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Anesthesiology Dec 2020Several models describing the pharmacokinetics of ketamine are published with differences in model structure and complexity. A systematic review of the literature was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several models describing the pharmacokinetics of ketamine are published with differences in model structure and complexity. A systematic review of the literature was performed, as well as a meta-analysis of pharmacokinetic data and construction of a pharmacokinetic model from raw data sets to qualitatively and quantitatively evaluate existing ketamine pharmacokinetic models and construct a general ketamine pharmacokinetic model.
METHODS
Extracted pharmacokinetic parameters from the literature (volume of distribution and clearance) were standardized to allow comparison among studies. A meta-analysis was performed on studies that performed a mixed-effect analysis to calculate weighted mean parameter values and a meta-regression analysis to determine the influence of covariates on parameter values. A pharmacokinetic population model derived from a subset of raw data sets was constructed and compared with the meta-analytical analysis.
RESULTS
The meta-analysis was performed on 18 studies (11 conducted in healthy adults, 3 in adult patients, and 5 in pediatric patients). Weighted mean volume of distribution was 252 l/70 kg (95% CI, 200 to 304 l/70 kg). Weighted mean clearance was 79 l/h (at 70 kg; 95% CI, 69 to 90 l/h at 70 kg). No effect of covariates was observed; simulations showed that models based on venous sampling showed substantially higher context-sensitive half-times than those based on arterial sampling. The pharmacokinetic model created from 14 raw data sets consisted of one central arterial compartment with two peripheral compartments linked to two venous delay compartments. Simulations showed that the output of the raw data pharmacokinetic analysis and the meta-analysis were comparable.
CONCLUSIONS
A meta-analytical analysis of ketamine pharmacokinetics was successfully completed despite large heterogeneity in study characteristics. Differences in output of the meta-analytical approach and a combined analysis of 14 raw data sets were small, indicative that the meta-analytical approach gives a clinically applicable approximation of ketamine population parameter estimates and may be used when no raw data sets are available.
Topics: Adult; Anesthetics, Dissociative; Child; Humans; Ketamine
PubMed: 32997732
DOI: 10.1097/ALN.0000000000003577 -
Anaesthesia Jul 2021Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti-emetics are available for clinical practice, there is... (Meta-Analysis)
Meta-Analysis
Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti-emetics are available for clinical practice, there is currently no comparative ranking of efficacy and safety of these drugs to inform clinical practice. We performed a systematic review with network meta-analyses to compare, and rank in terms of efficacy and safety, single anti-emetic drugs and their combinations, including 5-hydroxytryptamine , dopamine-2 and neurokinin-1 receptor antagonists; corticosteroids; antihistamines; and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anaesthesia. We systematically searched for placebo-controlled and head-to-head randomised controlled trials up to November 2017 (updated in April 2020). We assessed how trustworthy the evidence was using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence In Network Meta-Analysis (CINeMA) approaches for vomiting within 24 h postoperatively, serious adverse events, any adverse event and drug class-specific side-effects. We included 585 trials (97,516 participants, 83% women) testing 44 single drugs and 51 drug combinations. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 trials, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared with placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single neurokinin-1 receptor antagonists were as effective as other drug combinations. Out of the 10 effective single drugs, certainty of evidence was high for aprepitant, with risk ratio (95%CI) 0.26 (0.18-0.38); ramosetron, 0.44 (0.32-0.59); granisetron, 0.45 (0.38-0.54); dexamethasone, 0.51 (0.44-0.57); and ondansetron, 0.55 (0.51-0.60). It was moderate for fosaprepitant, 0.06 (0.02-0.21) and droperidol, 0.61 (0.54-0.69). Granisetron and amisulpride are likely to have little or no increase in any adverse event compared with placebo, while dimenhydrinate and scopolamine may increase the number of patients with any adverse event compared with placebo. So far, there is no convincing evidence that other single drugs effect the incidence of serious, or any, adverse events when compared with placebo. Among drug class specific side-effects, evidence for single drugs is mostly not convincing. There is convincing evidence regarding the prophylactic effect of at least seven single drugs for postoperative vomiting such that future studies investigating these drugs will probably not change the estimated beneficial effect. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.
