du cancer, et les tiers payeurs peuvent ne remboursera pas pour les traitements anti-douleur non invasives. Ainsi, les cliniciens devraient travailler avec les organismes de réglementation, les initiatives de la douleur du cancer de l'Etat, ou d'autres groupes pour éliminer ces système de soins de santé obstacles à la gestion efficace de la douleur. (Ceux-ci et d'autres obstacles à la gestion efficace de la douleur sont énumérés ci-dessous.) Les changements dans la prestation des soins de santé peuvent créer des effets dissuasifs supplémentaires pour les cliniciens de pratiquer une gestion efficace de la douleur.

Le modifications à la Loi Food and Drug Administration des États-Unis de 2007 oblige les fabricants à fournir l'évaluation des risques et des stratégies d'atténuation (REMS) pour des médicaments choisis pour assurer que les avantages l'emportent sur les risques. Un élément majeur de REMS nécessite prescripteurs pour obtenir la formation afin que ces médicaments peuvent être utilisés en toute sécurité.

Obstacles à la gestion efficace de la douleur

Les problèmes liés aux professionnels de soins de santé:

Connaissance insuffisante de l'évaluation de la douleur management.Poor de la douleur. [4,5,6] Préoccupation sur la réglementation des substances.Fear contrôlée de la dépendance du patient. [5] de préoccupation au sujet des effets secondaires des analgésiques. [4] de préoccupation patients devenir tolérants aux analgésiques .Problems liés aux patients:

Réticence à signaler à propos de pain.Concern distraire médecins du traitement de disease.Fear sous-jacente que la douleur signifie maladie est worse.Concern de ne pas être un «bon» patient.Reluctance de prendre la douleur medications.Fear de toxicomanie ou d'être pensée comme un toxicomane . (Cette crainte peut être plus prononcé chez les patients minoritaires.) [7] Les inquiétudes sur les effets secondaires incontrôlables (tels que la constipation, la nausée, ou une opacification de la pensée) .Concern environ devenir tolérant à la douleur medications.Poor observance du régime analgésique prescrit. [ 8] Les obstacles financiers [5] Les problèmes liés au système de soins de santé.:

Faible priorité accordée au traitement de la douleur cancéreuse. [4] de remboursement inadéquate pour l'évaluation de la douleur et treatment.The traitement le plus approprié ne peut être remboursé ou peut-être trop coûteux pour les patients et les familles. [5] Réglementation restrictive des substances.Problems contrôlées de disponibilité de le traitement ou l'accès à it.Opioids indisponibles dans pharmacy.Unaffordable les médicaments du patient.

La flexibilité est la clé de la gestion de la douleur du cancer. Comme les patients varient dans le diagnostic, stade de la maladie, les réponses à la douleur et interventions, et les préférences personnelles, afin gestion de la douleur de must. L'approche clinique recommandée décrite ci-dessous souligne l'accent sur la participation des patients.

1. Renseignez-vous sur la douleur régulièrement. Évaluer la douleur et des symptômes associés utilisant systématiquement brèves outils d'évaluation. L'évaluation devrait inclure une discussion sur les symptômes courants rencontrés par les patients atteints de cancer et comment chaque symptôme sera traitée. [2,3] Demander à un patient à identifier son symptôme le plus gênant, ce est également une valeur clinique parce que le symptôme le plus gênant, ce est pas toujours le plus sévère, comme l'a démontré dans une étude de 146 patients en phase palliative du traitement pour le poumon, gastro-intestinal, ou le cancer du sein. [9]
2. Croyez-patient et la famille des rapports de douleurs et ce soulage la douleur. (Mises en garde comprennent les patients souffrant de détresse psychologique importante / existentielle et les patients souffrant de troubles cognitifs.) [10,11]
3. Choisissez les options anti-douleur appropriés pour le patient, la famille, et le réglage.
4. Offrir des interventions en temps opportun, logique, de façon coordonnée.
5. Responsabiliser les patients et leurs familles. Permettre aux patients de contrôler leur cours autant que possible.

Faits saillants de la gestion des patients

La gestion efficace de la douleur est mieux réalisée par une approche d'équipe impliquant les patients, leurs familles et les fournisseurs de soins de santé. Le clinicien devrait:

Initier des mesures de anticonstipation prophylactiques chez tous les patients (sauf ceux souffrant de diarrhée) avant ou pendant l'administration d'opiacés. (Reportez-vous à la section de la constipation chez les effets secondaires de la section opioïdes de ce résumé pour plus d'informations.) Discutez douleur et sa gestion avec les patients et leurs patients de families.Encourage être des participants actifs dans leurs patients care.Reassure qui sont réticents à signaler la douleur qu'il ya beaucoup de moyens sûrs et efficaces pour soulager pain.Consider le coût des médicaments proposés et documentés technologies.Share évaluation de la douleur et de la gestion avec d'autres cliniciens qui traitent les patient.Know État / réglementations locales concernant les substances réglementées.

Dans ce résumé, à moins d'indication contraire, les preuves et les questions de pratique en ce qui concerne les adultes sont discutées. La preuve et l'application de pratiques liées aux enfants peuvent différer considérablement des informations relatives aux adultes. Lorsque des renseignements précis sur la garde des enfants est disponible, elle est résumée sous sa propre rubrique.

Les essais cliniques actuels

Consultez la liste de NCI des essais cliniques sur le cancer pour essais américains de soutien et de soins palliatifs sur la douleur qui sont accepte maintenant les participants. La liste des essais peut être encore réduit par emplacement, la drogue, l'intervention, et d'autres critères.

Informations générales sur les essais cliniques est également disponible sur le site Web du NCI.

Références:

1. Weiss SC, Emanuel LL, Fairclough DL, et al .: Comprendre l'expérience de la douleur chez les patients en phase terminale. Lancet 357 (9265): 1311-5, 2001.
2. Meuser T, Pietruck C, Radbruch L, et al .: Les symptômes pendant le traitement de la douleur cancéreuse suivantes OMS-directives: une étude longitudinale de suivi de la prévalence des symptômes, la gravité et l'étiologie. La douleur 93 (3): 247-57, 2001.
3. Patrick DL, Ferketich SL, PS Frame, et al .: National Institutes of State-of-the-sciences de la santé Déclaration Conférence: La gestion des symptômes en Cancer: la douleur, la dépression et la fatigue, Juillet 15-17 J Natl 2002. Cancer Inst 95 (15): 1110-7, 2003.
4. Breivik H, N Cherny, Collett B, et al .: la douleur liée au cancer: une enquête pan-européenne de la prévalence, le traitement et les attitudes des patients. Ann Oncol 20 (8): 1420-1433, 2009.
5. Sun V, Borneman T, Piper B, et al .: Les obstacles à l'évaluation et la gestion des douleurs dans la survie au cancer. J Cancer SURVIV 2 (1): 65-71, 2008.
6. Bruera E, Willey JS, Ewert-Flannagan PA, et al .: évaluation de l'intensité de la douleur par des infirmières de chevet et de consultants en soins palliatifs: une étude rétrospective. Cancer Support Soins 13 (4): 228-31, 2005.
7. Anderson KO, Richman SP, Hurley J, et al gestion de la douleur du cancer .: parmi mal ambulatoire minoritaires: les besoins et les obstacles perçus à un contrôle optimal. Cancer 94 (8): 2295-304, 2002.
8. Miaskowski C, Dodd MJ, West C, et al .: manque de respect avec le régime analgésique: un obstacle important à une gestion efficace de la douleur cancéreuse. J Clin Oncol 19 (23): 4275-9, 2001.
9. J Hoekstra, Vernooij-Dassen MJ, de Vos R, et al .: La valeur ajoutée d'évaluer le symptôme «plus gênant» parmi les patients atteints de cancer en phase palliative. Patient Couns Educ 65 (2): 223-9, 2007.
10. Allen RS, Haley NOUS, Petit BJ, et al .: douleur rapports par les patients atteints de cancer de soins palliatifs plus et aidants naturels: le rôle du fonctionnement cognitif. Gerontologist 42 (4): 507-14, 2002.
11. Bruera E, C Sweeney, Willey J, et al .: Perception d'inconfort par des parents et des infirmières chez les patients en phase terminale qui ne répondent pas avec le cancer: une étude prospective. J douleur Symptôme Gérer 26 (3): 818-26, 2003.

Défaut d'évaluer la douleur est un facteur critique conduisant à undertreatment. L'évaluation comprend le clinicien et le patient. L'évaluation devrait se produire dans les cas suivants:

A chaque intervalles réguliers de encounter.At cliniques après le début de chaque nouvelle treatment.At rapport de pain.At un intervalle de temps approprié après l'intervention pharmacologique ou non pharmacologique (par exemple, 15 à 30 minutes après la pharmacothérapie parentérale et 1 heure après l'administration orale).

Identifier l'étiologie de la douleur est important de sa gestion. Les cliniciens qui traitent des patients atteints de cancer devraient reconnaître les syndromes de douleur du cancer commune (voir liste ci-dessous). Un diagnostic rapide et le traitement de ces syndromes peuvent réduire la morbidité associée à une douleur non soulagée. Peuvent avoir besoin de composantes culturelles distinctes doit être intégrée dans une évaluation multidimensionnelle de la douleur. [1,2,3,4] Avis de la douleur cancéreuse avec un accent sur la douleur neuropathique décrit pathophysiologies ainsi que pharmacothérapies disponibles et expérimentaux. [5,6] [ Niveau de preuve: II]

Commune syndromes de douleur: la douleur associée à la tumeur

lésions osseuses / métastases

l'expansion de la moelle osseuse
Syndrome vertébrale
L'infiltration locale
Base de la participation du crâne
Viscéral

Capsule hépatique distension
Syndrome rétropéritonéale
Occlusion intestinale
obstruction urétérale
Neuropathies / plexopathies

Neuropathies crâniennes

DiseaseBase leptoméningée de métastases du crâne
Mononeuropathies
Polyneuropathies

Brachial, col de l'utérus, sacrée
Syndrome de la queue de cheval
Syndrome paranéoplasique

Ostéoarthropathie
Gynécomastie
Neuropathie sensorimotrice

Commune syndromes de douleur: la douleur secondaire aux traitements

Traitement post-rayonnement

Entérite
Fibrose radique
Ostéoradionécrose
Myélopathie
Neuropathie / plexopathies

Brachial, sacrée
Douleur fusée après radiopharmaceutique
cystite radio-induite
Post-chimiothérapie

Arthralgie, myalgie

Inhibiteurs de l'aromatase
La nécrose avasculaire
Douleurs abdominales chroniques
Mucite
Neuropathie

Produits à base de platine: cisplatine, du carboplatine, oxaliplatinTaxanes: paclitaxel, alcaloïdes docetaxelVinca: vincristine, vinblastineEpothilones: IxabepiloneOthers: bortézomib, lénalidomide, la thalidomide
Traitement hormonal post-

torche de la douleur osseuse
Arthralgie, myalgie
Postopératoire

Postopératoire aiguë ou de douleur procédurale
Douleur du membre fantôme / douleur postamputation
Syndrome Postnephrectomy
syndrome postmastectomie
Syndrome post-thoracotomie
Curage Post-radical
Plancher pelvien myalgie
Les bisphosphonates

Les douleurs osseuses, ostéonécrose

Évaluation initiale

L'objectif de l'évaluation initiale de la douleur est de caractériser la physiopathologie de la douleur et de déterminer l'intensité de la douleur et son impact sur la capacité du patient à fonctionner. Par exemple, une étude a évalué l'association entre la détresse psychologique et la douleur chez 120 patients atteints de cancer avancé. intensité de la douleur et la douleur qui interfère avec la capacité de marche, travail normal, et les relations avec d'autres personnes, tel que mesuré par le Brief Pain Inventory (version grec), se sont révélés être des prédicteurs significatifs de l'anxiété, tel que mesuré par l'Hospital Anxiety and Depression Scale sur analyse multivariée. En utilisant les mêmes outils, les auteurs ont également constaté des douleurs qui affectaient jouissance de la vie était un prédicteur de la dépression [7] [Niveau de preuve: II]. Les facteurs qui peuvent influencer la réponse analgésique et entraîner des douleurs persistantes, citons l'évolution nociception raison de la progression de la maladie , les effets secondaires intraitables, la tolérance, la douleur neuropathique, et métabolites opioïdes [8] [Niveau de preuve: IV]. Le suivantes sont essentielles à l'évaluation initiale:

Évaluation médicale et la douleur history.Physical examination.Psychosocial et spirituelle détaillée [9]. [Niveau de preuve: IV] Histoire de l'abus de substances chez le patient et l'évaluation family.Diagnostic.

L'expérience de la douleur du cancer est complexe et comprend des dimensions physiques, psychosociaux et spirituels. Il n'y a aucune mesure de classification de la douleur universellement acceptée qui aide à prédire la complexité de la gestion de la douleur, en particulier pour les patients souffrant de douleurs du cancer, qui peuvent être plus difficiles à traiter. Les cliniciens et les chercheurs ne ont pas un langage commun pour discuter et comparer les résultats de l'évaluation et de la gestion de la douleur cancéreuse. Oncologues utilisent le système tumeur, ganglions, métastases (TNM) comme un langage universel pour décrire une variété de cancers. La nécessité d'un système de classification similaire pour la douleur cancéreuse abouti à l'élaboration du système de stadification Edmonton. [10,11] Ce système a été affiné dans deux rapports qui ont rassemblé des preuves construction de validité en utilisant un panel international d'experts en la matière [12] et une étude multicentrique à déterminer la fiabilité inter et la valeur prédictive. [13] Le développement d'un système de classification internationalement reconnue pour la douleur cancéreuse pourrait jouer un rôle important dans l'amélioration de l'évaluation de la douleur cancéreuse, permettent une évaluation plus significative du pronostic clinique et le traitement, et mieux permettre aux chercheurs de comparer les résultats en matière de gestion de la douleur cancéreuse [14] [Niveau de preuve: II].

Patient Self-rapport

Le pilier de l'évaluation de la douleur est l'auto-rapport du patient; Toutefois, les aidants naturels sont souvent utilisés comme des procurations pour les rapports des patients, en particulier dans les situations où les barrières de communication existent, tels que les difficultés de valeur ou linguistiques cognitives. membres de la famille qui agissent comme mandataires généralement, en tant que groupe, signalent des niveaux plus élevés de douleur que les auto-évaluations des patients, mais il ya des variations individuelles [15,16] [Niveau de preuve: II]. Les différences dans l'évaluation du clinicien intensité de la douleur sont également significative. Une étude rétrospective de 41 dossiers de patients utilisant les qualifications de la douleur des consultants en soins palliatifs que l'étalon-or a trouvé bon accord avec les évaluations effectuées par les infirmières de chevet (infirmières autorisées [IA] et aides-infirmières cliniques [CNA]) quand la douleur ne était pas présente ou a été doux, mais pauvres accord pour la douleur modérée ou sévère. (sensibilité: IA, 45%; CNA, 30%) [17] [Niveau de preuve: III]

des outils d'évaluation de la douleur peuvent être unidimensionnelle ou multidimensionnelle. De multiples outils d'évaluation existent. Parmi les outils les plus couramment utilisés de chevet sont échelles numériques de notation, échelles verbales, échelles visuelles analogiques, et les échelles d'image [18,19] [Niveau de preuve: IV]. Intensité de la douleur lors de l'évaluation initiale a été démontré être un prédicteur important de la complexité de la gestion de la douleur subséquente (ie, la nécessité d'approches plus pharmacologique et multidimensionnelle) et la longueur de temps pour obtenir un contrôle de la douleur stable [20] [Niveau de preuve: II]. Pour améliorer la gestion de la douleur dans tous les milieux, les cliniciens devraient enseigner aux familles à utiliser des outils d'évaluation de la douleur dans leurs maisons. Le clinicien devrait aider le patient à décrire:

Douleur

Écoutez mots descriptifs du patient quant à la qualité de la douleur; ceux-ci fournissent des indices précieux à son étiologie. Susciter les caractéristiques temporelles, y compris l'apparition, la durée et la variation diurne. Renseignez-vous sur une découverte ou la douleur épisodique (une augmentation transitoire de la douleur qui se produit dans plus de la douleur persistante). Certains patients peuvent avoir des douleurs épisodiques sans douleur persistante [21] [Niveau de preuve: IV].

Emplacement

Demandez au patient pour indiquer l'emplacement exact de la douleur sur son corps, ou sur un schéma corporel, et si la douleur irradie.

Changements dans Motif

Changements dans le profil de la douleur ou le développement de nouvelles douleurs devraient déclencher une réévaluation de diagnostic et la modification du plan de traitement. Une douleur persistante indique la nécessité d'envisager d'autres étiologies (par exemple, liés à la progression de la maladie ou de traitement) et de remplacement (peut-être plus invasive) traitements.

Intensité ou Gravité

Encourager le patient à tenir un journal des scores de douleur d'intensité à signaler lors de visites de suivi ou par téléphone. Des exemples de simples échelles d'auto-évaluation des douleurs d'intensité comprennent les échelles analogiques simples, descriptives, numériques et visuels.

Facteurs aggravants et de soulagement

Demandez au patient d'identifier les facteurs qui causent le plus de douleur et aussi ce qui soulage la douleur.

Réponse cognitive de la douleur

Les évaluations cognitives de la douleur peuvent être basées sur une gamme de variables psychologiques tels que le contrôle perçu, sens attribué à l'expérience de la douleur, la peur de la mort et de désespoir. [22] Toutes ces variables semblent contribuer à l'expérience de la douleur et de la souffrance cancer. Une étude des femmes atteintes du cancer du sein métastatique a constaté que bien que le site de métastase ne avait pas prévu l'intensité du rapport de la douleur, une plus grande dépression et la croyance que la douleur représentait la propagation de la maladie significativement prédit le degré de la douleur ressentie. [23] Il a également été ont rapporté que les patients qui pensaient que leur douleur représenté progression de la maladie signalé plus d'interférences liées à la douleur avec la fonction [24] [Niveau de preuve: II].

Déficience cognitive

Remarque comportement qui suggère la douleur chez les patients qui sont cognitivement déficients ou qui ont des problèmes de communication relatives à l'éducation, la langue, l'origine ethnique, ou de la culture. La déficience cognitive elle-même et le degré de déficience cognitive peuvent avoir un impact patients auto-évaluation de la douleur. Les données préliminaires suggèrent que des degrés légers de déficience cognitive sont associés à une augmentation intensité de la douleur-rapport chez les patients âgés atteints de cancer qui reçoivent des soins palliatifs. [15] En revanche, les résidents des foyers de soins souffrant de troubles cognitifs sont moins susceptibles de signaler la douleur. Utilisez appropriées (par exemple, simples ou traduits) des outils d'évaluation de la douleur.

Objectifs pour le contrôle de la douleur

Documenter outil d'évaluation de la douleur préféré du patient et les objectifs pour le contrôle de la douleur (comme les scores sur une échelle de douleur) utilisation .Encourage du journal de la douleur: Le journal quotidien de la douleur est un outil bien établi dans la recherche sur la gestion des symptômes et dans la pratique clinique. Avantages de l'utilisation d'un journal de la douleur comprennent conscience de la douleur, les conseils aux comportements de gestion de la douleur, le sentiment accru de contrôle, et un outil de communication accrue. [25] Il est difficile d'obtenir une bonne observance douleur journal avec les adolescents qui éprouvent des douleurs chroniques intenses .

Examen clinique

Un examen physique approfondi est nécessaire pour déterminer la physiopathologie de la douleur. Les caractéristiques spécifiques de l'examen neurologique tels que altération des sensations (hypoesthésie, hyperesthésie, hyperpathie, allodynie) dans une zone douloureuse sont évocateurs de la douleur neuropathique. Les signes physiques de la croissance tumorale et les métastases sont également importantes à identifier.

