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Cureus Sep 2023Patients with diminished renal function necessitate special care. In patients with chronic kidney disease (CKD), opioid analgesics should be prescribed based on the... (Review)
Review
Patients with diminished renal function necessitate special care. In patients with chronic kidney disease (CKD), opioid analgesics should be prescribed based on the severity of renal insufficiency; this will determine treatment options at the beginning and throughout the management of pain in CKD patients. The dosage of hydrophilic drugs and drugs with active metabolites should be adjusted according to the severity of CKD, and the process of treatment should be monitored by modifying drug dosages as necessary for background and breakthrough pain. Patients with CKD may benefit from opioid analgesics that are lipophilic, such as methadone, fentanyl, and buprenorphine, as the first line; however, fentanyl is inappropriate for patients undergoing hemodialysis. Opioid prescription in CKD patients is the subject of this systematic review, which aims to compare their safety and efficacy. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. Using three databases (PubMed, ScienceDirect, and Google Scholar), we collected and reviewed articles, including literature reviews, randomized control trials (RCTs), and systematic reviews published between 1980 and 2022, to enable us to gather enough valuable data on this rare topic. After applying appropriate filters, a total of 109 results were obtained. They were further screened and subjected to quality assessment tools, which finally yielded 11 studies included in this systematic review. This consisted of two RCTs, two systematic reviews, and seven narrative reviews. This review focused on the safety and appropriate use of opioids in patients with CKD. The accumulation of morphine and codeine metabolites may result in neurotoxic side effects. Hydromorphone and oxycodone are considered safe to administer but require careful adjustments in dosage. Common comorbidities among patients with CKD may amplify opioid-related adverse effects.
PubMed: 37727840
DOI: 10.7759/cureus.45485 -
Pain Practice : the Official Journal of... Mar 2024Assessment of the efficacy and safety of perioperative intravenous ketamine in reducing incidence and severity of chronic postsurgical pain. (Meta-Analysis)
Meta-Analysis Review
STUDY OBJECTIVE
Assessment of the efficacy and safety of perioperative intravenous ketamine in reducing incidence and severity of chronic postsurgical pain.
STUDY DESIGN
A systematic review and meta-analysis of randomized controlled trials (RCTs).
DATA SOURCES
The following data sources were systematically searched: MEDLINE, CENTRAL, and EMBASE (till 02/2021).
PATIENTS
Adult patients undergoing any surgery.
INTERVENTIONS
Perioperative use of intravenous ketamine as an additive analgesic drug compared to placebo, no active control treatment, and other additive drugs.
MEASUREMENTS
Primary outcomes were number of patients with chronic postsurgical pain after 6 months and ketamine related adverse effects. Secondary outcomes were chronic postsurgical pain incidence after 3 and 12 months, chronic postsurgical neuropathic pain incidence, chronic postsurgical moderate to severe pain incidence, intensity of chronic postsurgical pain at rest, and during movement, oral morphine consumption after 3, 6, and 12 months and incidence of opioid-related adverse effects.
MAIN RESULTS
Thirty-six RCTs were included with a total of 3572 patients. Ketamine compared to placebo may result in no difference in the number of patients with chronic postsurgical pain after 6 months (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.71-1.05; I = 34%; 16 studies; low-certainty evidence). Ketamine may reduce the incidence of chronic postsurgical neuropathic pain after 3 months in comparison to placebo (RR 0.78, 95% CI 0.62-0.99, I = 31%, seven trials, low-certainty evidence). Ketamine compared to placebo may increase the risk for postoperative nystagmus (RR 9.04, 95% CI 1.15-70.90, I 30%, two trials, low-certainty evidence) and postoperative visual disturbances (RR 2.29, 95% CI 1.05-4.99, I 10%, seven trials, low-certainty evidence).
CONCLUSIONS
There is low-certainty evidence that perioperative ketamine has no effect on chronic postsurgical pain in adult patients. Low-certainty evidence suggests that ketamine compared to placebo may reduce incidence of chronic postsurgical neuropathic pain after 3 months. Questions like ideal dosing, treatment duration and more patient-related outcome measures remain unanswered, which warrants further studies.
