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Clinical Toxicology (Philadelphia, Pa.) May 2024Pulmonary edema is a rare complication occurring after naloxone administration, but the causal relationship remains insufficiently investigated. We aimed to determine... (Review)
Review
INTRODUCTION
Pulmonary edema is a rare complication occurring after naloxone administration, but the causal relationship remains insufficiently investigated. We aimed to determine the likelihood of naloxone as the causative agent in published cases of pulmonary edema.
METHODS
A literature search was conducted across multiple databases, utilizing database-specific search terms such as "pulmonary edema/chemically induced" and "naloxone/adverse effects." Each case report was evaluated using the Naranjo scale, a standardized causality assessment algorithm.
RESULTS
We identified 49 published case reports of pulmonary edema following naloxone administration. The median total dose of naloxone was 0.2 mg for patients presenting following a surgical procedure and 4 mg for out-of-hospital opioid overdoses. Based on the Naranjo scale, the majority of cases were classified as "possible" ( = 38) or "probable" ( = 11) adverse reactions, while no "definite" cases of naloxone-induced pulmonary edema were identified. Many patients were classified as "possible" due to limited patient information or other potential risks, such as fluid administration or airway obstruction. Forty-six of 49 patients survived (94 percent).
DISCUSSION
Pulmonary edema may occur after both low and high doses of naloxone; however, low doses were primarily reported in the surgical population. Despite this complication, the majority of patients survived. Furthermore, no case report in our analysis was classified as a "definite" case of naloxone-induced pulmonary edema which limits the establishment of causality. Future studies should explore patient risk factors, including surgical versus outpatient setting and opioid-naïve versus opioid-tolerant for developing pulmonary edema and employ a causality assessment algorithm.
CONCLUSIONS
These case reports suggest pulmonary edema can occur following naloxone administration, irrespective of dose. According to the Naranjo scale, there were no definite cases of naloxone-induced pulmonary edema. Overall, we suggest the benefits of naloxone administration outweigh the risks. Naloxone should be administered to treat opioid overdoses while monitoring for the development of pulmonary edema.
Topics: Naloxone; Pulmonary Edema; Humans; Narcotic Antagonists; Analgesics, Opioid; Opiate Overdose; Drug Overdose
PubMed: 38865087
DOI: 10.1080/15563650.2024.2348108 -
Annals of Cardiac Anaesthesia Jan 2024Cardiac surgeries often result in significant postoperative pain, leading to considerable use of opioids for pain management. However, excessive opioid use can lead to... (Meta-Analysis)
Meta-Analysis
Cardiac surgeries often result in significant postoperative pain, leading to considerable use of opioids for pain management. However, excessive opioid use can lead to undesirable side effects and chronic opioid use. This systematic review and meta-analysis aimed to evaluate whether preoperative intrathecal morphine could reduce postoperative opioid consumption in patients undergoing cardiac surgery requiring sternotomy. We conducted a systematic search of Cochrane, EMBASE, and MEDLINE databases from inception to May 2022 for randomized controlled trials that evaluated the use of intrathecal morphine in patients undergoing cardiac surgery. Studies that evaluated intrathecal administration of other opioids or combinations of medications were excluded. The primary outcome was postoperative morphine consumption at 24 h. Secondary outcomes included time to extubation and hospital length of stay. The final analysis included ten randomized controlled trials, with a total of 402 patients. The results showed that postoperative morphine consumption at 24 h was significantly lower in the intervention group (standardized mean difference -1.43 [-2.12, -0.74], 95% CI, P < 0.0001). There were no significant differences in time to extubation and hospital length of stay. Our meta-analysis concluded that preoperative intrathecal morphine is associated with lower postoperative morphine consumption at 24 h following cardiac surgeries, without prolonging the time to extubation. The use of preoperative intrathecal morphine can be considered part of a multimodal analgesic and opioid-sparing strategy in patients undergoing cardiac surgery.
Topics: Humans; Cardiac Surgical Procedures; Morphine; Injections, Spinal; Analgesics, Opioid; Randomized Controlled Trials as Topic; Pain, Postoperative; Length of Stay
PubMed: 38722114
DOI: 10.4103/aca.aca_48_23 -
The Cochrane Database of Systematic... May 2024Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants. Dexmedetomidine is increasingly being used in children and infants despite not being licenced for analgesia in this group.
OBJECTIVES
To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023.
SELECTION CRITERIA
We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety.
AUTHORS' CONCLUSIONS
Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.
