A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults.

BACKGROUND: Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available. METHODS: We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome. RESULTS: Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001). CONCLUSIONS: Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial. (Funded by the Australian National Health and Medical Research Council and others; PROSPERO number CRD42021278869.).

Quantifying the Impact of Alternative Definitions of Sepsis-Associated Acute Kidney Injury on its Incidence and Outcomes: A Systematic Review and Meta-Analysis.

OBJECTIVES: To derive a pooled estimate of the incidence and outcomes of sepsis-associated acute kidney injury (SA-AKI) in ICU patients and to explore the impact of differing definitions of SA-AKI on these estimates. DATA SOURCES: Medline, Medline Epub, EMBASE, and Cochrane CENTRAL between 1990 and 2023. STUDY SELECTION: Randomized clinical trials and prospective cohort studies of adults admitted to the ICU with either sepsis and/or SA-AKI. DATA EXTRACTION: Data were extracted in duplicate. Risk of bias was assessed using adapted standard tools. Data were pooled using a random-effects model. Heterogeneity was assessed by using a single covariate logistic regression model. The primary outcome was the proportion of participants in ICU with sepsis who developed AKI. DATA SYNTHESIS: A total of 189 studies met inclusion criteria. One hundred fifty-four reported an incidence of SA-AKI, including 150,978 participants. The pooled proportion of patients who developed SA-AKI across all definitions was 0.40 (95% CI, 0.37-0.42) and 0.52 (95% CI, 0.48-0.56) when only the Risk Injury Failure Loss End-Stage, Acute Kidney Injury Network, and Improving Global Outcomes definitions were used to define SA-AKI. There was significant variation in the incidence of SA-AKI depending on the definition of AKI used and whether AKI defined by urine output criteria was included; the incidence was lowest when receipt of renal replacement therapy was used to define AKI (0.26; 95% CI, 0.24-0.28), and highest when the Acute Kidney Injury Network score was used (0.57; 95% CI, 0.45-0.69; p < 0.01). Sixty-seven studies including 29,455 participants reported at least one SA-AKI outcome. At final follow-up, the proportion of patients with SA-AKI who had died was 0.48 (95% CI, 0.43-0.53), and the proportion of surviving patients who remained on dialysis was 0.10 (95% CI, 0.04-0.17). CONCLUSIONS: SA-AKI is common in ICU patients with sepsis and carries a high risk of death and persisting kidney impairment. The incidence and outcomes of SA-AKI vary significantly depending on the definition of AKI used.

Oxygenation during the apnoeic phase preceding intubation in adults in prehospital, emergency department, intensive care and operating theatre environments.