L'information obtenue à partir de la synthèse de l'histoire, l'examen physique et des évaluations diagnostiques est utilisée pour générer un diagnostic de la douleur par rapport à l'étiologie (cancer, son traitement, ou autre) et physiopathologie (somatique, viscérale, et / ou neuropathique). Ce diagnostic, en conjonction avec des facteurs contributifs psychosociaux et spirituels, est utilisé pour générer un plan de traitement de la douleur globale.

L'évaluation des résultats de la gestion de la douleur

Les résultats liés à la douleur: Les cliniciens doivent documenter et être conscients des résultats de traitement de la douleur. Il est utile de penser à des résultats liés à la douleur comme étant essentiellement mesurées de deux façons: réduit l'intensité de la douleur et l'amélioration du fonctionnement psychosocial. En utilisant des échelles de notation de l'intensité de la douleur à son paroxysme et, en moyenne et en utilisant des échelles d'interférence de la douleur peut aider les cliniciens à surveiller les résultats. Mesure du pourcentage de soulagement de la douleur est également utile, si la mesure de la satisfaction des patients est moins utile en raison des faibles attentes patients détiennent parfois pour le contrôle de la douleur. [26,27]

La consommation de drogues résultats: Les cliniciens qui prescrivent les opioïdes chroniques devraient aussi surveiller et prise de drogue les comportements des documents patients. Les résultats liés à la toxicomanie chez les patients cancéreux sont rares, mais néanmoins on doit vérifier régulièrement; ces évaluations peuvent être rassurant pour les patients. Tolérance et de dépendance ne sont pas la dépendance connexe. Documentation de la conformité des patients en ce qui concerne les changements dans le dosage et la durée des ordonnances est essentielle dans toute pratique de la douleur.

L'évaluation clinique de comportements de consommation de drogues chez les patients médicalement malades avec la douleur est complexe. Aberrant la consommation de drogue de la gestion de la douleur cancéreuse est liée à l'histoire prémorbide de la toxicomanie et de la probabilité d'un autre traitement de la douleur. Un questionnaire pilote a été utilisée pour caractériser les comportements et les attitudes liés à la drogue dans le cancer et les malades du SIDA. Malgré les limites, cette étude met en évidence une grande variation de potentiel entre les différentes populations de soins palliatifs dans les habitudes du passé et du présent aberrantes comportements de consommation de drogues et la nécessité d'une approche de dépistage cliniquement utiles. Les implications pour la prise en charge psychosociale et pharmacologique des symptômes tels que la douleur, ainsi que tout comportement aberrant, restent floues. [28,29,30]

Précédent abus de drogues est susceptible de conduire à des besoins spécifiques pour le dosage approprié pendant le traitement de la douleur cancéreuse. Une étude prospective ouverte a comparé la morphine dosage et l'efficacité chez les patients SIDA avec et sans précédent de la toxicomanie. Les résultats ont démontré que les deux groupes ont bénéficié, mais les patients ayant des antécédents d'usage de drogues nécessaire et toléré des doses de morphine beaucoup plus élevés pour obtenir un contrôle de la douleur stable [31] [Niveau de preuve: II]. Cette étude devrait accroître la confiance dans la fourniture de gestion de la douleur appropriés aux patients . qui ont des antécédents d'usage de drogues [32] [Niveau de preuve: IV]

Références:

1. Chung JW, Wong savoirs traditionnels, Yang JC: Le modèle de lentille: évaluation de la douleur du cancer dans un contexte chinois. Nurs Cancer 23 (6): 454-61, 2000.
2. Cleeland CS, Nakamura Y, Mendoza TR, et al .: Dimensions de l'impact de la douleur du cancer dans un échantillon de quatre pays: de nouvelles informations de mise à l'échelle multidimensionnelle. Douleur 67 (2-3): 267-73, 1996.
3. Greenwald HP: différences interethniques dans la perception de la douleur. La douleur 44 (2): 157-63, 1991.
4. Bates MS, Edwards WT, Anderson KO: influences ethnoculturelles sur la variation dans la perception de la douleur chronique. La douleur 52 (1): 101-12, 1993.
5. Beaux PG, Miaskowski C, le juge Paice: relever les défis de la gestion de la douleur cancéreuse. J Oncol soutien 2 (6 Suppl 4): 5-22; quizz 23-4, 2004 Nov-décembre
6. Mañas A, Monroy JL, Ramos AA, et al .: Prévalence de la douleur neuropathique en radiothérapie unités d'oncologie. Int J Oncol Biol Phys Radiât 81 (2): 511-20, 2011.
7. Mystakidou K, Tsilika E, Parpa E, et al .: La détresse psychologique des patients atteints de cancer avancé: l'influence et la contribution de la gravité de la douleur et l'interférence de la douleur. Cancer Nurs 29 (5): 400-5, 2006 Sep-octobre
8. Mercadante S, Portenoy RK: opioïdes douleur cancéreuse mal sensible. Partie 1: considérations cliniques. J douleur Symptôme Gérer 21 (2): 144-50, 2001.
9. Otis-Vert S, Sherman R, Perez M, et al .: Un modèle psychosocial et spirituel intégrée pour la gestion de la douleur cancéreuse. Cancer Prat 10 (Suppl 1): S58-65, 2002 mai-juin
10. Bruera E, K MacMillan, Hanson J, et al .: Le système de classification d'Edmonton pour la douleur cancéreuse: rapport préliminaire. La douleur 37 (2): 203-9, 1989.
11. Bruera E, T Schoeller, Wenk R, et al .: Une évaluation multicentrique prospective du système de mise en scène d'Edmonton pour la douleur cancéreuse. J douleur Symptôme Gérer 10 (5): 348-55, 1995.
12. Nekolaichuk CL, Fainsinger RL, Lawlor PG: Une étude de validation d'un système de classification de la douleur pour les patients atteints de cancer avancé utilisant des experts de contenu: le Système de classification Edmonton pour la douleur cancéreuse. Palliat Med 19 (6): 466-76, 2005.
13. Fainsinger RL, Nekolaichuk CL, Lawlor PG, et al .: Une étude multicentrique de l'Staging System Edmonton révisé pour classer la douleur du cancer chez les patients atteints de cancer avancé. J douleur Symptôme Gérer 29 (3): 224-37, 2005.
14. Fainsinger RL, Nekolaichuk CL: Un système de classification "TNM» pour la douleur cancéreuse: le Système de classification Edmonton pour la douleur cancéreuse (ECS-CP). Cancer Support Soins 16 (6): 547-55, 2008.
15. Allen RS, Haley NOUS, Petit BJ, et al .: douleur rapports par les patients atteints de cancer de soins palliatifs plus et aidants naturels: le rôle du fonctionnement cognitif. Gerontologist 42 (4): 507-14, 2002.
16. Black B, M. K, Beaux P, et al .: Les relations entre la douleur, les symptômes nonpain, et la qualité des mesures de la vie chez les personnes âgées atteintes de cancer reçoivent des soins palliatifs. Douleur Med 12 (6): 880-9, 2011.
17. Bruera E, Willey JS, Ewert-Flannagan PA, et al .: évaluation de l'intensité de la douleur par des infirmières de chevet et de consultants en soins palliatifs: une étude rétrospective. Cancer Support Soins 13 (4): 228-31, 2005.
18. Jensen MP, Karoly P: Mesure de la douleur cancéreuse du patient par l'intermédiaire d'auto-évaluation. Dans: Chapman CR, Foley KM, questions actuelles et émergentes dans la douleur cancéreuse de eds: la recherche et la pratique. New York, NY: Raven Press, 1993, pp 193-218.
19. Holen JC, Hjermstad MJ, Loge JH, et al .: outils d'évaluation de la douleur: le contenu est approprié pour une utilisation dans les soins palliatifs? J douleur Symptôme Gérer 32 (6): 567-80, 2006.
20. Fainsinger RL, Fairchild A, Nekolaichuk C, et al .: est l'intensité de la douleur un prédicteur de la complexité de la gestion de la douleur cancéreuse? J Clin Oncol 27 (4): 585-90, 2009.
21. Mercadante S, L Radbruch, Caraceni A, et al .: épisodique (percée) la douleur: conférence de consensus d'un groupe de travail d'experts de l'Association européenne de soins palliatifs. Cancer 94 (3): 832-9, 2002.
22. Mystakidou K, Tsilika E, Parpa E, et al .: Explorer les relations entre la dépression, le désespoir, l'état cognitif, la douleur et la spiritualité chez les patients atteints de cancer avancé. Arche Psychiatr Nurs 21 (3): 150-61, 2007.
23. Spiegel D, Bloom JR: douleur dans le cancer du sein métastatique. Cancer 52 (2): 341-5, 1983.
24. Daut RL, Cleeland CS: La prévalence et la gravité de la douleur dans le cancer. Cancer 50 (9): 1913-8, 1982.
25. Schumacher KL, Koresawa S, West C, et al .: L'utilité d'un journal quotidien de gestion de la douleur pour les patients externes souffrant de douleur liée au cancer. Oncol Nurs Forum 29 (9): 1304-1313, 2002.
26. Rhodes DJ, Koshy RC, Waterfield WC, et al .: faisabilité de l'évaluation quantitative de la douleur dans la pratique ambulatoire en oncologie. J Clin Oncol 19 (2): 501-8, 2001.
27. Hwang SS, Chang VT, Kasimis B: résultats dynamique de gestion de la douleur du cancer: la relation entre la sévérité de la douleur, soulagement de la douleur, l'interférence fonctionnelle, la satisfaction et la qualité globale de la vie au fil du temps. J douleur Symptôme Gérer 23 (3): 190-200, 2002.
28. Passik SD, Kirsh KL, MV McDonald, et al .: Une enquête pilote d'attitudes et de comportements drogue prenant aberrantes dans des échantillons de cancer et du SIDA. J douleur Symptôme Gérer 19 (4): 274-86, 2000.
29. Kirsh KL, LA Whitcomb, Donaghy K, et al .: abus et de dépendance chez les patients médicalement questions malades souffrant de douleurs: tentatives de clarification des termes et étude empirique. Clin J douleur 18 (4 Suppl): S52-60, 2002 Jul-août
30. Passik SD, Kirsh KL, Whitcomb L, et al .: Un nouvel outil pour évaluer et les résultats le document de la douleur chez les patients souffrant de douleurs chroniques recevant un traitement opioïde. Clin Ther 26 (4): 552-61, 2004.
31. Kaplan R, Slywka J, Slagle S, et al .: A titré analgésique morphinique schéma comparant les toxicomanes et les non-utilisateurs avec la douleur liée au SIDA. J douleur Symptôme Gérer 19 (4): 265-73, 2000.
32. LA Whitcomb, Kirsh KL, Passik SD: problèmes d'abus de substances dans la douleur cancéreuse. Curr Douleur Mal de tête Rep 6 (3): 183-90, 2002.

Principes de base de gestion de la douleur du cancer

L'Organisation mondiale de la Santé (OMS) a décrit une échelle analgésique en trois étapes comme un cadre pour la gestion de la douleur. [1] Il se agit d'une approche par étapes en fonction de la sévérité de la douleur. Si la douleur est légère, on peut commencer par prescrire un Étape 1 analgésique comme l'acétaminophène ou un médicament anti-inflammatoire non stéroïdien (AINS). Les effets négatifs potentiels doivent être notées, en particulier les effets indésirables rénaux et gastro-intestinaux des AINS. Si la douleur persiste ou se aggrave malgré des augmentations de doses appropriées, un changement à un analgésique étape 2 ou 3 est indiqué. La plupart des patients souffrant de douleur cancéreuse, il faudra un analgésique étape 2 ou 3. Étape 1 peut être ignorée chez les patients présentant au début de la douleur modérée à sévère en faveur de l'étape 2 ou 3. A chaque étape, un médicament adjuvant ou modalité tels que la radiothérapie peuvent être considérés comme chez des patients sélectionnés. Recommandations de l'OMS sont basées sur la disponibilité mondiale de médicaments et non pas strictement sur la pharmacologie.

Analgésiques doivent être donnés "par la bouche, par l'horloge, par l'échelle et de l'individu." [1] Cette option exige une programmation régulière de l'analgésique, et pas seulement au besoin. En outre, de sauvetage-doses pour les percées de douleur doivent être ajoutés. La voie orale est préférée dans la mesure où un patient est capable d'avaler. Chaque traitement analgésique doit être ajustée pour les circonstances individuelles du patient et la condition physique.

Acétaminophène et médicaments anti-inflammatoires

AINS sont efficaces pour le soulagement de la douleur légère et peut avoir un effet dose-épargnant opioïde qui aide à réduire les effets secondaires lorsqu'il est administré avec des opioïdes pour la douleur modérée à sévère. L'acétaminophène est inclus avec l'aspirine et autres AINS, car il a analgésique similaire puissance, si elle n'a pas d'activité anti-inflammatoire périphérique [2] [Niveau de preuve: I]. Les effets secondaires peuvent survenir à tout moment, et les patients qui prennent de l'acétaminophène ou les AINS, patients surtout les personnes âgées, devraient être suivis attentivement. [3,4,5] Il est de plus en plus question de savoir si les AINS sont utiles et ont des effets opioïdes épargne importantes. Une méta-analyse [6] suggère que l'utilité des AINS est limitée et qu'ils ne le font pas de manière significative doses d'opioïdes de rechange. Une autre étude suggère que les AINS sont utiles et réduisent la nécessité d'une augmentation de la dose d'opioïdes; Toutefois, seuls les patients avec une progression de la douleur après 1 semaine de la stabilisation des opioïdes ont été sélectionnés pour l'étude [7] [Niveau de preuve: I].

Les coxibs sont une sous-classe d'AINS destinés à inhiber sélectivement la cyclooxygénase-2 (COX-2). [8] Le développement de ces médicaments a été basée sur l'hypothèse que la COX-2 a été la source des prostaglandines E 2 et I 2, qui médient l'inflammation et que la COX-1 a été la source de prostaglandines dans les mêmes épithélium gastrique, avec l'avantage potentiel d'ulcération gastro-intestinale et moins de saignements et l'absence d'inhibition des plaquettes sur les AINS classiques. Les comparaisons directes entre inhibiteurs COX-2 sont peu nombreux. Une méta-analyse systématique des inhibiteurs COX-2 par rapport aux AINS traditionnels ou différents inhibiteurs de la COX-2 pour la douleur postopératoire suggère que le rofécoxib, 50 mg, et de parécoxib, 40 mg, sont aussi puissants que les AINS traditionnels pour la douleur postopératoire après des interventions chirurgicales mineures et majeures et ont une plus longue durée d'action après la chirurgie dentaire. Le rofécoxib a été trouvé pour fournir un effet analgésique supérieure à celle avec le célécoxib, 200 mg. Les données étaient insuffisantes pour commenter sur la toxicité [9] [Niveau de preuve: I].

Il ya trois coxibs qui ont été approuvés par la US Food and Drug Administration (FDA): le célécoxib, le rofécoxib et valdécoxib. Le 30 Septembre 2004, le rofécoxib a été retiré du marché après une étude a démontré que les sujets dans un essai de prévention du cancer du côlon qui a pris le médicament à des doses plus élevées que typique sur une base à long terme ont eu une augmentation significative de l'incidence de grave complications thromboemboliques. La question qui reste sans réponse est de savoir si l'augmentation du risque se applique à tous les inhibiteurs COX-2, avec la prudence que le fardeau de la preuve incombe à ceux qui pourraient prétendre que ce est un problème pour le rofécoxib seul et ne se étend pas à d'autres coxibs. [8 , 10] Le 7 Avril 2005, le valdécoxib a été retiré du marché. FDA demande également les fabricants de tous les AINS sur ordonnance commercialisés, y compris le célécoxib (Celebrex), de réviser l'étiquetage (notice) pour leurs produits afin d'inclure un avertissement en boîte, en soulignant le potentiel de risque accru d'événements cardiovasculaires et / ou de la grave, potentiellement mortelle saignements gastro-intestinaux associés à l'utilisation de ces médicaments.

Dosage

Use patient response to determine the effective dosing interval for aspirin, acetaminophen, and other NSAIDs listed in Table 1. When pain relief is not attained with the maximum dosage of one NSAID, try other drugs within this category before abandoning NSAID therapy.

Route of administration

Use readily available oral tablets, capsules, or liquid. During intervals of nausea and vomiting, use suppositories, unless the nausea is NSAID related. Ketorolac tromethamine is the only NSAID available for parenteral use.

Contraindications

Patients taking NSAIDs are at risk for platelet dysfunction that may impair blood clotting. Table 1 lists NSAIDs with minimal antiplatelet activity.

Other side effects

Observe patients carefully for adverse effects, which range from mild gastrointestinal discomfort to more serious problems, including the following:

Gastric ulceration.Hepatic dysfunction.Myocardial infarction.Renal failure.

Because both NSAIDs and other drugs (eg, warfarin, methotrexate, digoxin, cyclosporine, oral antidiabetic agents, and sulfonamide-containing drugs) are highly protein-bound, there is potential for altered efficacy or toxicity when they are given simultaneously.

Table 1. Dosing Recommendations for Acetaminophen and NSAIDs a

Drogue Usual Dose for Adults and Children ≥50 kg Body Weight Usual Dose for Adults and Children b <50 kg Body Weight
bid = twice a day; IV = intravenous; NSAID = nonsteroidal anti-inflammatory drug; q = every; tid = 3 times a day.
a Only the NSAIDs listed here have FDA approval for use as simple analgesics, but clinical experience has also been gained with other drugs.
b Acetaminophen and NSAID dosages for adults weighing less than 50 kg should be adjusted for weight.
c Acetaminophen lacks the peripheral anti-inflammatory and antiplatelet activities of the other NSAIDs.
d The standard against which other NSAIDs are compared. May inhibit platelet aggregation for longer than 1 week and may cause bleeding. Aspirin is not recommended for pain in children.
e May have minimal antiplatelet activity.
f Administration with antacids may decrease absorption.
g Use limited to 5 days or fewer.
h Coombs-positive autoimmune hemolytic anemia has been associated with prolonged use.
I Has the same gastrointestinal toxic effects as oral NSAIDs.
Orally Administered Acetaminophen and Over-the-counter NSAIDs
acetaminophen c 650 mg q4h 10–15 mg/kg q4h
975 mg q6h 15–20 mg/kg q4h (rectal)
aspirin d 650 mg q4h 10–15 mg/kg q4h
975 mg q6h 15–20 mg/kg q4h (rectal)
ibuprofen (Motrin, Advil) 400–600 mg q6h 5–10 mg/kg q4–6h
magnesium salicylate (Doan's, Magan, Mobidin, others) 650 mg q4h
naproxen (Naprosyn, Aleve) 250–275 mg q6–8h 5 mg/kg q8h
naproxen sodium (Anaprox) 275 mg q6–8h
Prescription NSAIDs
carprofen (Rimadyl) 100 mg tid
choline magnesium trisalicylate e (Trilisate) 1,000–1,500 mg q6–8h 25 mg/kg q6–8h
choline salicylate e (Arthropan) 870 mg q3–4h
diclofenac (oral) (Voltaren - 1% topical; Pennsaid - 1.5% topical) 50 mg bid–tid oral; 32 g/d topical Flector (patch): 1 patch bid
diflunisal f (Dolobid) 500 mg q12h
etodolac (Lodine) 200–400 mg q6–8h
fenoprofen calcium (Nalfon) 300–600 mg q6h
ketoprofen (Orudis) 25–60 mg q6–8h
ketorolac tromethamine g (Toradol) 10 mg q4–6h to a maximum of 40 mg/d
IV administration should not exceed 5 days
meclofenamate sodium h (Meclomen) 50–100 mg q6h
mefenamic acid (Ponstel) 250 mg q6h
sodium salicylate (Anacin, Bufferin) 325–650 mg q3–4h
Parenteral NSAIDs
acetaminophen injection 1,000 mg q6h (adults) 15 mg/kg max, 75 mg/kg in 24 h (children aged <13 y)
ketorolac tromethamine g,i (Toradol) 60 mg initially, then 30 mg q6h
IV administration should not exceed 5 days

Opioids

Opioids, the major class of analgesics used in management of moderate-to-severe pain, are effective, are easily titrated, and have a favorable benefit-to-risk ratio.