Topics: Adult; Anesthesia, General; Antiemetics; Female; Humans; Male; Network Meta-Analysis; Postoperative Nausea and Vomiting; Treatment Outcome
PubMed: 33170514
DOI: 10.1111/anae.15295 -
British Journal of Anaesthesia Feb 2022The certainty that prehabilitation improves postoperative outcomes is not clear. The objective of this umbrella review (i.e. systematic review of systematic reviews) was...
BACKGROUND
The certainty that prehabilitation improves postoperative outcomes is not clear. The objective of this umbrella review (i.e. systematic review of systematic reviews) was to synthesise and evaluate evidence for prehabilitation in improving health, experience, or cost outcomes.
METHODS
We performed an umbrella review of prehabilitation systematic reviews. MEDLINE, Embase, Cochrane, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Joanna Briggs Institute's database, and Web of Science were searched (inception to October 20, 2020). We included all systematic reviews of elective, adult patients undergoing surgery and exposed to a prehabilitation intervention, where health, experience, or cost outcomes were reported. Evidence certainty was assessed using Grading of Recommendations Assessment, Development and Evaluation. Primary syntheses of any prehabilitation were stratified by surgery type.
RESULTS
From 1412 titles, 55 systematic reviews were included. For patients with cancer undergoing surgery who participate in any prehabilitation, moderate certainty evidence supports improvements in functional recovery. Low to very low certainty evidence supports reductions in complications (mixed, cardiovascular, and cancer surgery), non-home discharge (orthopaedic surgery), and length of stay (mixed, cardiovascular, and cancer surgery). There was low to very low certainty evidence that exercise prehabilitation reduces the risk of complications, non-home discharge, and length of stay. There was low to very low certainty evidence that nutritional prehabilitation reduces risk of complications, mortality, and length of stay.
CONCLUSIONS
Low certainty evidence suggests that prehabilitation may improve postoperative outcomes. Future low risk of bias, randomised trials, synthesised using recommended standards, are required to inform practice. Optimal patient selection, intervention design, and intervention duration must also be determined.
Topics: Adult; Elective Surgical Procedures; Humans; Length of Stay; Nutrition Therapy; Patient Selection; Postoperative Complications; Preoperative Exercise; Randomized Controlled Trials as Topic; Systematic Reviews as Topic
PubMed: 34922735
DOI: 10.1016/j.bja.2021.11.014 -
Critical Care (London, England) May 2020Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic...
Gastrointestinal dysfunction in the critically ill: a systematic scoping review and research agenda proposed by the Section of Metabolism, Endocrinology and Nutrition of the European Society of Intensive Care Medicine.
BACKGROUND
Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies.
METHODS
This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds.
RESULTS
Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness.
CONCLUSIONS
Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.
Topics: Critical Care; Critical Illness; Diagnostic Imaging; Europe; Gastrointestinal Diseases; Humans; Nutritional Status
PubMed: 32414423
DOI: 10.1186/s13054-020-02889-4 -
British Journal of Anaesthesia Jun 2022There are very few patient-centred global outcome measures of recovery in the days or weeks after surgery. This meta-analysis evaluated the psychometric properties and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are very few patient-centred global outcome measures of recovery in the days or weeks after surgery. This meta-analysis evaluated the psychometric properties and clinical acceptability of the 15-item quality of recovery (QoR-15) scale.
METHODS
We searched bibliographic databases for studies undertaking psychometric evaluation of the QoR-15 or using the QoR-15 as an outcome measure after surgery. Record screening, data extraction, and quality assessments were independently done by two researchers. Weighted averages estimating overall summary statistics across all the studies were calculated using random-effects meta-analysis. Pooled correlation coefficients were transformed using a Fisher z-transformation and then back-transformed to calculate pooled results. The four co-primary endpoints were validity, reliability, responsiveness, and clinical utility of the QoR-15 scale.
