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Journal of Clinical Medicine Dec 2023Despite the potential benefits of intrathecal morphine (ITM), the precise role and dosing of ITM in robotic assisted surgery (RAS) remains unclear. This systematic... (Review)
Review
Despite the potential benefits of intrathecal morphine (ITM), the precise role and dosing of ITM in robotic assisted surgery (RAS) remains unclear. This systematic review explores real-world evidence to evaluate the efficacy and outcomes of ITM in patients undergoing RAS. In accordance with PRISMA guidelines, a comprehensive search was conducted on four databases: MEDLINE, Embase, Cochrane Library and APA PsycInfo. Primary outcomes included pain scores at rest and on exertion at 24- and 48-h time intervals, and secondary outcomes aimed to explore the side effects of ITM. A meta-analysis was conducted to determine mean differences. A risk of bias assessment was conducted via the Cochrane Risk of Bias 2 tool. A total of 9 RCTs involving 619 patients were included in this review, of which 298 patients were administered ITM. Significant pain score reductions were observed both at rest (MD = -27.15; 95% CI [-43.97, -10.33]; I = 95%; = 0.002) and on exertion (MD = -25.88; 95% CI [-37.03, -14.72]; I = 79%; = 0.0003) 24 h postoperatively in the ITM groups, accompanied by a notable decrease in postoperative IV morphine equivalent consumption at 24 h (MD = -20.13; 95% CI [-30.74, -9.52]; I = 77%; = 0.0002). ITM improved pain scores both at rest and on exertion at 24 and 48 h intervals, concurrently reducing the need for postoperative opioid consumption, but at the cost of an increased incidence of adverse events.
PubMed: 38202144
DOI: 10.3390/jcm13010137 -
British Journal of Anaesthesia Sep 2023Neuraxial opioids provide effective analgesia for Caesarean delivery, however, pruritus can be a troubling side-effect. Effective agents to prevent pruritus are needed.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuraxial opioids provide effective analgesia for Caesarean delivery, however, pruritus can be a troubling side-effect. Effective agents to prevent pruritus are needed. Our objective was to perform an updated systematic review and network meta-analysis to provide clinicians with a comparison of relative efficacy of available interventions to reduce the incidence of pruritus, induced by either intrathecal or epidural single-shot morphine, in women undergoing Caesarean delivery.
METHODS
Databases systematically searched (up to January 2022) included PubMed MEDLINE, Web of Science, EBSCO CINAHL, Embase, LILACS, and two Cochrane databases. We included randomised, controlled trials involving adult female patients undergoing Caesarean delivery. We pooled trials comparing interventions used for preventing pruritus after Caesarean delivery and performed a Bayesian model network meta-analysis.
RESULTS
The final primary network included data from comparisons of 14 distinct interventions (including placebo) used to reduce the incidence of pruritus in 6185 participants. We judged five interventions to be 'definitely superior' to placebo: propofol, opioid agonist-antagonists (neuraxial), opioid antagonists, opioid agonist-antagonists (systemic), and serotonin antagonists. For the network evaluating the incidence of severe pruritus (warranting additional therapeutic treatment of pruritus), data were available for 14 interventions (including placebo) in 4489 patients. For this outcome, we judged three interventions to be 'definitely superior' to placebo: dopamine antagonists (neuraxial) and systemic and neuraxial opioid agonist-antagonists.
CONCLUSION
Our analysis found several interventions to be effective in reducing the incidence of pruritus. Although sub-hypnotic doses of propofol appear to have an antipruritic effect, replication of this finding and further investigation of optimal dosing are warranted.
SYSTEMATIC REVIEW PROTOCOL
PROSPERO (CRD42022367058).
Topics: Pregnancy; Adult; Humans; Female; Morphine; Analgesics, Opioid; Propofol; Network Meta-Analysis; Bayes Theorem; Cesarean Section; Pruritus
PubMed: 37455197
DOI: 10.1016/j.bja.2023.05.028 -
Pain Practice : the Official Journal of... Nov 2023Epidural analgesia is a common technique for managing perioperative and obstetric pain. Patients with cancer who cannot tolerate opioids or not responding to... (Review)
Review
BACKGROUND
Epidural analgesia is a common technique for managing perioperative and obstetric pain. Patients with cancer who cannot tolerate opioids or not responding to conventional treatment may benefit from epidural analgesia. Therefore, this systematic review aimed to analyze the efficacy and safety of epidural analgesia in patients with intractable cancer pain.
