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The Cochrane Database of Systematic... Apr 2016This is the third updated version of a Cochrane review first published in Issue 4, 2003 of The Cochrane Library and first updated in 2007. Morphine has been used for... (Review)
Review
BACKGROUND
This is the third updated version of a Cochrane review first published in Issue 4, 2003 of The Cochrane Library and first updated in 2007. Morphine has been used for many years to relieve pain. Oral morphine in either immediate release or modified release form remains the analgesic of choice for moderate or severe cancer pain.
OBJECTIVES
To determine the efficacy of oral morphine in relieving cancer pain, and to assess the incidence and severity of adverse events.
SEARCH METHODS
We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9); MEDLINE (1966 to October 2015); and EMBASE (1974 to October 2015). We also searched ClinicalTrials.gov (1 October 2015).
SELECTION CRITERIA
Published randomised controlled trials (RCTs) using placebo or active comparators reporting on the analgesic effect of oral morphine in adults and children with cancer pain. We excluded trials with fewer than 10 participants.
DATA COLLECTION AND ANALYSIS
One review author extracted data, which were checked by another review author. There were insufficient comparable data for meta-analysis to be undertaken or to produce numbers needed to treat (NNTs) for the analgesic effect. We extracted any available data on the number or proportion of participants with 'no worse than mild pain' or treatment success (very satisfied, or very good or excellent on patient global impression scales).
MAIN RESULTS
We identified seven new studies in this update. We excluded six, and one study is ongoing so also not included in this update. This review contains a total of 62 included studies, with 4241 participants. Thirty-six studies used a cross-over design ranging from one to 15 days, with the greatest number (11) for seven days for each arm of the trial. Overall we judged the included studies to be at high risk of bias because the methods of randomisation and allocation concealment were poorly reported. The primary outcomes for this review were participant-reported pain and pain relief.Fifteen studies compared oral morphine modified release (Mm/r) preparations with morphine immediate release (MIR). Fourteen studies compared Mm/r in different strengths; six of these included 24-hour modified release products. Fifteen studies compared Mm/r with other opioids. Six studies compared MIR with other opioids. Two studies compared oral Mm/r with rectal Mm/r. Three studies compared MIR with MIR by a different route of administration. Two studies compared Mm/r with Mm/r at different times and two compared MIR with MIR given at a different time. One study was found comparing each of the following: Mm/r tablet with Mm/r suspension; Mm/r with non-opioids; MIR with non-opioids; and oral morphine with epidural morphine.In the previous update, a standard of 'no worse than mild pain' was set, equivalent to a score of 30/100 mm or less on a visual analogue pain intensity scale (VAS), or the equivalent in other pain scales. Eighteen studies achieved this level of pain relief on average, and no study reported that good levels of pain relief were not attained. Where results were reported for individual participants in 17 studies, 'no worse than mild pain' was achieved by 96% of participants (362/377), and an outcome equivalent to treatment success in 63% (400/638).Morphine is an effective analgesic for cancer pain. Pain relief did not differ between Mm/r and MIR. Modified release versions of morphine were effective for 12- or 24-hour dosing depending on the formulation. Daily doses in studies ranged from 25 mg to 2000 mg with an average of between 100 mg and 250 mg. Dose titration was undertaken with both instant release and modified release products. A small number of participants did not achieve adequate analgesia with morphine. Adverse events were common, predictable, and approximately 6% of participants discontinued treatment with morphine because of intolerable adverse events.The quality of the evidence is generally poor. Studies are old, often small, and were largely carried out for registration purposes and therefore were only designed to show equivalence between different formulations.