The predictable consequences of long-term opioid administration—tolerance and physical dependence—are often confused with psychological dependence (addiction) that manifests as drug abuse. This misunderstanding can lead to ineffective prescribing, administering, or dispensing of opioids for cancer pain. The result is undertreatment of pain.[11]

Clinicians may be reluctant to give high doses of opioids to patients with advanced disease because of a fear of respiratory depression. Many patients with cancer pain become opioid tolerant during long-term opioid therapy. Therefore, the clinician's fear of shortening life by increasing opioid doses is usually unfounded.

Opioid types

Opioids are classified as full morphine-like agonists, partial agonists, or mixed agonist-antagonists, depending on the specific receptors to which they bind and their activity at these receptors. The benefits of using opioids and the risks associated with their use vary among individuals.

Morphine is the most commonly used opioid in cancer pain management, largely for reasons of availability and familiarity;[12] however, it is useful to be familiar with more than one type of opioid. Wide interindividual variability in response to both the analgesic and adverse effects of opioids is recognized.[13] Some patients may not experience adequate pain control despite appropriate dose adjustments, while others may develop intolerable adverse effects to one particular opioid (see below). Alternative opioids include hydromorphone, oxycodone, oxymorphone, methadone, and fentanyl. Knowledge of several medications and formulations gives the caregiver much more flexibility in tailoring a regime to a particular patient's needs.

Short-acting opioids are generally recommended when opioid therapy is being initiated for the first time or when patients are medically unstable or the pain intensity is highly variable. Once stable, patients can be switched to a controlled-release or slow-release formulation. This is more convenient and promotes compliance. (Refer to Table 3 in the Principles of Opioid Administration section of this summary for more information.)

Full agonists

Morphine, hydromorphone, codeine, oxycodone, oxymorphone, hydrocodone, methadone, levorphanol, and fentanyl are classified as full agonists because their effectiveness with increasing doses is not limited by a ceiling. Full agonists will not reverse or antagonize the effects of other full agonists given simultaneously.

Morphine

The most commonly used opioid, morphine, is readily available in several forms, including sustained-release (8–24 hours duration of effectiveness) formulations for oral administration.

Other agonists

For the patient who experiences dose-limiting side effects with one oral opioid (eg, hallucinations, nightmares, dysphoria, nausea, or mental clouding), other oral opioids should be tried before abandoning one route in favor of another.

Methadone

Methadone has had a revival in interest for the management of cancer pain. Published reports have been in the form of case reports,[14,15,16,17,18,19,20][Level of evidence: III] outcome surveys,[21,22,23,24,25][Level of evidence: II][Level of evidence: III] and reviews.[26,27,28][Level of evidence: IV] Success has been reported with oral, intravenous (IV), and suppository methadone use. Subcutaneous methadone has been reported to cause tissue irritation at the injection site but has been used effectively in some patients without clinically significant local toxicity.[29][Level of evidence: II]

Methadone is a synthetic opioid agonist that has been reported to have a number of unique characteristics. These include excellent oral and rectal absorption, no known active metabolites, prolonged duration of action resulting in longer administration intervals, and lower cost than other opioids. Methadone is available as a pill, an elixir, and for parenteral use. Methadone has an average oral bioavailability of approximately 80% (range, 41%–99%).[30]

Morphine is the international gold standard for first-line treatment of cancer pain. Methadone, however, can be considerably less expensive than existing rapid-release or sustained-release morphine or other opioid options. A randomized trial of 103 patients compared the effectiveness and side effects of morphine and methadone as first-line treatments for cancer pain. The outcome of successful pain management was similar for both groups; however, there were significantly more opioid-related dropouts in the methadone group. This study did not demonstrate superior analgesic effectiveness or overall tolerability of methadone over morphine as a first-line treatment for cancer pain. Despite this finding, the authors of this report suggested that study limitations did not allow definitive conclusions that methadone could not be a useful first-line opioid. Further research exploring other doses and schedules of methadone should still be explored.[31][Level of evidence: I]

Because of its long and unpredictable half-life and relatively unknown equianalgesic dose as compared with other opioids, methadone has been generally used by pain specialists with experience in its use. The utility of methadone in cancer pain and difficult cancer pain syndromes such as neuropathic pain has become more widely appreciated and has gained increasing acceptance for use in hospital and hospice settings and by clinicians who are not pain specialists.[32][Level of evidence: II] The methadone preparation widely used in the United States is a racemic mix of the d-isomer and l-isomer of methadone. The d-isomer has antagonist activity at the N-methyl-D-aspartate (NMDA) receptor and may be beneficial in controlling neuropathic pain.

Another controversy related to methadone is the concern that this drug may be associated with a prolonged QTc interval and may lead to torsades de pointes and ventricular arrhythmia. A number of studies have raised this concern. A series of 132 patients taking methadone revealed statistically significant mean increases in QTc of 10.2 to 13.2 milliseconds, yet no episodes of torsades de pointes were reported.[33][Level of evidence: III] This result raises the issue of the clinical significance of this effect. In another retrospective review of 520 patients treated with methadone for cancer pain, no change in QTc was seen in the 56 patients who had electrocardiograms 3 months before and after starting methadone.[34,35] Another study of 100 cancer patients revealed a baseline electrocardiogram in 28%, with only one demonstrating a clinically significant increase in QTc at week 2.[36] Avoidance of concomitant medications that prolong QTc interval [37] or that share common metabolism pathways with methadone [34] is recommended. In high-risk situations, clinicians could consider electrocardiogram monitoring and other clinical precautions such as correcting electrolyte abnormalities.

When converting from another opioid to methadone, the calculated equianalgesic dose ratio of methadone varies depending on the oral morphine-equivalent daily dose (MEDD) of the previous opioid.[38][Level of evidence: II];[22][Level of evidence: III] One guideline for choosing an appropriate initial dose of methadone based on the oral MEDD of the previous opioid is shown in Table 2. For example, a patient who has been using sustained-release morphine at 80 mg every 8 hours (240 mg/d) would be appropriately switched to methadone at a dose of 10 mg every 8 hours (30 mg/d, an 8:1 conversion ratio). In contrast, a patient who is taking sustained-release morphine at a total daily dose of 60 mg/d might be switched to an oral methadone dose of 5 mg every 8 hours (15 mg/d, a 4:1 conversion ratio).

Table 2. Method 1: Initial Methadone Dose Based on Oral MEDD a

Oral MEDD (mg/d) Initial Dose Ratio (oral morphine:oral methadone)
MEDD = morphine-equivalent daily dose.
a Reprinted with permission from Fisch and Cleeland.[39]
b Great caution must be used when converting to methadone when very high opioid doses have been used. Often, only a portion of the total opioid dose is converted initially, with further conversions taking place over several days to weeks.
<30 2: 1
30–99 4:1
100–299 8: 1
300–499 12: 1
500–999 15: 1
> 1000 20:1 or greater b

To be conservative, one might estimate that methadone is roughly twice as potent when administered via IV versus oral administration. Thus, a patient with well-controlled pain on a stable oral methadone dose of 10 mg every 8 hours might be given IV methadone at an initial dose of 5 mg every 8 hours if IV use is necessary. Subcutaneous use of methadone may cause skin irritation in some patients but has been used successfully.

In addition to the method described in Table 2, several methods of switching to methadone have been proposed.[22,40,41][Level of evidence: III];[42,43][Level of evidence: II];[44] Some rely on patient-controlled analgesia with fixed doses and flexible intervals, some require fixed intervals and fixed doses, while others stagger the conversion over a few days. Whatever method is chosen, this kind of switch can be safe and effective as long as regular assessments are provided over time, and there is an appreciation of the equianalgesic dose ratio of methadone to morphine in opioid-tolerant patients.

Method 2: Staggered or 3-day Switchover [43]

One approach calls for a gradual switch over 3 to 5 days to decrease the risk of relative overdosing. An equianalgesic dose of methadone is first calculated, using an equianalgesic dose ratio of morphine to methadone of 10:1 (ie, methadone is approximately ten times more potent than morphine). The caveat in using a ratio of 10:1 is that variations in ratios have been noted, depending on the dose of the previous opioid. The ratio may be much higher (12:1 or even higher) in patients being switched from high doses of morphine to methadone. The following example is given to illustrate this method:

A patient who is on the equivalent of 450 mg/d of oral morphine (quick-release morphine 75 mg orally every 4 hours) needs to be switched to methadone. Using a ratio of 10:1, the predicted equivalent daily oral dose of methadone, once the switch is completed, will be 45 mg.On day 1 of the switch, the daily morphine dose is reduced by one-third to approximately 300 mg (morphine 50 mg orally every 4 hours), and one-third of the predicted daily methadone dose is added, divided into three doses per 24 hours (ie, methadone 5 mg orally every 8 hours). Morphine continues to be given for rescue doses.On day 2 of the switch, the patient is reassessed. If no problems have developed, the morphine dose is reduced by another third (ie, morphine 25 mg orally every 4 hours), and the methadone dose is increased by another third (ie, methadone 10 mg orally every 8 hours).On day 3 of the switch, the patient is reassessed.

If there are complications such as significant somnolence, but the pain is still not under good control, the methadone dose is increased to 15 mg every 8 hours, and the morphine is discontinued.A rescue dose of methadone or a short half-life opioid is added, as needed. The rescue dose is calculated at 5% to 15% of the total daily dose.If the patient has good pain control but shows signs of relative overdosing (eg, significant somnolence), the methadone dose is not increased (ie, it remains at the day 2 level or may even be decreased, if needed), and the morphine is discontinued. Method 3: Ad Libitum [40]

This approach calls for the previous dose to be discontinued and a single fixed-dose of methadone to be given at the start, calculated using an equianalgesic dose ratio of morphine to methadone of 10:1 (ie, morphine 10 mg being roughly equivalent to 1 mg of methadone), but to a maximum of 50 mg of methadone per dose. After the initial single priming dose, the same dose is administered every 3 hours as needed. When the clinician observes the patient's demand for rescue doses reduces or stabilizes (indicating steady-state being reached), which is usually on day 4 to 7, the daily requirement is recalculated and the dose is given every 8 to 12 hours.

Method 4: Initial Priming Followed By Variable Conversion [42]

In this method, an opioid-naïve patient is started on 3 to 5 mg of methadone every 8 hours, and a nonnaïve patient is started on a dose of methadone that is equivalent to 50% of the estimated daily morphine dose. These doses are initially given for 3 days. Once the patient has acceptable pain relief for 6 to 8 hours, the dose is changed to a single fixed dose once a day and rescue doses are given as needed. This method is probably best suited for opioid-naïve patients (in relatively unlikely situations where more frequently used opioids such as morphine are not available) or patients who are, for one reason or another, being switched from relatively low doses of morphine or other opioids.

Method 5: German Model [41]

This method is suggested when patients are being switched from high equivalent daily doses of morphine (>600 mg/d orally). The morphine or other opioid the patient is receiving is stopped. Methadone at a dose of 5 to 10 mg orally is started every 4 hours and rescue doses of 5 to 10 mg every hour are allowed as needed. On the second to third days of the switch, the methadone dose is increased by up to 30% every 4 hours until sufficient pain relief is achieved and no significant adverse effects are noted. After exactly 72 hours following the switch to methadone, the dose is changed from every 4 hours to every 8 hours, and the interval of rescue doses is increased to every 3 hours as needed at the same single dose as established on days 2 to 3. The dose can then be increased by up to 30% if further upward titration is required.

In some countries, there are restrictions on the ability of physicians to prescribe methadone that do not apply to other opioids. In the United States, this pertains to methadone for maintenance of addiction. Methadone is not restricted when used for pain management; however, physicians should carefully document the use of methadone.[45] It should be noted that ratios are different for switching from methadone to a morphine-like opioid.[22]

Meperidine (Demerol)

Useful for brief courses (a few days) to treat acute pain, meperidine is not recommended in treating persistent cancer pain because of its short duration of action (2.5–3.5 hours) and its neurotoxic metabolite, normeperidine. Accumulation of this metabolite, particularly when renal function is impaired, causes central nervous system (CNS) stimulation that may lead to delirium or seizures. Seizures are typically preceded by development of multifocal myoclonus, which can serve as a warning sign.

Tapentadol

Tapentadol is a centrally acting analgesic with a dual mode of action, as a mu-opioid receptor agonist and norepinephrine reuptake inhibitor.[46,47] In 2009, the FDA approved immediate-release tapentadol for the management of moderate to severe pain. In August 2011, the FDA also approved the extended-release formulation of tapentadol for the management of moderate to severe chronic pain. As with other mu-opioid receptor agonists, use of tapentadol may be associated with respiratory depression, sedation, nausea, and constipation. No studies have been published in cancer pain. In the noncancer setting, there appear to be fewer gastrointestinal adverse effects with tapentadol than with oxycodone.[46,47] Cases of life-threatening serotonin syndrome have been reported with the concurrent use of tapentadol and serotonergic drugs (this includes serotonin reuptake inhibitors; serotonin and norepinephrine reuptake inhibitors; tricyclic antidepressants; triptans; drugs that affect the serotonergic neurotransmitter system, such as mirtazapine, trazodone, and tramadol; and drugs that impair metabolism of serotonin). Extended-release tapentadol has not been evaluated in patients with a predisposition to seizure disorder.

Tramadol

Tramadol can be considered an atypical opioid analgesic that has a dual action. It is a weak mu-opioid agonist that also inhibits the reuptake of norepinephrine and serotonin.[48][Level of evidence: IV];[49][Level of evidence: I] It is believed that both mechanisms work synergistically to provide analgesic benefit with a potency that is approximately one-tenth that of morphine [50][Level of evidence: II] and approximately equivalent to codeine. The most common side effects reported with tramadol are drowsiness, constipation, dizziness, nausea, and orthostatic hypotension.[48] There is also a risk of precipitating seizures in patients with a previous history or in patients who are receiving medications that could reduce the seizure threshold. The use of other serotonergic medications (eg, selective serotonin reuptake inhibitors [SSRIs] and serotonin-norepinephrine reuptake inhibitors [SNRIs]) together with tramadol has the potential to increase the risk of the serotonin syndrome. Tramadol is available in short- and long-acting formulations and in fixed combination with acetaminophen. The recommended starting dose of oral tramadol is 50 mg 1 or 2 times a day, with gradual titration up to a maximum of 400 mg/d.[48] There is also the option of using tramadol via the rectal or subcutaneous route in patients who are unable to tolerate oral medication.[51][Level of evidence: I];[52]

Partial agonists

Partial agonists such as buprenorphine are subject to a ceiling effect and are less effective analgesics than full agonists at opioid receptors. A 7-day buprenorphine patch is available; the maximum dose is 20 μg per hour because of the potential for prolonged QTc wave interval.[53]

Mixed agonist-antagonists

Mixed agonist-antagonists block or are neutral at one type of opioid receptor while activating a different opioid receptor. Mixed agonist-antagonists are contraindicated for use in the patient receiving an opioid agonist because they may precipitate a withdrawal syndrome and increase pain. Mixed agonist-antagonists include pentazocine (Talwin), butorphanol tartrate (Stadol), dezocine (Dalgan), and nalbuphine hydrochloride (Nubain). Their analgesic effectiveness is limited by a dose-related ceiling effect.

Principles of opioid administration

Most patients with cancer pain require fixed-schedule dosing to manage the constant pain and prevent the pain from worsening.[54][Level of evidence: II] An Italian study of patients whose baseline pain was well controlled on morphine when admitted to a palliative care unit found that most episodes of breakthrough pain were rapidly controlled with IV morphine equivalent to 20% of the calculated equianalgesic total daily dose. Adverse effects were uncommon.[55][Level of evidence: II] An as-needed rescue dose (breakthrough dose) should be combined with the regular fixed-schedule opioid to control the episodic exacerbation of pain, often referred to as breakthrough pain. When this pain is elicited by an action such as weight-bearing, breathing, or defecation, it is termed incident pain. Rescue or breakthrough doses can be given hourly or more frequently as needed, depending on route of administration, pharmacokinetic properties of the drug, and presence or absence of side effects. The breakthrough dose is generally calculated to be 10% to 20% of the total dose of the fixed schedule.[56][Level of evidence: III] Adherence rates are improved when patients are prescribed around-the-clock opioids compared with as-needed prescribing.[57][Level of evidence: I] Preliminary data suggest that the intensity of incident pain related to bone metastases may be diminished by increasing the dose of the scheduled opioid above that needed for control of baseline pain, while maintaining it below that associated with the development of limiting side effects.[58][Level of evidence: II]

Dosage

The appropriate dosing interval is determined by the opioid and formulation used. The analgesic effects of short-acting oral opioids such as morphine, hydromorphone, codeine, and oxycodone begin within a half hour after administration and last for approximately 4 hours. The dosing interval of these drugs is usually 4 hours. In patients given controlled-release formulations of morphine, hydromorphone, codeine, or oxycodone, relief should begin in 1 hour, peak in 2 to 3 hours, and last for 12 hours (controlled-release codeine is not available in the United States); these formulations are usually prescribed in 12-hour intervals. The analgesic effect of transdermal fentanyl begins approximately 12 hours after the application of the patch, peaks in 24 to 48 hours, and lasts for approximately 72 hours. Patches are therefore changed every 72 hours. In a select group of patients who consistently experience end-of-dose failure despite increases in the patch doses, the dosing interval can be increased to every 48 hours (<10% of patients on fentanyl patches). Transdermal fentanyl is not recommended for control of acute pain or poorly controlled pain because there is a delayed onset of action until reaching steady-state either with new use or with a change in the dose. Patients receiving transdermal fentanyl may be switched to a continuous IV or subcutaneous infusion of fentanyl using a conversion ratio of 1:1 to facilitate more rapid titration.[59][Level of evidence: III]

Dose titration

To date, dose titration is largely patient-driven, as determined by the balance of analgesia with side effects.[60][Level of evidence: II] For example, while morphine dose correlates with peak-and-trough plasma concentrations of a parent drug and its metabolites morphine-3-glucuronide and morphine-6-glucuronide, studies are conflicting with regard to the association between plasma levels of morphine and its metabolites versus analgesia as measured by pain scores.[61][Level of evidence: II] The strong opioid agonists have no maximum dose or ceiling dose. The appropriate dose is the amount of opioid that controls pain with the fewest side effects. Dose titration should continue until good pain relief is achieved or intolerable side effects develop that cannot otherwise be controlled. The goal is to achieve a favorable balance between analgesia and side effects through gradual adjustment of the dose. If analgesic tolerance appears to be occurring, the dose can be increased or consideration given to switching the opioid, especially if higher doses are required.