METHODS
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials to identify studies on patients with cancer who received epidural analgesia. We assessed the quality of all included studies using the risk-of-bias tool or Newcastle-Ottawa scale. The primary outcome was pain relief after epidural analgesia, and the secondary outcome was quality of life, analgesic consumption, and adverse events. The studies were grouped based on the medications used for epidural analgesia. A descriptive synthesis was performed following the Synthesis Without Meta-analysis reporting guideline.
RESULTS
Our systematic review included nine randomized controlled trials (n = 340) and 15 observational studies (n = 926). Two randomized controlled trials suggested that epidural opioids were not superior to systemic opioids in relieving pain. Epidural opioids combined with local anesthetics or adjuvants, including calcitonin, clonidine, ketamine, neostigmine, methadone, and dexamethasone, offered better analgesic effects. No significant difference in pain relief between an intermittent bolus and a continuous infusion of epidural morphine was observed. Epidural opioids had more analgesic effects on nociceptive pain than neuropathic pain. The methods used to evaluate the quality of life and the corresponding results were heterogeneous among studies. Six observational studies demonstrated that some patients could have decreased opioid consumption after epidural analgesia. Adverse events, including complications and drug-related side effects, were reported in 23 studies. Five serious complications, such as epidural abscess and hematoma, required surgical management. The heterogeneity and methodological limitations of the studies hindered meta-analysis and evidence-level determination.
CONCLUSION
Coadministration of epidural opioids, local anesthetics, and adjuvants may provide better pain relief for intractable cancer pain. However, we must assess the patients to ensure that the benefits outweigh the risks before epidural analgesia. Therefore, further high-quality studies are required.
Topics: Female; Humans; Pregnancy; Analgesia, Epidural; Analgesics; Analgesics, Opioid; Anesthetics, Local; Cancer Pain; Neoplasms; Pain, Postoperative; Quality of Life
PubMed: 37455298
DOI: 10.1111/papr.13273 -
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 -
British Journal of Anaesthesia Dec 2023Fascial plane blocks provide effective analgesia after midline laparotomy; however, the most efficacious technique has not been determined. We conducted a systematic... (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy and safety of non-neuraxial analgesic techniques for midline laparotomy: a systematic review and frequentist network meta-analysis of randomised controlled trials.
BACKGROUND
Fascial plane blocks provide effective analgesia after midline laparotomy; however, the most efficacious technique has not been determined. We conducted a systematic review and network meta-analysis of randomised controlled trials to synthesise the evidence with respect to pain, opioid consumption, and adverse events.
METHODS
We searched Ovid MEDLINE, Embase, Cochrane Central, and Scopus databases for studies comparing commonly used non-neuraxial analgesic techniques for midline laparotomy in adult patients. The co-primary outcomes of the study were 24-h cumulative opioid consumption and 24-h resting pain score, reported as i.v. morphine equivalents and 11-point numerical rating scale, respectively. We performed a frequentist meta-analysis using a random-effects model and a cluster-rank analysis of the co-primary outcomes.
RESULTS
Of 6115 studies screened, 67 eligible studies were included (n=4410). Interventions with the greatest reduction in 24-h cumulative opioid consumption compared with placebo/no intervention were single-injection quadratus lumborum block (sQLB; mean difference [MD] -16.1 mg, 95% confidence interval [CI] -29.9 to -2.3, very low certainty), continuous transversus abdominis plane block (cTAP; MD -14.0 mg, 95% CI -21.6 to -6.4, low certainty), single-injection transversus abdominis plane block (sTAP; MD -13.7 mg, 95% CI -17.4 to -10.0, low certainty), and continuous rectus sheath block (cRSB; MD -13.2 mg, 95% CI -20.3 to -6.1, low certainty). Interventions with the greatest reduction in 24-h resting pain score were cRSB (MD -1.2, 95% CI -1.8 to -0.6, low certainty), cTAP (MD -1.0, 95% CI -1.7 to -0.2, low certainty), and continuous wound infusion (cWI; MD -0.7, 95% CI -1.1 to -0.4, low certainty). Clustered-rank analysis including the co-primary outcomes showed cRSB and cTAP blocks to be the most efficacious interventions.