AUTHORS' CONCLUSIONS
The conclusions have not changed for this update. The effectiveness of oral morphine has stood the test of time, but the randomised trial literature for morphine is small given the importance of this medicine. Most trials recruited fewer than 100 participants and did not provide appropriate data for meta-analysis. Only a few reported how many people had good pain relief, but where it was reported, over 90% had no worse than mild pain within a reasonably short time period. The review demonstrates the wide dose range of morphine used in studies, and that a small percentage of participants are unable to tolerate oral morphine. The review also shows the wide range of study designs, and inconsistency in cross-over designs. Trial design was frequently based on titration of morphine or comparator to achieve adequate analgesia, then crossing participants over in cross-over design studies. It was not clear if these trials were sufficiently powered to detect any clinical differences between formulations or comparator drugs. New studies added to the review for the previous update reinforced the view that it is possible to use modified release morphine to titrate to analgesic effect. There is qualitative evidence that oral morphine has much the same efficacy as other available opioids.
Topics: Administration, Oral; Adult; Analgesics, Opioid; Child; Humans; Morphine; Neoplasms; Pain; Randomized Controlled Trials as Topic
PubMed: 27105021
DOI: 10.1002/14651858.CD003868.pub4 -
The Cochrane Database of Systematic... Apr 2023Neonates might be exposed to numerous painful procedures due to diagnostic reasons, therapeutic interventions, or surgical procedures. Options for pain management... (Review)
Review
BACKGROUND
Neonates might be exposed to numerous painful procedures due to diagnostic reasons, therapeutic interventions, or surgical procedures. Options for pain management include opioids, non-pharmacological interventions, and other drugs. Morphine, fentanyl, and remifentanil are the opioids most often used in neonates. However, negative impact of opioids on the structure and function of the developing brain has been reported.
OBJECTIVES
To evaluate the benefits and harms of opioids in term or preterm neonates exposed to procedural pain, compared to placebo or no drug, non-pharmacological intervention, other analgesics or sedatives, other opioids, or the same opioid administered by a different route.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was December 2021.
SELECTION CRITERIA
We included randomized controlled trials conducted in preterm and term infants of a postmenstrual age (PMA) up to 46 weeks and 0 days exposed to procedural pain where opioids were compared to 1) placebo or no drug; 2) non-pharmacological intervention; 3) other analgesics or sedatives; 4) other opioids; or 5) the same opioid administered by a different route.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were pain assessed with validated methods and any harms. We used a fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, and their confidence intervals (CI). We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We included 13 independent studies (enrolling 823 newborn infants): seven studies compared opioids to no treatment or placebo (the main comparison in this review), two studies to oral sweet solution or non-pharmacological intervention, and five studies (of which two were part of the same study) to other analgesics and sedatives. All studies were performed in a hospital setting. Opioids compared to placebo or no drug Compared to placebo, opioids probably reduce pain score assessed with the Premature Infant Pain Profile (PIPP)/PIPP-Revised (PIPP-R) scale during the procedure (MD -2.58, 95% CI -3.12 to -2.03; 199 participants, 3 studies; moderate-certainty evidence); may reduce Neonatal Infant Pain Scale (NIPS) during the procedure (MD -1.97, 95% CI -2.46 to -1.48; 102 participants, 2 studies; low-certainty evidence); and may result in little to no difference in pain score assessed with the Douleur Aiguë du Nouveau-né (DAN) scale one to two hours after the procedure (MD -0.20, 95% CI -2.21 to 1.81; 42 participants, 1 study; low-certainty evidence). The evidence is very uncertain about the effect of opioids on pain score assessed with the PIPP/PIPP-R scale up to 30 minutes after the procedure (MD 0.14, 95% CI -0.17 to 0.45; 123 participants, 2 studies; very low-certainty evidence) or one to two hours after the