RESULTS
A total of 26 unique studies met the eligibility criteria, yielding up to 22 847 patients across 16 countries, in 15 languages. A further 172 studies in a further 18 countries and six languages used the QoR-15 as an outcome measure. The QoR-15 had excellent discriminant validity, with the mean difference in QoR-15 scores in patients with and without postoperative complications (9.6; 95% confidence interval [CI], 5.9-13.3; P<0.001), and good convergent validity (for a global visual analogue recovery scale, pooled r=0.63; 95% CI, 0.54-0.71). There was excellent reliability: internal consistency (pooled α=0.85; 95% CI, 0.83-0.87), split-half reliability=0.80 (95% CI, 0.75-0.84), and test-retest reliability=0.97 (95% CI, 0.95-0.98). There was also high responsiveness (pooled standardised response mean=0.87; 95% CI, 0.65-1.08), patient recruitment into evaluation studies (96%; 95% CI, 93-99), and excellent completion and return rates (91%; 95% CI, 84-96). The mean time to complete the QoR-15 was 2.7 (95% CI, 2.2-3.1) min.
CONCLUSIONS
The QoR-15 is a valid, reliable, and responsive patient-centred outcome metric in surgical patients. It is highly acceptable to both patients and clinicians.
REGISTRATION
Open Science Framework Identifier: DOI 10.17605/OSF.IO/78HTA.
Topics: Anesthesia Recovery Period; Humans; Outcome Assessment, Health Care; Psychometrics; Reproducibility of Results; Surveys and Questionnaires
PubMed: 35430086
DOI: 10.1016/j.bja.2022.03.009 -
Anaesthesia May 2022Neuraxial anaesthesia is widely utilised for elective caesarean section, but the prevalence of inadequate intra-operative anaesthesia is unclear. We aimed to determine... (Review)
Review
Neuraxial anaesthesia is widely utilised for elective caesarean section, but the prevalence of inadequate intra-operative anaesthesia is unclear. We aimed to determine the prevalence of inadequate neuraxial anaesthesia for elective caesarean section; prevalence of conversion from neuraxial anaesthesia to general anaesthesia following inadequate neuraxial anaesthesia; and the effect of mode of anaesthesia. We searched studies reporting inadequate neuraxial anaesthesia that used ≥ ED95 doses (effective dose in 95% of the population) of neuraxial local anaesthetic agents. Our primary outcome was the prevalence of inadequate neuraxial anaesthesia, defined as the need to convert to general anaesthesia; the need to repeat or abandon a planned primary neuraxial technique following incision; unplanned administration of intra-operative analgesia (excluding sedatives); or unplanned epidural drug supplementation. Fifty-four randomised controlled trials were included (3497 patients). The overall prevalence of requirement for supplemental analgesia or anaesthesia was 14.6% (95%CI 13.3-15.9%); 510 out of 3497 patients. The prevalence of general anaesthesia conversion was 2 out of 3497 patients (0.06% (95%CI 0.0-0.2%)). Spinal/combined spinal-epidural anaesthesia was associated with a lower overall prevalence of inadequate neuraxial anaesthesia than epidural anaesthesia (10.2% (95%CI 9.0-11.4%), 278 out of 2732 patients vs. 30.3% (95%CI 26.5-34.5%), 232 out of 765 patients). Further studies are needed to identify risk factors, optimise detection and management strategies and to determine long-term effects of inadequate neuraxial anaesthesia.
Topics: Anesthesia, Epidural; Anesthesia, General; Anesthesia, Obstetrical; Anesthesia, Spinal; Cesarean Section; Female; Humans; Pregnancy
PubMed: 35064923
DOI: 10.1111/anae.15657 -
Minerva Anestesiologica Dec 2022The aim of this systemic review and meta-analysis was to evaluate the efficacy and safety of remimazolam compared with propofol when used for procedural sedation and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The aim of this systemic review and meta-analysis was to evaluate the efficacy and safety of remimazolam compared with propofol when used for procedural sedation and general anesthesia.
