High Dose Opioids in Pediatric Palliative Care
2003; Elsevier BV; Volume: 25; Issue: 5 Linguagem: Inglês
10.1016/s0885-3924(03)00071-x
ISSN1873-6513
Autores Tópico(s)Pain Management and Opioid Use
ResumoTo the Editor: It is axiomatic that there is no "upper limit" when prescribing opioid medication to end-of-life patients.1Galloway K.S. Yaster M. Pain and symptom control in terminally ill children.Pediatr Clin N Am. 2000; 47: 711-746Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar Nevertheless, outside the pain management and palliative care fields, there is an ongoing problem with the underuse of analgesics, particularly in pediatrics.2Hiraga K. Mizuguchi T. Takeda F. The incidence of cancer pain and improvement of pain management in Japan.Postgrad Med J. 1991; 67: S14-S25PubMed Google Scholar, 3Schechter N. The undertreatment of pain in children an overview.Ped Clin N Am. 1989; 36: 781-794PubMed Google Scholar, 4Wolfe J. He G. Klar N. et al.Symptoms and suffering at the end of life in children with cancer.N Eng J Med. 2000; 342: 326-333Crossref PubMed Scopus (915) Google Scholar References in the pediatric literature provide starting doses, but do not show how high these doses often rise in order to adequately treat pain. There are a few reports documenting extremely high opioid doses used for children at the end of life.5Collins J. Berde C. Grier H. Nachmanoff D. Kinney H. Massive opioid resistance in an infant with a localized metastasis to the midbrain periaqueductal gray.Pain. 1995; 63: 271-275Abstract Full Text PDF PubMed Scopus (16) Google Scholar, 6Collins J. Grier H. Kinney H. Berde C. Control of severe pain in children with terminal malignancy.J Pediatr. 1995; 126: 653-657Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar, 7Sirkiä K. Hovi L. Pouttu J. Saarinen-Pihkala U. Pain medication during terminal care of children with cancer.J Pain Symptom Manage. 1998; 15: 220-226Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar We wish to add to the field of pediatric palliative care and pain management by describing our experience with opioids in a pediatric hospice. We reviewed the charts of all patients who died as inpatients at a pediatric hospice. Patients on the program who did not die in hospice, but at home or in hospital, were excluded. Canuck Place Children's Hospice, the Research Review Committee of Children's & Women's Health Center of British Columbia, and the Ethics Review Board of the University of British Columbia approved this study. Canuck Place Children's Hospice is a free-standing hospice in Vancouver, Canada, offering services to children and families living with progressive, life-limiting conditions. The hospice provides care for patients from birth to age 19. There are approximately 220 families on the program. The hospice has 10 beds and, through inpatient and community programs, provides respite, symptom management, transition planning, end-of-life care and bereavement services. Information was obtained about the child's diagnoses; age; length of final stay; and non-opioid adjuvant drugs used. Included in the opioid analysis were the following: indication; type and amount used; maximum dose; reason for rotation, if applicable; route; side effects; number of days prior to death that maximum dose was achieved; and whether or not symptoms were adequately controlled. Standard pain assessment tools were used where possible, including numeric (0–10) rating scales and visual analog scales. Tools were not used in all cases, due to the heterogeneous population, which included children with severe neurological impairment, and to evolving hospice practices. When standardized tools were not used, we relied upon pain and comfort assessments as recorded by nurses and physicians in the progress notes. For analysis, all opioid doses were converted to intravenous morphine equivalent, using a standard table.8Doyle D. Hanks G. MacDonald N. Oxford textbook of palliative medicine. Oxford University Press, New York1998Google Scholar Opioid doses were calculated based on a 24-hour period and reported in mg/kg/hr. During the period January 1995 to June 2001, 80 patients on the Canuck Place Children's Hospice program died. Forty-four of these patients died in hospice (21 male, 23 female); others died elsewhere. The median duration of end-of-life stay was 8 days, with a range of 0 days to 147 