The severity of the pain and the opioid formulation chosen determine the rate of titration. The dose of immediate-release formulations can be increased on a daily basis if necessary until pain relief is adequate. Among patients receiving relatively low doses of opioids, those with uncontrolled moderate-intensity pain require daily increases of between 25% and 50% to their previous dose, while patients with severe uncontrolled pain may require a higher increase. At higher opioid doses, increases of 20% to 30% would be more prudent. Rapid dose escalation requires close monitoring for both efficacy and side effects. Preliminary data suggest that titration with sustained-release daily morphine is equivalent to titration with immediate-release morphine administered every 4 hours by an expert group of clinicians, but standard practice is to use a short-acting opioid for initial titration.[62][Level of evidence: I]

Occasionally, doses may need to be reduced or, rarely, stopped. This may occur when patients become pain free as a result of cancer treatment, including treatments such as nerve blocks and radiation therapy. Another time to consider reducing the dose is when a patient experiences significant opioid-related sedation that is accompanied by good pain control or when there is metabolite retention in the context of developing and/or worsening renal failure. In situations where interventions achieve complete pain relief, rapid opioid tapering rather than abrupt discontinuation is recommended to avoid opioid withdrawal symptoms.

Different types of opioids

The debate regarding whether any individual opioid causes fewer side effects or is more effective is characterized by much speculation but little clinical evidence. These inconclusive findings have prompted expert working groups of the European Association of Palliative Care to recommend that there is currently little evidence of the clinical superiority of one opioid over another regarding the side-effect profile and/or analgesia.[12,13] Even constipation and other side effects may be positively affected by a switch. Compared with morphine, fentanyl may cause less constipation.[63][Level of evidence: II];[64][Level of evidence: I] Studies suggesting that oxycodone and hydromorphone may cause less nausea and hallucinations than morphine [65] are juxtaposed with other studies that found no significant differences between them.[66,67,68][Level of evidence: I] One study found that transdermal fentanyl was better tolerated than sustained-release oral morphine and equally effective.[69][Level of evidence: I]

Tolerance

Assume that patients actively abusing heroin or prescription opioids (including methadone) have some pharmacologic tolerance that will require higher starting doses and shorter dosing intervals.

Opioid therapy in special populations

Health professionals should check current recommendations for opioid use in older people, children, people who are cognitively impaired, and known or suspected drug abusers.

Opioid switching (Opioid rotation)

A series of case reports have demonstrated the clinical problem of inadequate pain control with escalating opioid doses in the presence of dose-limiting toxic effects, including hallucinations, confusion, hyperalgesia, myoclonus, sedation, and nausea.[17,23,70,71,72][Level of evidence: III] It was suggested that these problems could be managed by switching to an alternative opioid, with the result being improved pain management and decreased toxic effects. The improvement with opioid switching, although predominantly demonstrated initially with morphine, has also been reported with other opioids.[73,74,75][Level of evidence: III];[76][Level of evidence: II] A retrospective review over a 1-year period in a pediatric oncology center supports efficacy of this technique in children, with resolution of adverse opioid effects, largely pruritus, achieved in 90% of patients, while maintaining pain control.[77][Level of evidence: III]

Guidelines for switching from one opioid to another

Guidelines for opioid switching are intended to reduce the risk of relative overdosing or underdosing as one opioid is replaced by another. These guidelines require a working knowledge of an equianalgesic-dose table.[13,78][Level of evidence: IV] The equianalgesic-dose table provides only a broad guide for dose selection when switching from one opioid to another. Wide ranges in interindividual responses to the various opioids have been noted.[78][Level of evidence: IV] Therefore, because of incomplete cross-tolerance in most cases, the calculated dose-equivalent of a new drug must be reduced by 25% to 50% to ensure safety. These figures are based on clinical experience rather than empiric data. The selection of an alternative opioid is largely empirical. There is little clinical evidence to indicate that one opioid has therapeutic superiority over another opioid. A patient, for example, who requires a switch from morphine to another opioid can be switched to hydromorphone, oxycodone, fentanyl, or methadone.[79][Level of evidence: III];[80,81][Level of evidence: II] In one prospective study of 186 cancer patients being treated with morphine, 25% did not respond and required switching to another opioid (oxycodone). The primary reasons for switching included pain, confusion, drowsiness, nightmares, and nausea. Of the 47 patients who required switching to an alternative opioid, 37 (79%) obtained good relief. This result provides beginning evidence for the prevalence of the need to switch, as well as determining the success rate once switching occurs.[82][Level of evidence: II] Patients should be followed closely after a switch and should be reassessed, and the new opioid dose should be adjusted according to the intensity of pain and lack or presence of adverse effects.

Note: The values that appear in Table 3 are NOT recommended starting doses. Opioid doses are highly variable and should be based on the individual's previous responses and overall condition. Important cautions are contained in the footnotes.

Table 3. Approximate Dose Equivalents for Opioid Analgesics a

Drogue Oral Dose (mg) Parenteral Dose b
IV = intravenous; NA = not available.
a Published tables vary in the suggested doses that are equianalgesic to morphine. Many of these doses are based on clinical consensus rather than well-controlled trials. Clinical response is the criterion that must be applied for each patient; titration to clinical response is necessary. Because there is not complete cross-tolerance among these drugs, it is usually necessary to use a lower-than-equianalgesic dose when changing drugs and re-titrate according to response.
b Parenteral dosing includes IV and subcutaneous administration. Onset and duration may vary slightly between these routes; however, doses remain approximately equal. The intramuscular route is not recommended because of variability in uptake of the drug and painful injection.
c Caution: For morphine, hydromorphone, and oxymorphone, rectal administration is an alternate route for patients unable to take oral medications. Equianalgesic doses may differ from oral to parenteral doses because of pharmacokinetic differences. Note: A short-acting opioid should normally be used for initial therapy of moderate-to-severe pain.
d Caution: Doses of aspirin and acetaminophen in combination opioid/NSAID preparations must be adjusted to the patient's body weight.
e Transdermal fentanyl is an alternative. Transdermal fentanyl dosage is not calculated as equianalgesic to a single morphine dosage but is calculated based on a 24-hour opioid dose. See package insert for dosing calculations. Transdermal fentanyl should not be used in opioid-naive patients.
f Transmucosal and buccal fentanyl are also available and indicated for breakthrough pain, although they are not bioequivalent. Titration of either should be conducted gradually; neither should be used in opioid-naive patients.
g Caution: Methadone is much more potent than indicated in older published literature. On average, it is ten times more potent than morphine. However, its potency relative to morphine is not linear. When morphine at lower doses (eg, 30–60 mg/d orally) is switched to methadone, the potency may be 3 to 5 times; when switched from high doses (eg, >300 mg/d orally), the potency may be 12 times or even higher.
h Caution: The oral to IV dose ratio of methadone is not well established. The IV route is very seldom used, except in cancer centers with pain service familiar with parenteral methadone. Intravenous use of methadone in combination with chlorobutanol is associated with QTc wave prolongation.[37][Level of evidence: III] Subcutaneous administration may cause irritation.
Morphine c 30 10 mg
Codeine d 200 100 mg
Fentanyl e,f N / A 100 μg
Hydrocodone (Vicodin, Lortab, Norco) d 30–45 N / A
Hydromorphone (Dilaudid) c 8 2 mg
Levorphanol (Levo-Dromoran) 4 2 mg
Methadone g,h The conversion ratio of methadone is variable. Please refer to theOpioid typessection andOpioid switching (Opioid rotation)section.
Oxycodone (OxyContin) d 20-30 10–15 mg
Oxymorphone (Opana, Opana ER, and Opana IV) c 10 1 mg

It has been suggested that a less complicated approach than opioid switching would be reassessment of the clinical situation and use of adjuvant analgesics, decreasing the opioid dose if possible, use of medical management for opioid-related side effects, and correction of any contributing metabolic abnormalities.[83,84] Nevertheless, there does appear to be an emerging consensus that opioid switching does have a useful role when pain control remains inadequate with escalating opioid doses and opioid use results in unacceptable opioid-related side effects.[83,84,85][Level of evidence: IV]

Morphine, as the strong opioid of choice for the management of cancer pain, was used increasingly during the 1970s and 1980s.[86][Level of evidence: IV] Associated with this increasing experience was the clinical observation of the risk of accumulation of morphine metabolites, particularly in the presence of renal impairment. Morphine-6-glucuronide, an analgesic metabolite, was recognized as having a useful role in enhancing analgesia. A number of reports, however, have described seizures, cognitive impairment, nausea, and problems of myoclonus that were associated with accumulation of morphine-6-glucuronide.[86,87,88][Level of evidence: IV];[89,90,91][Level of evidence: II];[92,93][Level of evidence: III]

The potential role of morphine metabolites, in particular the ratio of 3-glucuronide to 6-glucuronide in the development of opioid-related toxicity, has been reported. The literature on this issue has been somewhat controversial. There is no disagreement that morphine metabolites increase in the presence of deteriorating renal function; however, there has been conflicting evidence regarding the role and ratios of the metabolites in patients exhibiting both a poor response to increasing morphine doses and associated toxicity.[94,95,96,97,98]

Switching from one opioid to another requires familiarity with a range of opioids and the use of opioid dose-conversion tables.[13,78] When using these ratios, it must be understood that the guidelines should be reviewed and the patients should be monitored more closely during the switching phase. One review has highlighted some important issues related to these tables.[78] Wide ranges in ratios are noted. In the case of methadone, it is much more potent than previously thought (on average ten times more potent), and its equianalgesic dose-ratio compared to other opioids changes according to the dose of the previous opioid; the higher the dose, the higher the ratio. (Note that potency does not denote more effectiveness but denotes the equivalent dose required to obtain the same effect.)

Route of administration

Oral administration is preferred in patients with intact gastrointestinal tracts because it is convenient and usually inexpensive. When patients cannot take oral medications, other less invasive routes (eg, rectal or transdermal) should be offered. Parenteral methods should be used only when simpler, less demanding, and less costly methods are inappropriate, ineffective, or unacceptable to the patient. In general, assessing the patient's response to several different oral opioids is advisable before abandoning the oral route in favor of anesthetic, neurosurgical, or other invasive approaches.

Rectal

Use this safe, inexpensive, effective route for delivery of opioids as well as nonopioids when patients have nausea or vomiting. Rectal administration is inappropriate for the patient who has diarrhea, anal/rectal lesions, mucositis, thrombocytopenia, or neutropenia. The use of suppositories is not always culturally acceptable and may not be practical for patients who are obese, have fractures, are physically unable to place the suppository in the rectum, or prefer other routes. When changing from the oral to the rectal route, begin with the same dosage as had been given orally, then titrate as needed.

Transdermal

Fentanyl patches are formulated to provide analgesia lasting up to 72 hours. This preparation is not suitable for rapid dose titration and should be used for relatively stable analgesic requirements when rapid increases or decreases in dosage are not likely to be needed.[99][Level of evidence: I];[100] In the chronic setting, considerable inter- and intraindividual variability may exist in the rate of absorption of fentanyl from transdermal patches in patients receiving a stable dose of transdermal fentanyl.[101,102][Level of evidence: II] Based on a case series, it has been proposed that conversion from transdermal to IV fentanyl using a 1:1 conversion ratio can be safe and effective during acute exacerbations of cancer pain.[59][Level of evidence: III] Although other opioids such as morphine are sometimes compounded into gel form for transdermal application, bioavailability studies demonstrate plasma levels of drug below the level of detection. This practice should not be supported.[103][Level of evidence: I]Transdermal buprenorphine has been used with success for the treatment of cancer-related pain in Europe, although studies in the United States are not yet published.[104][Level of evidence: I]

Transmucosal/Buccal (fentanyl)

Oral transmucosal fentanyl citrate is used for the relief of breakthrough pain. The lipid solubility of fentanyl allows rapid onset of pain relief. In open-label studies, 72% to 92% of patients found a dose that provided relief from breakthrough pain. Side effects in these studies were consistent with other opioid therapies, including sedation, constipation, stomatitis, and nausea.[105,106][Level of evidence: II] There is growing interest in the use of rapidly acting, highly lipophilic opioids such as fentanyl for the management of difficult breakthrough pain syndromes.[107][Level of evidence: I] An oral transmucosal fentanyl citrate compound for buccal administration has become available for this purpose.[108,109][Level of evidence: I] A double-blind, randomized, placebo-controlled study included 77 patients assigned to dose sequences of fentanyl buccal tablets (FBT). Results demonstrated that FBT was efficacious and safe in treating cancer-related breakthrough pain.[110,111][Level of evidence: I] Other opioids such as morphine, hydromorphone, and oxycodone are not very lipophilic and therefore not suited for buccal or sublingual administration. In the home setting, opioids are sometimes administered buccally or sublingually with erratic absorption that is likely via the lower gastrointestinal tract.

Intranasal

A phase III, double-blind, randomized, placebo-controlled, crossover trial included 120 patients to investigate the efficacy and tolerability of intranasal fentanyl spray, 50 µg to 200 µg, for treating breakthrough pain in opioid-tolerant cancer patients. Doses of 50 µg, 100 µg, and 200 µg demonstrated an effective clinical response at 10 minutes.[112] These results have been replicated.[113,114][Level of evidence: I] Long-term safety, tolerability, and sustained efficacy have been demonstrated over a 16-week, multicenter, open-label study.[115]

Parenteral: IV and subcutaneous

IV administration provides a rapid onset of analgesia within 2 to 10 minutes. The duration of action after a bolus dose may be shorter than with other routes. This route may be useful if a patient cannot swallow and IV access is established.The subcutaneous route is as effective as the IV route.[12,116][Level of evidence: I] In some situations, it may even be more convenient, especially if patients are being cared for at home or in a hospice. To facilitate administration via this route, a 25- or 27-gauge butterfly needle can be inserted subcutaneously and left in place for up to 7 days at a time. The anterior thighs, abdomen, upper arms, subclavicular area, and upper back are possible areas for needle insertion. The site should be monitored for signs of infection or irritation and should be changed if these are noted. The bioavailability of parenterally administered opioids (morphine, hydromorphone, oxycodone, and codeine) is generally two to three times that of the oral route.[117][Level of evidence: II] The dose therefore needs to be halved or decreased by a third when switching from the oral to the subcutaneous and IV routes, respectively (refer to the Approximate Dose Equivalents for Opioid Analgesics table). Opioids administered parenterally may be given either intermittently (usually every 4 hours) or by a continuous infusion. With some exceptions, these two methods appear to be similarly effective.[118][Level of evidence: I]

Other routes

Some studies suggest that the use of inhaled opioids for the management of pain and cancer-related shortness of breath are, with some exceptions, not more effective than systemic administration.[119][Level of evidence: II];[120][Level of evidence: IV] Their absorption via this route is unpredictable. The intramuscular administration of opioids is not recommended.

Patient-controlled analgesia

Patient-controlled analgesia (PCA) may be used to determine the opioid dose needs when initiating opioid therapy. Once the pain is well controlled, a regular opioid dose can be instituted on the basis of the PCA doses required. This method is contraindicated in patients with cognitive impairment or patients with significant psychological contribution to their pain experience.

Intraspinal

The intraspinal administration of opioids (epidural or intrathecal), especially when combined with a local anesthetic, can be helpful in a very small select group of patients with intractable pain. Use of the epidural or intrathecal route requires skill and expertise that may not be available in all settings. Table 4 presents the advantages and disadvantages of intraspinal administration. Intrathecal opioid therapy has been FDA approved since 1991, and the utility of an implantable drug delivery system (IDDS) to deliver spinal opioids has been compared with comprehensive medical management (CMM) (based on the Agency for Health Care Policy and Research 1994 cancer pain management guidelines) in a randomized trial. There were 202 patients enrolled in this unblinded study. Of the 101 patients randomized to the IDDS, 51 actually received this therapy. Sixteen of these patients (31%) had serious adverse effects. Patients using the IDDS experienced more than 20% reduction in both pain and opioid toxicity more often than the CMM group ( P = .02). These data and further analysis in follow-up reports [121,122][Level of evidence: I] suggest that the use of an IDDS delivery system may offer benefit for some cancer patients. More research is needed to determine which subsets of patients will benefit the most from this device, and what the proper timing should be for a trial of intrathecal opioids.[123][Level of evidence I];[124][Level of evidence: II] An open-label study demonstrated that patients with refractory cancer pain experienced better pain relief, fewer opioid-associated side effects, and decreased systemic opioid use when managed with patient-activated intrathecal delivery of morphine via an implanted delivery system. The device was implanted in 119 patients. There were 7 serious adverse events related to the device and 55 serious adverse events related to the implant and delivery-system refill procedures. The FDA denied the application for market approval of this system.[80][Level of evidence: II]

Table 4. Advantages and Disadvantages of Intraspinal Drug Administration

Système Avantages Inconvénients
PCA = patient-controlled analgesia.
Percutaneous temporary catheter Used extensively both intraoperatively and postoperatively. Mechanical problems include catheter dislodgment, kinking, or migration.
Useful when prognosis is limited (<1 month). Increased risk of infection.
Permanent silicone-rubber epidural Catheter implantation is a minor procedure.
Dislodgment and infection less common than with temporary catheters.
Can deliver bolus injections, continuous infusions, or PCA (with or without continuous delivery).
Subcutaneous implanted injection port Increased stability, less risk of dislodgment. Implantation more invasive than external catheters.
Can deliver bolus injections or continuous infusions (with or without PCA). Approved only for epidural catheter in United States.
Potential for infection increases with frequent injections.
Subcutaneous reservoir Potentially reduced infection in comparison with external system. Difficult to access, and fibrosis may occur after repeated injection.
Implanted pumps (continuous and programmable) Potentially decreased risk of infection. Need for more extensive operative procedure.
Need for specialized equipment with programmable systems.

Drugs and routes to be avoided

Table 5 and Table 6 present data on drugs and routes of administration not recommended for the management of cancer pain.

Table 5. Drugs To Be Avoided for Treatment of Cancer Pain

Classe Drogue Rationale for NOT Recommending
CNS = central nervous system.
a Contains morphine, cocaine, ethanol, and, in some cases, chlorpromazine.
b Meperidine is the only analgesic in this combination.
Les opioïdes meperidine (Demerol) Short duration (2–3 h) of analgesia.
Repeated administration may lead to CNS toxicity (tremor, confusion, or seizures).
Opioid agonist-antagonists pentazocine (Talwin), butorphanol (Stadol), nalbuphine (Nubain) Risk of precipitating withdrawal in opioid-dependent patients.
Analgesic ceiling.
Possible production of unpleasant psychotomimetic effects (eg, dysphoria, delusions, hallucinations).
Agoniste partiel buprenorphine (Buprenex) Analgesic ceiling.
May precipitate withdrawal if administered with full opioid agonist.
Antagonistes naloxone (Narcan), naltrexone (ReVia) May precipitate withdrawal.
Limit use to treatment of life-threatening respiratory depression. Give in diluted form to opioid-tolerant patients.
Combination preparations Brompton's cocktail a No evidence of analgesic benefit in using Brompton's cocktail over single-opioid analgesics.
DPT (meperidine, promethazine, and chlorpromazine) b Efficacy is poor compared with that of other analgesics.
High incidence of adverse effects.
Anxiolytics alone benzodiazepines (eg, alprazolam [Xanax]; clonazepam [Ceberclon]; diazepam [Valium]; lorazepam [Ativan]) Analgesic properties not demonstrated except for some instances of neuropathic pain.
Added sedation from anxiolytics may compromise neurologic assessment in patients receiving opioids by facilitating the development of delirium.
Sedative/hypnotic drugs alone barbiturates, benzodiazepines Analgesic properties not demonstrated.
Added sedation from sedative/hypnotic drugs limits opioid dosing and may facilitate the development of delirium.

Table 6. Routes of Administration To Be Avoided for Treatment of Cancer Pain

Routes of Administration Rationale for Not Recommending
Intramusculaire Painful.
Absorption unreliable.
Should not be used in children or patients prone to develop dependent edema or patients with thrombocytopenia.
Transnasal The only drug approved by the FDA for transnasal administration is butorphanol, an agonist-antagonist drug that generally is not recommended. (See opioid agonist-antagonists inTable 5for more information.)

