N-acetylcysteine use among patients undergoing cardiac surgery: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Cardiac surgeries are complex procedures aiming to re-establish coronary flow and correct valvular defects. Oxidative stress, caused by inflammation and ischemia-reperfusion injury, is associated with these procedures, increasing the risk of adverse outcomes. N-acetylcysteine (NAC) acts as an antioxidant by replenishing the glutathione stores, and emerging evidence suggests that NAC may reduce the risk of adverse perioperative outcomes. We conducted a systematic review and meta-analysis to investigate the addition of NAC to a standard of care among adult patients undergoing cardiac surgery. METHODS: We searched four databases (PubMed, EMBASE, CENTRAL, LILACS) from inception to October 2018 and the grey literaure for randomized controlled trials (RCTs) investigating the effect of NAC on pre-defined outcomes including mortality, acute renal insufficiency (ARI), acute cardiac insufficiency (ACI), hospital length of stay (HLoS), intensive care unit length of stay (ICULoS), arrhythmia and acute myocardial infarction (AMI). Reviewers independently screened potentially eligible articles, extracted data and assessed the risk of bias among eligible articles. We used the GRADE approach to rate the overall certainty of evidence for each outcome. RESULTS: Twenty-nine RCTs including 2,486 participants proved eligible. Low to moderate certainty evidence demonstrated that the addition of NAC resulted in a non-statistically significant reduction in mortality (Risk Ratio (RR) 0.71; 95% Confidence Interval (CI) 0.40 to 1.25), ARI (RR 0.92; 95% CI 0.79 to 1.09), ACI (RR 0.77; 95% CI 0.44 to 1.38), HLoS (Mean Difference (MD) 0.21; 95% CI -0.64 to 0.23), ICULoS (MD -0.04; 95% CI -0.29 to 0.20), arrhythmia (RR 0.79; 95% CI 0.52 to 1.20), and AMI (RR 0.84; 95% CI 0.48 to 1.48). LIMITATIONS: Among eligible trials, we observed heterogeneity in the population and interventions including patients with and without kidney dysfunction and interventions that differed in route of administration, dosage, and duration of treatment. This observed heterogeneity was not explained by our subgroup analyses. CONCLUSIONS: The addition of NAC during cardiac surgery did not result in a statistically significant reduction in clinical outcomes. A large randomized placebo-controlled multi-centre trial is needed to determine whether NAC reduces mortality. REGISTRATION: PROSPERO CRD42018091191.

Commonly-used versus less commonly-used methods in the loss of resistance technique for identification of the epidural space: A systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: To summarize the efficacy of less-commonly used modern methods (e.g. epidrum, lidocaine, acoustic device, Macintosh balloon) compared to more commonly-used methods (i.e. air, saline, both) in the loss of resistance technique for identification of the epidural space. DESIGN: A systematic review. SETTING: A hospital-affiliated university. MEASUREMENTS: The following databases were searched: PubMed, CENTRAL, EMBASE, and LILACS. We used the GRADE approach to rate overall certainty of the evidence. RESULTS: Eight randomized trials including 1583 participants proved eligible. Results suggested a statistically significantly reduction in inability to locate the epidural space (RR 0.29, 95% CI 0.11, 0.77; P=0.01; I2=60%, risk difference (RD) 104/1000, moderate quality evidence), accidental intravascular catheter placement and accidental subarachnoid catheter placement (RR 0.35, 95% CI 0.21, 0.59; P<0.0001; I2=0%, risk difference (RD) 108/1000, moderate quality evidence), and unblocked segments (RR 0.37, 95% CI 0.18, 0.77; P=0.008; I2=0%, risk difference (RD) 56/1000, moderate quality evidence) with the use of epidrum, lidocaine, acoustic device, or modified Macintosh epidural balloon methods in comparison to air. Compared to saline, lidocaine presented higher rates of reduction in the inability to locate the epidural space (RR 0.31, 95% CI 0.12, 0.82; P=0.02; I2=not applicable). CONCLUSIONS: Moderate-quality evidence shows that less commonly-used modern methods such as epidrum, lidocaine and acoustic devices, are more efficacious compared to more commonly-used methods (i.e. air, saline, both) in terms of the loss of resistance technique for identification of the epidural space. These findings should be explored further in the context of the clinical practice among anaesthesiologists.