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General Hospital Psychiatry 2022We conducted an updated, comprehensive, and contemporary systematic review to examine the efficacy of existing pharmacologic agents employed for management of delirium... (Review)
Review
OBJECTIVE
We conducted an updated, comprehensive, and contemporary systematic review to examine the efficacy of existing pharmacologic agents employed for management of delirium symptoms among hospitalized adults.
METHODS
Searches of PubMed, Scopus, Embase, and Cochrane Library databases from inception to May 2021 were performed to identify studies investigating efficacy of pharmacologic agents for management of delirium.
RESULTS
Of 11,424 articles obtained from searches, a total of 33 articles (N = 3030 participants) of randomized or non-randomized trials, in which pharmacologic treatment was compared to active comparator, placebo, or no treatment, met all criteria and were included in this review. Medications used for management of delirium symptoms included antipsychotic medications (N = 27), alpha-2 agonists (N = 5), benzodiazepines (N = 2), antidepressants (n = 1), acetylcholinesterase inhibitors (N = 2), melatonin (N = 2), opioids (N = 1), and antiemetics (N = 2). Despite somewhat mixed findings and a relative lack of high-quality trials, it appears that antipsychotic medications (e.g., haloperidol, olanzapine, risperidone, or quetiapine) and dexmedetomidine have the potential to improve delirium outcomes.
CONCLUSIONS
Pharmacologic agents can reduce delirium symptoms (e.g., agitation) in some hospitalized patients. Additional double-blinded, randomized, placebo-controlled clinical trials are critically needed to investigate the efficacy of pharmacologic agents for diverse hospitalized populations (e.g., post-surgical patients, patients at the end-of-life, or in intensive care units).
Topics: Adult; Humans; Antipsychotic Agents; Delirium; Acetylcholinesterase; Haloperidol; Risperidone
PubMed: 36375344
DOI: 10.1016/j.genhosppsych.2022.10.010 -
Dexmedetomidine versus Midazolam in Procedural Sedation. A Systematic Review of Efficacy and Safety.PloS One 2017To systematically review the literature comparing the efficacy and safety of dexmedetomidine and midazolam when used for procedural sedation. (Review)
Review
OBJECTIVES
To systematically review the literature comparing the efficacy and safety of dexmedetomidine and midazolam when used for procedural sedation.
MATERIALS AND METHODS
We searched MEDLINE, EMBASE and COCHRANE for clinical trials comparing dexmedetomidine and midazolam for procedural sedation up to June 20, 2016. Inclusion criteria: clinical trial, human subjects, adult subjects (≥18 years), article written in English, German, French or Dutch, use of study medication for conscious sedation and at least one group receiving dexmedetomidine and one group receiving midazolam. Exclusion criteria: patients in intensive care, pediatric subjects and per protocol use of additional sedative medication other than rescue medication. Outcome measures for efficacy comparison were patient and clinician satisfaction scores and pain scores; outcome measures for safety comparison were hypotension, hypoxia, and circulatory and respiratory complications.
RESULTS
We identified 89 papers, of which 12 satisfied the inclusion and exclusion criteria; 883 patients were included in these studies. Dexmedetomidine was associated with higher patient and operator satisfaction than midazolam. Patients receiving dexmedetomidine experienced less pain and had lower analgesic requirements. Respiratory and hemodynamic safety were similar.
CONCLUSIONS
Dexmedetomidine is a promising alternative to midazolam for use in procedural sedation. Dexmedetomidine provides more comfort during the procedure for the patient and clinician. If carefully titrated, the safety profiles are similar.
Topics: Dexmedetomidine; Hemodynamics; Humans; Hypnotics and Sedatives; Midazolam; Respiration
PubMed: 28107373
DOI: 10.1371/journal.pone.0169525 -
British Journal of Anaesthesia Jun 2023Chronic postsurgical pain is common after surgery. Identification of non-opioid analgesics with potential for preventing chronic postsurgical pain is important, although... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic postsurgical pain is common after surgery. Identification of non-opioid analgesics with potential for preventing chronic postsurgical pain is important, although trials are often underpowered. Network meta-analysis offers an opportunity to improve power and to identify the most promising therapy for clinical use and future studies.