days. Thirty-two patients had cancer and twelve had other conditions (CNS dysgenesis not otherwise specified, 3; congenital syndromes, 4; metabolic disease, 3; immunologic/infectious disease, 2). Their ages ranged from 0 to 19 years. Forty-two of the 44 patients used at least one opioid drug; some patients required 2 or 3 different ones. Two patients received more than one opioid drug at a time, while two patients did not use any opioids whatsoever. The opioids used were morphine, hydromorphone, fentanyl and codeine. All of the patients used adjuvant analgesics and other symptom management drugs. The median opioid dose was 0.085 mg/kg/hr and the mean dose was 4.86 mg/kg/hr in intravenous morphine equivalents. The dose range was 0.001 to 73.9 mg/kg/hr (Fig. 1). The maximum opioid dose was reached on average 1 day prior to death (range 0 to 6 days). Based upon pain scores, comfort assessment tools and provider notes, almost all patients achieved adequate pain/symptom control at their maximum dose. Three of 44 patients did not obtain complete pain relief before death. Patients experienced symptoms at the end of life that may have been due to disease progression and/or side effects of opioids (Table 1). The symptoms/side effects included apnea, sedation, seizures or neurological excitation, as well as less severe effects such as pruritus. Of note, 10 patients did not experience any events even at their maximum opioid dose. Twelve patients required opioid switching, while 30 remained on the same drug throughout their end-of-life stay.Table 1Symptoms/Side Effects Present at Maximum Opioid Dose For Pediatric Hospice PatientsSymptom/Side EffectNo. of Patients (n = 42)%Constipation1740Nausea1536Sedation921Pruritus717Seizures or other CNS excitation614Apnea37Rash25>1 Symptom1433None1024 Open table in a new tab Previous reports described the use of high dose opioids in pediatric palliative care. In two reports, Miser et al. described the use of intravenous and subcutaneous morphine in hospitalized children with terminal malignancies; the median drug doses were 0.04 to 0.07 mg/kg/hr.9Miser A. Miser J. Clark B. Continuous intravenous infusion of morphine sulfate for control of severe pain in children with terminal malignancy.J Pediatr. 1980; 96: 930-932Abstract Full Text PDF PubMed Scopus (62) Google Scholar, 10Miser A. Davis D. Hughes C. Mulne A. Miser J. Continuous subcutaneous infusion of morphine in children with cancer.Am J Dis Child. 1983; 137: 383-385PubMed Google Scholar Sirkiä et al. reported that children dying of cancer used opioids in doses ranging from 0.007 to 2.3 mg/kg/hr morphine equivalent.7Sirkiä K. Hovi L. Pouttu J. Saarinen-Pihkala U. Pain medication during terminal care of children with cancer.J Pain Symptom Manage. 1998; 15: 220-226Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar Collins and his colleagues reported their most extreme cases, describing a group of 12 hospitalized patients with cancer who received "massive" opioid infusions, defined as greater than 3 mg/kg/hr intravenous morphine equivalent.5Collins J. Berde C. Grier H. Nachmanoff D. Kinney H. Massive opioid resistance in an infant with a localized metastasis to the midbrain periaqueductal gray.Pain. 1995; 63: 271-275Abstract Full Text PDF PubMed Scopus (16) Google Scholar, 6Collins J. Grier H. Kinney H. Berde C. Control of severe pain in children with terminal malignancy.J Pediatr. 1995; 126: 653-657Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar The maximal dose in their group ranged from 3.8 to 518 mg/kg/hr. These reports did not document side effects. Our study describes maximal opioid doses and side effects at the end-of-life in a heterogeneous pediatric population that may resemble the experience of palliative care teams in the community and in tertiary care hospitals. Non-oncology patients comprised 27% of the patients in this study; these children/adolescents also experienced symptom relief through the use of opioids and adjuvant analgesics, although their sources of pain may have been harder to characterize. In general, patients had their symptoms well controlled using combinations of opioids and adjuvant medications. Fear of side effects can be a major barrier to providing adequate analgesia at end-of-life in children, notwithstanding the patients' terminal course.11McGrath P. Finley G. Attitudes and beliefs about