BACKGROUND: Apnoeic oxygenation is the delivery of oxygen during the apnoeic phase preceding intubation. It is used to prevent respiratory complications of endotracheal intubation that have the potential to lead to significant adverse events including dysrhythmia, haemodynamic decompensation, hypoxic brain injury and death. Oxygen delivered by nasal cannulae during the apnoeic phase of intubation (apnoeic oxygenation) may serve as a non-invasive adjunct to endotracheal intubation to decrease the incidence of hypoxaemia, morbidity and mortality. OBJECTIVES: To evaluate the benefits and harms of apnoeic oxygenation before intubation in adults in the prehospital, emergency department, intensive care unit and operating theatre environments compared to no apnoeic oxygenation during intubation. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 4 November 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs that compared the use of any form of apnoeic oxygenation including high flow and low flow nasal cannulae versus no apnoeic oxygenation during intubation. We defined quasi-randomization as participant allocation to each arm by means that were not truly random, such as alternation, case record number or date of birth. We excluded comparative prospective cohort and comparative retrospective cohort studies, physiological modelling studies and case reports. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. hospital stay and 2. incidence of severe hypoxaemia. Our secondary outcomes were 3. incidence of hypoxaemia, 4. lowest recorded saturation of pulse oximetry (SpO2), 5. intensive care unit (ICU) stay, 6. first pass success rate, 7. adverse events and 8. MORTALITY: We used GRADE to assess certainty of evidence. MAIN RESULTS: We included 23 RCTs (2264 participants) in our analyses. Eight studies (729 participants) investigated the use of low-flow (15 L/minute or less), and 15 studies (1535 participants) investigated the use of high-flow (greater than 15 L/minute) oxygen. Settings were varied and included the emergency department (2 studies, 327 participants), ICU (7 studies, 913 participants) and operating theatre (14 studies, 1024 participants). We considered two studies to be at low risk of bias across all domains. None of the studies reported on hospital length of stay. In predominately critically ill people, there may be little to no difference in the incidence of severe hypoxaemia (SpO2 less than 80%) when using apnoeic oxygenation at any flow rate from the start of apnoea until successful intubation (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.66 to 1.11; P = 0.25, I² = 0%; 15 studies, 1802 participants; low-certainty evidence). There was insufficient evidence of any effect on the incidence of hypoxaemia (SpO2 less than 93%) (RR 0.58, 95% CI 0.23 to 1.46; P = 0.25, I² = 36%; 3 studies, 489 participants; low-certainty evidence). There may be an improvement in the lowest recorded oxygen saturation, with a mean increase of 1.9% (95% CI 0.75% to 3.05%; P < 0.001, I² = 86%; 15 studies, 1525 participants; low-certainty evidence). There may be a reduction in the duration of ICU stay with the use of apnoeic oxygenation during intubation (mean difference (MD) ‒1.13 days, 95% CI ‒1.51 to ‒0.74; P < 0.0001, I² = 46%; 5 studies, 815 participants; low-certainty evidence). There may be little to no difference in first pass success rate (RR 1.00, 95% CI 0.93 to 1.08; P = 0.79, I² = 0%; 8 studies, 826 participants; moderate-certainty evidence). There may be little to no difference in incidence of adverse events including oral trauma, arrhythmia, aspiration, hypotension, pneumonia and cardiac arrest when apnoeic oxygenation is used. There was insufficient evidence about any effect on mortality (RR 0.84, 95% CI 0.70 to 1.00; P = 0.06, I² = 0%; 6 studies, 1015 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There was some evidence that oxygenation during the apnoeic phase of intubation may improve the lowest recorded oxygen saturation. However, the differences in oxygen saturation were unlikely to be clinically significant. This did not translate into any measurable effect on the incidence of hypoxaemia or severe hypoxaemia in a group of predominately critically ill people. We were unable to assess the influence on hospital length of stay; however, there was a reduction in ICU stay in the apnoeic oxygenation group. The mechanism for this is unclear as there was little to no difference in first pass success or adverse event rates.

Association Between Selective Decontamination of the Digestive Tract and In-Hospital Mortality in Intensive Care Unit Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis.

Importance: The effectiveness of selective decontamination of the digestive tract (SDD) in critically ill adults receiving mechanical ventilation is uncertain. Objective: To determine whether SDD is associated with reduced risk of death in adults receiving mechanical ventilation in intensive care units (ICUs) compared with standard care. Data Sources: The primary search was conducted using MEDLINE, EMBASE, and CENTRAL databases until September 2022. Study Selection: Randomized clinical trials including adults receiving mechanical ventilation in the ICU comparing SDD vs standard care or placebo. Data Extraction and Synthesis: Data extraction and risk of bias assessments were performed in duplicate. The primary analysis was conducted using a bayesian framework. Main Outcomes and Measures: The primary outcome was hospital mortality. Subgroups included SDD with an intravenous agent compared with SDD without an intravenous agent. There were 8 secondary outcomes including the incidence of ventilator-associated pneumonia, ICU-acquired bacteremia, and the incidence of positive cultures of antimicrobial-resistant organisms. Results: There were 32 randomized clinical trials including 24 389 participants in the analysis. The median age of participants in the included studies was 54 years (IQR, 44-60), and the median proportion of female trial participants was 33% (IQR, 25%-38%). Data from 30 trials including 24 034 participants contributed to the primary outcome. The pooled estimated risk ratio (RR) for mortality for SDD compared with standard care was 0.91 (95% credible interval [CrI], 0.82-0.99; I2 = 33.9%; moderate certainty) with a 99.3% posterior probability that SDD reduced hospital mortality. The beneficial association of SDD was evident in trials with an intravenous agent (RR, 0.84 [95% CrI, 0.74-0.94]), but not in trials without an intravenous agent (RR, 1.01 [95% CrI, 0.91-1.11]) (P value for the interaction between subgroups = .02). SDD was associated with reduced risk of ventilator-associated pneumonia (RR, 0.44 [95% CrI, 0.36-0.54]) and ICU-acquired bacteremia (RR, 0.68 [95% CrI, 0.57-0.81]). Available data regarding the incidence of positive cultures of antimicrobial-resistant organisms were not amenable to pooling and were of very low certainty. Conclusions and Relevance: Among adults in the ICU treated with mechanical ventilation, the use of SDD compared with standard care or placebo was associated with lower hospital mortality. Evidence regarding the effect of SDD on antimicrobial resistance was of very low certainty.

The incidence of cerebral arterial vasospasm following aneurysmal subarachnoid haemorrhage: a systematic review and meta-analysis.

