Perioperative intravenous S-ketamine for acute postoperative pain in adults: A systematic review and meta-analysis

Study objectiveTo evaluate the effectiveness and safety of S-ketamine for pain relief and analgesic consumption in surgical patients.DesignSystematic review and meta-analysis of randomized controlled trials (RCTs).SettingPerioperative setting.PatientsA total of 905 adult patients undergoing surgery using general anesthesia: 504 patients in the S-ketamine group and 401 patients in the placebo group.InterventionIntravenous S-ketamine as an adjuvant to general anesthesia compared with placebo.MeasurementsThe primary outcomes were resting and movement pain scores (VAS/NRS 0–10) and morphine consumption within 4, 12, 24 and 48 h after surgery. The secondary outcomes included postoperative complications such as nausea, vomiting, and psychotomimetic adverse events. We used the guidelines of the Recommendation Assessment, Development, and Evaluation (GRADE) system to evaluate the level of certainty for the main results.Main resultsA total of 12 studies were included. The types of surgery included abdominal surgery, thoracotomy, gynecologic surgery, arthroscopic anterior cruciate ligament repair, cardiac surgery, laparoscopic cholecystectomy, lumbar spinal fusion surgery, radical prostatectomy, and hemorrhoidectomy. There were significant improvements in resting pain scores at 4, 12 and 24 h with S-ketamine versus placebo [4 h: standardized mean difference (SMD) -1.11; 95% confidence interval (CI): −1.53, −0.68, p < 0.00001; GRADE = moderate; 12 h: SMD −0.88; 95%CI: −1.42, −0.34, p = 0.001; GRADE = moderate; 24 h: SMD -0.39; 95%CI: −0.73, −0.06, p = 0.02; GRADE = moderate]. The incidence of pain scores at 48 h showed no statistical difference between the two groups (SMD -0.27; 95%CI: −1.12, 0.58, p = 0.53, GRADE = moderate). The movement pain scores were not significantly different between the two groups at each time point (4 h: SMD −0.34; 95%CI: −0.73, 0.05, p = 0.09, GRADE = moderate; 12 h: SMD −0.42; 95%CI: −1.46, 0.63, p = 0.44, GRADE = low; 24 h: SMD −0.58; 95%CI: −1.25, 0.09, p = 0.09, GRADE = moderate; 48 h: SMD −0.49; 95%CI: −1.11, 0.14, p = 0.13, GRADE = low). At 4 and 12 h after surgery, the consumption of morphine was significantly reduced in the S-ketamine group (4 h: SMD −0.98; 95%CI: −1.37, −0.06, p < 0.00001, GRADE = moderate; 12 h: SMD −1.36; 95%CI: −2.26, −0.46, p = 0.003, GRADE = low). There were no significant differences in morphine use at 24 and 48 h between the two groups (24 h: SMD −0.70; 95%CI: −1.42, 0.02, p = 0.06, GRADE = low; 48 h: SMD −0.79; 95%CI: −2.26, 1.03, p = 0.39, GRADE = low). The risk for nausea [relative risk (RR) = 1.04; 95%CI: 0.83, 1.30, p = 0.73], vomiting (RR = 1.07; 95%CI: 0.84, 1.38, p = 0.57), and psychotomimetic adverse events (RR = 1.57; 95%CI: 0.82, 2.99, p = 0.17) showed no significant increase in the S-ketamine group.ConclusionsIntravenous S-ketamine as an adjunct to general anesthesia is effective for assisting analgesia and decreases the intensity of pain and opioid requirements in a short period of time after surgery, but it may increase the psychotomimetic adverse event rate. Overall, the level of certainty is moderate to low.     

