Opioid use in palliative care of children and young people with cancer
Child; Female; Humans; Male; Great Britain; Adult; Analgesics; Questionnaires; Prospective Studies; Research Design; Longitudinal Studies; Therapeutic Equivalency; Prescriptions; adolescent; Preschool; infant; Administration; Oral; Pain/drug therapy/etiology; Palliative Care/methods; Infusions; Injections; Intravenous; Neoplasms/complications; Subcutaneous; Drug/statistics & numerical data; Opioid/administration & dosage/therapeutic use; Fentanyl/therapeutic use; Heroin/therapeutic use; Morphine/therapeutic use; Rectal
OBJECTIVE: Identify opioids prescribed, preferred routes, and doses among children with incurable cancer. STUDY DESIGN: Prospective survey with monthly questionnaires regarding patients 0 to 19 years old from oncology centers. Data were collected by professionals on each patient for 6 months or until death, and analyzed from patients who died. Impact of tumor was analyzed with Kruskal-Wallis and Mann-Whitney tests. Major opioid dosages are expressed as oral morphine equivalents. RESULTS: Of 185 children recruited, 164 (88 boys, 76 girls) died. Mean palliative care duration was 67 days. One hundred forty-seven (89.6%) received major opioids. Morphine, diamorphine, and fentanyl were prescribed in 75%, 57.9%, and 11.6%, respectively. Seventy-three (44.5%) received >1 major opioid. Median monthly maximum doses prescribed rose from 2.1 mg/kg/24 h (study entry) to 4.4 mg/kg/24 h (death) (P < .001); overall variable (0.09-1500 mg/kg/24 h, median 3.7 mg/kg/24 h). Opioids were given by the oral (117/164, 71.3%), intravenous (68/164, 41.5%), subcutaneous (40, 28%), rectal (20, 12.2%), and transdermal (18, 11%) routes. There was a shift to intravenous use as death approached. Numbers within each tumor group were too small to show significance. Children with solid tumors outside the central nervous system were likely to receive more opioids, be given multiple different opioids, and receive opioids in the last month. CONCLUSIONS: The study shows the United Kingdom practice of opioid use and provides comparator data for practice in children's palliative medicine.
2008
Hewitt M; Goldman A; Collins GS; Childs M; Hain R
The Journal Of Pediatrics
2008
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Journal Article
<a href="http://doi.org/10.1016/j.jpeds.2007.07.005" target="_blank" rel="noreferrer">10.1016/j.jpeds.2007.07.005</a>
Clinical use of methadone
Humans; Analgesics; Drug Interactions; Therapeutic Equivalency; Half-Life; Drug Administration Schedule; Pain/drug therapy; Receptors; Biological Availability; Opioid/adverse effects/pharmacokinetics/therapeutic use; Dosage Forms; Kidney Diseases/metabolism; Liver Diseases/metabolism; Methadone/adverse effects/pharmacokinetics/therapeutic use; Opioid-Related Disorders/drug therapy; Opioid/agonists; Substance Withdrawal Syndrome/etiology
Methadone hydrochloride is a mu-opioid agonist that has been used for the treatment of pain and for the management and maintenance of opioid withdrawal for over 50 years. Several characteristics make methadone a useful drug. However, these same characteristics and wide interpatient variability can make methadone difficult to use safely. A MEDLINE search was conducted on publications between January 1996 and May 2001 to identify literature relevant to this subject. Those publications were reviewed, and from them, other literature was identified and reviewed. Published studies demonstrate methadone's efficacy in pain management and in opioid withdrawal. However, interpatient variability in pharmacokinetic variables of methadone produces difficulties in developing guidelines for methadone use. Clinicians should not be deterred from use of this drug which has been shown to benefit patients in both pain management and methadone maintenance, but an individualized patient approach must be taken to use methadone safely.