PURPOSE: To describe a pooled estimated incidence of cerebral arterial vasospasm (aVSP) following aneurysmal subarachnoid haemorrhage (aSAH) and to describe sources of variation in the reported incidence. METHODS: We performed a systematic review and meta-analysis of randomised clinical trials (RCTs) and cohort studies. The primary outcome was the proportion of study participants diagnosed with aVSP. We assessed for heterogeneity based on mode of imaging, indication for imaging, study design and clinical characteristics at a study level. RESULTS: We identified 120 studies, including 19,171 participants. More than 40 different criteria were used to diagnose aVSP. The pooled estimate of the proportion of patients diagnosed with aVSP was 0.42 (95% CI 0.39 to 0.46, I2 = 96.5%). There was no evidence that the incidence aVSP was different, nor that heterogeneity was reduced, when the estimate was assessed by study type, imaging modalities, the proportion of participants with high grade CT scores or poor grade clinical scores. The pooled estimate of the proportion of study participants diagnosed with aVSP was higher in studies with routine imaging (0.47, 95% CI 0.43 to 0.52, I2 = 96.5%) compared to those when imaging was performed when indicated (0.30, 95% CI 0.25 to 0.36, I2 = 94.0%, p for between-group difference < 0.0005). CONCLUSION: The incidence of cerebral arterial vasospasm following aSAH varies widely from 9 to 93% of study participants. Heterogeneity in the reported incidence may be due to variation in the criteria used to diagnose aVSP. A standard set of diagnostic criteria is necessary to resolve the role that aVSP plays in delayed neurological deterioration following aSAH. PROSPERO REGISTRATION: CRD42020191895.

Comparison of Supraglottic Airway Devices With Endotracheal Intubation in Low-Risk Patients for Cesarean Delivery: Systematic Review and Meta-analysis.

BACKGROUND: The safety and adverse event rate of supraglottic airway (SGA) devices for cesarean delivery (CD) is poorly characterized. The primary aims of this review were to determine whether the first-pass success was higher and time to insertion for SGA was faster than endotracheal intubation for elective CD. The secondary aim was to determine the airway-related adverse event rate associated with SGA use compared to endotracheal intubation in elective CD under general anesthesia (GA). METHODS: Six databases were systematically searched until September 2019. Included studies reported on the use of SGA in comparison to endotracheal tube intubation. A comparative meta-analysis between SGA and endotracheal intubation was performed using RevMan 5.3 software. Dichotomous outcomes were reported using an odds ratio (OR) with 95% confidence interval (CI). The results for continuous outcomes were reported using a weighted mean difference (WMD) with 95% CI. RESULTS: Fourteen studies with 2236 patients compared SGA and endotracheal intubation. Overall, there was no statistically significant difference in first-attempt success rate (OR = 1.92; 95% CI, 0.85-4.32; I = 0%; P = .44). There was no clinically significant difference in time to insertion (WMD = -15.80 seconds; 95% CI, -25.30 to -6.31 seconds; I= 100%; P = .001). Similarly, there was no difference in any adverse event rate except sore throat which was reduced with the use of an SGA (OR = 0.16; 95% CI, 0.08-0.32; I= 53%; P < .001). CONCLUSIONS: Despite the reasonable insertion success rate and safety profile of SGAs demonstrated in this meta-analysis, the analysis remains underpowered and therefore inconclusive. At present, further studies are required before the use of an SGA as the first-line airway for an elective CD can be recommended.

Cricoid pressure during intubation: A systematic review and meta-analysis of randomised controlled trials.

PURPOSE: This systematic review and meta-analysis aimed to determine whether cricoid pressure protects against aspiration and whether this technique adversely affects intubating conditions in adult patients. METHODS: A systematic review of five databases was performed for randomised controlled trials comparing cricoid pressure to no cricoid or sham cricoid during intubation. The primary outcome was incidence of aspiration and the secondary outcomes included first attempt intubation success, time to intubation, Cormack and Lehane Grade 3 or 4 and difficult intubation. RESULTS: The search identified twelve high quality RCTs with 4,862 patients for inclusion. Among four studies reporting the primary outcome, there was no difference (RR=1.18; 95%CI=0.71 to 1.96; I2=0%; p=0.51). Only 3 studies were in patients at high risk of aspiration. There was significantly worse first attempt success (RR= 0.94; 95%CI= 0.89 to 0.99; I2=66%; p=0.02), time to intubation (WMD= 6.77seconds; 95%CI=4.40 to 9.14seconds; I2=97%) and laryngoscopy views (RR=1.69; 95%CI=1.41 to 2.02;I2=1%; p<0.00001) with cricoid pressure. CONCLUSIONS: Cricoid pressure failed to show any increase in protection from aspiration and may increase difficulty of intubation. Further studies in high-risk patients, such as intensive care patients, are required.