Depression as a predictor of postoperative delirium after cardiac surgery: a systematic review and meta-analysis

OBJECTIVESDepression is common in patients with cardiac disease. The importance of preoperative depression for development of postoperative delirium (POD) following cardiac surgery is not well known. The aim is to provide a summary estimate of depression as a predictor of POD following cardiac surgery.Open in a separate windowMETHODSSystematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science Core Collection and Psycinfo (Ovid) was performed from inception to October 2019, including cohort studies reporting odds ratios (ORs) and 95% confidence intervals (CIs) for POD following cardiac surgery in patients with preoperative depression compared to patients without depression. ORs and 95% CIs for POD were calculated using random-effects meta-analyses. Subgroup and sensitivity analyses were performed.RESULTSSeven studies were included with a combined study population of 2066 patients. The pooled prevalence of POD in the combined study population was 26% and preoperative depression was present in ∼9% of the total study population. All studies showed a positive association between preoperative depression and POD; and in 5 studies, the association was statistically significant. Patients with depression had a pooled OR of 2.31 (95% CI 1.37–3.90) for POD.CONCLUSIONSThis systematic review and meta-analysis confirm the findings that the previous association between preoperative depression and increased risk for developing POD reported for other patient groups is found also in cardiac surgery. Depression screening prior to cardiac surgery may be effective in identifying patients at higher risk for POD.     

Atrial fibrillation after cardiac surgery: A systematic review and meta-analysis

ObjectiveNew-onset postoperative atrial fibrillation (POAF) after cardiac surgery is common, with rates up to 60%. POAF has been associated with early and late stroke, but its association with other cardiovascular outcomes is less known. The objective was to perform a meta-analysis of the studies reporting the association of POAF with perioperative and long-term outcomes in patients with cardiac surgery.MethodsWe performed a systematic review and a meta-analysis of studies that presented outcomes for cardiac surgery on the basis of the presence or absence of POAF. MEDLINE, EMBASE, and the Cochrane Library were assessed; 57 studies (246,340 patients) were selected. Perioperative mortality was the primary outcome. Inverse variance method and random model were performed. Leave-one-out analysis, subgroup analyses, and metaregression were conducted.ResultsPOAF was associated with perioperative mortality (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.58-2.33), perioperative stroke (OR, 2.17; 95% CI, 1.90-2.49), perioperative myocardial infarction (OR, 1.28; 95% CI, 1.06-1.54), perioperative acute renal failure (OR, 2.74; 95% CI, 2.42-3.11), hospital (standardized mean difference, 0.80; 95% CI, 0.53-1.07) and intensive care unit stay (standardized mean difference, 0.55; 95% CI, 0.24-0.86), long-term mortality (incidence rate ratio [IRR], 1.54; 95% CI, 1.40-1.69), long-term stroke (IRR, 1.33; 95% CI, 1.21-1.46), and longstanding persistent atrial fibrillation (IRR, 4.73; 95% CI, 3.36-6.66).ConclusionsThe results suggest that POAF after cardiac surgery is associated with an increased occurrence of most short- and long-term cardiovascular adverse events. However, the causality of this association remains to be established.     

Intraoperative ketamine administration to prevent delirium or postoperative cognitive dysfunction: A systematic review and meta‐analysis

Background

Postoperative cognitive complications are associated with substantial morbidity and mortality. Ketamine has been suggested to have neuroprotective effects in various settings. This systematic review evaluates the effects of intraoperative ketamine administration on postoperative delirium and postoperative cognitive dysfunction (POCD).

Methods

Medline, Embase and Central were searched to 4 March 2018 without date or language restrictions. We considered randomised controlled trials (RCTs) comparing intraoperative ketamine administration versus no intervention in adults undergoing surgery under general anaesthesia. Primary outcomes were postoperative delirium and POCD. Non‐cognitive adverse events, mortality and length of stay were considered as secondary outcomes. Data were independently extracted. The quality of the evidence (GRADE approach) was assessed following recommendations from the Cochrane collaboration. Risk ratios were calculated for binary outcomes, mean differences for continuous outcomes. We planned to explore the effects of age, specific anaesthesia regimen, depth of anaesthesia and intraoperative haemodynamic events through subgroup analyses.