Side effects of opioids

Clinicians should anticipate and monitor for side effects. The more common adverse effects include nausea, somnolence, and constipation. These should be discussed with patients before starting opioids. Somnolence and nausea are more often encountered with initiation of opioid treatment but tend to resolve within a few days. Clinicians who follow patients during long-term opioid treatment should watch for potential side effects and manage them as the need arises.

Constipation

Anticipate the constipating effects of analgesics. Opioids compromise gastrointestinal tract peristaltic function (a nearly universal side effect). Consequently, stool within the gut lumen becomes excessively dehydrated. The cornerstones of effective prophylaxis, therefore, are measures aimed at keeping the patient well hydrated to maintain well-hydrated stool. Unless there are existing alterations in bowel patterns, such as bowel obstruction or diarrhea, all patients using opioids should be started on a laxative bowel regimen and receive education for bowel management. Patients who do not adequately respond to an aggressive regimen with stool softeners may benefit from the addition of mild osmotic agents (eg, 70% sorbitol solution, lactulose, milk of magnesia), polyethylene glycol, bulk-forming laxatives (eg, psyllium) with appropriate orally administered hydration, or mild cathartic laxatives (eg, senna). Stimulant cathartics (eg, senna, bisacodyl) may be useful in severely constipated patients; however, they may be relatively ineffective in situations in which stool has become desiccated. Opioid-induced constipation is a frequent cause of chronic nausea and is observed in 40% to 70% of patients receiving opioids.[64][Level of evidence: I] It appears to be dose-related, is characterized by large variability in individuals, and is opioid-receptor mediated via both central and peripheral mechanisms. Opioids extend the gastrointestinal transit time and desiccate the intraluminal content.[125] Unlike nausea, complete tolerance to this effect does not generally develop, and most patients require laxative/stool-softener therapy for as long as they take opioids. A plain x-ray of the abdomen may be helpful in assessing the extent of fecal load.[126]

Initiating a regular laxative regimen emphasizes prevention of opioid-induced constipation. Recommendations regarding laxative treatment have been largely based on clinical experiences and observations. Combinations of a sennoside and a stool softener such as docusate are generally suggested.[127] Reports that fentanyl causes less constipation than oral morphine are interesting but need to be confirmed in further prospective studies.[128][Level of evidence: III];[63][Level of evidence: II] One study demonstrated decreased laxative use in patients on transdermal fentanyl as compared with patients receiving oral morphine treatment.[63] One meta-analysis has revealed a significant difference in favor of transdermal fentanyl for constipation, although this included only three randomized controlled clinical trials.[129] Whether this decrease in laxative usage is clinically significant, however, and whether the decrease relates to the route of administration instead of the opioid type need to be demonstrated. In a single small series, opioid switching of morphine to methadone resulted in a reduction in constipation.[130] Severe opioid-induced constipation may occur. At an extreme it may be present as a severe ileus and pseudo bowel obstruction.[131] As is the case with opioid-induced nausea and constipation, management relies on the use of gastrointestinal prokinetic agents. The use of orally administered opioid-antagonists such as naloxone is being studied.[132][Level of evidence: II];[133][Level of evidence: I] Although the oral bioavailability of these medications is very limited, opioid withdrawal syndromes have been noted when higher doses have been used. Methylnaltrexone, a quaternary derivative of naltrexone, is an opioid antagonist that does not cross the blood-brain barrier. Preliminary studies suggest that it may be effective when given subcutaneously in the management of opioid-associated constipation without causing opioid withdrawal.[134][Level of evidence: I];[135,136] (Refer to the PDQ summaries on Gastrointestinal Complications, Nausea and Vomiting, and Nutrition in Cancer Care for more information.)

Nausea and vomiting

Nausea and vomiting (emesis) occur in approximately one-third to two-thirds of patients taking opioids.[137][Level of evidence: I];[138,139] Nausea and vomiting are common complications of early exposure to opioids and usually disappear within the first week of treatment. Appropriate antiemetic coverage during the opioid-initiation phase is usually effective in limiting these adverse effects. Nausea alone does not represent an allergic reaction to the opioid. Occasionally, nausea may be experienced when an opioid dose is significantly increased. An antiemetic should be available on an as-needed basis to address this situation.

Three main mechanisms underlie opioid-related nausea and vomiting.[140] The predominant mechanism appears to be stimulation of the chemoreceptor trigger zone, where dopamine is the main neurotransmitter. Another mechanism is reduced gastrointestinal motility, including delayed gastric emptying. Nausea via increased vestibular sensitivity is uncommon.

Multiple antiemetic regimens have been proposed for the management of opioid-induced emesis, but prospective studies comparing one regimen over another are lacking.[140] Metoclopramide or domperidone are generally recommended as first-line agents because they improve gastrointestinal motility and are antidopaminergic.[140,141] Metoclopramide can be administered orally or subcutaneously at doses of 10 mg 4 times a day or every 4 hours, depending on the severity of the nausea. Rescue doses should also be ordered on an as-needed basis. Extrapyramidal-related adverse effects are a potential complication of these medications. The incidence of extrapyramidal reactions is low with domperidone, but this drug is not available in a parenteral formulation. The antihistamines act on the histamine receptors in the vomiting center and on vestibular afferents. They are generally reserved for cases in which vestibular sensitivity, often manifesting as motion-induced nausea, is suspected or for cases in which bowel obstruction precludes the use of gastrointestinal prokinetic agents. Haloperidol may also be used under the latter circumstances. The phenothiazines are an alternative group of antiemetics, but extrapyramidal and anticholinergic adverse effects may be dose-limiting. Chlorpromazine has modest antiemetic activity but a high incidence of sedation, postural hypotension, and anticholinergic adverse effects, whereas piperazine derivatives such as prochlorperazine are stronger antiemetics but cause more extrapyramidal side effects. Anticholinergic side effects also limit the use of anticholinergic agents such as hyoscine hydrobromide (scopolamine) in opioid-induced nausea, particularly in patients with advanced cancer. These patients seem to be more vulnerable to these adverse effects. The role of 5-HT 3 -receptor antagonists such as ondansetron in ameliorating opioid-induced nausea is not clear.[142][Level of evidence: III]

There appear to be differences between individual patients in the extent to which different opioids cause nausea.[143] These differences form the basis for the strategy of switching from one opioid to another when a particular opioid produces persistent nausea.[144,145] Switching the route, specifically from the oral to the parenteral, has also been suggested, but the study supporting this strategy is small.[146][Level of evidence: II]

Nausea and vomiting can sometimes persist beyond the opioid-initiation phase or occur de novo in patients on long-term opioid treatment. Nausea and vomiting may become chronic in nature. The multicausal nature of the problem needs to be recognized because management is directed at identifying and addressing the various causes.[147] Constipation is a common contributing cause. Chronic nausea has been associated with the accumulation of active opioid metabolites.[93][Level of evidence: III] A number of strategies are suggested to manage chronic nausea, including switching the opioid or decreasing the dose when pain is well controlled. (Refer to the PDQ summary on Nausea and Vomiting for more information.)

Cognitive and other neurotoxic side effects of opioids

Opioid-related neurotoxicity may manifest as cognitive impairment, hallucinations, delirium, generalized myoclonus, hyperalgesia and/or allodynia. Patients who have renal impairment or who are taking higher doses of opioids are at greater risk of developing these side effects. The mechanisms underlying these side effects are unclear, but the opioid metabolites are implicated. When patients present with generalized pain of an unknown source and the opioid dose has been recently increased, hyperalgesia should be considered as a possible diagnosis.[148,149] The etiological contribution of opioids to cognitive impairment and delirium in the cancer patient is often difficult to determine. This is the case particularly in patients with advanced disease in which the baseline vulnerability is associated with multisystem impairment, and the concurrent administration of other psychotropic agents can complicate the assessment of etiology. Nonetheless, opioid-induced cognitive problems have been reported.[150,151] In addition to cognitive impairment within the context of delirium, other effects include myoclonus, hyperalgesia, perceptual disturbance, and seizures.[152] Although the remarkable characteristics, potential severity, and impact of delirium contribute to its dominance in the spectrum of opioid-related cognitive dysfunction, more subtle psychomotor and cognitive opioid effects have been described. Neuropsychological testing has been used to study these more-subtle effects in less-advanced cancer disease,[153][Level of evidence: II] chronic nonmalignant pain,[137][Level of evidence: I];[154][Level of evidence: II] and in healthy volunteers.[155][Level of evidence: I] Collectively, studies of neuropsychological testing have demonstrated somewhat mixed findings,[156] with some detecting opioid-associated impairment in certain aspects of psychomotor or cognitive function [154][Level of evidence: II] and others detecting minimal or no impairment.[137][Level of evidence: I];[153] Clinical experience and some studies suggest that patients become tolerant of the sedating effects that accompany either the initiation of opioid therapy or dose increases,[157][Level of evidence: II] thereby allowing patients who are otherwise physically able, and on stable opioid doses, to safely engage in activities such as driving.[153,158]

Decreased brain cholinergic activity is recognized as one of the potential underlying pathophysiological mechanisms of delirium.[159,160][Level of evidence: II] In the case of meperidine, the anticholinergic activity associated with its active metabolite normeperidine is suspected to be the basis of the cognitive impairment and delirium occurring in association with this opioid.[161,162] Other opioid metabolites have been studied in relation to the generation of neuroexcitatory states in animal laboratory models and delirium in human subjects. A series of animal studies have demonstrated neuroexcitatory states in association with morphine metabolites, morphine-3-glucuronide (M-3-G) [163] and normorphine-3-glucuronide,[164] and the hydromorphone metabolite, hydromorphone-3-glucuronide.[165][Level of evidence: II] In a hospice study of 36 patients with advanced cancer receiving morphine, both M-3-G and morphine-6-glucuronide (M-6-G) levels were studied in relation to the development of side effects, which included nausea and vomiting in 10 patients and cognitive impairment in 9 patients.[166][Level of evidence: II] Creatinine levels, and plasma levels of M-3-G, M-6-G, and dose-corrected M-3-G and M-6-G, were higher in the 19 patients with side effects, suggesting that the elevation of morphine metabolites in association with renal impairment was associated with opioid toxicity, including cognitive impairment. Evidence is extensive demonstrating elevation of opioid-metabolite levels in the setting of renal impairment,[91,98,166][Level of evidence: II];[167,168] and some studies have noted an association with features of neurotoxicity, including cognitive impairment.[151,166][Level of evidence: II] An accumulation of opioid metabolites possibly also occurs during dehydration, which was suggested as a contributory factor in a prospective study of predominantly opioid-related delirium.[169][Level of evidence: II] Switching to another opioid is one strategy for abating the side effects in cases in which accumulation of active metabolites is considered responsible for side effects such as generalized myoclonus, sedation, confusion, or chronic nausea.[26]

Managing cognitive and other neurotoxic effects of opioids

The general management approach to opioid-induced delirium requires a multidimensional assessment to determine the presence of other potentially treatable contributory factors such as dehydration, other centrally acting medications, sepsis, and hypercalcemia.[150,169,170] Clinical experience suggests that the presence of tactile hallucinations and myoclonus,[84] although not exclusively associated with opioid toxicity, raise the suspicion of this cause. A careful assessment can also identify prognostic factors associated with greater difficulty in achieving pain control, the need for higher opioid doses, and consequently greater risk of opioid-induced delirium. (Refer to the PDQ summary on Cognitive Disorders and Delirium for more information.) These factors include neuropathic pain, incidental pain, tolerance, somatization of psychological distress, and a positive history of drug or alcohol abuse.[171][Level of evidence: II]

In addition to searching for underlying reversible causes of delirium, the symptomatic management of delirium requires the addition of a neuroleptic agent to control agitation and perceptual or delusional disturbance. Haloperidol is regarded as the drug of choice in this context,[172] and methotrimeprazine and chlorpromazine are considered useful alternatives,[173][Level of evidence: I];[174][Level of evidence: IV] especially when a greater level of sedation is required. Midazolam, a sedating and short-acting benzodiazepine given by continuous infusion, is sometimes necessary, especially in the case of nonreversible delirium.[175][Level of evidence: III] Typical anxiolytics, including lorazepam, can be used to manage comorbid anxiety; however, they may contribute to the occurrence of delirium, so they should be used sparingly, if at all. Early data suggest that some atypical antipsychotics may be beneficial in improving pain control and decreasing opioid requirements in the cancer patient with mild cognitive impairment and/or anxiety. It is unclear whether this benefit is due to a primary effect or to its secondary impact on cognitive impairment and/or anxiety.[176][Level of evidence: II]

The specific management approach to opioid-induced cognitive and other neurotoxic side effects involves either a dose reduction, a change in route, or an opioid switch.[177][Level of evidence: II] If the pain is well controlled, and the cognitive and neurotoxic side effects are not severe, modest opioid dose reduction may be effective. The rationale for switching opioids, commonly referred to as opioid switching, is that a more favorable balance between analgesia and side effects can be achieved, often with a lower dose than that predicted by the conventional analgesic table.[85,150,178] This can reflect incomplete cross-tolerance among opioids in relation to analgesic and other effects.[179] It is also possible that switching to a new opioid could allow for the elimination of potentially toxic opioid metabolites.[180][Level of evidence: III];[150,181] Reduction in opioid dose in the context of an opioid-induced delirium has not been systematically evaluated but is also likely to have beneficial results. Although there is growing evidence to suggest a beneficial role for opioid switching,[145][Level of evidence: II];[180,182] controversy persists over the relative value of opioid switching versus dose reduction.[83]

Cognitive benefit has been reported with the use of methylphenidate in patients receiving a continuous infusion of opioids for cancer pain.[183][Level of evidence: I] The psychostimulant benefit is likely to relate to mitigation of sedation associated with upward dose titration of opioid.[184][Level of evidence: II] Although psychostimulants have been advocated for hypoactive delirium,[185][Level of evidence: IV] any evidence of perceptual or delusional disturbance is considered a contraindication. An open-label study of donepezil, a long-acting selective acetylcholinesterase inhibitor, suggests that it relieves opioid-associated fatigue and sedation in patients who are receiving opioids for cancer pain.[186][Level of evidence: II]

Respiratory depression

Patients receiving long-term opioid therapy generally develop tolerance to the respiratory-depressant effects of these agents. However, concerns about respiratory depression with opioid use remain prevalent among clinicians and patients. Clinicians experienced in end-of-life care recognize that such concerns are generally exaggerated, though empirical research in the area is sparse. One observational study of 30 patients that evaluated the effect of parenteral opioid titration for the control of acute exacerbation of cancer pain showed no association between parenteral opioid titration and hypoventilation at pain control, as measured by change in end-tidal CO 2 respiratory rate or oxygen saturation.[187]

When indicated for reversal of opioid-induced respiratory depression, naloxone titrated in small increments or as an infusion should be administered to improve respiratory function without reversing analgesia. The patient should be monitored carefully until the episode of respiratory depression resolves. The opioid antagonists have a short half-life and may have to be given repeatedly until the agonist drug is sufficiently cleared.[188]

Subacute overdose

Perhaps more common than acute respiratory depression, subacute overdose may manifest as slowly progressive (hours to days) somnolence and respiratory depression. Before analgesic doses are reduced, advancing disease must be considered, especially in the dying patient. Generally, withholding one or two doses of an opioid analgesic is adequate to assess whether mental and respiratory depression are opioid related. If symptoms resolve after temporary opioid withdrawal, reduce the scheduled opioid dosage by 25%. If symptoms do not abate, but the patient complains of or exhibits signs of increased pain, or if symptoms referable to opioid withdrawal occur, consider alternative causes for CNS depression and reinstate analgesic treatment. Ongoing assessment is essential to maintain adequate pain relief.

Effects of opioids on sexual function

Reduced libido is a well-known phenomenon for those using heroin or those in a methadone maintenance program; however, clinicians prescribing opioids for pain poorly understand this effect. Early case studies of persons using heroin or methadone described diminished libido, sexual dysfunction, reduced testosterone levels in men, and amenorrhea in women.[189,190,191,192][Level of evidence: II];[193,194] These effects resolve after the opioid has been discontinued. Other case reports of patients receiving opioids for relief of chronic pain suggest these same findings.[195,196][Level of evidence: III] The long-term effects of reduced testosterone and amenorrhea are not well known. Sexuality is an essential component of quality of life in many patients, including patients with advanced disease.[197][Level of evidence: III] Patients should be assessed for changes in libido and sexual dysfunction. If these changes are distressing to the patient, serum testosterone levels may be obtained. Should the patient seek improvement in libido and performance, treatment is often empirical, keeping in mind that there are many potential causes of changes in sexual function. Treatment includes using nonopioids for pain, adding adjuvant analgesics in the hope the opioid dose may be reduced, or replacing testosterone through injections or a patch (if not contraindicated). More research is needed to understand the relationship between opioids and sexual function, as well as the most effective treatment strategies. (Refer to the PDQ summary on Sexuality and Reproductive Issues for more information.)

Other opioid side effects

Dry mouth, urinary retention, pruritus, dysphoria, euphoria, sleep disturbances, and inappropriate secretion of antidiuretic hormone are less common.

Adjuvant Drugs

Adjuvant drugs are valuable during all phases of pain management to enhance analgesic efficacy, treat concurrent symptoms, and provide independent analgesia for specific types of pain.[198][Level of evidence: IV] Adverse drug reactions are common, however, and there are wide interindividual and ethnic differences in drug metabolism.[199][Level of evidence: IV] A survey on symptom severity and management in 593 cancer patients treated for an average of 51 days reported that during this time, anticonvulsants were used in 11.8% of patients, antidepressants in 16%, corticosteroids in 28%, and bisphosphonates in 7.3%.[200][Level of evidence: III] Patients with advanced cancer on palliative medicine services are reported to receive on average five medications for symptom relief, and as a result are at high risk of drug interactions.[199] A further note of caution appears in another study that questioned the concept of opioid-sparing effects of co-analgesics.[201][Level of evidence: III] Nevertheless, adjuvant analgesics have been extensively studied and reviewed in noncancer settings and are generally endorsed as an important intervention in the provision of adequate pain management (see Table 7).[202,203,204,205][Level of evidence: IV] Few trials compare adjuvant analgesics in the cancer setting.