METHODS
We conducted a PRISMA-NMA-compliant systematic review and network meta-analysis of randomised controlled trials of non-opioid analgesics for chronic postsurgical pain. Outcomes included incidence and severity of chronic postsurgical pain, serious adverse events, and chronic opioid use.
RESULTS
We included 132 randomised controlled trials with 23 902 participants. In order of efficacy, i.v. lidocaine (odds ratio [OR] 0.32; 95% credible interval [CrI] 0.17-0.58), ketamine (OR 0.64; 95% CrI 0.44-0.92), gabapentinoids (OR 0.67; 95% CrI 0.47-0.92), and possibly dexmedetomidine (OR 0.36; 95% CrI 0.12-1.00) reduced the incidence of chronic postsurgical pain at ≤6 months. There was little available evidence for chronic postsurgical pain at >6 months, combinations agents, chronic opioid use, and serious adverse events. Variable baseline risk was identified as a potential violation to the network meta-analysis transitivity assumption, so results are reported from a fixed value of this, with analgesics more effective at higher baseline risk. The confidence in these findings was low because of problems with risk of bias and imprecision.
CONCLUSIONS
Lidocaine (most effective), ketamine, and gabapentinoids could be effective in reducing chronic postsurgical pain ≤6 months although confidence is low. Moreover, variable baseline risk might violate transitivity in network meta-analysis of analgesics; this recommends use of our methods in future network meta-analyses.
SYSTEMATIC REVIEW PROTOCOL
PROSPERO CRD42021269642.
Topics: Humans; Analgesics, Non-Narcotic; Network Meta-Analysis; Ketamine; Analgesics; Pain, Postoperative; Lidocaine; Analgesics, Opioid
PubMed: 37059625
DOI: 10.1016/j.bja.2023.02.041 -
Anaesthesia Mar 2023The effects of dexmedetomidine in adults undergoing cardiac surgery are inconsistent. We conducted a systematic review and meta-analysis to analyse the effects of... (Meta-Analysis)
Meta-Analysis Review
The effects of dexmedetomidine in adults undergoing cardiac surgery are inconsistent. We conducted a systematic review and meta-analysis to analyse the effects of peri-operative dexmedetomidine in adults undergoing cardiac surgery. We searched MEDLINE via Pubmed, EMBASE, Scopus and Cochrane for relevant randomised controlled trials between 1 January 1990 and 1 March 2022. We used the Joanna Briggs Institute methodology checklist to assess study quality and the GRADE approach to certainty of evidence. We assessed the sensitivity of results to false data. We used random-effects meta-analyses to analyse the primary outcomes: durations of intensive care and tracheal intubation. We included 48 trials of 6273 participants. Dexmedetomidine reduced the mean (95%CI) duration of intensive care by 5.0 (2.2-7.7) h, p = 0.001, and tracheal intubation by 1.6 (0.6-2.7) h, p = 0.003. The relative risk (95%CI) for postoperative delirium was 0.58 (0.43-0.78), p = 0.001; 0.76 (0.61-0.95) for atrial fibrillation, p = 0.015; and 0.49 (0.25-0.97) for short-term mortality, p = 0.041. Bradycardia and hypotension were not significantly affected. Trial sequential analysis was consistent with the primary meta-analysis. Adjustments for possible false data reduced the mean (95%CI) reduction in duration of intensive care and tracheal intubation by dexmedetomidine to 3.6 (1.8-5.4) h and 0.8 (0.2-1.4) h, respectively. Binary adjustment for methodological quality at a Joanna Briggs Institute score threshold of 10 did not alter the results significantly. In summary, peri-operative dexmedetomidine reduced the durations of intensive care and tracheal intubation and the incidence of short-term mortality after adult cardiac surgery. The reductions in intensive care stay and tracheal intubation may or may not be considered clinically useful, particularly after adjustment for possible false data.