2002
Layson-Wolf C; Goode JV; Small RE
Journal of Pain and Palliative Care Pharmacotherapy
2002
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Journal Article
<a href="http://doi.org/10.1080/j354v16n01_04" target="_blank" rel="noreferrer">10.1080/j354v16n01_04</a>
Patient-controlled analgesia for mucositis pain in children: a three-period crossover study comparing morphine and hydromorphone
Child; Humans; Pain Measurement; Analgesics; Treatment Outcome; Therapeutic Equivalency; Analgesia; Analysis of Variance; Double-Blind Method; Cross-Over Studies; adolescent; Non-U.S. Gov't; Research Support; Comparative Study; Pain/drug therapy/etiology; Inflammation/complications; Patient-Controlled; Hydromorphone/adverse effects/pharmacokinetics/therapeutic use; Morphine/adverse effects/pharmacokinetics/therapeutic use; Mucous Membrane; Opioid/adverse effects/pharmacokinetics/therapeutic use
OBJECTIVES: (1) To test the safety and efficacy of a clinical protocol for administering opioid by using patient-controlled analgesia (PCA) for the management of mucositis pain in children after bone marrow transplantation, (2) to compare the efficacy, side-effect profile, and potency ratio of morphine with those of hydromorphone by using PCA as the method of opioid administration, and (3) to obtain pharmacokinetic data on hydromorphone and morphine in this population of children. METHODS: In this double-blind, three-period crossover study, patients were randomly assigned to receive either morphine (group 1) or hydromorphone (group 2) initially by means of PCA on days 1, 2, and 3 (period 1), to be followed on days 4, 5, and 6 (period 2) with the alternative opioid, followed by the opioid used at the commencement of the study on days 7, 8, and 9 (period 3). A clinical protocol for calculating the PCA commencement opioid dose and subsequent opioid-dose escalation was tested by measures of safety and efficacy. Measures of pain intensity and opioid side effects were made during the three periods. On the last study day (day 10), patients received a continuous infusion of opioid derived from the previous 24-hour PCA opioid requirement, and blood specimens were collected and stored for subsequent opioid analysis. RESULTS: Ten patients were enrolled in this study. Rapid escalation in opioid requirement commonly occurred at the commencement of PCA, followed by a variable plateau phase and then deescalation of opioid requirement after mucositis resolution. The measures demonstrated the safety and efficacy of the clinical protocol. In the concentrations used, there was no statistical difference between the mean daily pain, sedation, nausea and vomiting, and pruritus scores for both opioids (Friedman test). The analysis of variance of the log-total opioid doses per patient during periods 1, 2, and 3 indicated that patients used 27% more hydromorphone than expected from its presumed 7:1 ratio relative to morphine potency used in the PCA infusions. The mean plasma hydromorphone concentration was 4.7 ng/ml (range, 1.9 to 8.9 ng/ml), and the mean clearance was 51.7 ml/min per kilogram of body weight (range, 28.6 to 98.2 ml/min per kilogram). The mean plasma morphine, morphine-6-glucuronide, and morphine-3-glucuronide concentrations were 40.0 ng/ml (range, 15 to 62.5), 168.2 ng/ml (range, 54.4 to 231.9), and 391.0 ng/ml (range, 149.4 to 921.7), respectively. The mean morphine clearance was 34.3 ml/min per kilogram of body weight (range, 19.3 to 58.3). The mean molar ratios of morphine-6-glucuronide/morphine, morphine-3-glucoronide/morphine, and morphine-3-glucuronide/morphine-6-glucuronide were 2.48 (range, 1.4 to 3.3), 5.82 (range, 3.4 to 9.1), and 2.46 (range, 1.1 to 3.3), respectively. CONCLUSIONS: The safety and efficacy of a clinical protocol for the administration of opioids by means of PCA for mucositis pain after bone marrow transplantation was demonstrated. In this small study, hydromorphone was not superior to morphine in terms of analgesia or the side-effect profile: a larger study would be needed to show a difference. The clearances of hydromorphone and morphine in the children studied were generally greater than those previously recorded, but this finding may be related to disease or treatment variables. Apart from clearance, the morphine pharmacokinetics in the study population were similar to those previously recorded. Hydromorphone may be less potent in this population of children than indicated by adult equipotency tables.
1996
Collins J J; Geake J; Grier HE; Houck CS; Thaler HT; Weinstein HJ; Twum-Danso NY; Berde CB
The Journal Of Pediatrics
1996
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/s0022-3476(96)70156-7" target="_blank" rel="noreferrer">10.1016/s0022-3476(96)70156-7</a>
Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio?
