Glucagon-like peptide-1 receptor agonists: a narrative review of clinical pharmacology and implications for peri-operative practice.

BACKGROUND: Glucagon-like peptide-1 receptor agonists are used increasingly in the management of patients living with type 2 diabetes mellitus and obesity. In patients using glucagon-like peptide-1 receptor agonists, a key concern in the peri-operative period is the increased risk of pulmonary aspiration due to delayed gastric emptying. This review provides an overview of the pharmacodynamic and pharmacokinetic properties of glucagon-like peptide-1 receptor agonists and the risk of delayed gastric emptying and aspiration. METHODS: We conducted searches of MEDLINE and EMBASE databases of articles published before January 2024 using the keywords and medical subject headings: incretins; glucagon-like peptide-1; GLP-1; glucagon-like peptide-1 receptor agonists; GLP-1 RA; peri-operative period; perioperative; peri-operative; stomach emptying; gastric emptying; pulmonary aspiration; aspiration; food regurgitation; and regurgitation. The evidence was analysed, synthesised and reported narratively. RESULTS: A total of 1213 articles were located after duplicates were removed. Two authors screened the titles and abstracts to identify those studies which assessed specifically the risk of delayed gastric emptying and pulmonary aspiration or regurgitation in the peri-operative period. We searched manually the reference lists of relevant studies to identify any additional case reports. Ten studies were identified. Available evidence was limited to case reports, case series and observational work. CONCLUSIONS: There is insufficient evidence to put forward definitive guidance regarding the ideal cessation period for glucagon-like peptide-1 receptor agonists before elective surgery. Precautionary practice is required until more evidence becomes available. We suggest an individualised, evidence-based approach. In patients living with type 2 diabetes mellitus, there is concern that prolonged cessation before surgery will have a detrimental effect on peri-operative glycaemic control and discussion with an endocrinologist is advised. For patients taking glucagon-like peptide-1 receptor agonists for weight management, these drugs should be withheld for at least three half-lives before an elective surgical procedure.

Association between intraoperative oliguria and postoperative acute kidney injury in non-cardiac surgical patients: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the association between intraoperative oliguria and the risk of postoperative acute kidney injury (AKI) in patients undergoing non-cardiac surgery. METHODS: The MEDLINE and EMBASE databases were searched up to August 2022 for studies in adult patients undergoing non-cardiac surgery, where the association between intraoperative urine output and the risk of postoperative AKI was assessed. Both randomised and non-randomised studies were eligible for inclusion. Study selection and risk of bias assessment were independently performed by two investigators. The risk of bias was evaluated using the Newcastle-Ottawa scale. We performed meta-analysis of the reported multivariate adjusted odds ratios for the association between intraoperative oliguria (defined as urine output < 0.5 mL/kg/hr) and the risk of postoperative AKI using the inverse-variance method with random effects models. We conducted sensitivity analyses using varying definitions of oliguria as well as by pooling unadjusted odds ratios to establish the robustness of the primary meta-analysis. We also conducted subgroup analyses according to surgery type and definition of AKI to explore potential sources of clinical or methodological heterogeneity. RESULTS: Eleven studies (total 49,252 patients from 11 observational studies including a post hoc analysis of a randomised controlled trial) met the selection criteria. Seven of these studies contributed data from a total 17,148 patients to the primary meta-analysis. Intraoperative oliguria was associated with a significantly elevated risk of postoperative AKI (pooled adjusted odds ratio [OR] 1.74; 95% confidence interval [CI] 1.36-2.23, p < 0.0001, 8 studies). Sensitivity analyses supported the robustness of the primary meta-analysis. There was no evidence of any significant subgroup differences according to surgery type or definition of AKI. CONCLUSIONS: This study demonstrated a significant association between intraoperative oliguria and the risk of postoperative AKI, regardless of the definitions of oliguria or AKI used. Further prospective and multi-centre studies using standardised definitions of intraoperative oliguria are required to define the thresholds of oliguria and establish strategies to minimise the risk of AKI.

Continuous local anaesthetic wound infusion for postoperative pain after midline laparotomy for colorectal resection in adults.