procedure (MD -0.83, 95% CI -2.42 to 0.75; 54 participants, 2 studies; very low-certainty evidence). No studies reported any harms. The evidence is very uncertain about the effect of opioids on episodes of bradycardia (RR 3.19, 95% CI 0.14 to 72.69; 172 participants, 3 studies; very low-certainty evidence). Opioids may result in an increase in episodes of apnea compared to placebo (RR 3.15, 95% CI 1.08 to 9.16; 199 participants, 3 studies; low-certainty evidence). The evidence is very uncertain about the effect of opioids on episodes of hypotension (RR not estimable, risk difference 0.00, 95% CI -0.06 to 0.06; 88 participants, 2 studies; very low-certainty evidence). No studies reported parent satisfaction with care provided in the neonatal intensive care unit (NICU). Opioids compared to non-pharmacological intervention The evidence is very uncertain about the effect of opioids on pain score assessed with the Crying Requires oxygen Increased vital signs Expression Sleep (CRIES) scale during the procedure when compared to facilitated tucking (MD -4.62, 95% CI -6.38 to -2.86; 100 participants, 1 study; very low-certainty evidence) or sensorial stimulation (MD 0.32, 95% CI -1.13 to 1.77; 100 participants, 1 study; very low-certainty evidence). The other main outcomes were not reported. Opioids compared to other analgesics or sedatives The evidence is very uncertain about the effect of opioids on pain score assessed with the PIPP/PIPP-R during the procedure (MD -0.29, 95% CI -1.58 to 1.01; 124 participants, 2 studies; very low-certainty evidence); up to 30 minutes after the procedure (MD -1.10, 95% CI -2.82 to 0.62; 12 participants, 1 study; very low-certainty evidence); and one to two hours after the procedure (MD -0.17, 95% CI -2.22 to 1.88; 12 participants, 1 study; very low-certainty evidence). No studies reported any harms. The evidence is very uncertain about the effect of opioids on episodes of apnea during (RR 3.27, 95% CI 0.85 to 12.58; 124 participants, 2 studies; very low-certainty evidence) and after the procedure (RR 2.71, 95% CI 0.11 to 64.96; 124 participants, 2 studies; very low-certainty evidence) and on hypotension (RR 1.34, 95% CI 0.32 to 5.59; 204 participants, 3 studies; very low-certainty evidence). The other main outcomes were not reported. We identified no studies comparing different opioids (e.g. morphine versus fentanyl) or different routes for administration of the same opioid (e.g. morphine enterally versus morphine intravenously).
AUTHORS' CONCLUSIONS
Compared to placebo, opioids probably reduce pain score assessed with PIPP/PIPP-R scale during the procedure; may reduce NIPS during the procedure; and may result in little to no difference in DAN one to two hours after the procedure. The evidence is very uncertain about the effect of opioids on pain assessed with other pain scores or at different time points. No studies reported if any harms occurred. The evidence is very uncertain about the effect of opioids on episodes of bradycardia or hypotension. Opioids may result in an increase in episodes of apnea. No studies reported parent satisfaction with care provided in the NICU. The evidence is very uncertain about the effect of opioids on any outcome when compared to non-pharmacological interventions or to other analgesics. We identified no studies comparing opioids to other opioids or comparing different routes of administration of the same opioid.
Topics: Humans; Infant; Infant, Newborn; Analgesics; Analgesics, Opioid; Apnea; Bradycardia; Fentanyl; Hypotension; Morphine; Pain; Pain, Procedural
PubMed: 37019853
DOI: 10.1002/14651858.CD015056.pub2 -
Supportive Care in Cancer : Official... May 2023To perform a systematic review and meta-analysis of publications to evaluate the analgesic efficacy and safety of percutaneous splanchnic nerve neurolysis (SNN) for... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To perform a systematic review and meta-analysis of publications to evaluate the analgesic efficacy and safety of percutaneous splanchnic nerve neurolysis (SNN) for cancer-related pain.
METHODS
We searched PubMed, Cochrane Library, and Ichushi-Web for English or Japanese articles published up to July 2022 and reporting patients who underwent percutaneous SNN for cancer-related pain. The outcome measures assessed in the systematic review and meta-analysis were the pain measurement scales and morphine equivalents daily dose (MEDD) before and after the intervention and the rate of complications.