Topics: Adult; Humans; Dexmedetomidine; Cardiac Surgical Procedures; Emergence Delirium; Critical Care; Bradycardia
PubMed: 36535747
DOI: 10.1111/anae.15947 -
Intensive Care Medicine Jul 2022Conventional gabaminergic sedatives such as benzodiazepines and propofol are commonly used in mechanically ventilated patients in the intensive care unit (ICU).... (Meta-Analysis)
Meta-Analysis
Conventional gabaminergic sedatives such as benzodiazepines and propofol are commonly used in mechanically ventilated patients in the intensive care unit (ICU). Dexmedetomidine is an alternative sedative that may achieve lighter sedation, reduce delirium, and provide analgesia. Our objective was to perform a comprehensive systematic review summarizing the large body of evidence, determining if dexmedetomidine reduces delirium compared to conventional sedatives. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov and the WHO ICTRP from inception to October 2021. Independent pairs of reviewers identified randomized clinical trials comparing dexmedetomidine to other sedatives for mechanically ventilated adults in the ICU. We conducted meta-analyses using random-effects models. The results were reported as relative risks (RRs) for binary outcomes and mean differences (MDs) for continuous outcomes, with corresponding 95% confidence intervals (CIs). In total, 77 randomized trials (n = 11,997) were included. Compared to other sedatives, dexmedetomidine reduced the risk of delirium (RR 0.67, 95% CI 0.55 to 0.81; moderate certainty), the duration of mechanical ventilation (MD - 1.8 h, 95% CI - 2.89 to - 0.71; low certainty), and ICU length of stay (MD - 0.32 days, 95% CI - 0.42 to - 0.22; low certainty). Dexmedetomidine use increased the risk of bradycardia (RR 2.39, 95% CI 1.82 to 3.13; moderate certainty) and hypotension (RR 1.32, 95% CI 1.07 to 1.63; low certainty). In mechanically ventilated adults, the use of dexmedetomidine compared to other sedatives, resulted in a lower risk of delirium, and a modest reduction in duration of mechanical ventilation and ICU stay, but increased the risks of bradycardia and hypotension.
Topics: Adult; Bradycardia; Critical Illness; Delirium; Dexmedetomidine; Humans; Hypnotics and Sedatives; Hypotension; Intensive Care Units; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 35648198
DOI: 10.1007/s00134-022-06712-2 -
Anaesthesia Jun 2019Intra-operative remifentanil is associated with increased postoperative analgesic requirements and opioid consumption. Dexmedetomidine has characteristics suggesting it... (Comparative Study)
Comparative Study Meta-Analysis Review
Intra-operative remifentanil is associated with increased postoperative analgesic requirements and opioid consumption. Dexmedetomidine has characteristics suggesting it may substitute for intra-operative remifentanil during general anaesthesia, but existing literature has reported conflicting results. We undertook this meta-analysis to investigate whether general anaesthesia including dexmedetomidine would result in less postoperative pain than general anaesthesia including remifentanil. The MEDLINE and PubMed electronic databases were searched up to October 2018. Only randomised trials including patients receiving general anaesthesia and comparing dexmedetomidine with remifentanil administration were included. Meta-analyses were performed mostly employing a random effects model. The primary outcome was pain score at rest (visual analogue scale, 0-10) at two postoperative hours. The secondary outcomes included: pain score at rest at 24 postoperative hours; opioid consumption at 2 and 24 postoperative hours; and rates of hypotension, bradycardia, shivering and postoperative nausea and vomiting. Twenty-one randomised trials, including 1309 patients, were identified. Pain scores at rest at two postoperative hours were lower in the dexmedetomidine group, with a mean difference (95%CI) of -0.7 (-1.2 to -0.2), I = 85%, p = 0.004, and a moderate quality of evidence. Secondary pain outcomes were also significantly better in the dexmedetomidine group. Rates of hypotension, shivering and postoperative nausea and vomiting were at least twice as frequent in patients who received remifentanil. Time to analgesia request was longer, and use of postoperative morphine and rescue analgesia were less, with dexmedetomidine, whereas episodes of bradycardia were similar between groups. There is moderate evidence that intra-operative dexmedetomidine during general anaesthesia improves pain outcomes during the first 24 postoperative hours, when compared with remifentanil, with fewer side effects.
Topics: Analgesia; Analgesics, Non-Narcotic; Analgesics, Opioid; Anesthesia, General; Dexmedetomidine; Humans; Intraoperative Care; Pain, Postoperative; Remifentanil
PubMed: 30950522
DOI: 10.1111/anae.14657 -
European Journal of Anaesthesiology Sep 2021Complex spinal procedures are associated with intense pain in the postoperative period. Adequate peri-operative pain management has been shown to correlate with improved...