PROTOCOL REGISTRATION
Prospero CRD42021223625, 07.01.2021.
Topics: Adult; Humans; Ketamine; Analgesics; Pain, Postoperative; Morphine; Neuralgia
PubMed: 37971167
DOI: 10.1111/papr.13314 -
Anaesthesia Jun 2024Intrathecal diamorphine is believed to provide postoperative analgesia but is associated with adverse effects such as nausea and vomiting. There is little evidence of... (Review)
Review
BACKGROUND
Intrathecal diamorphine is believed to provide postoperative analgesia but is associated with adverse effects such as nausea and vomiting. There is little evidence of synthesis regarding intrathecal diamorphine in the contemporary literature. We performed a systematic review, meta-analysis with meta-regression and trial sequential analysis to determine the magnitude of intrathecal diamorphine efficacy and safety.
METHODS
We systematically searched the literature for trials comparing intrathecal diamorphine with a control group in patients undergoing all types of surgery. The primary efficacy and safety outcomes were intravenous morphine consumption and incidence of postoperative nausea and vomiting at 24 h following surgery, respectively.
RESULTS
Twelve trials were identified, which included data for 712 patients. Intrathecal doses of diamorphine ranged from 100 μg to 2500 μg. Intravenous morphine consumption at 24 h postoperatively was significantly reduced in the intrathecal diamorphine group, with a mean difference (95%CI) of -8 mg (-11 to -6), I = 93%, p < 0.001. There was a significant difference between three intrathecal diamorphine dosing subgroups but without correlation: mean differences (95%CI) -1 mg (-3-0), -26 mg (-40 to -11) and -6 mg (-15-4) in patients receiving doses of 0-200 μg, 201-400 μg and > 400 μg, respectively (p = 0.003). Intrathecal diamorphine increased postoperative nausea and vomiting with a risk ratio (95%CI) of 1.37 (1.19-1.58), I = 7%, p < 0.001. There were no differences in postoperative nausea and vomiting between the three intrathecal diamorphine dosing subgroups. There was no correlation observed with meta-regression of the primary efficacy and safety outcomes. The quality of evidence for all outcomes was very low.
CONCLUSION
There is very low level of evidence that intrathecal diamorphine provides effective analgesia after surgery, while increasing postoperative nausea and vomiting with doses > 200 μg.
PubMed: 38922818
DOI: 10.1111/anae.16359 -
Cureus Jan 2024Adolescent idiopathic scoliosis (AIS) often necessitates spinal fusion surgery in pediatric patients, posing significant challenges in postoperative pain management.... (Review)
Review
Adolescent idiopathic scoliosis (AIS) often necessitates spinal fusion surgery in pediatric patients, posing significant challenges in postoperative pain management. Standard care involves the administration of intravenous opioids perioperatively, often requiring high doses to achieve adequate analgesia following an operation. This increases the risk of adverse events, may delay recovery and prolong hospital stay, and increases the likelihood of future abuse and dependence. In this systematic review and meta-analysis, we assess the safety and effectiveness of intrathecal morphine (ITM) in pediatric patients undergoing posterior spinal fusion. Ovid Embase and MEDLINE were searched in October 2023 for articles that directly compared ITM use with standard pain management approaches for pediatric patients undergoing posterior spinal fusion. Our primary outcome was postoperative pain scores. Secondary outcomes included opioid usage details, adverse events, and blood loss. Of the 384 unique studies identified, nine studies (one randomized control trial, one prospective review, and seven retrospective reviews) met the inclusion criteria. The total number of patients within the ITM and control groups were 1384 and 676, respectively. Meta-analysis revealed significantly lower pain scores in the ITM group (standardized mean difference (SMD): -1.30 (-2.29, -0.31); p = 0.01). Similarly, ITM patients had significantly lower opioid usage, both intraoperatively (mean difference (MD): -0.71 mg/kg (-0.99, -0.44); p < 0.00001) as well as postoperatively (SMD: -2.10 (-3.48, -0.73); p = 0.003), and significantly lower blood loss (MD: -0.88 L (-1.34, -0.43); p = 0.0001). The occurrence of adverse events was similar across both groups. Our analysis of the available data demonstrates that a low to moderate dose of ITM is a safe and effective adjunct to improve standard postoperative care without increasing the risk of respiratory depression. When compared to control, ITM patients had superior analgesia while using fewer opioids had significantly reduced intraoperative blood loss when ITM was administered before spinal fusion, and had a similar complication profile. While further studies are warranted to establish optimal dosing, these findings underscore the potential of ITM as a valuable addition to multimodal pain management.