CONCLUSIONS
Based on current evidence, continuous rectus sheath block and continuous transversus abdominis plane block were the most efficacious non-neuraxial techniques at reducing 24-h cumulative opioid consumption and 24-h resting pain scores after midline laparotomy (low certainty). Future studies should compare techniques for upper vs lower midline laparotomy and other non-midline abdominal incisions.
CLINICAL TRIAL REGISTRATION
PROSPERO Registration Number: CRD42021269044.
Topics: Adult; Humans; Analgesics, Opioid; Laparotomy; Network Meta-Analysis; Morphine; Pain; Pain, Postoperative
PubMed: 37770254
DOI: 10.1016/j.bja.2023.08.024 -
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 -
Cureus Jan 2024Post-dural puncture headache (PDPH) is occasionally an inevitable side effect of neuraxial anesthesia, which can happen after spinal anesthesia or if an accidental dural... (Review)
Review
Post-dural puncture headache (PDPH) is occasionally an inevitable side effect of neuraxial anesthesia, which can happen after spinal anesthesia or if an accidental dural puncture (ADP) happens during epidural anesthesia. The treatment and prevention options for PDPH differ widely from one institution to another. The management of PDPH is heterogeneous in many institutions because of the absence of clear guidelines and protocols for the management of PDPH. This study aimed to summarize all articles published during the past decade that discussed the treatment or prevention of PDPH. From 2013 to 2023, 345 publications were filtered for all treatment and prevention approaches used for PDPH patients. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guidelines were followed for conducting this systematic review, and 38 articles were included for analysis and review. Existing data come from small randomized clinical trials and retrospective or prospective cohort studies. This review supports the effect of oral pregabalin and intravenous aminophylline in both treatment and prevention. Intravenous mannitol, intravenous hydrocortisone, triple prophylactic regimen, and neostigmine plus atropine combination showed effective and beneficial outcomes. On the other hand, neither neuraxial morphine nor epidural dexamethasone showed promising results. Consequently, the use of neuraxial morphine or epidural dexamethasone for the prevention of PDPH remains questionable. Regarding the posture of the patient and its consequences on the incidence of the headache, lateral decubitus is better than a sitting position, and a prone position is better than a supine position. Smaller non-cutting needles play a role in avoiding PDPH. Minimally invasive nerve blocks, including sphenopalatine ganglion or greater occipital nerves, are satisfyingly effective. Epidural blood patches remain the more invasive but the gold standard and ultimate solution in patients resisting medical therapy. This study highlights the need for larger research to define the best approach to prevent and treat PDPH.
PubMed: 38361721
DOI: 10.7759/cureus.52330 -
BMC Pediatrics Aug 2023Children in acute pain often receive inadequate pain relief, partly from difficulties administering injectable analgesics. A rapid-acting, intranasal (IN) analgesic may... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Children in acute pain often receive inadequate pain relief, partly from difficulties administering injectable analgesics. A rapid-acting, intranasal (IN) analgesic may be an alternative to other parenteral routes of administration. Our review compares the efficacy, safety, and acceptability of intranasal analgesia to intravenous (IV) and intramuscular (IM) administration; and to compare different intranasal agents.
METHODS
We searched Cochrane Library, MEDLINE/PubMed, Embase, Web of Knowledge, Clinicaltrials.gov, Controlled-trials.com/mrcr, Clinicaltrialsregister.eu, Apps.who.int/trialsearch. We also screened reference lists of included trials and relevant systematic reviews. Studies in English from any year were included. Two authors independently assessed all studies. We included randomised trials (RCTs) of children 0-16, with moderate to severe pain; comparing intranasal analgesia to intravenous or intramuscular analgesia, or to other intranasal agents. We excluded studies of procedural sedation or analgesia. We extracted study characteristics and outcome data and assessed risk of bias with the ROB 2.0-tool. We conducted meta-analysis and narrative review, evaluating the certainty of evidence using GRADE. Outcomes included pain reduction, adverse events, acceptability, rescue medication, ease of and time to administration.