BACKGROUND
Complex spinal procedures are associated with intense pain in the postoperative period. Adequate peri-operative pain management has been shown to correlate with improved outcomes including early ambulation and early discharge.
OBJECTIVES
We aimed to evaluate the available literature and develop recommendations for optimal pain management after complex spine surgery.
DESIGN AND DATA SOURCES
A systematic review using the PROcedure SPECific postoperative pain managemenT methodology was undertaken. Randomised controlled trials and systematic reviews published in the English language from January 2008 to April 2020 assessing postoperative pain after complex spine surgery using analgesic, anaesthetic or surgical interventions were identified from MEDLINE, EMBASE and Cochrane Databases.
RESULTS
Out of 111 eligible studies identified, 31 randomised controlled trials and four systematic reviews met the inclusion criteria. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol, cyclo-oxygenase (COX)-2 specific-inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs), intravenous ketamine infusion and regional analgesia techniques including epidural analgesia using local anaesthetics with or without opioids. Limited evidence was found for local wound infiltration, intrathecal and epidural opioids, erector spinae plane block, thoracolumbar interfascial plane block, intravenous lidocaine, dexmedetomidine and gabapentin.
CONCLUSIONS
The analgesic regimen for complex spine surgery should include pre-operative or intra-operative paracetamol and COX-2 specific inhibitors or NSAIDs, continued postoperatively with opioids used as rescue analgesics. Other recommendations are intra-operative ketamine and epidural analgesia using local anaesthetics with or without opioids. Although there is procedure-specific evidence in favour of intra-operative methadone, it is not recommended as it was compared with shorter-acting opioids and due to its limited safety profile. Furthermore, the methadone studies did not use non-opioid analgesics, which should be the primary analgesics to ultimately reduce overall opioid requirements, including methadone. Further qualitative randomised controlled trials are required to confirm the efficacy and safety of these recommended analgesics on postoperative pain relief.
Topics: Analgesia, Epidural; Analgesics, Opioid; Anesthetics, Local; Humans; Pain Management; Pain, Postoperative
PubMed: 34397527
DOI: 10.1097/EJA.0000000000001448 -
Anaesthesia Mar 2022Video-assisted thoracoscopic surgery has become increasingly popular due to faster recovery times and reduced postoperative pain compared with thoracotomy. However,...
Video-assisted thoracoscopic surgery has become increasingly popular due to faster recovery times and reduced postoperative pain compared with thoracotomy. However, analgesic regimens for video-assisted thoracoscopic surgery vary significantly. The goal of this systematic review was to evaluate the available literature and develop recommendations for optimal pain management after video-assisted thoracoscopic surgery. A systematic review was undertaken using procedure-specific postoperative pain management (PROSPECT) methodology. Randomised controlled trials published in the English language, between January 2010 and January 2021 assessing the effect of analgesic, anaesthetic or surgical interventions were identified. We retrieved 1070 studies of which 69 randomised controlled trials and two reviews met inclusion criteria. We recommend the administration of basic analgesia including paracetamol and non-steroidal anti-inflammatory drugs or cyclo-oxygenase-2-specific inhibitors pre-operatively or intra-operatively and continued postoperatively. Intra-operative intravenous dexmedetomidine infusion may be used, specifically when basic analgesia and regional analgesic techniques could not be given. In addition, a paravertebral block or erector spinae plane block is recommended as a first-choice option. A serratus anterior plane block could also be administered as a second-choice option. Opioids should be reserved as rescue analgesics in the postoperative period.