PubMed: 38318548
DOI: 10.7759/cureus.51754 -
Molecular Psychiatry Apr 2024The elucidation of synaptic density changes provides valuable insights into the underlying brain mechanisms of substance use. In preclinical studies, synaptic density...
The elucidation of synaptic density changes provides valuable insights into the underlying brain mechanisms of substance use. In preclinical studies, synaptic density markers, like spine density, are altered by substances of abuse (e.g., alcohol, amphetamine, cannabis, cocaine, opioids, nicotine). These changes could be linked to phenomena including behavioral sensitization and drug self-administration in rodents. However, studies have produced heterogeneous results for spine density across substances and brain regions. Identifying patterns will inform translational studies given tools that now exist to measure in vivo synaptic density in humans. We performed a meta-analysis of preclinical studies to identify consistent findings across studies. PubMed, ScienceDirect, Scopus, and EBSCO were searched between September 2022 and September 2023, based on a protocol (PROSPERO: CRD42022354006). We screened 6083 publications and included 70 for meta-analysis. The meta-analysis revealed drug-specific patterns in spine density changes. Hippocampal spine density increased after amphetamine. Amphetamine, cocaine, and nicotine increased spine density in the nucleus accumbens. Alcohol and amphetamine increased, and cannabis reduced, spine density in the prefrontal cortex. There was no convergence of findings for morphine's effects. The effects of cocaine on the prefrontal cortex presented contrasting results compared to human studies, warranting further investigation. Publication bias was small for alcohol or morphine and substantial for the other substances. Heterogeneity was moderate-to-high across all substances. Nonetheless, these findings inform current translational efforts examining spine density in humans with substance use disorders.
PubMed: 38561468
DOI: 10.1038/s41380-024-02519-3 -
Korean Journal of Anesthesiology Dec 2023Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not been elucidated. In this network meta-analysis and systematic review, we compared the influence of control and individual NSAIDs on the indices of analgesia, side effects, and quality of recovery.
METHODS
CDSR, CINAHL, CRCT, Embase, LILACS, PubMed, and Web of Science were searched for randomized controlled trials comparing a specific NSAID to either control or another NSAID in elective or emergency cesarean section under general or neuraxial anesthesia. Network plots and league tables were constructed, and the quality of evidence was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis.
RESULTS
We included 47 trials. Cumulative intravenous morphine equivalent consumption at 24 h, the primary outcome, was examined in 1,228 patients and 18 trials, and control was found to be inferior to diclofenac, indomethacin, ketorolac, and tenoxicam (very low quality evidence owing to serious limitations, imprecision, and publication bias). Indomethacin was superior to celecoxib for pain score at rest at 8-12 h and celecoxib + parecoxib, diclofenac, and ketorolac for pain score on movement at 48 h. In regard to the need for and time to rescue analgesia COX-2 inhibitors such as celecoxib were inferior to other NSAIDs.
CONCLUSIONS
Our review suggests the presence of minimal differences among the NSAIDs studied. Nonselective NSAIDs may be more effective than selective NSAIDs, and some NSAIDs such as indomethacin might be preferable to other NSAIDs.
Topics: Humans; Pregnancy; Female; Diclofenac; Ketorolac; Celecoxib; Cesarean Section; Network Meta-Analysis; Anti-Inflammatory Agents, Non-Steroidal; Indomethacin; Pain
PubMed: 37066603
DOI: 10.4097/kja.23014 -
Minerva Anestesiologica 2024Ketamine is reported as a potent opioid alternative that provides significant reduction in pain with no severe adverse events. However, some studies didn't find its use... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Ketamine is reported as a potent opioid alternative that provides significant reduction in pain with no severe adverse events. However, some studies didn't find its use satisfactory and reported less reduction in pain score with ketamine. The purpose of this study is to compare the efficacy and safety of ketamine versus morphine for the treatment of acute pain in emergency situations.