RESULTS
Pooled pain measurement scores at pre-intervention, 1-2 weeks, and at 1, 2, 3, and 6 months post-intervention were 6.65 (95% confidence interval [CI], 5.77-7.67, I = 97%), 2.79 (95% CI, 2.00-3.88, I = 88%), 2.82 (95% CI, 2.49-3.20, I = 55%), 2.86 (95% CI, 2.64-3.10, I = 0%), 2.99 (95% CI, 2.56-3.46, I = 82%), and 3.09 (95% CI, 1.44-6.65, I = 70%), respectively. Mean MEDD was described in 8 of the 11 included articles. In all 8 articles, MEDD decreased up to 3 months post-intervention. The pooled minor complication rates for diarrhea and hypotension were 28% (95% CI, 13-49%, I = 85%) and 31% (95% CI, 16-51%, I = 80%), respectively. The pooled major complication rate was 2% (95% CI, 1-2%, I = 0%).
CONCLUSIONS
Analysis indicates that percutaneous SNN for cancer-related pain can be performed safely with sustained reduction of pain measurement scales while reducing the administration of opioids.
Topics: Humans; Cancer Pain; Splanchnic Nerves; Analgesics; Pain; Analgesics, Opioid; Morphine; Neoplasms
PubMed: 37148332
DOI: 10.1007/s00520-023-07746-y -
Journal of Sleep Research Jun 2022The present study was conducted to systematically evaluate the acute effect of morphine on obstructive sleep apnea (OSA). The PubMed, Embase, Cochrane Library,... (Meta-Analysis)
Meta-Analysis Review
The present study was conducted to systematically evaluate the acute effect of morphine on obstructive sleep apnea (OSA). The PubMed, Embase, Cochrane Library, Clinicaltrials.gov, China National Knowledge Infrastructure (CNKI), and Wan-Fang databases were searched for randomised controlled trials studying the influence of morphine on OSA published up to May 24, 2021. The Cochrane risk of bias tool was used to assess study quality and meta-analysis was performed on the included clinical trial results to quantify the impact of morphine on various sleep and respiratory parameters. Three studies (n = 132 patients) were ultimately examined. There were no significant differences between patients with OSA taking morphine and placebo/non-opioids with respect to the sleep Apnea-Hypopnea Index (mean difference [MD] 1.78, 95% confidence interval [CI] -2.41, 5.98; p > 0.05); Oxygen Desaturation Index (MD 1.49, 95% CI -3.21, 6.19; p > 0.05); Obstructive Sleep Apnea Index (MD 0.83, 95% CI -2.08, 3.75; p > 0.05); Hypopnea Index (MD -0.01, 95% CI -2.64, 2.63; p > 0.05); lowest oxygen saturation (MD 0.68, 95% CI -4.50, 5.86; p > 0.05); or sleep oxygen saturation >90% (MD 0.10, 95% CI -1.14, 1.34; p > 0.05). In conclusion, a single dose of 30 or 40 mg morphine does not have a significant effect on sleep or respiratory outcomes compared to placebo in patients with OSA, challenging the orthodoxy that opioids worsen OSA.
Topics: Analgesics, Opioid; Humans; Morphine; Oxygen; Sleep; Sleep Apnea, Obstructive
PubMed: 34806800
DOI: 10.1111/jsr.13523 -
Journal of Clinical Medicine Nov 2022Introduction: Recent studies showed that balanced opioid-free anesthesia is feasible and desirable in several surgical settings. However, in thoracic surgery, scientific... (Review)
Review
Introduction: Recent studies showed that balanced opioid-free anesthesia is feasible and desirable in several surgical settings. However, in thoracic surgery, scientific evidence is still lacking. Thus, we conducted the first systematic review and meta-analysis of opioid-free anesthesia in this field. Methods: The primary outcome was the occurrence of any complication. Secondary outcomes were the length of hospital stay, recovery room length of stay, postoperative pain at 24 and 48 h, and morphine equivalent consumption at 48 h. Results: Out of 375 potentially relevant articles, 6 studies (1 randomized controlled trial and 5 observational cohort studies) counting a total of 904 patients were included. Opioid-free anesthesia compared to opioid-based anesthesia, was associated with a lower rate of any complication (74 of 175 [42%] vs. 200 of 294 [68%]; RR = 0.76; 95% CI, 0.65−0.89; p < 0.001; I2 = 0%), lower 48 h morphine equivalent consumption (MD −14.5 [−29.17/−0.22]; p = 0.05; I2 = 95%) and lower pain at 48 h (MD −1.95 [−3.6/0.3]; p = 0.02, I = 98%). Conclusions: Opioid-free anesthesia in thoracic surgery is associated with lower postoperative complications, and less opioid demand with better postoperative analgesia at 48 h compared to opioid-based anesthesia.