Results

Six RCTs were included. The incidence of postoperative delirium did not differ between groups (4 trials, 557 patients, RR 0.83, 95% CI [0.25, 2.80]), but patients receiving ketamine seemed at lower risk of POCD (3 trials, 163 patients, RR 0.34, 95% CI [0.15, 0.73]). However, both analyses presented limitations. Therefore, the quality of the evidence (GRADE) was deemed low (postoperative delirium) and very low (POCD).

Conclusion

The effect of ketamine on postoperative delirium remains unclear but its administration may offer some protection towards POCD. Large, well‐designed randomised trials are urgently needed to further clarify the efficacy of ketamine on neurocognitive outcomes.

     

Perioperative goal-directed hemodynamic therapy in noncardiac surgery: a systematic review and meta-analysis

Study objectiveGoal-directed fluid therapy (GDHT) has been proposed as a method to reduce complications and mortality.DesignMeta-analysis of the effects of perioperative GDHT in adult noncardiac surgery on mortality and postoperative complications was performed using the PRISMA methodology. A systematic search was performed in MEDLINE, PubMed, EMBASE, and the Cochrane Library (last update, October 2014). Inclusion criteria were as follows: randomized clinical trials (RCTs) in which perioperative GDHT was compared with conventional fluid management in noncardiac surgery. Exclusion criteria were as follows: trauma and pediatric surgery studies. End points were mortality and number of patients with complications.SettingDistrict general hospital.PatientsThirty-nine RCTs were initially identified, with 8 fulfilling the inclusion criteria. Two RCTs were added by manual search, resulting in 10 RCTs in the final analysis, including 1527 patients.MeasurementsThose studies that fulfilled the entry criteria were examined in full and subjected to quantifiable analysis, predefined subgroup analysis (stratified by supraphysiological or physiological hemodynamic goal and by time the intervention was carried out, perioperative or postoperative), and predefined sensitivity analysis.Main ResultsA significant reduction was observed in mortality associated with GDHT compared with conventional fluid therapy (risk ratio, 0.63; 95% confidence interval, 0.42-0.94; P = .02). However, no differences were found in the number of patients with complications (risk ratio, 0.75; 95% confidence interval, 0.50-1.17; P = .21), and the sensitivity analysis did not confirm the results.ConclusionsThis meta-analysis, with its limitations, shows that the use of perioperative GDHT may reduce postoperative mortality, but it is unable to show a reduction in the number of patients with complications.     

Pharmacological management to prevent ileus in major abdominal surgery: a systematic review and meta-analysis

Background

Prolonged ileus is a common complication following gastrointestinal surgery, with an incidence of up to 40 %. Investigations examining pharmacological treatment of ileus have proved largely disappointing; however, recently, several compounds have been shown to have benefited when used as prophylaxis to prevent ileus.

Objective

This review aimed to evaluate the safety and efficacy of compounds which have been recently developed or repurposed to reduce bowel recovery time, thereby preventing ileus.

Data sources

Data were taken from a systematic review of the MEDLINE, EMBASE and Cochrane Library Databases, in addition to manual searching of reference lists up to April 2015. No limits were applied.

Study selection

Only randomized trials were eligible for inclusion.

Interventions

Opioid receptor antagonists, ghrelin receptor agonists and serotonin receptor agonists used for the prevention of postoperative ileus in gastrointestinal surgery.

Main outcome measures

Outcomes of time to first defecation, first flatus and composite bowel recovery endpoints (GI2 and GI3) were used to determine efficacy. Pooled treatment effects were presented as the standard mean difference or as hazard ratios alongside the corresponding 95 % confidence intervals. Risk of bias was assessed using the Cochrane risk of bias framework.

Results

A total of 17 studies were included in the final analysis. The μ-opioid receptor antagonist alvimopan and serotonin receptor agonists appeared to significantly shorten the duration of ileus. The use of Ghrelin receptor agonists did not appear to have any effect in five trials. No publication bias was detected.

