Analgesic Effects of Intraperitoneal Lidocaine in Adults Undergoing Surgery: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

OBJECTIVE: The administration of local anaesthesia in intraperitoneal space as part of the multi-modal analgesic regimen has shown to be effective in reducing postoperative pain. Recent studies demonstrated that intraperitoneal lidocaine may provide analgesic effects. Primary objective was to determine the impact of intraperitoneal lidocaine on postoperative pain scores at rest. DESIGN: We carried out a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were searched from their inception date until May 2023. Randomized clinical trials (RCT) comparing intraperitoneal lidocaine and placebo in adults undergoing surgery were included. RESULTS: Our systematic review included 24 RCTs (n = 1,824). The intraperitoneal lidocaine group was significantly associated with lower postoperative pain scores at rest (MD: -0.87, 95% CI: -1.04 to -0.69) and at movement (MD: -0.50, 95% Cl: -0.93 to -0.08) among adult patients after surgery. Its administration also significantly decreased morphine consumption (MD: -6.42 mg, 95% Cl: -11.56 to -1.27), lowered the incidence of needing analgesia (OR: 0.22, 95% Cl: 0.14 to 0.35). Intraperitoneal lidocaine statistically reduced time to resume regular diet (MD: 0.16 days; 95% Cl: -0.31 to -0.01), and lowered postoperative incidence of nausea and vomiting (OR: 0.54, 95% Cl: 0.39 to 0.75). CONCLUSIONS: In this review, our findings should be interpreted with caution. Future studies are warranted to determine the optimal dose of administering intraperitoneal lidocaine among adult patients undergoing surgery.

Paramedian versus midline approach of spinal anesthesia: a systematic review and meta-analysis with trial sequential analysis.

PURPOSE: Midline approach of spinal anesthesia has been widely used for patients undergoing surgical procedures. However, it might not be effective for obstetric patients and elderly with degenerative spine changes. Primary objective was to examine the success rate at the first attempt between the paramedian and midline spinal anesthesia in adults undergoing surgery. METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were searched from their starting date until February 2023. Randomized clinical trials (RCTs) comparing the paramedian versus midline approach of spinal anesthesia were included. The primary outcome was the success rate at the first attempt of spinal anesthesia. RESULTS: Our review included 36 RCTs (n = 5379). Compared to the midline approach, paramedian approach may increase success rate at the first attempt but the evidence is very uncertain (OR: 0.47, 95% CI 0.27-0.82, ρ = 0.007, level of evidence:very low). Our pooled data indicates that the paramedian approach likely reduced incidence of post-spinal headache (OR: 2.07, 95% CI 1.51-2.84, ρ < 0.00001, level of evidence:moderate). The evidence suggests that the paramedian approach may result in a reduction in the occurrence of paresthesia (OR: 1.61, 95% CI 1.06-2.45, ρ = 0.03, level of evidence:low). CONCLUSIONS: Our meta-analysis of 36 RCTs showed that paramedian approach may result in little to no difference in success rate at the first attempt owing to its very low level of evidence. However, given the low level of evidence and studies with small sample sizes, these findings need to be interpreted with caveat. CLINICAL TRIAL REGISTRATION NUMBER: CRD42023397781.

Bispectral Index (BIS) Monitoring and Postoperative Delirium in Elderly Patients Undergoing Surgery: A Systematic Review and Meta-Analysis With Trial Sequential Analysis.

OBJECTIVE: To examine the effect of bispectral index (BIS)-guided anesthesia on the incidence of postoperative delirium (POD) in elderly patients undergoing surgery. DESIGN: A systematic review, meta-analysis, and trial sequential analysis (TSA). SETTING: In the operating room, postoperative anesthesia care units (PACU), and ward. PARTICIPANTS: Elderly patients (>60 years old) undergoing surgery. INTERVENTIONS: The EMBASE, MEDLINE, and CENTRAL databases were searched systematically from their inception until December 2020 for randomized controlled trials comparing BIS and usual care or blinded BIS. MEASUREMENTS AND MAIN RESULTS: Ten trials (N = 3,891) were included for quantitative meta-analysis. In comparison to the control group, there was no significant difference in the incidence of POD in elderly patients randomized to BIS-guided anesthesia (odds ratio [OR] 0.71, 95% CI 0.47-1.08, I2 = 76%, p = 0.11, level of evidence = very low, TSA = inconclusive). The authors' review demonstrated that elderly patients with BIS-guided anesthesia were significantly associated with a lower incidence of postoperative cognitive dysfunction (POCD) (OR 0.64, 95% CI 0.46-0.88, p = 0.006), extubation time (mean difference [MD] -3.38 minutes, 95% CI -4.38 to -2.39, p < 0.00001), time to eye opening (MD -2.17 minutes, 95% CI -4.21 to -0.14, p = 0.04), and time to discharge from the PACU (MD -10.77 minutes, 95% CI -11.31 to - 10.23, p < 0.00001). CONCLUSION: The authors' meta-analysis demonstrated that BIS-guided anesthesia was not associated with a reduced incidence of POD, but it was associated with a reduced incidence of POCD and improved recovery parameters.