Topics: Analgesics; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Drug Therapy, Combination; Humans; Nerve Block; Pain Management; Pain, Postoperative; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Thoracic Surgery, Video-Assisted
PubMed: 34739134
DOI: 10.1111/anae.15609 -
Journal of Psychiatric Research Jun 2020We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of pharmacological interventions for the treatment and prevention of... (Meta-Analysis)
Meta-Analysis Review
We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of pharmacological interventions for the treatment and prevention of delirium. Electronic databases including PubMed, Google Scholar, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and MEDLINE were searched published up to February 22, 2019. A total of 108 randomized controlled trials (RCTs) investigating pharmacotherapy on delirium were included for analysis, and the strength of evidence (SoE) was evaluated for critical outcomes. In terms of treatment, quetiapine (low SoE), morphine (low SoE), and dexmedetomidine (moderate SoE) were effective in the intensive care unit (ICU) patients. In terms of prevention, dexmedetomidine (high SoE) and risperidone (high SoE) significantly reduced the incidence of delirium in ICU surgical patients, while ramelteon (high SoE) reduced the incidence of delirium in ICU medical patients. Despite the efficacy, dexmedetomidine and risperidone demonstrated higher drop-out rate (moderate to high SoE). Haloperidol and other antipsychotics, except for quetiapine and risperidone, showed no benefit. None of the agents showed benefit in non-ICU patients. In conclusion, dexmedetomidine may be a drug of choice for both treating and preventing delirium of the ICU and postsurgical patients. However, it may be less tolerable, and side-effects should be adequately managed. Current evidence does not support the routine use of antipsychotics. For medical patients, oral ramelteon might be useful for prevention.
Topics: Antipsychotic Agents; Delirium; Haloperidol; Humans; Network Meta-Analysis; Risperidone
PubMed: 32302794
DOI: 10.1016/j.jpsychires.2020.03.012 -
Intensive Care Medicine Sep 2021To compare the effects of prevention interventions on delirium occurrence in critically ill adults. (Meta-Analysis)
Meta-Analysis
PURPOSE
To compare the effects of prevention interventions on delirium occurrence in critically ill adults.
METHODS
MEDLINE, Embase, PsychINFO, CINAHL, Web of Science, Cochrane Library, Prospero, and WHO international clinical trial registry were searched from inception to April 8, 2021. Randomized controlled trials of pharmacological, sedation, non-pharmacological, and multi-component interventions enrolling adult critically ill patients were included. We performed conventional pairwise meta-analyses, NMA within Bayesian random effects modeling, and determined surface under the cumulative ranking curve values and mean rank. Reviewer pairs independently extracted data, assessed bias using Cochrane Risk of Bias tool and evidence certainty with GRADE. The primary outcome was delirium occurrence; secondary outcomes were durations of delirium and mechanical ventilation, length of stay, mortality, and adverse effects.
RESULTS
Eighty trials met eligibility criteria: 67.5% pharmacological, 31.3% non-pharmacological and 1.2% mixed pharmacological and non-pharmacological interventions. For delirium occurrence, 11 pharmacological interventions (38 trials, N = 11,993) connected to the evidence network. Compared to placebo, only dexmedetomidine (21/22 alpha agonist trials were dexmedetomidine) probably reduces delirium occurrence (odds ratio (OR) 0.43, 95% Credible Interval (CrI) 0.21-0.85; moderate certainty). Compared to benzodiazepines, dexmedetomidine (OR 0.21, 95% CrI 0.08-0.51; low certainty), sedation interruption (OR 0.21, 95% CrI 0.06-0.69; very low certainty), opioid plus benzodiazepine (OR 0.27, 95% CrI 0.10-0.76; very low certainty), and protocolized sedation (OR 0.27, 95% CrI 0.09-0.80; very low certainty) may reduce delirium occurrence but the evidence is very uncertain. Dexmedetomidine probably reduces ICU length of stay compared to placebo (Ratio of Means (RoM) 0.78, CrI 0.64-0.95; moderate certainty) and compared to antipsychotics (RoM 0.76, CrI 0.61-0.98; low certainty). Sedative interruption, protocolized sedation and opioids may reduce hospital length of stay compared to placebo, but the evidence is very uncertain. No intervention influenced mechanical ventilation duration, mortality, or arrhythmia. Single and multi-component non-pharmacological interventions did not connect to any evidence networks to allow for ranking and comparisons as planned; pairwise comparisons did not detect differences compared to standard care.
CONCLUSION
Compared to placebo and benzodiazepines, we found dexmedetomidine likely reduced the occurrence of delirium in critically ill adults. Compared to benzodiazepines, sedation-minimization strategies may also reduce delirium occurrence, but the evidence is uncertain.
Topics: Adult; Bayes Theorem; Critical Illness; Delirium; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 34379152
DOI: 10.1007/s00134-021-06490-3