Topics: Humans; Dexmedetomidine; Infant, Newborn; Respiration, Artificial; Hypnotics and Sedatives; Randomized Controlled Trials as Topic; Analgesics, Opioid; Morphine; Analgesia; Analgesics, Non-Narcotic
PubMed: 38695625
DOI: 10.1002/14651858.CD012361.pub2 -
British Journal of Anaesthesia Jun 2024Dopamine antagonists, 5-HT antagonists, and dexamethasone are frequently used in obstetrics to prevent postoperative nausea and vomiting (PONV). However, the superiority... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dopamine antagonists, 5-HT antagonists, and dexamethasone are frequently used in obstetrics to prevent postoperative nausea and vomiting (PONV). However, the superiority of any drug class is yet to be established. This network meta-analysis aimed to compare the efficacy of these antiemetics for PONV prophylaxis in women receiving neuraxial morphine for Caesarean delivery.
METHODS
We searched PubMed, Embase, CENTRAL, Web of Science, and Wanfang Data for eligible randomised controlled trials. Primary outcomes were the incidences of postoperative nausea (PON) and postoperative vomiting (POV) within 24 h after surgery. We used a Bayesian random-effects model and calculated odds ratios with 95% credible intervals for dichotomous data. We performed sensitivity and subgroup analyses for primary outcomes.
RESULTS
A total of 33 studies with 4238 women were included. In the primary analyses of all women, 5-HT antagonists, dopamine antagonists, dexamethasone, and 5-HT antagonists plus dexamethasone significantly reduced PON and POV compared with placebo, and 5-HT antagonists plus dexamethasone were more effective than monotherapy. In the subgroup analyses, similar results were seen in women receiving epidural morphine or intrathecal morphine alone but not in women receiving intrathecal morphine with fentanyl or sufentanil. However, most included studies had some concerns or a high risk of bias, and the overall certainty of the evidence was low or very low.
CONCLUSIONS
Combined 5-HT antagonists plus dexamethasone are more effective than monotherapy in preventing PONV associated with neuraxial morphine after Caesarean delivery. Future studies are needed to determine the role of prophylactic antiemetics in women receiving intrathecal morphine and lipophilic opioids.
SYSTEMATIC REVIEW PROTOCOL
PROSPERO CRD42023454602.
Topics: Humans; Postoperative Nausea and Vomiting; Morphine; Female; Antiemetics; Cesarean Section; Pregnancy; Dexamethasone; Network Meta-Analysis; Analgesics, Opioid; Dopamine Antagonists; Serotonin 5-HT3 Receptor Antagonists; Randomized Controlled Trials as Topic
PubMed: 38627136
DOI: 10.1016/j.bja.2024.03.010 -
Journal of Clinical Anesthesia Aug 2024Following robot assisted abdominal surgery, the pain can be moderate in severity. Neuraxial analgesia may decrease the activity of the detrusor muscle, reduce the... (Review)
Review
STUDY OBJECTIVE
Following robot assisted abdominal surgery, the pain can be moderate in severity. Neuraxial analgesia may decrease the activity of the detrusor muscle, reduce the incidence of bladder spasm and provide effective somatic and visceral analgesia. In this systematic review, we assessed the role of neuraxial analgesia in robot assisted abdominal surgery.
DESIGN
Systematic review.
SETTINGS
Robot assisted abdominal surgery.
PATIENTS
Adults.
INTERVENTIONS
Subsequent to a search of the electronic databases, observational studies and randomized controlled trials that assessed the effect of neuraxial analgesia instituted at induction of anesthesia or intraoperatively in adult and robot assisted abdominal surgery were considered for inclusion. The outcomes of observational studies as well as randomized controlled trials which were not subjected to meta-analysis were presented in descriptive terms. Meta-analysis was conducted if an outcome of interest was reported by two or more randomized controlled trials.
MAIN RESULTS
We included 19 and 11 studies that investigated spinal and epidural analgesia in adults, respectively. The coprimary outcomes were the pain score at rest at 24 h and the cumulative intravenous morphine consumption at 24 h. Spinal analgesia with long acting neuraxial opioid did not decrease the pain score at rest at 24 h although it reduced the cumulative intravenous morphine consumption at 24 h by a mean difference (95%CI) of 14.88 mg (-22.13--7.63; p < 0.0001, I = 50%) with a low and moderate quality of evidence, respectively, on meta-analysis of randomized controlled trials. Spinal analgesia with long acting neuraxial opioid had a beneficial effect on analgesic indices till the second postoperative day and a positive influence on opioid consumption up to and including the 72 h time point. The majority of studies demonstrated the use of spinal analgesia with long acting neuraxial opioid to lead to no difference in the incidence of postoperative nausea and vomiting, and the occurrence of pruritus was found to be increased with spinal analgesia with long acting neuraxial opioid in recovery but not at later time points. No difference was revealed in the incidence of urinary retention. The evidence in regard to the quality of recovery-15 score at 24 h and hospital length of stay was not fully consistent, although most studies indicated no difference between spinal analgesia and control for these outcomes. Epidural analgesia in robot assisted abdominal surgery was shown to decrease the pain on movement at 12 h but it had not been studied with respect to its influence on the pain score at rest at 24 h or the cumulative intravenous morphine consumption at 24 h. It did not reduce the pain on movement at later time points and the evidence related to the hospital length of stay was inconsistent.