Prophylactic Topical Tranexamic Acid Versus Placebo in Surgical Patients: A Systematic Review and Meta-analysis∗.

OBJECTIVES: Perioperative bleeding remains a major concern to all clinicians caring for perioperative patients. Due to the theoretical risk of thromboembolic events associated with tranexamic acid (TXA) when administered intravenously, topical route of TXA has been extensively studied, but its safety and efficacy profile remain unclear in the literature. The primary aim of this review was to assess the effect of topical TXA on incidence of blood transfusion and mortality in adults undergoing surgery. DATA SOURCES: EMBASE, MEDLINE, CENTRAL, and ISI Web of Science were systematically searched from their inception until May 31, 2019. REVIEW METHODS: Parallel-arm randomized controlled trials were included. RESULTS: Seventy-one trials (7539 participants: orthopedics 5450 vs nonorthopedics 1909) were included for quantitative meta-analysis. In comparison to placebo, topical TXA significantly reduced intraoperative blood loss [mean difference (MD) -36.83 mL, 95% confidence interval (CI) -54.77 to -18.88, P < 0.001], total blood loss (MD -319.55 mL, 95% CI -387.42 to -251.69, P < 0.001), and incidence of blood transfusion [odds ratio (OR) 0.30, 95% CI 0.26-0.34, P < 0.001]. Patients who received topical TXA were associated with a shorter length of hospital stay (MD -0.28 days, 95% CI -0.47 to -0.08, P = 0.006). No adverse events associated with the use of topical TXA were observed, namely mortality (OR 0.78, 95% CI 0.45-1.36, P = 0.39), pulmonary embolism (OR 0.73, 95% CI 0.27-1.93, P = 0.52), deep vein thrombosis (OR 1.07, 95% CI 0.65-1.77, P = 0.79), myocardial infarction (OR 0.79, 95% CI 0.21-2.99, P = 0.73), and stroke (OR 0.85, 95% CI 0.28-2.57, P = 0.77). Of all included studies, the risk of bias assessment was "low" for 20 studies, "unclear" for 26 studies and "high" for 25 studies. CONCLUSIONS: In the meta-analysis of 71 trials (7539 patients), topical TXA reduced the incidence of blood transfusion without any notable adverse events associated with TXA in adults undergoing surgery. PROSPERO: CRD 42018111762.

The effect of ketamine on emergence agitation in children: A systematic review and meta-analysis.

BACKGROUND: Ketamine is believed to reduce the incidence of emergence agitation in children undergoing surgery or procedure. However, recent randomized controlled trials reported conflicting findings. AIMS: To investigate the effect of ketamine on emergence agitation in children. METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were systematically searched from their start date until February 2019. Randomized controlled trials comparing intravenous ketamine and placebo in children were sought. The primary outcome was the incidence of emergence agitation. Secondary outcomes included postoperative pain score, duration of discharge time, and the adverse effects associated with the use of ketamine, namely postoperative nausea and vomiting, desaturation, and laryngospasm. RESULTS: Thirteen studies (1125 patients) were included in the quantitative meta-analysis. The incidence of emergence agitation was 14.7% in the ketamine group and 33.3% in the placebo group. Children receiving ketamine had a lower incidence of emergence agitation, with an odds ratio being 0.23 (95% confidence interval: 0.11 to 0.46), certainty of evidence: low. In comparison with the placebo, ketamine group achieved a lower postoperative pain score (odds ratio: -2.42, 95% confidence interval: -4.23 to -0.62, certainty of evidence: very low) and lower pediatric anesthesia emergence delirium scale at 5 minutes after operation (odds ratio: -3.99, 95% confidence interval: -5.03 to -2.95; certainty of evidence: moderate). However, no evidence was observed in terms of incidence of postoperative nausea and vomiting, desaturation, and laryngospasm. CONCLUSION: In this meta-analysis of 13 randomized controlled trials, high degree of heterogeneity and low certainty of evidence limit the recommendations of ketamine for the prevention of emergence agitation in children undergoing surgery or imaging procedures. However, the use of ketamine is well-tolerated without any notable adverse effects across all the included trials. PROSPERO REGISTRATION: CRD42019131865.

