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Pediatric Palliative Care

Use of Opioids for the Management of Pain

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Abstract

Pediatric palliative care (PPC) is provided to children experiencing life-limiting diseases (LLD) or life-threatening diseases (LTD). Sixty to 90% of children with LLD/LTD undergoing PPC receive opioids at the end of life. Analgesia is often insufficient. Reasons include a lack of knowledge concerning opioid prescribing and adjustment of opioid dose to changing requirements. The choice of first-line opioid is based on scientific evidence, pain pathophysiology, and available administration modes. Doses are calculated on a bodyweight basis up to a maximum absolute starting dose.

Morphine remains the gold standard starting opioid in PPC. Long-term opioid choice and dose administration is determined by the pathology, analgesic effectiveness, and adverse effect profile. Slow-release oral morphine remains the dominant formulation for long-term use in PPC with hydromorphone slow-release preparations being the first rotation opioid when morphine shows severe adverse effects. The recently introduced fentanyl transdermal therapeutic system with a drug-release rate of 12.5μg/hour matches the lower dose requirements of pediatric cancer pain control. Its use may be associated with less constipation compared with morphine use. Though oral transmucosal fentanyl citrate has reduced bioavailability (25%), it inherits potential for breakthrough pain management. However, the gold standard breakthrough opioid remains immediate-release morphine. Buprenorphine is of special clinical interest as a result of its different administration routes, long duration of action, and metabolism largely independent of renal function. Antihyperalgesic effects, induced through antagonism at the κ-receptor, may contribute to its effectiveness in neuropathic pain. Methadone also has a long elimination half-life (19 [SD 14] hours) and NMDA receptor activity although dose administration is complicated by highly variable morphine equianalgesic equivalence (1:2.5–20). Opioid rotation to methadone requires special protocols that take this into account. Strategies to minimize adverse effects of long-term opioid treatment include dose reduction, symptomatic therapy, opioid rotation, and administration route change. Patient- or nurse-controlled analgesia devices are useful when pain is rapidly changing, or in terminal care where analgesic requirements may escalate. In this article, we present detailed pediatric pharmacokinetic and pharmacodynamic data for opioids, their indications and contraindications, as well as dose-administration regimens that include practical strategies for opioid switching and dose reduction. Additionally, we discuss the problem of hyperalgesia and the use of adjuvant drugs to support opioid therapy.

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. B. Zernikow has received consultancies from Mundipharma, JanssenCilag, Reckitt-Benckieser, and Bristol-Myers Squibb; speaking honoraria from AstraZeneca, Aventis, Boots Healthcare, Bristol-Myers Squibb, Cephalon, Grünenthal, JanssenCilag, Mundipharma, and Pfizer; and grants from AstraZeneca. E. Michel, F. Craig, and B. Anderson have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Vodafone Foundation Institute for Children’s Pain Therapy and Paediatric Palliative Care, Children’s Hospital Datteln, Witten/Herdecke University, Dr.-Friedrich-Steiner-Str. 5, D 45711, Datteln, Germany

    Boris Zernikow

  2. Department of Paediatric Haematology and Oncology, University Children’s Hospital Münster, Münster, Germany

    Boris Zernikow

  3. Children’s Hospital, Ortenau Klinikum, Offenburg, Germany

    Erik Michel

  4. Paediatric Palliative Care Team, Great Ormond Street Hospital for Children NHS Trust, London, England

    Finella Craig

  5. Department of Anaesthesiology, University of Auckland, Auckland, New Zealand

    Brian J. Anderson

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  1. Boris Zernikow
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Correspondence to Boris Zernikow.

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Zernikow, B., Michel, E., Craig, F. et al. Pediatric Palliative Care. Pediatr-Drugs 11, 129–151 (2009). https://doi.org/10.2165/00148581-200911020-00004

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