Limitations

Most of the trials were poorly reported and of mixed quality. Future studies must focus on the development of a set of core outcomes.

Conclusions

There is evidence to make a strong recommendation for the use of alvimopan in major gastrointestinal surgery to reduce postoperative ileus. Further randomized trials are required to establish whether serotonin receptor agonists are of use. Identifying a low-cost compound to promote bowel recovery following surgery could reduce complications and shorten duration of hospital admissions.

     

Effect of dexmedetomidine on delirium during sedation in adult patients in intensive care units: A systematic review and meta-analysis

Study objectiveTo compare the effect of sedation protocols with and without dexmedetomidine on delirium risk and duration in adult patients in intensive care units (ICUs).DesignA meta-analysis of randomized controlled trials.Review methodsWe searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and ISI Web of Science from inception to September 3, 2020. We included studies comparing the effect of dexmedetomidine-based sedation on delirium risk with non-dexmedetomidine-based sedation in adult patients in ICUs. We pooled the data using a random-effects model using Review Manager 5.2, and assessed publication bias using Stata 11.0. The quality of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation system.Main resultsWe included 36 studies involving 9623 participants. The use of dexmedetomidine was associated with reduced risk of delirium (risk ratio [RR], 0.63; 95% confidence interval [CI], 0.54–0.75; very low-quality evidence), but higher incidences of hypotension and bradycardia during hospital stay. Dexmedetomidine was also associated with shorter durations of ICU stay, hospital stay and mechanical ventilation. Dexmedetomidine did not affect ICU mortality (RR, 1.01; 95% CI, 0.89–1.14; low-quality evidence), hospital mortality (RR, 1.01; 95% CI, 0.91–1.12; very low-quality evidence), or 30-day mortality (RR, 0.77; 95% CI, 0.58–1.01; moderate-quality evidence), or duration of delirium (mean difference, −0.74 days; 95% CI, −1.83 to 0.36 days; very low-quality evidence). We identified publication bias for risk and duration of delirium, length of ICU stay, and hospital stay.ConclusionsLow- or very low-quality evidence suggests that dexmedetomidine was associated with a clinically-small reduction of delirium risk, ICU/hospital stay and mechanical ventilation duration, but were not associated with improved mortality or shorter delirium duration in ICU patients. These findings were inconclusive because of publication bias, heterogeneity, and limited sample size. Significant adverse effects of dexmedetomidine include hypotension and bradycardia.PROSPERO registration number: CRD42018095358.     

Perioperative strategies to reduce risk of myocardial injury after non-cardiac surgery (MINS): A narrative review

Myocardial injury is a frequent complication of surgical patients after having non-cardiac surgery that is strongly associated with perioperative mortality. While intraoperative anesthesia-related deaths are exceedingly rare, about 1% of patients undergoing non-cardiac surgery die within the first 30 postoperative days. Given the number of surgeries performed annually, death following surgery is the second leading cause of death in the United States. Myocardial injury after non-cardiac surgery (MINS) is defined as an elevation in troponin concentrations within 30 days postoperatively. Although typically asymptomatic, patients with MINS suffer myocardial damage and have a 10% risk of death within 30 days after surgery and excess risks of mortality that persist during the first postoperative year. Many factors for the development of MINS are non-modifiable, such as preexistent coronary artery disease. Preventive measures, systematic approaches to surveillance and treatment standards are still lacking, however many factors are modifiable and should be considered in clinical practice: the importance of hemodynamic control, adequate oxygen supply, metabolic homeostasis, the use of perioperative medications such as statins, anti-thrombotic agents, beta-blockers, or anti-inflammatory agents, as well as some evidence regarding the choice of sedative and analgesic for anesthesia are discussed. Also, as age and complexity in comorbidities of the surgical patient population increase, there is an urgent need to identify patients at risk for MINS and develop prevention and treatment strategies. In this review, we provide an overview of current screening standards and promising preventive options in the perioperative setting and address knowledge gaps requiring further investigation.     