The effect of nalbuphine on prevention of emergence delirium in children: a systematic review with meta-analysis.

BACKGROUND: Emergence delirium remains a major postoperative concern for children undergoing surgery. Nalbuphine is a synthetic mixed agonist-antagonist opioid, which is believed to reduce the incidence of emergence delirium in children. The primary objective was to examine the effect of nalbuphine on emergence delirium in children undergoing surgery. METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were searched from their starting dates until April 2023. Randomized Clinical Trials (RCT) and observational studies comparing nalbuphine and control in children undergoing surgery were included. RESULTS: Eight studies (n = 1,466 patients) were eligible for inclusion of data analysis. Compared to the control, our pooled data showed that the nalbuphine group was associated with lower incidence of emergence delirium (RR = 0.38, 95% CI [0.30, 0.47], p < 0.001) and reduced postoperative pain scores (MD = -0.98, 95% CI [-1.92, -0.04], p = 0.04). CONCLUSIONS: This review showed the administration of nalbuphine is associated with significant decrease in the incidence of emergence delirium and postoperative pain scores among children undergoing surgery. However, due to limited sample size, high degree of heterogeneity and low level of evidence, future adequately powered trials are warranted to explore the efficacy of nalbuphine on emergence delirium among the pediatric population.

Effects of perioperative dexmedetomidine on delayed graft function following renal transplant: a systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects, has been suggested in recent studies to possess renoprotective properties. Dexmedetomidine may reduce the incidence of delayed graft function and contribute to effective pain control post-renal transplantation. The primary objective of this systematic review was to assess whether dexmedetomidine decreases the occurrence of delayed graft function in renal transplant patients. METHODS: Databases including MEDLINE, EMBASE, and CENTRAL were comprehensively searched from their inception until March 2023. The inclusion criteria covered all Randomized Clinical Trials (RCTs) and observational studies comparing dexmedetomidine to control in adult patients undergoing renal transplant surgery. Exclusions comprised case series and case reports. RESULTS: Ten RCTs involving a total of 1358 patients met the eligibility criteria for data synthesis. Compared to the control group, the dexmedetomidine group demonstrated a significantly lower incidence of delayed graft function (OR = 0.71, 95% CI 0.52-0.97, p = 0.03, GRADE: Very low, I2 = 0%). Dexmedetomidine also significantly prolonged time to initiation of rescue analgesia (MD = 6.73, 95% CI 2.32-11.14, p = 0.003, GRADE: Very low, I2 = 93%) and reduced overall morphine consumption after renal transplant (MD = -5.43, 95% CI -7.95 to -2.91, p < 0.0001, GRADE: Very low, I2 = 0%). The dexmedetomidine group exhibited a significant decrease in heart rate (MD = -8.15, 95% CI -11.45 to -4.86, p < 0.00001, GRADE: Very low, I2 = 84%) and mean arterial pressure compared to the control group (MD = -6.66, 95% CI -11.27 to -2.04, p = 0.005, GRADE: Very low, I2 = 87%). CONCLUSIONS: This meta-analysis suggests that dexmedetomidine may potentially reduce the incidence of delayed graft function and offers a superior analgesia profile as compared to control in adults undergoing renal transplants. However, the high degree of heterogeneity and inadequate sample size underscore the need for future adequately powered trials to confirm these findings.