RESULTS
We included 12 RCTs with a total of 1163 children aged 3 to 20, most below 10 years old, with a variety of conditions. Our review shows that: - There may be little or no difference in pain relief (single dose IN vs IV fentanyl MD 4 mm, 95% CI -8 to 16 at 30 min by 100 mm VAS; multiple doses IN vs IV fentanyl MD 0, 95%CI -0.35 to 0.35 at 15 min by Hannallah score; single dose IN vs IV ketorolac MD 0.8, 95% CI -0.4 to 1.9 by Faces Pain Scale-Revised), adverse events (single dose IN vs IV fentanyl RR 3.09, 95% CI 0.34 to 28.28; multiple doses IN vs IV fentanyl RR 1.50, 95%CI 0.29 to 7.81); single dose IN vs IV ketorolac RR 0.716, 95% CI 0.23 to 2.26), or acceptability (single dose IN vs IV ketorolac RR 0.83, 95% CI 0.66 to 1.04) between intranasal and intravenous analgesia (low certainty evidence). - Intranasal diamorphine or fentanyl probably give similar pain relief to intramuscular morphine (narrative review), and are probably more acceptable (RR 1.60, 95% CI 1.42 to 1.81) and tolerated better (RR 0.061, 95% CI 0.03 to 0.13 for uncooperative/negative reaction) (moderate certainty); adverse events may be similar (narrative review) (low certainty). - Intranasal ketamine gives similar pain relief to intranasal fentanyl (SMD 0.05, 95% CI -0.20 to 0.29 at 30 min), while having a higher risk of light sedation (RR 1.74, 95% CI 1.30 to 2.35) and mild side effects (RR 2.16, 95% CI 1.72 to 2.71) (high certainty). Need for rescue analgesia is probably similar (RR 0.85, 95% CI 0.62 to 1.17) (moderate certainty), and acceptability may be similar (RR 1.15, 95% CI 0.89 to 1.48) (low certainty).
CONCLUSIONS
Our review suggests that intranasal analgesics are probably a good alternative to intramuscular analgesics in children with acute moderate to severe pain; and may be an alternative to intravenous administration. Intranasal ketamine gives similar pain relief to fentanyl, but causes more sedation, which should inform the choice of intranasal agent.
Topics: Child; Humans; Ketorolac; Ketamine; Pain; Analgesia; Fentanyl
PubMed: 37596559
DOI: 10.1186/s12887-023-04203-x -
Anaesthesia Dec 2023Acute postoperative pain remains a critical treatment priority and has prompted a search for technologies and techniques to assist with intra-operative analgesic... (Meta-Analysis)
Meta-Analysis
Acute postoperative pain remains a critical treatment priority and has prompted a search for technologies and techniques to assist with intra-operative analgesic monitoring and management. Anaesthetists traditionally rely on clinical judgement to guide intra-operative analgesia, but several emerging technologies such as the nociception level index herald the possibility of routine intra-operative analgesia monitoring. However, the impact of devices like nociception level index on postoperative outcomes has not been proven. We undertook a systematic review and meta-analysis of articles which compared nociception level index-guided analgesia to standard care. The primary outcomes were pain intensity and opioid consumption during the first 60-120 min after surgery. Secondary outcomes were the incidence of postoperative nausea and vomiting and duration of stay in the post-anaesthesia care unit. Ten studies, collectively including 662 patients and published between 2019 and 2023, met inclusion criteria for both the qualitative systematic review and quantitative meta-analysis. Risk of methodological bias was generally low or unclear, and six studies reported a significant conflict of interest relevant to their findings. Our meta-analysis was performed using a random-effects model. It found statistically significant benefits of nociception level index-guided analgesia for early postoperative pain (mean (95%CI) difference -0.46 (-0.88 to -0.03) on an 11-point scale, p = 0.03), and opioid requirement (mean (95%CI) difference -1.04 (-1.94 to -0.15) mg intravenous morphine equivalent, p = 0.02). Our meta-analysis of the current literature finds that nociception level index-guided analgesia statistically significantly reduces reported postoperative pain intensity and opioid consumption but fails to show clinically relevant outcomes. We found no evidence that nociception level index-guided analgesia affected postoperative nausea and vomiting nor duration of stay in the post-anaesthesia care unit.
Topics: Humans; Analgesics, Opioid; Postoperative Nausea and Vomiting; Nociception; Analgesia; Pain, Postoperative
PubMed: 37864430
DOI: 10.1111/anae.16148 -
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