EVIDENCE ACQUISITION
Data sources were PubMed, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicaTrials.gov, searched up to March 21, 2022. RCTs comparing remimazolam and propofol in patients undergoing procedural sedation or general anesthesia were searched. Pooled risk ratios (RRs) or standardized mean difference, 95% CIs, and P values were estimated for end points using the fixed- and random-effects statistical model. The trial sequential analysis was used for sensitivity analysis.
EVIDENCE SYNTHESIS
Ten studies with 1813 patients were included. Compared with propofol, remimazolam had lower success rate of sedation/general anesthesia (RR, 1.02; 95% CI: 1.01 to 1.03; P=0.004; N.=1402). However, remimazolam had lower incidence of hypoxia, hypotension, and injection pain than propofol. No difference in incidence of nausea and vomiting, time to awake and to discharge was found. Subgroup studies showed that remimazolam had lower success rate than propofol when used for procedural sedation, not general anesthesia. The trial sequential analysis adjusted confidence interval was 1.01 to 1.04 for success rate.
CONCLUSIONS
Remimazolam could be alternatively used in procedural sedation and general anesthesia. Additional research is needed to develop higher quality evidence on the use of remimazolam, especially in general anesthesia.
Topics: Humans; Anesthesia, General; Benzodiazepines; Hypnotics and Sedatives; Hypotension; Propofol
PubMed: 36326772
DOI: 10.23736/S0375-9393.22.16817-3 -
Critical Care (London, England) Sep 2023Cardiac surgery-associated acute kidney injury (CSA-AKI) is frequent. While two network meta-analyses assessed the impact of pharmacological interventions to prevent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiac surgery-associated acute kidney injury (CSA-AKI) is frequent. While two network meta-analyses assessed the impact of pharmacological interventions to prevent CSA-AKI, none focused on non-pharmacological interventions. We aim to assess the effectiveness of non-pharmacological interventions to reduce the incidence of CSA-AKI.
METHODS
We searched PubMed, Embase, Central and clinical trial registries from January 1, 2004 (first consensus definition of AKI) to July 1, 2023. Additionally, we conducted manual screening of abstracts of major anesthesia and intensive care conferences over the last 5 years and reference lists of relevant studies. We selected all randomized controlled trials (RCTs) assessing a non-pharmacological intervention to reduce the incidence of CSA-AKI, without language restriction. We excluded RCTs of heart transplantation or involving a pediatric population. The primary outcome variable was CSA-AKI. Two reviewers independently identified trials, extracted data and assessed risk of bias. Random-effects meta-analyses were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence.
RESULTS
We included 86 trials (25,855 patients) evaluating 10 non-pharmacological interventions to reduce the incidence of CSA-AKI. No intervention had high-quality evidence to reduce CSA-AKI. Two interventions were associated with a significant reduction in CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion (RR, 0.55 [95% CI 0.40-0.76], I = 0%; P = 0.44) and remote ischemic preconditioning (RR, 0.86 [0.78-0.95]; I = 23%; P = 0.07). Pulsatile flow during cardiopulmonary bypass was associated with a significant reduction in CSA-AKI incidence but with very low quality of evidence (RR = 0.69 [0.48; 0.99]; I = 53%; P < 0.01). We found high quality of evidence for lack of effect of restrictive transfusion strategy (RR, 1.02 [95% CI 0.92; 1.12; P = 0.67; I = 3%) and tight glycemic control (RR, 0.86 [95% CI 0.55; 1.35]; P = 0.25; I = 26%).
CONCLUSIONS
Two non-pharmacological interventions are likely to reduce CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion and remote ischemic preconditioning.
Topics: Child; Humans; Cardiac Surgical Procedures; Acute Kidney Injury; Anesthesia; Anesthesiology; Cardiopulmonary Bypass
PubMed: 37700297
DOI: 10.1186/s13054-023-04640-1 -
Journal of Clinical Anesthesia Nov 2021To review the effects of prone position and supine position on oxygenation parameters in patients with Coronavirus Disease 2019 (COVID-19). (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVE
To review the effects of prone position and supine position on oxygenation parameters in patients with Coronavirus Disease 2019 (COVID-19).