Apneic Oxygenation for Pediatric Endotracheal Intubation: A Narrative Review.

Apneic oxygenation (ApOx) has shown to be effective in adult populations in a variety of settings, including prehospital, emergency departments, intensive care units, and elective surgery. This review aims to assess the available literature for ApOx in the pediatric population to determine its effects on hypoxemia, safe apnea times, and flow rates employed safely.

Tramadol as an adjunct to intra-articular local anaesthetic infiltration in knee arthroscopy: a systematic review and meta-analysis.

BACKGROUND: Arthroscopic knee surgery is a common technique used in Australia. Post-operative pain is common and can lead to delayed discharge and impair early mobilization. Use of local anaesthesia can reduce pain while avoiding systemic side effects. This systematic review and meta-analysis aimed to establish the use of tramadol as an adjunct to intra-articular local anaesthetic infiltration in knee arthroscopy in the current literature. METHODS: Two independent reviewers performed a systematic search of four databases, where 24 articles were identified with six studies (four high-quality and two low-quality randomized controlled trials), with a total of 334 patients were included for analysis. RevMan 5.3 software (The Nordic Cochrane Centre, Copenhagen, Denmark) was used to perform the data analysis. The studies included focused on outcomes such as pain scores, breakthrough analgesia, total analgesia, time to discharge and adverse events related to the use of tramadol as an adjunctive therapy. RESULTS: This study found that using tramadol as an adjunct to intra-articular local anaesthetic infiltration in arthroscopic knee surgery reduced post-operative pain and increased time to breakthrough analgesia without an increase in side effects. CONCLUSION: This meta-analysis suggests that tramadol is an efficacious adjunct for use in intra-articular local anaesthetic infiltration following arthroscopic knee surgery.

Standard dose epinephrine versus placebo in out of hospital cardiac arrest: A systematic review and meta-analysis.

INTRODUCTION: Out of hospital cardiac arrest (OHCA) is a time critical and heterogeneous presentation. The most appropriate management strategies remain an issue for debate. The aim of this systematic review and meta-analysis was to determine the association of epinephrine versus placebo with return of spontaneous circulation, survival to hospital admission, survival to hospital discharge and neurological outcomes in out of hospital cardiac arrest. METHODS: A systematic review of five databases was performed from inception to August 2018. Only randomised controlled trials were considered eligible for inclusion. The primary outcome was survival to hospital discharge. Secondary outcomes were ROSC, survival to hospital admission, neurological function on discharge and three-month survival. All studies were assessed for level of evidence and risk of bias. RESULTS: Five randomised controlled trials with 17,635 patients were identified for inclusion. Use of epinephrine was associated with increased ROSC (OR = 3.10; 95% CI = 2.16 to 4.45; I2 = 74%; p < 0.0001) and increased survival to hospital admission OR = 2.52; 95% CI = 1.63 to 3.88; I2 = 94%; p < 0.0001). However, epinephrine was not associated with increased survival to discharge (OR = 1.09; 95% CI = 0.48 to 2.47; I2 = 77%; p = 0.84) or differences in neurological outcomes (OR = 0.81; 95% CI = 0.34 to 1.96). DISCUSSION: This study was a systematic review and meta-analysis of epinephrine versus placebo in OHCA. The use of epinephrine was associated with improved ROSC and survival to hospital admission. However, use of epinephrine was not associated with a significant difference in survival to hospital discharge, neurological outcomes or survival to 3 months. Further research is required to control for the confounders during inpatient management.

Intra-articular Alpha-2 Agonists as an Adjunct to Local Anesthetic in Knee Arthroscopy: A Systematic Review and Meta-Analysis.

The infiltration of local anesthetic has been shown to reduce postoperative pain in knee arthroscopy. Several studies have shown that the addition of agents such as magnesium and nonsteroidal antiinflammatory drugs (NSAIDs) result in an increased time to first analgesia and overall reduction in pain. The aim of this systematic review and meta-analysis was to determine whether the addition of an α-2 agonist (A2A) to intra-articular local anesthetic, results in a reduction in postoperative pain. Four major databases were systematically searched for relevant randomized controlled trials (RCTs) up to July 2017. RCTs containing a control group receiving a local anesthetic and an intervention group receiving the same with the addition of an A2A were included in the review. The included studies were assessed for level of evidence and risk of bias. The data were then analyzed both qualitatively and where appropriate by meta-analysis. We reviewed 12 RCTs including 603 patients. We found that the addition of an A2A resulted in a significant reduction in postoperative pain up to 24 hours. The addition of the A2A increased time to first analgesia request by 258.85 minutes (p < 0.00001). Total 24-hour analgesia consumption was analyzed qualitatively with all included studies showing a significant reduction in total analgesia requirement. Interestingly, none of the studies found an increase in side effects associated with the A2A. This study provides strong evidence for the use of A2As as a means to reduce postoperative pain post arthroscopic knee surgery, without a corresponding increase in side effects.