EVIDENCE ACQUISITION
The PubMed, MEDLINE, PsycINFO EMBASE, Cochrane Library, PROSPERO registry platform, and ClinicalTrials.gov websites were queried in accordance with the PRISMA guidelines in order to locate relevant studies. According to the predefined PICOS criteria, articles were included and event data pertaining to changes in Visual Analog Scale or Numeric Rating Scale pain scales were extracted. Using RevMan and MedCalc, a meta-analysis was conducted to compare the effects of ketamine and morphine for the treatment of acute pain.
EVIDENCE SYNTHESIS
Twelve studies met the criteria for inclusion in this meta-analysis. Ketamine was found to be more effective than morphine at reducing pain scores, with an odds ratio of 0.60 (95% CI 0.48 to 0.76). Similarly, no severe adverse events related to ketamine were reported in any study, and it has a low-risk ratio of 0.78 (95% CI 0.70 to 0.87). Egger's Test P values (0.3052) and Begg's Test P values (0.3869) indicate a low risk of bias, and the Bland-Altman plot demonstrates a high degree of concordance.
CONCLUSIONS
Ketamine is a potent and effective alternative to morphine for the management of acute pain, and it reduces pain score significantly with minimal side effects.
Topics: Humans; Morphine; Ketamine; Acute Pain; Analgesics, Opioid; Pain Management
PubMed: 37930103
DOI: 10.23736/S0375-9393.23.17561-4 -
The Cochrane Database of Systematic... Sep 2023Lumbar puncture (LP) is a common invasive procedure, most frequently performed to diagnose infection. Physicians perform LP in newborn infants with the help of an... (Review)
Review
BACKGROUND
Lumbar puncture (LP) is a common invasive procedure, most frequently performed to diagnose infection. Physicians perform LP in newborn infants with the help of an assistant using a strict aseptic technique; it is important to monitor the infant during all the steps of the procedure. Without adequate analgesia, LP can cause considerable pain and discomfort. As newborns have increased sensitivity to pain, it is crucial to adequately manage the procedural pain of LP in this population.
OBJECTIVES
To assess the benefits and harms, including pain, discomfort, and success rate, of any pharmacological intervention during lumbar puncture in newborn infants, compared to placebo, no intervention, non-pharmacological interventions, or other pharmacological interventions.
SEARCH METHODS
We searched CENTRAL, PubMed, Embase, and three trial registries in December 2022. We also screened the reference lists of included studies and related systematic reviews for studies not identified by the database searches.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-RCTs comparing drugs used for pain management, sedation, or both, during LP. We considered the following drugs suitable for inclusion. • Topical anesthetics (e.g. eutectic mixture of local anesthetics [EMLA], lidocaine) • Opioids (e.g. morphine, fentanyl) • Alpha-2 agonists (e.g. clonidine, dexmedetomidine) • N-Methyl-D-aspartate (NMDA) receptor antagonists (e.g. ketamine) • Other analgesics (e.g. paracetamol) • Sedatives (e.g. benzodiazepines such as midazolam) DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We used the fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD) or standardized mean difference (SMD) for continuous data, with their 95% confidence intervals (CIs). Our main outcomes were successful LP on first attempt, total number of LP attempts, episodes of bradycardia, pain assessed with validated scales, episodes of desaturation, number of episodes of apnea, and number of infants with one or more episodes of apnea. We used the GRADE approach to evaluate the certainty of the evidence.