DESIGN
Systematic review and meta-analysis of non-randomized trials.
PATIENTS
Databases of EMBASE, MEDLINE and CENTRAL were systematically searched from its inception until March 2021.
INTERVENTIONS
COVID-19 patients being positioned in the prone position either whilst awake or mechanically ventilated.
MEASUREMENTS
Primary outcomes were oxygenation parameters (PaO₂/FiO₂ ratio, PaCO₂, SpO₂). Secondary outcomes included the rate of intubation and mortality rate.
RESULTS
Thirty-five studies (n = 1712 patients) were included in this review. In comparison to the supine group, prone position significantly improved the PaO₂/FiO₂ ratio (study = 13, patients = 1002, Mean difference, MD 52.15, 95% CI 37.08 to 67.22; p < 0.00001) and SpO₂ (study = 11, patients = 998, MD 4.17, 95% CI 2.53 to 5.81; p ≤0.00001). Patients received prone position were associated with lower incidence of mortality (study = 5, patients = 688, Odd ratio, OR 0.44, 95% CI 0.24 to 0.80; p = 0.007). No significant difference was noted in the incidence of intubation rate (study = 5, patients = 626, OR 1.20, 95% CI 0.77 to 1.86; p = 0.42) between the supine and prone groups.
CONCLUSION
Our meta-analysis demonstrated that prone position improved PaO₂/FiO₂ ratio with better SpO₂ than supine position in COVID-19 patients. Given the limited number of studies with small sample size and substantial heterogeneity of measured outcomes, further studies are warranted to standardize the regime of prone position to improve the certainty of evidence. PROSPERO Registration: CRD42021234050.
Topics: COVID-19; Humans; Prone Position; Respiration, Artificial; SARS-CoV-2; Supine Position
PubMed: 34182261
DOI: 10.1016/j.jclinane.2021.110406 -
Anaesthesia Oct 2019Rotator cuff repair can be associated with significant and difficult to treat postoperative pain. We aimed to evaluate the available literature and develop...
Rotator cuff repair can be associated with significant and difficult to treat postoperative pain. We aimed to evaluate the available literature and develop recommendations for optimal pain management after rotator cuff repair. A systematic review using procedure-specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials published in English from 1 January 2006 to 15 April 2019 assessing postoperative pain after rotator cuff repair using analgesic, anaesthetic or surgical interventions were identified from MEDLINE, Embase and Cochrane Databases. Out of 322 eligible studies identified, 59 randomised controlled trials and one systematic review met the inclusion criteria. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol, cyclo-oxygenase-2 inhibitors, intravenous dexamethasone, regional analgesia techniques including interscalene block or suprascapular nerve block (with or without axillary nerve block) and arthroscopic surgical technique. Limited evidence was found for pre-operative gabapentin, perineural adjuncts (opioids, glucocorticoids, or α-2-adrenoceptor agonists added to the local anaesthetic solution) or postoperative transcutaneous electrical nerve stimulation. Inconsistent evidence was found for subacromial/intra-articular injection, and for surgical technique-linked interventions, such as platelet-rich plasma. No evidence was found for stellate ganglion block, cervical epidural block, specific postoperative rehabilitation protocols or postoperative compressive cryotherapy. The analgesic regimen for rotator cuff repair should include an arthroscopic approach, paracetamol, non-steroidal anti-inflammatory drugs, dexamethasone and a regional analgesic technique (either interscalene block or suprascapular nerve block with or without axillary nerve block), with opioids as rescue analgesics. Further randomised controlled trials are required to confirm the influence of the recommended analgesic regimen on postoperative pain relief.
Topics: Guidelines as Topic; Humans; Orthopedic Procedures; Pain Management; Pain, Postoperative; Randomized Controlled Trials as Topic; Rotator Cuff
PubMed: 31392721
DOI: 10.1111/anae.14796