medication and pain management in children.J Palliat Care. 1996; 12: 46-50PubMed Google Scholar Therefore, it is worth noting that 24% (n = 10) of patients experienced no symptoms that might be attributed to opioids, and only 7% (n = 3) patients experienced apnea, potentially the most disconcerting adverse event. Many of the other symptoms/side effects that were present can be addressed through opioid rotation, additional medication or comfort measures. Furthermore, there is overlap between side effects due to medications and symptoms due to terminal illness, and the medication cannot be necessarily implicated. Therefore, fear of side effects should not be an obstacle to pain control. There are limitations to this study. First, as a retrospective study, it captures data only for the patients who died in hospice. Of the 80 patients on program who died during the 5-year study period, some 36 were outside the hospice, and we did not always have sufficient or reliable information regarding their medication use or effects. Moreover, hospice physicians prescribed medication using a common approach; this was not true for children in the community or in hospital, who were cared for by other teams. For these reasons, we limited the analysis to hospice inpatients. A second limitation was the inability to use a single set of standardized measures for pain and symptom control. In part, this was due to changing hospice practice with continuing evolution of tools to assess pain, especially in non-verbal children. In a prospective study, we would ideally have all patients assessed by a standard set of tools. While there is now emerging agreement about the importance of assessing and treating children's pain, there are still barriers to overcome. One barrier is lack of complete understanding of opioid use by non-palliative care physicians, and information that can guide practitioners to dose appropriately.3Schechter N. The undertreatment of pain in children an overview.Ped Clin N Am. 1989; 36: 781-794PubMed Google Scholar, 4Wolfe J. He G. Klar N. et al.Symptoms and suffering at the end of life in children with cancer.N Eng J Med. 2000; 342: 326-333Crossref PubMed Scopus (915) Google Scholar, 11McGrath P. Finley G. Attitudes and beliefs about medication and pain management in children.J Palliat Care. 1996; 12: 46-50PubMed Google Scholar, 12Cox T.H. An evaluation of postoperative pain management in pediatric patients at a university teaching hospital.Hosp Pharm. 1995; 30: 980-996PubMed Google Scholar, 13Broome M. Richtsmeier A. Maikler V. Alexander M. Pediatric pain practices a national survey of health professionals.J Pain Symptom Manage. 1996; 11: 312-320Abstract Full Text PDF PubMed Scopus (66) Google Scholar, 14Jacob E. Puntillo K.A. Variability of analgesic practices for hospitalized children on different pediatric specialty units.J Pain Symptom Manage. 2000; 20: 59-67Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar, 15Liben S. Pediatric palliative medicine obstacles to overcome.J Palliat Care. 1996; 12: 24-28PubMed Google Scholar, 16Ljungman G. Kreuger A. Gordh T. et al.Treatment of pain in pediatric oncology a Swedish nationwide survey.Pain. 1996; 68: 385-394Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar World Health Organization guidelines17WHO Cancer pain relief and palliative care in children. World Health Organization, Geneva1998Google Scholar recommend a starting dose of morphine at 0.03–0.05 mg/kg/hr in pediatrics. We concur, but have evidence that significant increases are necessary and will provide symptom relief without unmanageable adverse effects. In summary, opioids titrated significantly upwards beyond usual starting doses may be required in pediatric palliative care. Adverse events at these high doses occur, but are often minor or can be readily managed. Moreover, adverse events may also be end-of-life symptoms, and cannot be necessarily attributed to the drug; they should not be barriers to providing adequate pain control. We believe that research should be directed towards a number of areas in pediatric palliative care including: education strategies to improve medication use; optimal drug regimens; non-opioid analgesics; and symptom management for life-limiting conditions other than cancer, especially those with neurological dysfunction.
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