PubMed: 36498529
DOI: 10.3390/jcm11236955 -
Archives of Disease in Childhood Oct 2021To systematically review available paediatric literature on comparisons between morphine (Mo) and hydromorphone (Hm), to guide clinicians to rationally use these... (Comparative Study)
Comparative Study
OBJECTIVE
To systematically review available paediatric literature on comparisons between morphine (Mo) and hydromorphone (Hm), to guide clinicians to rationally use these medications.
DESIGN
Systematic review within four databases for all studies published from 1963 to July 2019.
SETTING
All paediatric settings.
ELIGIBILITY
All studies comparing Mo to Hm in individuals younger than 21 years.
MAIN OUTCOME MEASURES
The primary outcome was to compare clinical efficacy and side effects of Mo and Hm. The secondary outcomes were the comparison of pharmacokinetic profiles and the description of predefined Mo to Hm conversion ratios used across the paediatric literature.
RESULTS
Among 754 abstracts reviewed, 59 full-text articles met inclusion criteria and 24 studies were included in the analysis: 4 studies compared pharmacodynamics of Mo and Hm and 20 studies reported the use of a predefined Mo to Hm conversion ratio. Most studies had a poor methodological quality. Available evidence suggests that, when given intravenously, the equianalgesic ratio of Mo to Hm is 5:1. Intravenous administration with this ratio results in a similar rate of adverse effects, including pruritus and nausea. The epidural administration with a ratio of 10:1 results in more pruritus and urinary retention with Mo than Hm. Pharmacokinetic data were reported in only one study. A wide range of pre-established ratios for different routes of administration were reported, but few were based on evidence.
CONCLUSION
Current literature does not permit a rational choice between Mo and Hm. A ratio of 5:1 seems adequate for intravenous administration and leads to a similar rate of adverse effects.
Topics: Administration, Intravenous; Adolescent; Analgesics, Opioid; Child; Child, Preschool; Humans; Hydromorphone; Infant; Infant, Newborn; Morphine; Nausea; Pain; Pruritus; Urinary Retention
PubMed: 33461958
DOI: 10.1136/archdischild-2020-319059 -
Palliative & Supportive Care Oct 2022Cancer-related dyspnea is a common symptom in patients with cancer. It has also been reported to be a predictor of poorer prognosis, which can then change clinical... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Cancer-related dyspnea is a common symptom in patients with cancer. It has also been reported to be a predictor of poorer prognosis, which can then change clinical treatment and advance care planning. Currently, no definitive recommendation for pharmacologic agents for cancer-related dyspnea exists. The aim of this systematic review and network meta-analysis is to compare pharmacologic agents for the prophylaxis and treatment of cancer-related dyspnea.
METHODS
A search was conducted in the databases of PubMed, Embase, and Cochrane CENTRAL through May 2021. Standardized mean differences (SMDs), as reported by studies or calculated from baseline and follow-up dyspnea scores, were amalgamated into a summary SMD and 95% confidence interval (CI) using a restricted maximum likelihood multivariate network meta-analysis.
RESULTS
Twelve studies were included in this review; six reported on prophylaxis of exertional dyspnea, five on treatment of everyday dyspnea, and one on treatment of episodic dyspnea. Morphine sulfate was better at controlling everyday dyspnea than placebo (SMD 1.210; 95% CI: 0.415-2.005). Heterogeneity in study design and comparisons, however, led to some concerns with the underlying consistency assumption in network meta-analysis design.