CONCLUSIONS
Spinal analgesia with long acting neuraxial opioid had a favourable effect on analgesic indices and opioid consumption, and is recommended by the authors, but the evidence for spinal analgesia with short acting neuraxial opioid and epidural analgesia was limited.
Topics: Humans; Pain, Postoperative; Analgesia, Epidural; Abdomen; Robotic Surgical Procedures; Analgesics, Opioid; Pain Measurement; Morphine; Treatment Outcome; Randomized Controlled Trials as Topic; Anesthesia, Spinal; Adult
PubMed: 38599160
DOI: 10.1016/j.jclinane.2024.111468 -
Neurosurgical Review Apr 2024In recent years, nonsteroidal anti-inflammatory drug (NSAIDs), which are considered to affect the prognosis of spinal surgery, have been widely used in perioperative... (Meta-Analysis)
Meta-Analysis
In recent years, nonsteroidal anti-inflammatory drug (NSAIDs), which are considered to affect the prognosis of spinal surgery, have been widely used in perioperative analgesia in spinal surgery, but the relationship between these two factors remains unclear. The purpose of this study was to explore the effect of perioperative use of NSAIDs on the prognosis of patients treated with spinal surgery. We systematically searched PubMed, Embase, and Cochrane Library for relevant articles published on or before July 14, 2023. We used a random-effect model for the meta-analysis to calculate the standardized mean difference (SMD) with a 95% confidence interval (CI). Sensitivity analyses were conducted to analyze stability. A total of 23 randomized clinical trials including 1457 participants met the inclusion criteria. Meta-analysis showed that NSAIDs were significantly associated with postoperative morphine use (mg) (SMD = -0.90, 95% CI -1.12 to -0.68) and postoperative pain (SMD = -0.71, 95% CI -0.85 to -0.58). These results were further confirmed by the trim-and-fill procedure and leave-one-out sensitivity analyses. The current study shows that perioperative use of NSAIDs appears to be an important factor in reducing postoperative pain and morphine use in patients undergoing spinal surgery. However, well-designed, high-quality randomized controlled trials (RCTs) are still required.
Topics: Humans; Anti-Inflammatory Agents, Non-Steroidal; Morphine Derivatives; Pain, Postoperative; Randomized Controlled Trials as Topic; Spine
PubMed: 38578529
DOI: 10.1007/s10143-024-02371-7 -
Journal of Comparative Effectiveness... May 2024In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of... (Comparative Study)
Comparative Study Review
Gastrointestinal adverse effects associated with the use of intravenous oliceridine compared with intravenous hydromorphone or fentanyl in acute pain management utilizing adjusted indirect treatment comparison methods.
In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of treatments versus a common comparator (either placebo or active treatment). For acute pain management, the effects of oliceridine have been compared in clinical trials to morphine but not to fentanyl or hydromorphone. To assess the comparative safety (specifically differences in the incidence of nausea, vomiting and opioid-induced respiratory depression [OIRD]) between oliceridine and relevant comparators (fentanyl and hydromorphone) through ITC analysis. A systematic literature review identified randomized clinical trials with oliceridine versus morphine and morphine versus fentanyl or hydromorphone. The ITC utilized the common active comparator, morphine, for the analysis. A total of six randomized controlled trials (oliceridine - 2; hydromorphone - 3; fentanyl - 1) were identified for data to be used in the ITC analyses. The oliceridine data were reported in two studies (plastic surgery and orthopedic surgery) and were also reported in a pooled analysis. The ITC focused on nausea and vomiting due to limited data for OIRD. When oliceridine was compared with hydromorphone in the ITC analysis, oliceridine significantly reduced the incidence of nausea and/or vomiting requiring antiemetics compared with hydromorphone (both orthopedic surgery and pooled data), while results in plastic surgery were not statistically significant. When oliceridine was compared with hydromorphone utilizing data from Hong, the ITC only showed a trend toward reduced risk of nausea and vomiting with oliceridine that was not statistically significant across all three comparisons (orthopedic surgery, plastic surgery and combined). An ITC comparing oliceridine with a study of fentanyl utilizing the oliceridine orthopedic surgery data and combined orthopedic and plastic surgery data showed a trend toward reduced risk that was not statistically significant. In ITC analyses, oliceridine significantly reduced the incidence of nausea and/or vomiting or the need for antiemetics in orthopedic surgery compared with hydromorphone and a non-significant trend toward reduced risk versus fentanyl.