Prone ventilation in intubated COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: The efficacy and safety profiles of prone ventilation among intubated Coronavirus Disease 2019 (COVID-19) patients remain unclear. The primary objective was to examine the effect of prone ventilation on the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) in intubated COVID-19 patients. METHODS: Databases of MEDLINE, EMBASE and CENTRAL were systematically searched from inception until March 2021. Case reports and case series were excluded. RESULTS: Eleven studies (n = 606 patients) were eligible. Prone ventilation significantly improved PaO2/FiO2 ratio (studies: 8, n = 579, mean difference 46.75, 95% CI 33.35‒60.15, p < 0.00001; evidence: very low) and peripheral oxygen saturation (SpO2) (studies: 3, n = 432, mean difference 1.67, 95% CI 1.08‒2.26, p < 0.00001; evidence: ow), but not the arterial partial pressure of carbon dioxide (PaCO2) (studies: 5, n = 396, mean difference 2.45, 95% CI 2.39‒7.30, p = 0.32; evidence: very low), mortality rate (studies: 1, n = 215, Odds Ratio 0.66, 95% CI 0.32‒1.33, p = 0.24; evidence: very low), or number of patients discharged alive (studies: 1, n = 43, Odds Ratio 1.49, 95% CI 0.72‒3.08, p = 0.28; evidence: very low). CONCLUSION: Prone ventilation improved PaO2/FiO2 ratio and SpO2 in intubated COVID-19 patients. Given the substantial heterogeneity and low level of evidence, more randomized- controlled trials are warranted to improve the certainty of evidence, and to examine the adverse events of prone ventilation.

Effect of prone versus supine position in COVID-19 patients: A systematic review and 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.

The effect of melatonin on delirium in hospitalised patients: A systematic review and meta-analyses with trial sequential analysis.

OBJECTIVES: Melatonin is an endogenous hormone, which regulates circadian rhythms and promotes sleep. In recent years, several randomised controlled trials examining the prophylactic use of melatonin to prevent delirium were published with conflicting findings. The primary aim of this review was to determine the effect of melatonin on the incidence of delirium in hospitalised patients. DATA SOURCES: MEDLINE, EMBASE and CENTRAL were systematically searched from their inception until December 2018. REVIEW METHODS: All randomised clinical trials were included. RESULTS: Sixteen trials (1634 patients) were included in this meta-analysis. Incidence of delirium was not significantly lower in patients who received melatonin, with an odd ratio, OR (95%Cl) of 0.55 (0.24-1.26); ρ = 0.16, certainty of evidence = low, trial sequential analysis = inconclusive. However, patients who randomised to melatonin had a significantly shorter length of stay in intensive care units, with a mean difference, MD (95%CI) of -1.84 days (-2.46, -1.21); ρ < 0.001. No differences were demonstrated in the need for physical restraints (OR 95%Cl 0.65; 0.31-1.37; ρ = 0.26) and the requirement of sedative agents (OR 95%Cl 0.86; 0.48-1.55; ρ = 0.62). CONCLUSIONS: In summary, the results of this meta-analysis of sixteen trials neither support nor oppose the use of melatonin in the prevention of delirium of hospitalised patients. We identified high heterogeneity across all the included trials and low certainty of evidence with potential type II error. Future multi-centre, adequately powered randomised controlled trials are warranted to provide more certainty on the use of melatonin for the prevention of delirium. PROSPERO: CRD42019123546.

Acute Kidney Injury Associated with Cardiac Surgery: a Comprehensive Literature Review.

OBJECTIVE: To comprehensively understand cardiac surgeryassociated acute kidney injury (CSA-AKI) and methods of prevention of such complication in cardiac surgery patients. METHODS: A comprehensive literature search was performed using the electronic database to identify articles describing acute kidney injury (AKI) in patients that undergone cardiac surgery. There was neither time limit nor language limit on the search. The results were narratively summarized. RESULTS: All the relevant articles have been extracted; results have been summarized in each related section. CSA-AKI is a serious postoperative complication and it can contribute to a significant increase in perioperative morbidity and mortality rates. Optimization of factors that can reduce CSA-AKI, therefore, contributes to a better postoperative outcome. CONCLUSION: Several factors can significantly increase the rate of AKI; identification and minimization of such factors can lead to lower rates of CSA-AKI and lower perioperative morbidity and mortality rates.

Association of obstructive sleep apnea and postoperative cardiac complications: A systematic review and meta-analysis with trial sequential analysis.