RETRACTED: Sublingual buprenorphine versus intravenous or intramuscular morphine in acute pain: A systematic review and meta-analysis of randomized control trials.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Authors. The authors have provided a clarification stating that the article does not clearly or fully disclose that it better represents a subset of a previously published manuscript in the British Journal of Anaesthesia (White LD, Hodge A, Vlok R, Hurtado G, Eastern K, Melhuish TM. Efficacy and adverse effects of buprenorphine in acute pain management: systematic review and meta-analysis of randomized controlled trials. (Br J Anaesth. 2018;120:668-678). The papers presented in their meta-analysis are a subset of those in their previous review in the British Journal of Anaesthesia, and do not present additional information beyond their previously published work.

Advanced airway management in out of hospital cardiac arrest: A systematic review and meta-analysis.

OBJECTIVES: To assess the difference in survival and neurological outcomes between endotracheal tube (ETT) intubation and supraglottic airway (SGA) devices used during out-of-hospital cardiac arrest (OHCA). METHODS: A systematic search of five databases was performed by two independent reviewers until September 2018. Included studies reported on (1) OHCA or cardiopulmonary resuscitation, and (2) endotracheal intubation versus supraglottic airway device intubation. Exclusion criteria (1) stimulation studies, (2) selectively included/excluded patients, (3) in-hospital cardiac arrest. Odds Ratios (OR) with random effect modelling was used. Primary outcomes: (1) return of spontaneous circulation (ROSC), (2) survival to hospital admission, (3) survival to hospital discharge, (4) discharge with a neurologically intact state. RESULTS: Twenty-nine studies (n = 539,146) showed that overall, ETT use resulted in a heterogeneous, but significant increase in ROSC (OR = 1.44; 95%CI = 1.27 to 1.63; I2 = 91%; p < 0.00001) and survival to admission (OR = 1.36; 95%CI = 1.12 to 1.66; I2 = 91%; p = 0.002). There was no significant difference in survival to discharge or neurological outcome (p > 0.0125). On sensitivity analysis of RCTs, there was no significant difference in ROSC, survival to admission, survival to discharge or neurological outcome (p > 0.0125). On analysis of automated chest compression, without heterogeneity, ETT provided a significant increase in ROSC (OR = 1.55; 95%CI = 1.20 to 2.00; I2 = 0%; p = 0.0009) and survival to admission (OR = 2.16; 95%CI = 1.54 to 3.02; I2 = 0%; p < 0.00001). CONCLUSIONS: The overall heterogeneous benefit in survival with ETT was not replicated in the low risk RCTs, with no significant difference in survival or neurological outcome. In the presence of automated chest compressions, ETT intubation may result in survival benefits.

Buprenorphine versus Morphine in Paediatric Acute Pain: A Systematic Review and Meta-Analysis.

INTRODUCTION: In lab-based studies, buprenorphine appears to have a ceiling effect on respiratory depression but not on analgesia. There is increasing evidence in adult patients that buprenorphine has no ceiling effect on analgesia or side effects. The aim of this study was to investigate the efficacy and adverse effects of buprenorphine versus morphine in paediatric acute pain. METHODS: A systematic review of five databases was performed until May 2018. Only randomised controlled trials were eligible for inclusion. The outcomes of interest included pain, respiratory depression, nausea, sedation, dizziness, and pruritus. RESULTS: Four randomised controlled trials (n=195) were included. The only outcome measuring analgesic efficacy was time to breakthrough analgesia. Buprenorphine had a significant increase in time to breakthrough analgesia by 114.98 minutes compared to morphine (95% CI = 42.94 to 187.01; I2 = 0; p=0.002). There was no significant difference in the rates of adverse effects. CONCLUSIONS: Buprenorphine provided a longer duration of analgesia than morphine. This in combination with its unique sublingual preparation could prove particularly advantageous in the paediatric population. The studies included are likely underpowered to detect differences in the incidence of adverse effects; therefore, the same precautions should be taken as with any other opioid.