BACKGROUND: Colorectal resection through a midline laparotomy is a commonly performed surgical procedure to treat various bowel conditions. The typical postoperative hospital stay after this operation is 6 to 10 days. The main factors hindering early recovery and discharge are thought to include postoperative pain and delayed return of bowel function.Continuous infusion of a local anaesthetic into tissues surrounding the surgical incision via a multi-lumen indwelling wound catheter placed by the surgeon prior to wound closure may reduce postoperative pain, opioid consumption, the time to return of bowel function, and the length of hospital stay. OBJECTIVES: To evaluate the efficacy and adverse events of continuous local anaesthetic wound infusion for postoperative pain after midline laparotomy for colorectal resection in adults. SEARCH METHODS: We searched the CENTRAL, MEDLINE and Embase databases to January 2019 to identify trials relevant to this review. We also searched reference lists of relevant trials and reviews for eligible trials. Additionally, we searched two clinical trials registers for ongoing trials. SELECTION CRITERIA: We considered randomised controlled trials (including non-standard designs) or quasi-randomised controlled trials comparing continuous wound infusion of a local anaesthetic versus a placebo or a sham after midline laparotomy for colorectal resection in adults. We did not compare continuous local anaesthetic wound infusion to other techniques, such as transverse abdominis plane block or thoracic epidural analgesia. We allowed non-randomised analgesic co-interventions carried out equally in the intervention and control groups. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials for inclusion and assessed their quality using the Cochrane 'Risk of bias' tool. We extracted data using standardised forms, including pain at rest and on movement (10-point scale), opioid consumption via a patient-controlled analgesia (PCA) system (mg morphine equivalent), postoperative opioid-related adverse events, the time to rescue analgesia, the time to first flatus and to first bowel movement, the time to ambulation, the length of hospital stay, serious postoperative adverse events, and patient satisfaction. We quantitatively synthesised the data by meta-analysis. We summarised and graded the certainty of the evidence for critical outcomes using the GRADEpro tool and created a 'Summary of findings' table. MAIN RESULTS: This review included six randomised controlled trials that enrolled a total of 564 adults undergoing elective midline laparotomy for colorectal resection comparing continuous wound infusion of a local anaesthetic to a normal saline placebo. Due to 23 post-randomisation exclusions, a total of 541 participants contributed data to the analysis of at least one outcome (local anaesthetic 268; control 273). Most participants were aged 55 to 65 years, with normal body mass index and low to moderate anaesthetic risk (American Society of Anesthesiologists class I-III). Random sequence generation, allocation concealment, and blinding were appropriately carried out in most trials. However, we had to downgrade the certainty of the evidence for most outcomes due to serious study limitations (risk of bias), inconsistency, indirectness, imprecision and reporting bias.Primary outcomesOn postoperative day 1, pain at rest (mean difference (MD) -0.59 (from 3.1), 95% confidence interval (CI) -1.12 to -0.07; 5 studies, 511 participants; high-certainty evidence), pain on movement (MD -1.1 (from 6.1), 95% CI -2.3 to -0.01; 3 studies, 407 participants; low-certainty evidence) and opioid consumption via PCA (MD -12 mg (from 41 mg), 95% CI -20 to -4; 6 studies, 528 participants; moderate-certainty evidence) were reduced in the local anaesthetic group compared to the control group.Secondary outcomesThere was a reduction in the time to first bowel movement (MD -0.67 from 4.4 days, 95% CI -1.17 to -0.17; 4 studies, 197 participants; moderate-certainty evidence) and the length of hospital stay (MD -1.2 from 7.4 days, 95% CI -2.0 to -0.3; 4 studies, 456 participants; high-certainty evidence) in the local anaesthetic group compared to the control group.There was no evidence of a difference in any serious postoperative adverse events until hospital discharge (RR 1.04, 95% CI 0.68 to 1.58; 6 studies, 541 participants; low-certainty evidence) between the two study groups. AUTHORS' CONCLUSIONS: After elective midline laparotomy for colorectal resection, continuous wound infusion of a local anaesthetic compared to a normal saline placebo reduces postoperative pain at rest and the length of hospital stay, on the basis of high-certainty evidence. This means we are very confident that the effect estimates for these outcomes lie close to the true effects. There is moderate-certainty evidence to indicate that the intervention probably reduces opioid consumption via PCA and the time to first bowel movement. This means we are moderately confident that effect estimates for these outcomes are likely to be close to the true effects, but there is a possibility that they are substantially different. The intervention may reduce postoperative pain on movement, however, this conclusion is based on low-certainty evidence. This means our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect. There is low-certainty evidence to indicate that the intervention may have little or no effect on the rates of any serious postoperative adverse events until hospital discharge. High-quality randomised controlled trials to evaluate the intervention with a focus on important clinical and patient-centred outcomes are needed.

The Impact of Residual Neuromuscular Blockade, Oversedation, and Hypothermia on Adverse Respiratory Events in a Postanesthetic Care Unit: A Prospective Study of Prevalence, Predictors, and Outcomes.