Effect of dexmedetomidine for prevention of acute kidney injury after cardiac surgery: an updated systematic review and meta-analysis

BackgroundAcute kidney injury (AKI) is a serious complication related to cardiac surgery. Several studies have been conducted to investigate the effect of dexmedetomidine administration on AKI prevention.ObjectiveTo assess if dexmedetomidine is associated with a protective effect of renal function after cardiac surgery. And the aim of conducting this meta-analysis is to summarize the literature and determine the clinical utility of dexmedetomidine administration in patients undergoing cardiac surgery.MethodsPubMed, Cochrane Library, and EMBASE databases were comprehensively searched for all randomized controlled trials (RCTs) published before 1 December, 2021 that investigated the effect of dexmedetomidine on AKI prevention.ResultsOur analysis included 16 studies involving 2148 patients. Compared with the control group, dexmedetomidine administration significantly reduced AKI incidence (OR, 0.47; 95% CI, 0.36–0.61; p <  0.00001; I² = 26%) and the length of stay in the intensive care unit (ICU) but did not alter mortality rate, length of stay in the hospital, and mechanical ventilation time. Furthermore, the incidence of delirium among patients treated with dexmedetomidine was significantly decreased.ConclusionDexmedetomidine administration has a positive effect on preventing AKI and postoperative delirium after cardiac surgery and significantly reduces the length of stay in the ICU.     

Multi-disciplinary and pharmacological interventions to reduce post-operative delirium in elderly patients: A systematic review and meta-analysis

Study objectiveAn estimated 80% of older people undergoing surgery develop postoperative delirium (POD) making them a high-risk group. Research in this area is growing fast but there is no established consensus on strategies for POD prevention or management. A systematic review and meta-analysis were conducted to synthesise data on clinical interventions used to reduce POD among older people undergoing elective and emergency surgery.MethodsA range of database searches generated 336 papers. A total of 25 studies met the inclusion criteria and were assessed using the Joanna Briggs Institute Critical Appraisal Checklist. The studies were undertaken across the world.ResultsThis review identified a range of intervention approaches: comparisons between anaesthetic and sedatives agents, medication-specific interventions and multidisciplinary models of care. Results found more consistencies across multidisciplinary interventions than the pharmacological interventions. In pooled analyses, haloperidol (OR 0.74; 95% CI (confidence interval) 0.44, 1.26) was not statistically significantly associated with reduced POD incidence any more than a placebo.ConclusionThere is a need to implement multidisciplinary interventions, as well as collaboration between clinicians on pre- and postoperative care practices regarding pharmacological interventions to more effectively reduce and manage POD in older people.     

Prophylactic intravenous tranexamic acid and thromboembolism in non-cardiac surgery: a systematic review,meta-analysis and trial sequential analysis

Tranexamic acid is an antifibrinolytic drug that is widely used during surgery, but there are concerns about its thromboembolic effects. We aimed to investigate the effect of prophylactic intravenous tranexamic acid on thromboembolic outcomes in patients undergoing non-cardiac surgery. The MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched. Randomised controlled trials comparing intravenous tranexamic acid with placebo or no treatment in patients undergoing non-cardiac surgery were included. The primary outcome was a composite of peri-operative cardiovascular thromboembolic events, defined as any deep vein thrombosis, pulmonary embolism, myocardial ischaemia/infarction or cerebral ischaemia/infarction. A total of 191 randomised controlled trials (40,621 patients) were included in the review. The primary outcome occurred in 4.5% of patients receiving intravenous tranexamic acid compared with 4.9% of patients in the control group. Our analysis showed that there was no difference between groups for composite cardiovascular thromboembolic events (risk ratio 1.02, 95%CI 0.94–1.11, p = 0.65, I² 0%, n = 37,512). This finding remained robust when sensitivity analysis was performed with continuity correction and in studies with a low risk of bias. However, in trial sequential analysis, our meta-analysis only achieved 64.6% of the required information size. There was no association between intravenous tranexamic acid and seizure rate or mortality rate within 30 days. Intravenous tranexamic acid was associated with a reduced blood transfusion rate compared with control (9.9% vs. 19.4%, risk ratio 0.46, 95%CI 0.41–0.51, p < 0.0001). It was encouraging to see the evidence that the administration of intravenous tranexamic in patients undergoing non-cardiac surgery was not associated with an increased risk of thromboembolic outcomes. However, our trial sequential analysis demonstrated that currently available evidence is not yet sufficient to reach a firm conclusion.     