CONCLUSION
Optimal pharmacologic interventions for cancer-related dyspnea could not be determined based on this analysis. Further trials are needed to report on the efficacy of pharmacologic interventions for the prophylaxis and treatment of cancer-related dyspnea.
Topics: Dyspnea; Humans; Morphine; Neoplasms; Network Meta-Analysis
PubMed: 36111729
DOI: 10.1017/S1478951521001656 -
Pain Reports Sep 2023Chronic wounds adversely affect quality of life. Pain is associated with chronic wounds, and its impact can vary according to wound aetiology, condition, and patient... (Review)
Review
Chronic wounds adversely affect quality of life. Pain is associated with chronic wounds, and its impact can vary according to wound aetiology, condition, and patient factors. This systematic review examined the effectiveness of topical interventions in the management chronic wound-related pain guided by PRISMA recommendations of randomised controlled trials (RCTs) where pain reduction is the primary outcome. Inclusion criteria were adults (older than 18 years) with chronic venous, arterial, diabetic, or pressure ulcers where pain has been managed through topical administration of pharmacological/nonpharmacological agents. Searches were conducted in Ovid Embase, Ovid MEDLINE, EBSCOhost, CINAHL, CENTRAL, PubMed, Web of Science, and Scopus. Studies were screened for eligibility; risk of bias and data were extracted by 2 independent assessors. Searches retrieved 10,327 titles and abstracts (7760 after deduplication). Nine full texts (1323 participants) examining ibuprofen (n = 4), morphine (n = 2), BWD + PHMB [polihexanide-containing biocellulose wound dressing] (n = 1), and EMLA (n = 2) were included. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Meta-analysis was not possible, but initial exploration suggests improved outcomes (reduced pain) for ibuprofen when compared with controls. Two studies involving morphine showed conflicting findings. Included studies often had small samples, and considering confounding factors (eg, comorbidities), the results should be interpreted with caution. Review of included studies suggests that topical interventions may provide pain relief in individuals with chronic wounds. Further adequately powered RCTs are recommended to assess the efficacy of topical interventions for the management of chronic wound-related pain.
PubMed: 37711431
DOI: 10.1097/PR9.0000000000001073 -
The Cochrane Database of Systematic... May 2017This review replaces an earlier review, "Methadone for chronic non-cancer pain in adults". This review serves to update the original and includes only studies of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review replaces an earlier review, "Methadone for chronic non-cancer pain in adults". This review serves to update the original and includes only studies of neuropathic pain. Methadone belongs to a class of analgesics known as opioids, that are considered the cornerstone of therapy for moderate-to-severe postsurgical pain and pain due to life-threatening illnesses; however, their use in neuropathic pain is controversial. Methadone has many characteristics that differentiate it from other opioids, which suggests that it may have a different efficacy and safety profile.
OBJECTIVES
To assess the analgesic efficacy and adverse events of methadone for chronic neuropathic pain in adults.
SEARCH METHODS
We searched the following databases: CENTRAL (CRSO), MEDLINE (Ovid), and Embase (Ovid), and two clinical trial registries. We also searched the reference lists of retrieved articles. The date of the most recent search was 30 November 2016.
SELECTION CRITERIA
We included randomised, double-blind studies of two weeks' duration or longer, comparing methadone (in any dose, administered by any route, and in any formulation) with placebo or another active treatment in chronic neuropathic pain.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. There were insufficient data to perform pooled analyses. We assessed the overall quality of the evidence for each outcome using GRADE and created a 'Summary of findings' table.