BACKGROUND: Residual neuromuscular blockade (RNMB) has been linked to adverse respiratory events (AREs) in the postanesthetic care unit (PACU). However, these events are often not attributed to RNMB by anesthesiologists because they may also be precipitated by other factors including obstructive sleep apnea, opioids, or hypnotic agents. Many anesthesiologists believe RNMB occurs infrequently and is rarely associated with adverse outcomes. This study evaluated the prevalence and predictors of RNMB and AREs. METHODS: This prospective cohort study included 599 adult patients undergoing general anesthesia who received neuromuscular blocking agents. Baseline demographic, surgical, and anesthetic variables were collected. RNMB was defined as a train-of-four ratio below 0.90 measured by electromyography on admission to the PACU. AREs were defined based on the modified Murphy's criteria. RESULTS: RNMB was present in 186 patients (31% [95% confidence interval (CI), 27%-35%]) on admission to the PACU. One or more AREs were experienced by 97 patients (16% [95% CI 13-19]). AREs were more frequent in patients with RNMB (21% vs 14%, P = .033). RNMB was significantly associated with age (adjusted relative risk [RR], 1.17 [95% CI, 1.06-1.29] per 10-year increase), type of operation (adjusted RR, 0.59 [95% CI, 0.34-0.99] for laparoscopic surgery compared with open abdominal surgery), and duration of operation (adjusted RR, 0.59 [95% CI, 0.39-0.86] for ≥90 minutes compared with <90 minutes). Using multivariate logistic regression, AREs were found to be independently associated with decreased level of consciousness (adjusted RR, 4.76 [95% CI, 1.49-6.76] for unrousable/unconscious compared with alert/awake) and lower core temperature (adjusted RR, 1.43 [95% CI, 1.04-1.92] per 1°C decrease). Although univariate analysis found a significant association between AREs and RNMB, the significance became borderline after adjusting for other covariates (adjusted RR, 1.46 [95% CI, 0.99-2.08]). CONCLUSIONS: The prevalence of RNMB in the PACU was >30%. Older age, open abdominal surgery, and duration of operation <90 minutes were associated with increased risk of RNMB in our patients. Our RR estimate for AREs was highest for depressed level of consciousness. When AREs occur in the PACU, potentially preventable causes including RNMB, hypothermia, and reduced level of consciousness should be readily identified and treated appropriately. Delaying extubation until the patient is awake and responsive may reduce AREs.

An ipsilateral comparison of acceleromyography and electromyography during recovery from nondepolarizing neuromuscular block under general anesthesia in humans.

BACKGROUND: Residual neuromuscular block is defined as a mechanomyography (MMG) or electromyography (EMG) train-of-four (TOF) ratio <0.90, and is common in patients receiving neuromuscular blocking drugs. Objective neuromuscular monitoring is the only reliable way to detect and exclude residual neuromuscular block. Acceleromyography (AMG) is commercially available and easy to use in the clinical setting. However, AMG is not interchangeable with MMG or EMG. Currently, it is unclear what value must be reached by AMG TOF ratio to reliably exclude residual neuromuscular block. METHODS: During spontaneous recovery from neuromuscular block, we monitored TOF ratio on the same arm using AMG at the adductor pollicis and EMG at the first dorsal interosseus. AMG and EMG TOF ratios were compared by the Bland-Altman analysis for repeated measurements. The precision of each device was assessed by the repeatability coefficient. A small repeatability coefficient indicates high precision of the device. The agreement between the devices was assessed by the bias and the 95% limits of agreement. Small bias and narrow limits of agreement indicate strong agreement. We defined clinically acceptable agreement between AMG and EMG as a bias <0.025 and limits of agreement within -0.050 to 0.050, provided that the control comparison between EMG and itself can fulfill these criteria. RESULTS: In 26 patients, 261 comparisons between AMG and EMG were made. The repeatability coefficient of AMG and EMG were 0.094 (95% confidence interval [CI], 0.088-0.100) and 0.051 (95% CI, 0.048-0.055), respectively. The bias between AMG and EMG TOF ratio was 0.176 (95% CI, 0.162-0.190), with limits of agreement -0.045 to 0.396 (95% CI, -0.067 to 0.419). CONCLUSIONS: AMG is less precise than EMG and overestimates EMG TOF ratio by at least 0.15. The lack of agreement cannot be attributed to instrumental imprecision or the baseline difference between successive measurements during spontaneous recovery of neuromuscular function. Residual neuromuscular block cannot be excluded on reaching an AMG TOF ratio of 1.00.