Table 7. Adjuvant Medications With Analgesic Activity

Classe Drogue Daily Dose Range a Studies Conducted in:
Cancer Patients Noncancer Patients
bid = twice a day; tid = 3 times a day.
a Starting doses should incorporate the lowest possible dose.
Antidépresseurs amitriptyline (Elavil) 10–25 mg every day [206][Level of evidence: I][207][Level of evidence: I] [208][Level of evidence: I]
desipramine (Norpramin) 10–150 mg every day [209][Level of evidence: II] [210][Level of evidence: II]
maprotiline (Ludiomil) 25 mg bid–50 mg tid [211][Level of evidence: I]
duloxetine (Cymbalta) 20 mg bid–30 mg bid [212][Level of evidence: I]
nortriptyline (Pamelor, Aventyl) 10–100 mg every day [213][Level of evidence: I]
venlafaxine (Effexor) 37.5–225 mg every day [214][Level of evidence: I][215][Level of evidence: II] [216][Level of evidence: I]
Anticonvulsivants carbamazépine (Tegretol) 100 mg tid–400 mg tid [217][Level of evidence: I]
valproate (Depacon) 500 mg tid–1,000 mg tid [218][Level of evidence: I]
la gabapentine (Neurontin) 100 mg tid–1,000 mg tid [219][Level of evidence: I][220][Level of evidence: II] [221][Level of evidence: II]
clonazepam (Klonopin) 0.5 mg bid–4 mg bid [222][Level of evidence: II]
lamotrigine (Lamictal) 25 mg bid–100 mg bid [223][Level of evidence: I]
prégabaline (Lyrica) 150 mg divided into 2 or 3 doses; increase to 300 mg starting at day 3–7; if needed, increase to 600 mg 7 days later [224][Level of evidence: I]
Les anesthésiques locaux mexiletine (Mexitil) 100 mg bid–300 mg tid [225][Level of evidence: I]
lidocaine patch (Lidoderm) 5% patch contains 700 mg; one patch, 12 hours on, 12 hours off [226][Level of evidence: II]
Les corticostéroïdes dexamethasone (Decadron) Voir le texte
prednisone Voir le texte
Les bisphosphonates clodronate Voir le texte
pamidronate (Aredia) Voir le texte
zoledronic acid (Zometa) Voir le texte [227][Level of evidence: II]
AINS Refer toTable 1for more information.
Divers baclofen (Lioresal) 5 mg tid–20 mg tid [228][Level of evidence: I]
calcitonin (Calcimar) 100–200 IU (subcutaneous or intranasal)
clonidine (Catapres) 0.1 mg bid–0.3 mg bid [229]
methylphenidate (Ritalin) 2.5 mg bid–20 mg bid [230][Level of evidence: I] [231][Level of evidence: II]
ketamine (Ketalar) Refer to theNMDA Receptor Antagonistssection of this summary for more information.

Antidepressants

The analgesic benefits of tricyclic antidepressants have been well established and are generally considered first-line therapy for many neuropathic pain syndromes.[202,203,204,205,232][Level of evidence: IV] Supporting evidence is strong for amitriptyline and desipramine, and there is endorsement of other newer antidepressants such as maprotiline and paroxetine. Patients with neuropathic pain characterized by continuous dysesthesias are generally believed to be the most likely to benefit from antidepressant management; however, a randomized placebo-controlled study of amitriptyline for neuropathic pain in cancer patients found only slight analgesic benefit with significantly worse adverse effects.[207][Level of evidence: I]The most common side effects of tricyclic antidepressants are the following:

Constipation.Dry mouth.Blurred vision.Cognitive changes.Tachycardia.Urinary retention. Caution has also been advised in treating patients with cardiac disease, and an electrocardiogram is sometimes recommended as a prudent measure. A slow upward titration is suggested as a good way to avoid side effects.[214][Level of evidence: I]

Anticonvulsivants

The group of commonly used anticonvulsants as adjuvant analgesics for neuropathic pain includes carbamazepine, valproate, phenytoin, and clonazepam.[202,203,204,205,232][Level of evidence: IV]

Clinical experience with carbamazepine is extensive, but use of this drug is limited in the cancer population because of concern that it causes bone marrow suppression, in particular leukopenia. Other common adverse effects include nystagmus, dizziness, diplopia, cognitive impairment, and mood and sleep disturbance.

Dosing guidelines for phenytoin are similar to those for the treatment for seizures.[202] This drug can be administered using a loading dose, which may be particularly useful in patients with severe pain.

Gabapentin is increasingly reported as useful for the management of neuropathic pain associated with cancer and its treatment.[219][Level of evidence: I];[220,233][Level of evidence: II];[234][Level of evidence: III];[235,236][Level of evidence: IV] Commonly reported side effects include somnolence, dizziness, ataxia, and fatigue.[205,234] One randomized open-label trial of gabapentin combined with an opioid (n = 38) versus an opioid alone (n = 37) for the management of neuropathic cancer pain suggests that the combination group achieved better relief than those receiving opioid monotherapy.[237][Level of evidence: I]

Clonazepam is an anticonvulsant from the benzodiazepine class and is commonly used for treating lancinating or paroxysmal neuropathic pain.[202] The patient must be monitored carefully for drowsiness and cognitive impairment.

Local anesthetics

The use of mexiletine has been described for chronic neuropathic pain.[202,203,205] Side effects are reported as common and include gastrointestinal toxicity, in particular nausea, and CNS side effects such as dizziness. Patients with a history of cardiac disease and those on higher doses are at increased risk of adverse effects, and it is recommended that they receive appropriate cardiac evaluation, including an electrocardiogram.

Corticosteroids

These drugs have achieved wide acceptance in the management of patients with cancer pain. They are indicated as adjuvant analgesics for cancer pain of bone, visceral, and neuropathic origin. Adverse effects include neuropsychiatric syndromes, gastrointestinal disturbances, proximal myopathy, hyperglycemia, aseptic necrosis, capillary fragility, and immunosuppression. The risk of adverse effects increases with the duration of use. As a result, use is often restricted to patients with a limited life expectancy; in addition, once effective pain control is obtained, it is commonly recommended that the dose be tapered as much as possible. Dosage recommendations vary from a trial of low-dose therapy such as dexamethasone 1 to 2 mg or prednisone 5 to 10 mg once or twice daily,[202] to a starting dose of dexamethasone 10 mg twice daily with subsequent tapering to the minimal effective dose.[238]

Another suggested use of corticosteroids is in high doses for short periods in patients with severe pain. This empirical approach recommends a regime of a single bolus of dexamethasone 100 mg IV followed by a small amount given 4 times per day and then tapered over the next few weeks.[202]

Although there is widespread acceptance of steroid therapy, mostly via the oral route but also subcutaneously and intravenously, data remain inadequate for definitive conclusions regarding efficacy and dosing guidelines.[239][Level of evidence: I];[202];[204,205,238,240,241,242,243][Level of evidence: IV]

Bisphosphonates

These drugs have been recommended for the management of bone pain as well as the prevention of skeletal complications in patients with metastatic bone disease.[244][Level of evidence: II];[202];[203,204,205,245,246,247][Level of evidence: IV] Their use in a study of breast cancer patients resulted in improved quality of life compared with that of patients not using bisphosphonates.[248][Level of evidence: I] The bisphosphonates most frequently used are clodronate, pamidronate,[249] and zoledronic acid.[250][Level of evidence: I]Clodronate can be given orally or intravenously. Dosage recommendations are oral clodronate, 1,600 mg/d; or IV clodronate, 600 to 1,500 mg every 2 to 3 weeks. Clodronate is not available in the United States.Pamidronate has been recommended in the dose range of 60 to 90 mg IV over 2 hours every 3 to 4 weeks; however, pooled results from two multicenter, double-blind, randomized, placebo-controlled trials (n = 350) using pamidronate (90 mg every 3 weeks) failed to demonstrate a benefit for bone pain.[251][Level of evidence: I]Zoledronic acid is a potent bisphosphonate that can be given as an IV bolus over 15 to 30 minutes in the dose range of 4 to 8 mg; however, the 8-mg dose has been associated with deterioration of renal function.[252,253,254,255][Level of evidence: I] The few studies to date suggest administration at 3- to 4-week intervals.[256][Level of evidence: IV]Ibandronate can be given orally or intravenously. Dosing recommendations are 50 mg orally daily or 6 mg intravenously every 3 to 4 weeks.[257][Level of evidence: I]Denosumab is a monoclonal antibody against the receptor activator of nuclear factor-kappa B ligand (RANKL), which is a form of the tumor necrosis factor superfamily. RANKL inhibition prevents osteoclast development and activation, resulting in decreased bone resorption, increased bone density, and reduction in the risk of fractures.[258]The FDA has highlighted the possibility of severe and sometimes incapacitating bone, joint, and/or muscle pain in patients who are taking bisphosphonates. The musculoskeletal pain may occur within days, months, or years after starting treatment with a bisphosphonate. This pain contrasts with the acute-phase response characterized by fever, chills, bone pain, myalgias, and arthralgias that may sometimes accompany initial administration of intravenous bisphosphonates. The FDA recommends that bisphosphonates be considered a possible cause of severe musculoskeletal pain in patients who present with these symptoms, and health care professionals should consider temporary or permanent discontinuation of the drug. The risk factors and the incidence of the association of this musculoskeletal pain with bisphosphonates remain unknown.[259]The use of bisphosphonates carries a risk of developing bisphosphonate-associated osteonecrosis (BON). (Refer to the Oral Toxicities Not Related to Chemotherapy or Radiation Therapy section in the PDQ summary on Oral Complications of Chemotherapy and Head/Neck Radiation for more information.)

Divers

Baclofène

This drug is generally used for spasticity but may also be used for the treatment of neuropathic pain.[202,203,205][Level of evidence: IV] Side effects include drowsiness, dizziness, ataxia, confusion, and nausea and vomiting. La calcitonine

Although the mechanism by which calcitonin produces analgesia is unknown, historically it has been recommended for the treatment of both bone and neuropathic pain.[202,203,205,245,246] However, a systematic review of randomized double-blind clinical trials assessing the efficacy of calcitonin for control of metastatic bone pain does not support its use.[260][Level of evidence: IV] Because only two of these studies were evaluated as well designed, further research is necessary. The utility of calcitonin for bone pain is unclear. Clonidine

This traditional antihypertensive can be given via the oral, epidural, or transdermal route and has been recommended as a trial for the management of neuropathic pain. Reported side effects include dry mouth, dizziness and hypotension, sedation, and constipation.[202,203,205][Level of evidence: IV] The maximum recommended dose is 2.4 mg/d. Psychostimulants

Psychostimulants such as dextroamphetamine, methylphenidate, and modafinil may enhance the analgesic effects of opioids.[183][Level of evidence: I];[184][Level of evidence: II];[204][Level of evidence: IV] They may also be used to diminish opioid-induced sedation when reducing the dose is not possible. NMDA Receptor Antagonists

There is increasing evidence for the importance of NMDA receptors and the possibility that NMDA antagonists may have a role in refractory cancer pain management.[202,261][Level of evidence: III] Ketamine in subanesthetic doses has been used in this setting.[262][Level of evidence: II] The severe psychomimetic adverse effects associated with this treatment, including vivid hallucinations, limit widespread use of ketamine. Coadministration of a neuroleptic or benzodiazepine is recommended to limit the emergence of these effects. Ketamine is generally given subcutaneously at a low starting dose such as 0.1 mg per kg of body weight per hour, with a gradual escalation. Oral ketamine may be a more potent analgesic and have a more favorable side-effect profile than parenteral ketamine.[247][Level of evidence: IV] One study suggests short-duration therapy of a continuous subcutaneous infusion of ketamine over 3 to 5 days. The initial dose is 100 mg/d; if pain control is inadequate, the dose is escalated to 300 mg/d and then to a maximum dose of 500 mg/d. Treatment is continued for 3 days at either the lowest effective dose or 500 mg/d and then discontinued.[261] A systematic review of the benefits and harms of ketamine in managing cancer pain revealed a general lack of studies and small subject numbers,[263,264][Level of evidence: IV] precluding a definitive conclusion on benefits and harms.Methadone, particularly the racemic mixture, appears to have significant NMDA-antagonist properties.[265] The d-isomer blocks the NMDA receptor and as a result may yield independent analgesic effects and perhaps reverse some analgesic tolerance to the opioid.[266][Level of evidence: II] This may explain the often-unanticipated high potency of methadone.Dextromethorphan (DM), a commonly prescribed antitussive, may also have NMDA-blocking properties.[266][Level of evidence: II] The clinical significance of this effect, however, is unclear and studies have not been able to determine at what dose these effects may manifest. Oral DM in doses of 60 or 90 mg given preoperatively and postoperatively has been shown to reduce pain intensity and opioid use after orthopedic oncology surgery.[267,268][Level of evidence: I] A randomized, double-blind, placebo-controlled study of 65 patients evaluated the efficacy and safety of DM or placebo with slow-release morphine. The dose of DM was 60 mg 4 times daily, increased after 7 days to 120 mg 4 times daily if tolerated. While the DM group showed somewhat more improvement than the placebo group, the differences were not significant; furthermore, the DM group experienced more toxic effects, particularly dizziness.[269][Level of evidence: I] The authors concluded that DM does not enhance opioid analgesia or modulate opioid tolerance enough in cancer patients to warrant continued use.Octreotide

Data from a case series of 16 patients with symptomatic hepatic metastases from a variety of nonneuroendocrine primary sites suggest that octreotide palliates pain and improves a variety of quality-of-life indices as measured by the EORTC QLQ-C30 questionnaire.[270][Level of evidence: II]

Under Investigation

Tétrodotoxine

A randomized, placebo-controlled study of subcutaneous tetrodotoxin was carried out on 77 cancer patients across 22 centers in Canada. While results did not achieve statistical significance, there was a trend toward improved pain control. This drug remains experimental and is not commercially available.[271][Level of evidence: I]Cannabinoids

Cannabis contains more than 60 cannabinoids and has been proposed as a potentially useful treatment for cancer-related pain. A multicenter, double-blind, randomized, placebo-controlled study included 177 cancer patients in a trial of an endocannabinoid system modulator. Positive analgesic effects were observed and merit further study.[272][Level of evidence: I]

Les essais cliniques actuels

Check NCI's list of cancer clinical trials for US supportive and palliative care trials about pain that are now accepting participants. La liste des essais peut être encore réduit par emplacement, la drogue, l'intervention, et d'autres critères.

Informations générales sur les essais cliniques est également disponible sur le site Web du NCI.

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Radiation Therapy

Radiation therapy (RT) has been established as an effective treatment for pain caused by bony metastases. Local, half-body, or whole-body RT enhances the effectiveness of analgesic drugs and other noninvasive therapies by directly affecting the cause of pain (ie, reducing primary and metastatic tumor bulk).[1][Level of evidence: I] RT reduces pain and its interference with function among ambulatory cancer patients with symptomatic bone metastases.[2]

External-beam radiation for bone metastases

External-beam radiation therapy (EBRT) produces significant reduction in bone pain in 50% to 80% of patients, with complete pain relief in 30% to 50% of patients.[3] Dose fractionation schedules utilized for painful bone metastases vary considerably. Common fractionation schemes include 30 Gy in ten fractions, 24 Gy in six fractions, 20 Gy in five fractions, and 8 Gy in one fraction. Single- or multiple-fraction regimens of EBRT are equally effective when RT is administered for pain relief; however, re-treatment is needed more frequently after single-fraction RT.[4][Level of evidence: I];[2] Fractionated RT courses have been associated with a need for re-treatment in 8% of patients versus a need for re-treatment in 20% of patients after a single fraction.[3,4,5,6,7,8][Level of evidence: I]

The dose and fractionation schedule must achieve a balance between the amount of RT required to kill tumor cells and the amount that would adversely affect normal cells or allow repair of damaged tissue. Data from several prospective randomized trials have failed to show any increased rates of long-term toxicity with single-fraction palliative RT compared with multiple-fraction therapy. In addition to pain control considerations, impact on the patient and caregiver related to the number of treatments delivered must be considered, with many patients finding increased convenience with single-fraction treatment. Another consideration is treatment cost, with single-dose fractionation regimens being less costly because of the smaller number of RT treatments delivered.

Stereotactic body RT (SBRT) is used to treat bone metastases by delivering large doses of RT in a highly conformal manner. Most commonly used to treat spinal metastatic disease, SBRT delivers large doses with a steep dose gradient, thereby potentially sparing adjacent neural structures. Most published data on SBRT have come from single-institution, retrospective studies. The complexities of target delineation, total dose, and fractionation have yet to be fully defined. SBRT may also be used when re-treatment is required in previously irradiated areas. Data regarding RT dose or patient selection for the treatment of recurrent, painful spinal bony metastases with SBRT are not yet definitive.[9]

Pain flare, defined as an increase in pain after palliative RT, can occur, although the incidence has not been well documented. A relatively small, prospective, randomized, controlled trial comparing 8 Gy in one fraction with 20 Gy in five fractions reported pain flare in 15 of 44 patients (34%) for a median duration of 3 days. The flare occurred in 10 of 23 patients (44%) in the 8-Gy group and in 5 of 21 patients (24%) in the 20-Gy group.[10][Level of evidence: I] A multicenter study included three outpatient clinics and 111 patients to determine the incidence of pain flare after palliative RT. Pain flare was defined in this study as an increase in pain severity before achieving pain relief as distinguished from progression of pain by requiring the worst pain score and analgesic intake return to baseline levels after the increase/flare. Most patients received 8 Gy in one fraction (64%) or 20 Gy in five fractions (25%). The overall pain flare incidence was 40% (39% with 8 Gy and 41% with multiple fractions).[11][Level of evidence: II]

The use of RT with bisphosphonates has been evaluated in several prospective trials. The combination of zoledronic acid with either higher-dose palliative RT (30 Gy in ten fractions) or lower-dose RT (15 Gy in five fractions) for the treatment of single or multiple osteolytic or osteoblastic painful bony metastases in breast cancer patients was evaluated in a phase IV, randomized, controlled trial.[12] Zoledronic acid, 4 mg, was given every 28 days starting with RT. There was no difference in analgesic or pain scores between the two regimens. However, it has not been shown that the combination of these agents with RT is superior to RT alone for pain relief. Additional prospective trials are needed.

Radiopharmaceuticals

Radiopharmaceuticals are also utilized in the palliation of painful bony metastases. Single intravenous injections of beta-emitting agents such as iodine 131, phosphorus-32-orthophosphate, and strontium 89 and newer agents such as rhenium 186 and samarium 153 can relieve pain in widespread bony metastases.[13,14][Level of evidence: II];[15,16] Response rates range from 20% to 85%, depending on the agent used.

These agents have most commonly been used to treat osteoblastic metastases when there are several symptomatic sites and/or when the number of sites exceeds reasonable treatment with EBRT. Small-volume osteolytic metastases may respond to radiopharmaceuticals, but large-volume osteolytic disease usually does not respond. In patients with inadequate pain relief, studies have demonstrated that approximately one-half of patients treated with radiopharmaceuticals respond to a second treatment. A prospective, multicenter, open-label trial of samarium suggested that multiple doses (ie, more than two doses) may be administered to patients with advanced cancer and painful bone metastases with repeated benefit and adequate safety if there was an initial response to the initial samarium dose.[17][Level of evidence: II]

Available data do not suggest that these radiopharmaceuticals eliminate the need for palliative EBRT.[9] Limited studies compare the effectiveness of one radiopharmaceutical with another. In a small randomized trial comparing strontium with samarium in patients with painful bony metastases, there was no statistically significant difference in the degree of analgesia seen. Toxicity, primarily hematologic, was likewise similar.[18]

Radiofrequency ablation

Radiofrequency ablation (RFA) is a relatively new method for treating symptomatic bony metastasis. Through the use of electromagnetic energy, RFA induces thermal energy that damages tissue around the inserted electrode. The destruction of tissue depends on the temperature achieved and the duration of heating. With the use of image guidance, the goal of RFA is to maintain temperatures between 55°C and 100°C for 4 to 6 minutes to achieve cell kill. Because of slow thermal conduction through tissue, treatment time may increase up to 30 minutes. Preliminary results suggest that RFA may achieve palliation in patients with painful bony metastases.[19,20,21,22];[23][Level of evidence: III]

In a nonconsecutive 27-month period, 43 patients underwent RFA. Of the 43 patients, 41 (95%) experienced a decrease in worst pain (at least 2 points on an 11-point scale) that continued for up to 24 hours. After peaking at week 1, the morphine-equivalent daily dose decreased significantly at weeks 8 and 12 before rising again at week 24. Three patients experienced adverse events that included a second-degree skin burn at the grounding pad site, transient bladder and bowel incontinence after treatment of a sacral lesion, and an acetabular fracture 6 weeks after RFA of a pelvic lesion.[22] Other uncontrolled case reports confirm these findings. Further study is needed to determine potential risks and benefits.