MAIN RESULTS
We included three studies (two RCTs and one quasi-RCT) that enrolled 206 newborns. One study included only term infants. All studies assessed topical treatment versus placebo or no intervention. The topical anesthetics were lidocaine 4%, lidocaine 1%, and EMLA. We identified no completed studies on opioids, non-steroidal anti-inflammatory drugs, alpha-2 agonists, NMDA receptor antagonists, other analgesics, sedatives, or head-to-head comparisons (drug A versus drug B). Based on very low-certainty evidence from one quasi-RCT of 100 LPs in 76 infants, we are unsure if topical anesthetics (lidocaine), compared to no anesthesia, has an effect on the following outcomes. • Successful LP on first attempt (first-attempts success in 48% of LPs in the lidocaine group and 42% of LPs in the control group) • Number of attempts per LP (mean 1.9 attempts, [standard error of the mean 0.2] in the lidocaine group, and mean 2.1 attempts [standard error of the mean 2.1] in the control group) • Episodes of bradycardia (0% of LPs in the lidocaine group and 4% of LPs in the control group) • Episodes of desaturation (0% of LPs in the lidocaine group and 8% of LPs in the control group) • Occurrence of apnea (RR 3.24, 95% CI 0.14 to 77.79; risk difference [RD] 0.02, 95% CI -0.03 to 0.08). Topical anesthetics compared to placebo may reduce pain assessed with the Neonatal Facial Coding System (NFCS) score (SMD -1.00 standard deviation (SD), 95% CI -1.47 to -0.53; I² = 98%; 2 RCTs, 112 infants; low-certainty evidence). No studies in this comparison reported total number of episodes of apnea. We identified three ongoing studies, which will assess the effects of EMLA, lidocaine, and fentanyl. Three studies are awaiting classification.
AUTHORS' CONCLUSIONS
The evidence is very uncertain about the effect of topical anesthetics (lidocaine) compared to no anesthesia on successful lumbar puncture on first attempt, the number of attempts per lumbar puncture, episodes of bradycardia, episodes of desaturation, and occurrence of apnea. Compared to placebo, topical anesthetics (lidocaine or EMLA) may reduce pain assessed with the NFCS score. One ongoing study will assess the effects of systemic treatment.
Topics: Humans; Infant, Newborn; Analgesics; Anesthetics, Local; Apnea; Bradycardia; Fentanyl; Hypnotics and Sedatives; Lidocaine; Lidocaine, Prilocaine Drug Combination; Pain; Spinal Puncture
PubMed: 37767875
DOI: 10.1002/14651858.CD015594.pub2 -
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 -
Seminars in Cardiothoracic and Vascular... Sep 2023Despite their extensive clinical use, opioids are characterized by several side effects. These complications, coupled with the ongoing opioid epidemic, have favored the... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Despite their extensive clinical use, opioids are characterized by several side effects. These complications, coupled with the ongoing opioid epidemic, have favored the rise of opioid-free-anesthesia (OFA). Herein, we perform the first pairwise meta-analysis of clinical outcomes for OFA vs opioid-based anesthesia (OBA) in patients undergoing cardiovascular and thoracic surgery.
METHODS
We comprehensively searched medical databases to identify studies comparing OFA and OBA in patients undergoing cardiovascular or thoracic surgery. Pairwise meta-analysis was performed using the Mantel-Haenszel method. Outcomes were pooled as risk ratios (RR) or standard mean differences (SMD) and their 95% confidence intervals (95% CI).
RESULTS
Our pooled analysis included 919 patients (8 studies), of whom 488 underwent surgery with OBA and 431 with OFA. Among cardiovascular surgery patients, compared to OBA, OFA was associated with significantly reduced post-operative nausea and vomiting (RR, 0.57; = .042), inotrope need (RR .84, = .045), and non-invasive ventilation (RR, .54; = .028). However, no differences were observed for 24hr pain score (SMD, -.35; = .510) or 48hr morphine equivalent consumption (SMD, -1.09; = .139). Among thoracic surgery patients, there was no difference between OFA and OBA for any of the explored outcomes, including post-operative nausea and vomiting (RR, 0.41; = .025).
CONCLUSION
Through the first pooled analysis of OBA vs OFA in a cardiothoracic-exclusive cohort, we found no significant difference in any of the pooled outcomes for thoracic surgery patients. Although limited to 2 cardiovascular surgery studies, OFA was associated with significantly reduced postoperative nausea and vomiting, inotrope need, and non-invasive ventilation in these patients. With growing use of OFA in invasive operations, further studies are needed to assess their efficacy and safety in cardiothoracic patients.
Topics: Humans; Analgesics, Opioid; Anesthesia; Nausea; Pain, Postoperative; Cardiovascular Surgical Procedures; Thoracic Surgical Procedures; Postoperative Nausea and Vomiting
PubMed: 37300532
DOI: 10.1177/10892532231180227