N-acetylcysteine to reduce renal failure after cardiac surgery: a systematic review and meta-analysis

Purpose: To assess the effect of N-acetylcysteine (NAC) on acute renal failure and important clinical outcomes after cardiac surgery. Methods: Two reviewers performed literature searches, using EMBASE and PubMed, of randomized controlled trials investigating the renoprotective effect of N-acetylcysteine in cardiac surgery. Treatment effects were calculated as relative risks (RR) with 95% confidence intervals (CI). Heterogeneity and publication bias were assessed using the I² test and funnel plots, respectively. Meta regression was performed to assess the effect of baseline renal function and the use of aprotinin on renal function. Results: Seven randomized controlled trials (RCTs) (n=1000) were identified. No study could demonstrate, either independently or meta-analytically, an improvement in the postoperative increase in creatinine, mortality (RR 0.93, 95% CI 0.4 to 2.07), renal failure requiring renal replacement therapy (RR 1.01, 95% CI 0.49 to 2.12), myocardial infarction (RR 0.88, 95% CI 0.36 to 1.88), atrial fibrillation (RR 0.88, 95% CI 0.70 to 1. 10), or stroke (RR 0.69, 95% CI 0.27 to 1.69). There was a small, though significant increase in postoperative blood loss among patients treated with NAC (weighted mean difference I 19 mL 95% CI 51, 187). After meta regression neither increase in postoperative creatinine (r²=0.33) nor renal replacement therapy (r²=0.04) was associated with the baseline creatinine or with NAC dose (r²=0.04). Conclusion: This analysis did not find that treatment with NAC was associated with clinical renal protection during cardiac surgery, or improvement in other clinical outcomes.     

Tranexamic acid in burn surgery: A systematic review and meta-analysis

Burn injury causes a coagulopathy that is poorly understood. After severe burns, significant fluid losses are managed by aggressive resuscitation that can lead to hemodilution. These injuries are managed by early excision and grafting, which can cause significant bleeding and further decrease blood cell concentration. Tranexamic acid (TXA) is an anti-fibrinolytic that has been shown to reduce surgical blood losses; however, its use in burn surgery is not well established. We performed a systematic review and meta-analysis to investigate the influence TXA may have on burn surgery outcomes. Eight papers were included, with outcomes considered in a random-effects model meta-analysis. Overall, when compared to the control group, TXA significantly reduced total volume blood loss (mean difference (MD) = −192.44; 95% confidence interval (CI) = −297.73 to − 87.14; P = 0.0003), the ratio of blood loss to burn injury total body surface area (TBSA) (MD = −7.31; 95% CI = −10.77 to −3.84; P 0.0001), blood loss per unit area treated (MD = −0.59; 95% CI = −0.97 to −0.20; P = 0.003), and the number of patients receiving a transfusion intraoperatively (risk difference (RD) = −0.16; 95% CI = −0.32 to − 0.01; P = 0.04). Additionally, there were no noticeable differences in venous thromboembolism (VTE) events (RD = 0.00; 95% CI = −0.03 to 0.03; P = 0.98) and mortality (RD = 0.00; 95% CI = −0.03 to 0.04; P = 0.86). In conclusion, TXA can potentially be a pharmacologic intervention that reduces blood losses and transfusions in burn surgery without increasing the risk of VTE events or mortality.