Invasive Palliative Interventions

Less-invasive analgesic approaches should precede invasive palliative approaches; however, for a minority of patients in whom behavioral, physical, and drug therapy do not alleviate pain, invasive therapies are useful.

Nerve blocks

Control of otherwise intractable pain can be achieved by the application of a local anesthetic or neurolytic agent. Nerve blocks are performed for several reasons:

Diagnostic: To determine the source of pain (eg, somatic versus sympathetic pathways). Therapeutic: To treat painful conditions that respond to nerve blocks (eg, celiac block for pain of pancreatic cancer). Prognostic: To predict the outcome of long-lasting interventions (eg, infusions, neurolysis, and rhizotomy). Preemptive: To prevent procedure-related pain.

A single injection of a nondestructive agent such as lidocaine or bupivacaine, alone or in combination with an anti-inflammatory corticosteroid for a longer-lasting effect, can provide local relief from nerve or root compression.[24] Placement of an infusion catheter at a sympathetic ganglion extends the sympathetic blockade from hours to days or weeks. Destructive agents such as ethanol or phenol can be used to effect neurolysis at sites identified by local anesthesia as appropriate for permanent pain relief and may also be used to cause destruction of central nervous system structures. The efficacy of neurolytic sympathetic blocks may vary depending on the underlying pain mechanisms involved. For patients with multiple pain mechanisms, neurolytic sympathetic blocks may serve as adjuvant techniques to analgesic medications.[25][Level of evidence: II]

Neurologic interventions

Neurosurgery can be performed to implant devices that deliver drugs or electrically stimulate neural structures. Surgical ablation of pain pathways should, like neurolytic blockade, be reserved for situations in which other therapies are ineffective or poorly tolerated. In general, the choice of neurosurgical procedure is based on location and type of pain (somatic, visceral, deafferentation), the patient's general condition and life expectancy, and the expertise and follow-up available.

Management of procedural pain

Many diagnostic and therapeutic procedures are painful to patients. Anticipated procedure-related pain should be treated prophylactically, integrating pharmacologic and nonpharmacologic interventions in a complementary style.

Local anesthetics and short-acting opioids can be used to manage procedure-related pain, when adequate time is allotted for the drug to achieve full therapeutic effect. Anxiolytics and sedatives may be used to reduce anxiety or to produce sedation.

Cognitive-behavioral interventions such as imagery or relaxation may be useful in managing procedure-related pain and anxiety. (Refer to the Cognitive-Behavioral Interventions section of this summary for examples of relaxation exercises.) Patients generally tolerate procedures better when they are informed about what to expect.

Offering the option for a relative or friend to accompany the patient for support can be useful.

Références:

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5. Foro Arnalot P, Fontanals AV, Galcerán JC, et al.: Randomized clinical trial with two palliative radiotherapy regimens in painful bone metastases: 30 Gy in 10 fractions compared with 8 Gy in single fraction. Radiother Oncol 89 (2): 150-5, 2008.
6. Sande TA, Ruenes R, Lund JA, et al.: Long-term follow-up of cancer patients receiving radiotherapy for bone metastases: results from a randomised multicentre trial. Radiother Oncol 91 (2): 261-6, 2009.
7. Kaasa S, Brenne E, Lund JA, et al.: Prospective randomised multicenter trial on single fraction radiotherapy (8 Gy x 1) versus multiple fractions (3 Gy x 10) in the treatment of painful bone metastases. Radiother Oncol 79 (3): 278-84, 2006.
8. Roos DE, Turner SL, O'Brien PC, et al.: Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05). Radiother Oncol 75 (1): 54-63, 2005.
9. Lutz S, Berk L, Chang E, et al.: Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline. Int J Radiat Oncol Biol Phys 79 (4): 965-76, 2011.
10. Loblaw DA, Wu JS, Kirkbride P, et al.: Pain flare in patients with bone metastases after palliative radiotherapy--a nested randomized control trial. Support Care Cancer 15 (4): 451-5, 2007.
11. Hird A, Chow E, Zhang L, et al.: Determining the incidence of pain flare following palliative radiotherapy for symptomatic bone metastases: results from three canadian cancer centers. Int J Radiat Oncol Biol Phys 75 (1): 193-7, 2009.
12. Atahan L, Yildiz F, Cengiz M, et al.: Zoledronic acid concurrent with either high- or reduced-dose palliative radiotherapy in the management of the breast cancer patients with bone metastases: a phase IV randomized clinical study. Support Care Cancer 18 (6): 691-8, 2010.
13. Cheng A, Chen S, Zhang Y, et al.: The tolerance and therapeutic efficacy of rhenium-188 hydroxyethylidene diphosphonate in advanced cancer patients with painful osseous metastases. Cancer Biother Radiopharm 26 (2): 237-44, 2011.
14. Liepe K, Runge R, Kotzerke J: Systemic radionuclide therapy in pain palliation. Am J Hosp Palliat Care 22 (6): 457-64, 2005 Nov-Dec.
15. Sartor O, Reid RH, Hoskin PJ, et al.: Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology 63 (5): 940-5, 2004.
16. Coronado M, Redondo A, Coya J, et al.: Clinical role of Sm-153 EDTMP in the treatment of painful bone metastatic disease. Clin Nucl Med 31 (10): 605-10, 2006.
17. Sartor O, Reid RH, Bushnell DL, et al.: Safety and efficacy of repeat administration of samarium Sm-153 lexidronam to patients with metastatic bone pain. Cancer 109 (3): 637-43, 2007.
18. Baczyk M, Czepczyński R, Milecki P, et al.: 89Sr versus 153Sm-EDTMP: comparison of treatment efficacy of painful bone metastases in prostate and breast carcinoma. Nucl Med Commun 28 (4): 245-50, 2007.
19. Dupuy DE, Liu D, Hartfeil D, et al.: Percutaneous radiofrequency ablation of painful osseous metastases: a multicenter American College of Radiology Imaging Network trial. Cancer 116 (4): 989-97, 2010.
20. Callstrom MR, Charboneau JW: Image-guided palliation of painful metastases using percutaneous ablation. Tech Vasc Interv Radiol 10 (2): 120-31, 2007.
21. Callstrom MR, Atwell TD, Charboneau JW, et al.: Painful metastases involving bone: percutaneous image-guided cryoablation--prospective trial interim analysis. Radiology 241 (2): 572-80, 2006.
22. Goetz MP, Callstrom MR, Charboneau JW, et al.: Percutaneous image-guided radiofrequency ablation of painful metastases involving bone: a multicenter study. J Clin Oncol 22 (2): 300-6, 2004.
23. Thacker PG, Callstrom MR, Curry TB, et al.: Palliation of painful metastatic disease involving bone with imaging-guided treatment: comparison of patients' immediate response to radiofrequency ablation and cryoablation. AJR Am J Roentgenol 197 (2): 510-5, 2011.
24. Wyse JM, Carone M, Paquin SC, et al.: Randomized, double-blind, controlled trial of early endoscopic ultrasound-guided celiac plexus neurolysis to prevent pain progression in patients with newly diagnosed, painful, inoperable pancreatic cancer. J Clin Oncol 29 (26): 3541-6, 2011.
25. Mercadante S, Fulfaro F, Casuccio A: Pain mechanisms involved and outcome in advanced cancer patients with possible indications for celiac plexus block and superior hypogastric plexus block. Tumori 88 (3): 243-5, 2002 May-Jun.

Patients should be encouraged to remain active and participate in self-care when possible. Noninvasive physical, integrative (complementary/alternative therapies), cognitive-behavioral, and psychosocial modalities are typically used in conjunction with pharmacotherapy to manage pain during all phases of treatment. These interventions have the potential to enhance pain control directly but also indirectly, by increasing a patient's sense of control over events. The effectiveness of these modalities depends on the patient's participation and communication of which methods best alleviate pain. Minority patients of various ethnicities have been noted to experience worse control of their pain, which may result from miscommunication issues within the medical setting. In a post hoc analysis of a small trial, minority (various ethnicities) (n = 15) and white (n = 52) cancer patients were randomly assigned either to a 20-minute individualized education-and-coaching session regarding pain management (including how to discuss their concerns with their physician) or to usual care. At baseline, minority patients reported significantly more pain than white patients (6.0 vs. 5.0), whereas at follow-up, disparities had been eliminated in the intervention group (4.0 vs. 4.3) but remained in the control group (6.4 vs. 4.7).[1][Level of evidence: I]

Physical Modalities

Generalized weakness, deconditioning, and musculoskeletal pain associated with cancer diagnosis and therapy may be treated by:

Heat

Avoid burns by wrapping the heat source (eg, hot pack or heating pad) in a towel. A timing device is useful to prevent burns from an electrical heating pad. The use of heat on recently irradiated tissue is contraindicated, and diathermy and ultrasound are not recommended for use over tumor sites.

Cold

Apply flexible ice packs that conform to body contours for periods not to exceed 15 minutes. Cold treatment reduces swelling and may provide longer-lasting relief than heat but should be used cautiously in patients with peripheral vascular disease and on tissue damaged by radiation therapy.

Exercice

Exercise strengthens weak muscles, mobilizes stiff joints, helps restore coordination and balance, and provides cardiovascular conditioning. Therapists and trained family or other caregivers can assist the functionally limited patient with range-of-motion exercises to help preserve strength and joint function. During episodes of acute pain, exercise should be limited to self-administered range-of-motion. Weight-bearing exercise should be avoided when bone fracture is likely.

Repositioning

Reposition the immobilized patient frequently to maintain correct body alignment, to prevent or alleviate pain, and to prevent pressure ulcers.

Immobilization

Use restriction of movement to manage acute pain or to stabilize fractures or otherwise compromised limbs or joints. Use adjustable elastic or thermoplastic braces to help maintain correct body alignment. Keep joints in positions of maximal function rather than maximal range. Avoid prolonged immobilization.

Stimulation Techniques

Transcutaneous Electrical Nerve Stimulation (TENS): Controlled low-voltage electrical stimulation applied to large myelinated peripheral nerve fibers via cutaneous electrodes to inhibit pain transmission. Patients with mild-to-moderate pain may benefit from a trial of TENS to see if it is effective in reducing the pain. TENS is a low-risk intervention. A small crossover study (N = 41) found that 72% of users rated TENS as effective or very effective, compared to those using the comparison intervention (27%) or placebo intervention (36%). Furthermore, a clinically meaningful number of participants was still using the TENS a year later (n = 10), in contrast to the other two conditions (combined n = 5). All three treatment arms were well tolerated, but there is no conclusive evidence demonstrating any benefit from TENS or transcutaneous spinal electroanalgesia (TSE) over placebo in this cancer pain population.[2][Level of evidence: I]

Integrative Modalities

Massage, Pressure, and Vibration

Physical stimulation techniques have direct mechanical effects on tissues and enhance relaxation when applied gently. Tumor masses should not be aggressively manipulated.

Massage therapy is an integrative modality that has been investigated as an adjunct to supportive care interventions in managing cancer-related pain. Preclinical and clinical trials have found that massage reduces pain by reducing cortisol levels, increasing serotonin and dopamine levels, stimulating the release of endorphins, and stimulating blood and lymphatic circulation. Massage may enhance the effects of analgesic medications and decrease inflammation and edema. There is a large body of evidence supporting the role of massage in reducing pain associated with muscle-related conditions such as muscle spasms and tension.[3,4,5,6] Massage may also play a role in the management of procedural pain.

In one of the largest randomized trials, 380 adults with advanced cancer received six sessions of either massage therapy or touch therapy for 30 minutes over a 2-week period.[3] While immediate improvements from massage therapy were significantly greater than those from touch therapy, the benefits were not sustained, according to the Brief Pain Inventory. However, a large number of patients were not included in the assessments of immediate outcomes or sustained outcomes. Data collectors were also not blinded to the study arm, which may have led to overreporting the effects of massage therapy or touch therapy.

A number of reviews exploring the role of massage in the management of cancer pain or other areas of supportive care have been published. In a Cochrane review of the role of massage therapy with or without aromatherapy as a component of supportive care,[7] three studies found a reduction in pain following intervention and reported reductions of 30% to 39% in pain scores after massage therapy, compared to usual care. Another study reported on the role of massage within the context of supportive care in cancer, highlighted pain, and concluded that evidence is encouraging but effect sizes are small.[5] Additional trials are needed.

While the benefit of massage therapy on cancer pain may be mixed, existing trials suggest that massage therapy is safe in patients with cancer. However, certain precautions should be taken when providing massage therapy to patients with cancer:

Avoid directly massaging any open wounds, hematomas, or areas with skin breakdown.Avoid massaging the site of the tumor.Avoid massaging areas with acute deep venous thrombosis.Avoid directly massaging radiated soft tissue.[8]

Acupuncture

Acupuncture applies needles, heat, pressure, and other treatments to one or more places on the skin known as acupuncture points and is often sought by patients with cancer for the management of pain. (Refer to the PDQ summary on Acupuncture for a comprehensive review of the evidence supporting the role of acupuncture for the management of pain.)

Music Interventions for Pain

Music Therapy and Music Medicine

There are generally two broad categories of music-based interventions referenced within health care research.

Music therapy is the clinical and evidence-based use of active and receptive, tailored, music-based interventions to accomplish individualized goals within a therapeutic relationship, delivered by a credentialed professional (music therapist-board certified, or MT-BC) who has completed an approved program in music therapy.[9]

Music therapists use a variety of music-based interventions that include live, interactive music making or carefully selected recorded music. Some examples include music improvisation, song writing and singing, and music relaxation.

A music therapist chooses interventions on the basis of an assessment of a patient's immediate and long-term needs (eg, pain management, anxiety reduction, coping strategies, and skills).

Music medicine is the use of passive music listening (usually prerecorded music) for distraction, delivered by a medical professional without specialized music training.[10]

Music therapy and music medicine interventions have been used to relieve acute and chronic pain related to noxious procedures and treatments and the disease process. Music reduces pain via the mutually inhibitory neuroanatomical pathways that are shared between pain and reward processing.[11] Neuroscience studies are consistent in suggesting that pleasant emotional responses to music activate brain structures related to reward, emotion, and attention and decrease activation in areas associated with aversive events.[12,13,14] Music from an individual's personal collection that elicits a positive emotional response has the most robust effect in increasing pain tolerance, decreasing anxiety, and increasing perceived control.[15,16,17]

Meta-analyses summarizing the effect of music on pain indicate small to moderate benefit, with a high level of heterogeneity. There is preliminary evidence that music interventions delivered by music therapists are more effective than music medicine interventions.[10,18]

Studies reporting rates of 50% pain reduction indicate that participants in music listening had a 70% greater probability of experiencing at least a 50% pain reduction than did controls (n = 4 studies).[19] There is also preliminary evidence that music reduces opioid requirements, but the benefits are small and the clinical importance is unclear.[19] Music-based interventions specifically for cancer patients found a moderate pain-reducing effect of a 0.54 standardized unit difference between music and usual-care groups (5 studies, n = 391).[20]

While initial results are promising, the quality of evidence for music and cancer pain studies is low, often because of wide confidence intervals and high variability in study quality.[20] Common sources of bias and low quality include nonblinding of participant and study personnel, lack of theory guiding music selection and delivery, and incomplete reporting of intervention details.[13,21,22]

Characteristics of Music Interventions for Pain

Characteristics of music interventions for pain include the following:

Music interventions can be used as adjuncts to analgesic medications.When available, live music is preferred, delivered by a board-certified music therapist.When recorded music is to be used, patients should be encouraged to choose music from their personal collections that is emotionally meaningful to them.When several pieces of music are to be used, they should be played so that up-tempo and more complex pieces are heard at the beginning, with tempo and overall complexity decreasing from beginning to end.A general orientation to music listening should be provided to patients and caregivers, to include the operation of any equipment and instructions to patients for when they need additional assistance.Music listening through headphones may be contraindicated during painful procedures because it prevents patients from hearing instructions or comments from physicians.[23]Music introduced before a procedure is more effective than music introduced during or after a procedure.[18]

Cognitive-Behavioral Interventions

Cognitive-behavioral interventions are an important part of a multimodal approach to pain management. They help the patient obtain a sense of control and develop coping skills to deal with the disease and its symptoms. Guidelines by a National Institutes of Health assessment panel suggest integration of pharmacologic and behavioral approaches for treatment of pain and insomnia.[24] Other studies suggest that behavioral interventions targeted to specific symptoms, such as pain and fatigue, can significantly reduce symptom burden and improve the quality of life for patients with cancer.[25][Level of evidence: I] Realistic expectations are needed for delivery of cognitive-behavioral interventions. One study [26][Level of evidence: I] of cognitive-behavioral interventions for pain management randomly assigned 57 patients (most of whom were women with metastatic breast cancer who were maintained on daily opioid use for pain) to three 20-minute interventions delivered by audiotape (progressive muscle relaxation [PMR], positive mood induction, or a distraction condition) or to a no-intervention control. The patients were provided the audiotapes by a research nurse, given brief instructions, and asked to use the tapes at least five times a week for 2 weeks; more than half of the patients reported complying with these instructions. The relaxation condition and the "distraction" condition (self-selected informational tapes) produced significant immediate effects on pain, but the positive mood induction tapes showed no effects. The effects, however, neither carried over to general symptom management nor affected pain management at other times. One conclusion of this study is that ideally, interventions should be matched to patient preferences; for more extended effects, additional instruction and support may be needed, as suggested by other studies.

Interventions introduced early in the course of illness are more likely to succeed because they can be learned and practiced by patients while they have sufficient strength and energy. Patients and their families should be given information about and encouraged to try several strategies, and to select one or more of these cognitive-behavioral techniques to use regularly:

Relaxation and Imagery

Simple relaxation techniques (see examples listed below) should be used for episodes of brief pain (eg, during procedures). Brief, simple techniques are preferred when the patient's ability to concentrate is compromised by severe pain, a high level of anxiety, or fatigue.

Hypnose

Hypnotic techniques may be used to induce relaxation and may be combined with other cognitive-behavioral strategies.[27][Level of evidence: I] Hypnosis is effective in relieving pain in individuals who can concentrate well, can use imagery, and are motivated to practice. A randomized but unblinded study of preoperative hypnosis in women undergoing excisional breast biopsy or lumpectomy revealed that women who underwent hypnosis required less propofol and lidocaine use during surgery and scored lower on measures of pain, nausea, fatigue, discomfort, and emotional upset at discharge.[28][Level of evidence: I]

Cognitive Distraction and Reframing

Focusing attention on stimuli other than pain or negative emotions accompanying pain may involve distractions that are internal (eg, counting, praying, or making self-statements such as "I can cope") or external (eg, listening to music, watching television, talking, listening to someone read, or using a visual focal point). In the related technique, cognitive reappraisal, patients learn to monitor and evaluate negative thoughts and replace them with more positive thoughts and images.

Patient/Family Education

Both oral and written information and instructions should be provided about pain, pain assessment, and the use of drugs and other methods of pain relief.[29,30,31][Level of evidence: I] Patient education should emphasize that almost all pain can be effectively managed. Major barriers to effective pain management (refer to the list of Barriers to Effective Cancer Pain Management in the Overview section of this summary) should be discussed to correct patient and family misconceptions. Health care providers need to take into consideration family members' interpretation of patient pain when providing pain management education services, as some caregivers overestimate patient pain.[32][Level of evidence: II] Educational intervention programs to help patients who have cancer and their families manage pain have been described and may improve clinical outcomes.[33][Level of evidence: II] These programs are based on adult learning principles and incorporate key strategies, including provision of information using academic detailing, skill building with ongoing nurse-coaching, and interactive nursing support.[34][Level of evidence: IV];[35][Level of evidence: I] Training partners to participate in management of cancer pain increases partner self-efficacy for controlling their loved one's pain and other symptoms.[36][Level of evidence: II]

Psychotherapy and Structured Support

Some patients benefit from short-term psychotherapy provided by trained professionals. Patients whose pain is particularly difficult to manage and who develop symptoms of clinical depression or adjustment disorder should be referred to a psychiatrist or psychologist for diagnosis. The relationship between poorly controlled pain, depression, and thoughts of suicide should not be ignored.