Cross-Sectional Studies; Female; Humans; Male; Analgesics; Prospective Studies; Aged; Middle Aged; Therapeutic Equivalency; Time Factors; Analgesia; Non-U.S. Gov't; Research Support; Administration; Oral; Pain/drug therapy; Dose-Response Relationship; Drug; Neoplasms/complications; Opioid/administration & dosage; Morphine/administration & dosage; Methadone/administration & dosage
PURPOSE: To define the dose ratio between morphine and methadone in relation to the previous morphine dose and the number of days needed to achieve the same level of analgesia in a group of patients with advanced cancer with pain who switched from morphine to oral methadone. PATIENTS AND METHODS: A cross-sectional prospective study of 38 consecutive cancer patients who switched from morphine to oral methadone was performed. The intensity of pain before, during, and after the switching period was assessed through a four-point verbal Likert scale. The relationship between previous morphine dose and the final equianalgesic methadone dose, dose ratio between morphine and methadone, and the number of days required to achieve equianalgesia have been examined by means of Pearson's correlation coefficient, scatter plots, and Cuzick's test for trend respectively. RESULTS: Before the switch, the median oral equivalent daily dose of morphine was 145 mg/d; after the switch, the median equianalgesic oral methadone dose was 21 mg/d. A median time of 3 days (range, 1 to 7 days) was necessary to achieve the equianalgesia with oral methadone; the lower the preswitching morphine dose, the fewer days necessary to achieve equianalgesia with oral methadone (P < .001). Dose ratios ranged from 2.5:1 to 14.3:1 (median, 7.75:1), which indicated that, in most cases, the dose ratio was much higher than that suggested by the published equianalgesic tables. A strong linear positive relationship between morphine and methadone equianalgesic doses was obtained (Pearson's correlation coefficient, 0.91). The dose ratio increased with the increase of the previous morphine dose with a much higher increase at low morphine doses. CONCLUSION: The results of our study confirm that methadone is a potent opioid, more potent than believed. Caution is recommended when switching from any opioid to methadone, especially in patients who are tolerant to high doses of opioids.
1998
Ripamonti C; Groff L; Brunelli C; Polastri D; Stavrakis A; De Conno F
Journal Of Clinical Oncology
1998
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Journal Article
<a href="http://doi.org/10.1200/jco.1998.16.10.3216" target="_blank" rel="noreferrer">10.1200/jco.1998.16.10.3216</a>
Methadone titration in opioid-resistant cancer pain
Female; Male; Pain Measurement; Adult; Analgesics; Aged; Therapeutic Equivalency; Drug Administration Schedule; 80 and over; Administration; Oral; Drug Tolerance; Human; Drug Resistance; Middle Age; Neoplasms/complications; Morphine/administration & dosage; Methadone/administration & dosage; Opioid/administration & dosage; Pain/diagnosis/drug therapy/etiology
AIM: To assess the use of methadone in patients with cancer pain who fail to respond to increasing doses of other opioids or experience intolerable side-effects from them. METHOD: Inpatients of a specialist palliative care unit were titrated onto oral methadone. The dose was calculated as 10% of the previous morphine equivalent dose, up to maximum of 40 mg, given every 3 h as required for analgesia. When daily requirements were stable it was divided into two regular doses. Pain was assessed on a five-point verbal rating score (VRS): a good response was defined as a fall in VRS of two points or more. Results are expressed as median (range). RESULTS: Thirty-three patients (13 men, 20 women, age 61 (34-91) years), 26 with inadequate analgesia and seven with intolerable opioid related side-effects, were converted to methadone from diamorphine (12), morphine (19) or fentanyl (two). Morphine equivalent dose was 480 (20-1200) mg/day prior to titration. Pain was neuropathic (11), nociceptive (three) or mixed (19). Stabilisation on methadone was complete in 3 (2-18) days in 29 (88%) patients at 80 (20-360) mg/day. Twenty-six (78%) had a good response. Four (12%) patients were withdrawn during titration (three entered terminal phase, one failed to respond). During follow-up 15 (45%) required alteration of methadone dose. Twenty-three (70%) patients were discharged home at 12 (4-26) days. In all cases the stable dose of methadone was less than the previous morphine equivalent, and there was a weak correlation between them. CONCLUSIONS: This method of methadone titration often results in improved pain control in patients with morphine resistance or intolerance. It requires careful titration in a specialist inpatient unit as there is no reliable formula for dose equivalence.
1999
Scholes CF; Gonty N; Trotman IF
European Journal Of Cancer Care
1999
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Journal Article