MAIN RESULTS
We included three studies, involving 105 participants. All were cross-over studies, one involving 19 participants with diverse neuropathic pain syndromes, the other two involving 86 participants with postherpetic neuralgia. Study phases ranged from 20 days to approximately eight weeks. All administered methadone orally, in doses ranging from 10 mg to 80 mg daily. Comparators were primarily placebo, but one study also included morphine and tricyclic antidepressants.The included studies had several limitations related to risk of bias, particularly incomplete reporting, selective outcome reporting, and small sample sizes.There were very limited data for our primary outcomes of participants with at least 30% or at least 50% pain relief. Two studies reported that 11/29 participants receiving methadone achieved 30% pain relief versus 7/29 participants receiving placebo. Only one study presented data in a manner that allowed us to calculate the number of participants with at least 50% pain relief. None of the 19 participants achieved a 50% reduction in pain intensity, either when receiving methadone or when receiving placebo. No study provided data for our other primary outcomes of Patient Global Impression of Change scale (PGIC) much or very much improved (equivalent to at least 30% pain relief) and PGIC very much improved (equivalent to at least 50% pain relief).For secondary efficacy outcomes, one study reported maximum and mean pain intensity and pain relief, and reported statistically significant improvements versus placebo for all outcomes with 20 mg daily doses of methadone, but not with 10 mg daily doses. The second study reported differences in pain reduction between methadone (n = 26) and morphine (n = 38) and found morphine to be statistically superior. The third study reported the number of responders (variously defined) for several pain and functional outcomes and found methadone to be statistically superior to placebo for the outcomes of categorical pain intensity and evoked pain. In the two studies that reported data, 0/29 participants withdrew due to lack of efficacy, whereas 4/29 participants withdrew due to adverse events while taking methadone versus 3/29 while taking placebo.One study reported incidences for several individual adverse events, but found a statistically significant increased incidence for methadone over placebo for only one event, dizziness. The other studies did not report data in a manner that enabled us to analyze adverse events. There were no serious adverse events or deaths reported.We assessed the quality of the evidence as very low for all efficacy and safety outcomes using GRADE, primarily because of the heterogeneity of study designs and populations, short durations, cross-over methodology, and few participants and events.
AUTHORS' CONCLUSIONS
The three studies provide very limited, very low quality evidence of the efficacy and safety of methadone for chronic neuropathic pain, and there were too few data for pooled analysis of efficacy or harm, or to have confidence in the results of the individual studies. No conclusions can be made regarding differences in efficacy or safety between methadone and placebo, other opioids, or other treatments.
Topics: Adult; Analgesics, Opioid; Cross-Over Studies; Humans; Methadone; Neuralgia; Pain Measurement; Patient Dropouts; Randomized Controlled Trials as Topic
PubMed: 28514508
DOI: 10.1002/14651858.CD012499.pub2 -
Pain Research & Management 2022The dose of intrathecal morphine is important because of its narrow therapeutic range. Due to a compounding error, pharmacy-compounded, ready-to-use syringes contained... (Review)
Review
BACKGROUND
The dose of intrathecal morphine is important because of its narrow therapeutic range. Due to a compounding error, pharmacy-compounded, ready-to-use syringes contained 1 mg ml morphine instead of the intended 50 mcg ml. Six patients consequently received this twenty-fold dose. This study aims to describe the serious adverse events in these six patients and a systematic review is added to describe the characteristics of serious adverse events after intrathecal morphine.
METHODS
A retrospective case series described all six patients that received the erroneous morphine intrathecally for analgesia after laparoscopic segmental colonic resections. The patients' charts were reviewed for the occurrence, timing, duration and management of adverse events, the vital signs at the night after surgery, and length of hospital stay. A systematic review investigated characteristics of serious adverse events after intrathecal morphine in a perioperative setting.
RESULTS
Four patients had a serious adverse event, which was respiratory depression combined with somnolence ( = 3) and hypotension ( = 1). The review yielded 63 cases with serious adverse events, predominantly somnolence and/or respiratory depression. The onset occurred between 2 and 24 hours after injection. The severity of symptoms varied and life-threatening respiratory depression only occurred after a dose >900 mcg or when potentiating medication was used. Naloxone did not affect analgesia. No prolonged sequalae occurred.
CONCLUSION
This study reveals that respiratory depression and somnolence are the predominant serious adverse events after intrathecal morphine in a perioperative setting and demonstrated a large variation in the presentation of symptoms.
Topics: Analgesia; Humans; Injections, Spinal; Morphine; Naloxone; Retrospective Studies
PubMed: 35311036
DOI: 10.1155/2022/4567192