Support Groups and Pastoral Counseling

Because many patients benefit from peer support groups, clinicians should be aware of locally active groups and offer this information to patients and their families. Pastoral counseling members of the health care team should participate in meetings to discuss patients' needs and treatment. They should also be a source of information on community resources for spiritual care and social support.

Relaxation Exercises [Note: Adapted and reprinted with permission from McCaffery M, Beebe A: Pain: Clinical Manual for Nursing Practice. St. Louis, Mo: CV Mosby Co, 1989.]

Exercise 1. Slow Rhythmic Breathing for Relaxation

1. Breathe in slowly and deeply, keeping your stomach relaxed and your shoulders relaxed.
2. As you breathe out slowly, feel yourself beginning to relax; feel the tension leaving your body.
3. Now breathe in and out slowly and regularly, at whatever rate is comfortable for you. Let the breath come all the way down to your stomach, as it completely relaxes.
4. To help you focus on your breathing and breathe slowly and rhythmically: (a) breathe in as you say silently to yourself, "in, two, three"; (b) breathe out as you say silently to yourself, "out, two, three." Or, each time you breathe out, say silently to yourself a word such as "peace" or "relax."
5. Do steps 1 through 4 only once or repeat steps 3 and 4 for up to 20 minutes.
6. End with a slow deep breath. As you breathe out say to yourself, "I feel alert and relaxed."

Exercise 2. Simple Touch, Massage, or Warmth for Relaxation

1. Touch and massage are age-old methods of helping others relax. Examples include the following:

Brief touch or massage (eg, handholding or briefly touching or rubbing a person's shoulder).Warm foot soak in a basin of warm water, or wrap the feet in a warm, wet towel.Massage (3–10 minutes) may consist of whole body or be restricted to back, feet, or hands. If the patient is modest or cannot move or turn easily in bed, consider massage of the hands and feet.
2. Use a warm lubricant (eg, a small bowl of hand lotion may be warmed in the microwave oven, or a bottle of lotion may be warmed by placing it in a sink of hot water for about 10 minutes).
3. Massage for relaxation is usually done with smooth, long, slow strokes. (Rapid strokes, circular movements, and squeezing of tissues tend to stimulate circulation and increase arousal.) However, try several degrees of pressure along with different types of massage (eg, kneading and stroking). Determine which is preferred.
4. Especially for the older person, a back rub that effectively produces relaxation may consist of no more than 3 minutes of slow, rhythmic stroking (about 60 strokes per minute) on both sides of the spinous process from the crown of the head to the lower back. Continuous hand contact is maintained by starting one hand down the back as the other hand stops at the lower back and is raised. Set aside a regular time for the massage. This gives the patient something to look forward to and depend on.

Exercise 3. Peaceful Past Experiences

Something may have happened to you a while ago that brought you peace and comfort. You may be able to draw on that past experience to bring you peace or comfort now. Think about these questions:

1. Can you remember any situation, even when you were a child, when you felt calm, peaceful, secure, hopeful, or comfortable?
2. Have you ever daydreamed about something peaceful? What were you thinking of?
3. Do you get a dreamy feeling when you listen to music? Do you have any favorite music?
4. Do you have any favorite poetry that you find uplifting or reassuring?
5. Have you ever been religiously active? Do you have favorite readings, hymns, or prayers? Even if you haven't heard or thought of them for many years, childhood religious experiences may still be very soothing.

Additional points: Some of the things you think of in answer to these questions, such as your favorite music or a prayer, can probably be recorded for you. Then you can listen to the tape whenever you wish. If your memory is strong, you may simply be able to close your eyes and recall the events or words.

Exercise 4. Active Listening to Recorded Music

1. Obtain the following:

A cassette player or tape recorder. (Small battery-operated machines are more convenient.)Earphones or a headset. (This is a more compelling stimulus than a speaker a few feet away, and it avoids disturbing others.)Cassette recording of music you like. (Most people prefer fast, lively music, but some people select relaxing music. Other options are comedy routines, sporting events, old radio shows, or stories.)
2. Mark time to the music, eg, tap out the rhythm with your finger or nod your head. This helps you concentrate on the music rather than your discomfort.
3. Keep your eyes open and focus steadily on one stationary spot or object. If you wish to close your eyes, picture something about the music.
4. Listen to the music at a comfortable volume. If the discomfort increases, try increasing the volume; decrease the volume when the discomfort decreases.
5. If these steps are not effective enough, try adding or changing one or more of the following: massage your body in rhythm to the music; try other music; mark time to the music in more than one manner (eg, tap your foot and finger at the same time).

Additional points: Many patients have found this technique to be helpful. It tends to be very popular, probably because the equipment is usually readily available and is a part of daily life. Other advantages are that it is easy to learn and is not physically or mentally demanding. If you are very tired, you may simply listen to the music and omit marking time or focusing on a spot.

Références:

1. Kalauokalani D, Franks P, Oliver JW, et al.: Can patient coaching reduce racial/ethnic disparities in cancer pain control? Secondary analysis of a randomized controlled trial. Pain Med 8 (1): 17-24, 2007 Jan-Feb.
2. Robb KA, Newham DJ, Williams JE: Transcutaneous electrical nerve stimulation vs. transcutaneous spinal electroanalgesia for chronic pain associated with breast cancer treatments. J Pain Symptom Manage 33 (4): 410-9, 2007.
3. Kutner JS, Smith MC, Corbin L, et al.: Massage therapy versus simple touch to improve pain and mood in patients with advanced cancer: a randomized trial. Ann Intern Med 149 (6): 369-79, 2008.
4. Calenda E: Massage therapy for cancer pain. Curr Pain Headache Rep 10 (4): 270-4, 2006.
5. Ernst E: Massage therapy for cancer palliation and supportive care: a systematic review of randomised clinical trials. Support Care Cancer 17 (4): 333-7, 2009.
6. Hughes D, Ladas E, Rooney D, et al.: Massage therapy as a supportive care intervention for children with cancer. Oncol Nurs Forum 35 (3): 431-42, 2008.
7. Fellowes D, Barnes K, Wilkinson S: Aromatherapy and massage for symptom relief in patients with cancer. Cochrane Database Syst Rev (2): CD002287, 2004.
8. Gecsedi RA: Massage therapy for patients with cancer. Clin J Oncol Nurs 6 (1): 52-4, 2002 Jan-Feb.
9. American Music Therapy Association.: AMTA Standards of Practice. Silver Spring, Md: American Music Therapy Association, 2011. Available online. Last accessed July 19, 2012.
10. Dileo C: Effects of music and music therapy on medical patients: a meta-analysis of the research and implications for the future. J Soc Integr Oncol 4 (2): 67-70, 2006.
11. Leknes S, Tracey I: A common neurobiology for pain and pleasure. Nat Rev Neurosci 9 (4): 314-20, 2008.
12. Blood AJ, Zatorre RJ: Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proc Natl Acad Sci USA 98 (20): 11818-23, 2001.
13. Blood AJ, Zatorre RJ, Bermudez P, et al.: Emotional responses to pleasant and unpleasant music correlate with activity in paralimbic brain regions. Nat Neurosci 2 (4): 382-7, 1999.
14. Salimpoor VN, Benovoy M, Longo G, et al.: The rewarding aspects of music listening are related to degree of emotional arousal. PLoS One 4 (10): e7487, 2009.
15. Mitchell LA, MacDonald RA: An experimental investigation of the effects of preferred and relaxing music listening on pain perception. J Music Ther 43 (4): 295-316, 2006.
16. Mitchell LA, MacDonald RA, Knussen C: An investigation of the effects of music and art on pain perception. Psychology of Aesthetics, Creativity, and the Arts 2 (3): 162-70, 2008.
17. Roy M, Peretz I, Rainville P: Emotional valence contributes to music-induced analgesia. Pain 134 (1-2): 140-7, 2008.
18. Standley JM: Music research in medical treatment. In: Smith DS, ed.: Effectiveness of Music Therapy Procedures: Documentation of Research and Clinical Practice. 3e éd. Silver Spring, Md: American Music Therapy Association, 2000, pp 1-64.
19. Cepeda MS, Carr DB, Lau J, et al.: Music for pain relief. Cochrane Database Syst Rev (2): CD004843, 2006.
20. Bradt J, Dileo C, Grocke D, et al.: Music interventions for improving psychological and physical outcomes in cancer patients. Cochrane Database Syst Rev (8): CD006911, 2011.
21. Burns DS: Theoretical rationale for music selection in oncology intervention research: an integrative review. J Music Ther 49 (1): 7-22, 2012.
22. Robb SL, Burns DS, Carpenter JS: Reporting guidelines for music-based interventions. J Health Psychol 16 (2): 342-52, 2011.
23. Kwekkeboom KL: Music versus distraction for procedural pain and anxiety in patients with cancer. Oncol Nurs Forum 30 (3): 433-40, 2003 May-Jun.
24. Integration of behavioral and relaxation approaches into the treatment of chronic pain and insomnia. NIH Technology Assessment Panel on Integration of Behavioral and Relaxation Approaches into the Treatment of Chronic Pain and Insomnia. JAMA 276 (4): 313-8, 1996 Jul 24-31.
25. Given B, Given CW, McCorkle R, et al.: Pain and fatigue management: results of a nursing randomized clinical trial. Oncol Nurs Forum 29 (6): 949-56, 2002.
26. Anderson KO, Cohen MZ, Mendoza TR, et al.: Brief cognitive-behavioral audiotape interventions for cancer-related pain: Immediate but not long-term effectiveness. Cancer 107 (1): 207-14, 2006.
27. Butler LD, Koopman C, Neri E, et al.: Effects of supportive-expressive group therapy on pain in women with metastatic breast cancer. Health Psychol 28 (5): 579-87, 2009.
28. Montgomery GH, Bovbjerg DH, Schnur JB, et al.: A randomized clinical trial of a brief hypnosis intervention to control side effects in breast surgery patients. J Natl Cancer Inst 99 (17): 1304-12, 2007.
29. Oliver JW, Kravitz RL, Kaplan SH, et al.: Individualized patient education and coaching to improve pain control among cancer outpatients. J Clin Oncol 19 (8): 2206-12, 2001.
30. Miaskowski C, Dodd M, West C, et al.: Randomized clinical trial of the effectiveness of a self-care intervention to improve cancer pain management. J Clin Oncol 22 (9): 1713-20, 2004.
31. Miaskowski C, Dodd M, West C, et al.: The use of a responder analysis to identify differences in patient outcomes following a self-care intervention to improve cancer pain management. Pain 129 (1-2): 55-63, 2007.
32. Redinbaugh EM, Baum A, DeMoss C, et al.: Factors associated with the accuracy of family caregiver estimates of patient pain. J Pain Symptom Manage 23 (1): 31-8, 2002.
33. Aubin M, Vézina L, Parent R, et al.: Impact of an educational program on pain management in patients with cancer living at home. Oncol Nurs Forum 33 (6): 1183-8, 2006.
34. West CM, Dodd MJ, Paul SM, et al.: The PRO-SELF(c): Pain Control Program--an effective approach for cancer pain management. Oncol Nurs Forum 30 (1): 65-73, 2003 Jan-Feb.
35. Lin CC, Chou PL, Wu SL, et al.: Long-term effectiveness of a patient and family pain education program on overcoming barriers to management of cancer pain. Pain 122 (3): 271-81, 2006.
36. Keefe FJ, Ahles TA, Sutton L, et al.: Partner-guided cancer pain management at the end of life: a preliminary study. J Pain Symptom Manage 29 (3): 263-72, 2005.

Patients and families may have difficulty remembering details of the pain management plan and should be given a written pain-management plan. The patient and family should receive clear instructions regarding telephone contact for more urgent questions relating to pain management.

Like other adults, older patients require comprehensive assessment and aggressive management of cancer pain. Older patients are at risk for undertreatment of pain, however, because of underestimation of their sensitivity to pain, the expectation that they tolerate pain well, and misconceptions about their ability to benefit from the use of opioids. Issues in assessing and treating cancer pain in older patients include:

Multiple chronic diseases and sources of pain.

Age and complex medication regimens place them at increased risk for drug-drug and drug-disease interactions.

Visual, hearing, motor, and cognitive impairments.

The use of simple descriptive, numeric, and visual-analog pain-assessment instruments may be impeded. Cognitively impaired patients may require simpler scales and more frequent pain assessment.

Nonsteroidal anti-inflammatory drug (NSAID) side effects.

Although effective alone or as adjuncts to opioids, NSAIDs are more likely to cause gastric and renal toxicity and other drug reactions such as cognitive impairment, constipation, and headaches in older patients. Alternative NSAIDs (eg, choline magnesium trisalicylate) or coadministration of misoprostol with NSAIDs should be considered to reduce gastric toxicity.

Opioid effectiveness.

Older persons tend to be more sensitive to the analgesic and central nervous system depressant effects of opioids. Peak opioid effects are generally greater and the duration of pain relief may be longer.

Patient-controlled analgesia.

Slower drug clearance and increased sensitivity to undesirable drug effects (eg, cognitive impairment) indicate the need for cautious initial dosing and subsequent titration and monitoring of continuous parenteral infusions.

Alternative routes of administration.

Although useful for patients who have nausea or vomiting, the rectal route may be inappropriate for elderly or infirm patients who are physically unable to place the suppository in the rectum.

Postoperative pain control.

Following surgery, surgeons and other health care team members should maintain frequent direct contact with the elderly patient to reassess the quality of pain management.

Change of setting.

Reassessment of pain management and appropriate changes should be made whenever the elderly patient moves (eg, from hospital to home or nursing home).

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But de ce résumé

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the pathophysiology and treatment of pain. Il est conçu comme une ressource pour informer et aider les cliniciens qui soignent les patients atteints de cancer. Il ne fournit pas de directives ou de recommandations officielles pour prendre des décisions de soins de santé.

Les examinateurs et mises à jour

This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of the National Cancer Institute (NCI). Le résumé reflète un examen indépendant de la littérature et ne représente pas un énoncé de politique de NCI ou de la National Institutes of Health (NIH).

les membres de la Commission de révision a récemment publié des articles chaque mois pour déterminer si un article doit:

être discuté lors d'une réunion, être cité avec le texte, orreplace ou mettre à jour un article existant qui est déjà cité.

Les modifications apportées aux résumés sont faites à travers un processus de consensus dans lequel les membres du Conseil d'évaluer la force de la preuve dans les articles publiés et de déterminer comment l'article devrait être inclus dans le résumé.

Des commentaires ou des questions sur le contenu de résumé doivent être soumis à Cancer.gov à travers le formulaire de contact du site Web. Ne pas communiquer avec les membres du Conseil individuels avec des questions ou des commentaires concernant les résumés. Les membres du Conseil ne seront pas répondre aux demandes individuelles.

Niveaux de preuve

Certaines des citations de référence dans ce résumé sont accompagnées d'une désignation au niveau de la preuve. Ces désignations visent à aider le lecteur à évaluer la force de la preuve à l'appui de l'utilisation des interventions ou des approches spécifiques. The PDQ Supportive and Palliative Care Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission d'utiliser cette Résumé

PDQ est une marque déposée. Bien que le contenu des documents PDQ peut être utilisé librement sous forme de texte, il ne peut être identifié comme une NCI PDQ résumé de l'information sur le cancer que si elle est présentée dans son intégralité et est régulièrement mis à jour. Toutefois, un auteur serait autorisé à écrire une phrase comme «PDQ information sur le cancer du résumé du NCI sur la prévention du cancer du sein indique les risques de façon succincte: [inclure extrait du résumé]."

La citation préférée pour ce résumé PDQ est:

National Cancer Institute: PDQ® Pain. Bethesda, MD: National Cancer Institute. Date de la dernière <JJ / MM / AAAA> modifié. Available at: http://cancer.gov/cancertopics/pdq/supportivecare/pain/HealthProfessional. Consulté <JJ / MM / AAAA>.

images dans ce résumé sont utilisés avec la permission de l'auteur (s), l'artiste et / ou de l'éditeur pour une utilisation dans les résumés PDQ seulement. L'autorisation d'utiliser les images en dehors du contexte de l'information PDQ doit être obtenue auprès du propriétaire (s) et ne peut être accordée par le National Cancer Institute. Informations sur l'utilisation des illustrations dans ce résumé, avec beaucoup d'autres images liées au cancer, est disponible en ligne Visuals, une collection de plus de 2000 images scientifiques.

Désistement

Les informations contenues dans ces résumés ne doit pas être utilisé comme une base pour la détermination de remboursement de l'assurance. Plus d'informations sur la couverture d'assurance est disponible sur Cancer.gov sur la face au cancer: financier, d'assurance, et la page d'information juridique page.

Contactez-Nous

Plus d'informations sur nous contactant ou recevoir de l'aide avec le site Web Cancer.gov peut être trouvé sur notre Contactez-nous pour l'aide page. Les questions peuvent également être soumis à Cancer.gov à travers le formulaire de contact du site Web.

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Pour plus d'informations, les résidents américains peuvent appeler de l'Institut national du cancer (NCI) Service d'information sur le cancer au 1-800-4-CANCER (1-800-422-6237) sans frais du lundi au vendredi 08h00-8h00 h, heure de l'Est. Un spécialiste de l'information sur le cancer formé est disponible pour répondre à vos questions.

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LiveHelp® service de chat en ligne du NCI offre aux internautes la possibilité de discuter en ligne avec un spécialiste de l'information. Le service est disponible 8:00-à-23h00 heure de l'Est, du lundi au vendredi. Spécialistes de l'information peuvent aider les internautes à trouver des informations sur les sites Web du NCI et répondent aux questions sur le cancer.

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Pour plus d'informations de la NCI, se il vous plaît écrire à cette adresse:

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Recherche sur le site Web du NCI

Le site Web du NCI offre un accès en ligne à l'information sur le cancer, les essais cliniques, et d'autres sites et d'organismes qui offrent un soutien et des ressources pour les patients atteints de cancer et leurs familles sur le Web. Pour une recherche rapide, utiliser la boîte de recherche dans le coin supérieur droit de chaque page Web. Les résultats pour un large éventail de termes de recherche incluront une liste de «meilleurs résultats», pages Web éditorial choisis qui sont le plus étroitement liés au terme de recherche saisi.

Il ya aussi beaucoup d'autres endroits pour obtenir des matériaux et des informations sur le traitement et les services cancer. Hôpitaux dans votre région peuvent avoir des informations sur les agences locales et régionales qui ont des informations sur les finances, pour se rendre et d'un traitement, de recevoir des soins à la maison et faire face aux problèmes liés au traitement du cancer.

Trouver Publications

Le NCI a brochures et autres matériaux pour les patients, les professionnels de santé et le public. Ces publications traitent types de cancer, les méthodes de traitement du cancer, faire face au cancer, et des essais cliniques. Certaines publications fournissent des informations sur les tests pour le cancer, les causes de cancer et la prévention, statistiques sur le cancer, et les activités de recherche du NCI. NCI sur ces matières et d'autres sujets peuvent être commandés en ligne ou imprimées directement à partir du NCI Locator Publications. Ces matériaux peuvent également être commandés par téléphone du au 1-800-4-CANCER (1-800-422-6237) sans frais Service d'information sur le cancer.

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