Topics: Humans; Hydromorphone; Fentanyl; Analgesics, Opioid; Acute Pain; Randomized Controlled Trials as Topic; Vomiting; Nausea; Administration, Intravenous; Respiratory Insufficiency; Pain Management; Quinuclidines; Spiro Compounds; Thiophenes
PubMed: 38497192
DOI: 10.57264/cer-2023-0041 -
Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
Drugs Mar 2024To evaluate the efficacy of opioids for people with acute musculoskeletal pain against placebo. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy of opioids for people with acute musculoskeletal pain against placebo.
STUDY DESIGN
Systematic review and meta-analyses of randomised, placebo-controlled trials of opioid analgesics for acute musculoskeletal pain in any setting. The primary outcomes were pain and disability at the immediate timepoint (< 24 h).
DATA SOURCES
Multiple databases were searched from their inception to February 22nd, 2023.
DATA SYNTHESIS
Continuous outcomes were converted to a 0-100 scale. Dichotomous outcomes were presented as risk differences. Risk of bias and certainty of evidence was assessed.
RESULTS
We located 17 trials (1 intravenous and 16 oral route of administration). For adults, high certainty evidence from 11 comparisons shows that oral opioids provide small benefits relative to placebo in the immediate term for pain (mean difference [MD] - 8.8 95% confidence interval [CI] - 12.0 to - 5.6). For disability, the difference is uncertain (MD - 6.2, 95% CI - 17.8 to 5.4). Opioid groups were at higher risk of adverse events (MD 14.3%, 95% CI 8.3-20.4%, very low certainty). There was moderate certainty evidence of a large effect of IV morphine on sciatica pain (MD -42.5, 95% CI - 49.9 to - 35.1, n = 197, 1 study). In paediatric populations, moderate certainty evidence from 3 trials shows that oral opioids probably do not provide benefit beyond that of placebo for pain (MD 6.1, 95% CI - 1.7 to 12.8) and there was no evidence for disability. There was low certainty evidence that there may be no difference in adverse events (MD 10.4%, 95% CI - 0.6 to 21.4%).
DISCUSSION
Intravenous morphine likely offers benefits, but oral opioids may not provide clinically meaningful benefits.
PROSPERO REGISTRATION
CRD42021249346.
Topics: Adult; Child; Humans; Analgesics, Opioid; Musculoskeletal Pain; Acute Pain; Morphine
PubMed: 38451443
DOI: 10.1007/s40265-024-01999-5 -
Substance Use & Addiction Journal Apr 2024Buprenorphine is among the most effective treatments for opioid use disorder. Even though the federal government recently eliminated the waiver requirement and patient...
BACKGROUND
Buprenorphine is among the most effective treatments for opioid use disorder. Even though the federal government recently eliminated the waiver requirement and patient limits applicable to office-based buprenorphine treatment (OBBT), among other settings, some states may still have policies imposing requirements on OBBT providers not required by federal law.
METHODS
We collected statutes and regulations from 50 US states and the District of Columbia (ie, 51 jurisdictions) between August 11 and November 30, 2022 using the Nexis Uni legal database and search terms related to OBBT counseling, dosage, and/or frequency of visits. We then used template analysis, a mixed deductive-inductive qualitative method, to analyze legal content.
RESULTS
Ten jurisdictions (20%) in 2022 had an OBBT counseling, dosage, and/or visit frequency requirement. Four jurisdictions had at least one law in each OBBT policy category examined. One-fifth of jurisdictions have OBBT policies not required under federal law. Five of these jurisdictions are among those with the highest overdose death rates per capita, according to publicly available data from 2021. Some OBBT requirements could potentially limit clinician interest in offering buprenorphine treatment or result in inadequate care (eg, if dosage limitations are too low.).
CONCLUSIONS
Even though a federal waiver is no longer required for OBBT, our results suggests that at least some jurisdictions have other OBBT requirements, such as counseling, dosage, and/or frequency requirements. Given the severity of the ongoing opioid overdose crisis, policymakers should carefully consider the extent to which OBBT requirements are evidence based.
Topics: Humans; Buprenorphine; Opioid-Related Disorders; Opiate Substitution Treatment; Counseling; Drug Overdose
PubMed: 38288697
DOI: 10.1177/29767342231223721