OBJECTIVES: The repetitive hypoxic and hypercapnia events of obstructive sleep apnea (OSA) are believed to adversely affect cardiopulmonary function, which make them vulnerable to a higher incidence of postoperative complications. The primary aim of this systematic review and meta-analysis was to examine the association of OSA and the composite endpoints of postoperative cardiac or cerebrovascular complications in adult undergoing non-cardiac surgery. DATA SOURCES: MEDLINE, EMBASE and CENTRAL were systematically searched from its inception until May 2019. REVIEW METHODS: All observational studies were included. RESULTS: Twenty-two studies (n = 3,033,814; 184,968 OSA vs 2,848,846 non-OSA) were included for quantitative meta-analysis. In non-cardiac surgery, OSA was significantly associated with a higher incidence of the composite endpoints of postoperative cardiac or cerebrovascular complications (odd ratio: 1.44, 95%CI: 1.17 to 1.78, ρ = 0.007, trial sequential analysis = conclusive; certainty of evidence = very low). In comparison to non-OSA, OSA patients were reported to have nearly 2.5-fold risk of developing pulmonary complications (odd ratio: 2.52, 95%CI: 1.92 to 3.31, ρ < 0.001, certainty of evidence = very low), postoperative delirium (odd ratio: 2.45, 95%CI: 1.50 to 4.01, ρ < 0.001, certainty of evidence = low) and acute kidney injury (odd ratio: 2.41, 95%CI: 1.93 to 3.02, ρ < 0.001, certainty of evidence = very low). CONCLUSIONS: This meta-analysis of 22 comparative studies demonstrated that OSA is a potential risk factor to postoperative adverse complications in adults undergoing non-cardiac surgery. However, the conclusions need to be interpreted with caution due to the nature of included observational studies with significant heterogeneity and low quality of evidence. PROSPERO: CRD42019136564.

Prone ventilation in intubated COVID-19 patients: a systematic review and meta-analysis

Abstract Background The efficacy and safety profiles of prone ventilation among intubated Coronavirus Disease 2019 (COVID-19) patients remain unclear. The primary objective was to examine the effect of prone ventilation on the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) in intubated COVID-19 patients. Methods Databases of MEDLINE, EMBASE and CENTRAL were systematically searched from inception until March 2021. Case reports and case series were excluded. Results Eleven studies (n = 606 patients) were eligible. Prone ventilation significantly improved PaO2/FiO2 ratio (studies: 8, n = 579, mean difference 46.75, 95% CI 33.35‒60.15, p < 0.00001; evidence: very low) and peripheral oxygen saturation (SpO2) (studies: 3, n = 432, mean difference 1.67, 95% CI 1.08‒2.26, p < 0.00001; evidence: ow), but not the arterial partial pressure of carbon dioxide (PaCO2) (studies: 5, n = 396, mean difference 2.45, 95% CI 2.39‒7.30, p= 0.32; evidence: very low), mortality rate (studies: 1, n = 215, Odds Ratio 0.66, 95% CI 0.32‒1.33, p= 0.24; evidence: very low), or number of patients discharged alive (studies: 1, n = 43, Odds Ratio 1.49, 95% CI 0.72‒3.08, p= 0.28; evidence: very low). Conclusion Prone ventilation improved PaO2/FiO2 ratio and SpO2 in intubated COVID-19 patients. Given the substantial heterogeneity and low level of evidence, more randomized- controlled trials are warranted to improve the certainty of evidence, and to examine the adverse events of prone ventilation.

Acute kidney injury associated with cardiac surgery: a comprehensive literature review

Abstract Objective: To comprehensively understand cardiac surgeryassociated acute kidney injury (CSA-AKI) and methods of prevention of such complication in cardiac surgery patients. Methods: A comprehensive literature search was performed using the electronic database to identify articles describing acute kidney injury (AKI) in patients that undergone cardiac surgery. There was neither time limit nor language limit on the search. The results were narratively summarized. Results: All the relevant articles have been extracted; results have been summarized in each related section. CSA-AKI is a serious postoperative complication and it can contribute to a significant increase in perioperative morbidity and mortality rates. Optimization of factors that can reduce CSA-AKI, therefore, contributes to a better postoperative outcome. Conclusion: Several factors can significantly increase the rate of AKI; identification and minimization of such factors can lead to lower rates of CSA-AKI and lower perioperative morbidity and mortality rates.