Early Versus Late Advanced Airway Management for Pediatric Patients With Out-of-Hospital Cardiac Arrest.

STUDY OBJECTIVE: To determine the association between early versus late advanced airway management and improved outcomes in pediatric out-of-hospital cardiac arrest. METHODS: We performed a retrospective cohort study using data from the out-of-hospital cardiac arrest registry in Japan. We included pediatric patients (<18 years) with out-of-hospital cardiac arrest who had received advanced airway management (tracheal intubation, supraglottic airway, and esophageal obturator). The main exposure was early (≤20 minutes) versus late (>20 minutes) advanced airway management. The primary and secondary outcome measurements were survival and favorable neurologic outcomes at 1 month, respectively. To address resuscitation time bias, we performed risk-set matching analyses using time-dependent propensity scores. RESULTS: Out of the 864 pediatric patients with both out-of-hospital cardiac arrest and advanced airway management over 67 months (2014 to 2019), we included 667 patients with adequate data (77%). Of these 667 patients, advanced airway management was early for 354 (53%) and late for 313 (47%) patients. In the risk-set matching analysis, the risk of both survival (risk ratio 0.98 for early versus late [95% confidence interval 0.95 to 1.02]) and favorable 1-month neurologic outcomes (risk ratio 0.99 [95% confidence interval 0.97 to 1.00]) was similar between early and late advanced airway management groups. In sensitivity analyses, with time to early advanced airway management defined as ≤10 minutes and ≤30 minutes, both outcomes were again similar. CONCLUSION: In pediatric out-of-hospital cardiac arrest, the timing of advanced airway management may not affect patient outcomes, but randomized controlled trials are needed to address this question further.

Association between sub-phenotypes identified using latent class analysis and neurological outcomes in patients with out-of-hospital cardiac arrest in Japan.

BACKGROUND: In patients who experience out-of-hospital cardiac arrest (OHCA), it is important to assess the association of sub-phenotypes identified by latent class analysis (LCA) using pre-hospital prognostic factors and factors measurable immediately after hospital arrival with neurological outcomes at 30 days, which would aid in making treatment decisions. METHODS: This study retrospectively analyzed data obtained from the Japanese OHCA registry between June 2014 and December 2019. The registry included a complete set of data on adult patients with OHCA, which was used in the LCA. The association between the sub-phenotypes and 30-day survival with favorable neurological outcomes was investigated. Furthermore, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by multivariate logistic regression analysis using in-hospital data as covariates. RESULTS: A total of, 22,261 adult patients who experienced OHCA were classified into three sub-phenotypes. The factor with the highest discriminative power upon patient's arrival was Glasgow Coma Scale followed by partial pressure of oxygen. Thirty-day survival with favorable neurological outcome as the primary outcome was evident in 66.0% participants in Group 1, 5.2% in Group 2, and 0.5% in Group 3. The 30-day survival rates were 80.6%, 11.8%, and 1.3% in groups 1, 2, and 3, respectively. Logistic regression analysis revealed that the ORs (95% CI) for 30-day survival with favorable neurological outcomes were 137.1 (99.4-192.2) for Group 1 and 4.59 (3.46-6.23) for Group 2 in comparison to Group 3. For 30-day survival, the ORs (95%CI) were 161.7 (124.2-212.1) for Group 1 and 5.78 (4.78-7.04) for Group 2, compared to Group 3. CONCLUSIONS: This study identified three sub-phenotypes based on the prognostic factors available immediately after hospital arrival that could predict neurological outcomes and be useful in determining the treatment strategy of patients experiencing OHCA upon their arrival at the hospital.

Efficacy of second-line anticonvulsant agents with adult status epilepticus: A systematic review and network meta-analysis.

BACKGROUND: Status epilepticus (SE) is potentially life-threatening, however, it is unclear which antiepileptic drugs (AEDs) should be used as second-line AEDs. OBJECTIVE: We conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing multiple second-line AEDs for SE to investigate the efficacy of AEDs. METHODS: We searched MEDLINE, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform Search Portal and included RCTs for patients aged ≥15 years with SE on December 31, 2023. We compared multiple second-line AEDs for SE including fosphenytoin (fPHT), lacosamide (LCM), levetiracetam (LEV), phenytoin (PHT), phenobarbital (PHB), and valproate (VPA). The primary and secondly outcomes were termination of seizures integrating the absence of seizure recurrence at 30 min and 60 min, and adverse events associated with AEDs, respectively, with expressing as relative risk (RR) with a 95% confidence interval (CI). We conducted a NMA using frequentist-based approach with multivariate random effects, and assessed the certainty based on the Grading of Recommendations, Assessment, Development, and Evaluations framework. RESULTS: Seven RCTs (n = 780) were included, and statistically significant difference was detected between VPA vs. PHB (RR, 0.67; 95% CI, 0.53-0.85; very low certainty), fPHT vs. PHB (RR, 0.66; 95% CI, 0.48-0.90; very low certainty), LCM vs. PHB (RR, 0.62; 95% CI, 0.41-0.93; very low certainty), and LEV vs. PHB (RR, 0.69; 95% CI, 0.51-0.94; very low certainty). Moreover, PHB was the highest in the ranking for termination of seizures. For adverse events, no significant reduction was observed owing to the selection of AEDs, although the ranking of PHB was the lowest. CONCLUSIONS: PHB may have been the most effective for seizure termination as second-line AEDs in adult patients with SE. However, the certainty of almost all comparisons was "very low", and careful interpretation is essential.

Naphazoline intoxication managed with minimally invasive cardiac output monitoring.

Naphazoline, a nonspecific alpha-adrenoceptor stimulant, is a potent vasoconstrictor used in nasal sprays, eye drops, and over-the-counter antiseptics. Naphazoline intoxication increases afterload by constricting the peripheral arteries, which can lead to complications including multiple organ failure. Although phentolamine, a nonselective alpha-adrenoceptor antagonist, and nicardipine, a calcium channel blocker, are used for the treatment of naphazoline intoxication, no established administration protocols currently exist. We present the case of a 32-year-old male with depression who ingested 150 mL of an antiseptic containing 0.1% naphazoline (equivalent to 150 mg of naphazoline). Five hours after ingestion, the patient was admitted to hospital exhibiting signs of naphazoline intoxication, such as bradycardia (46 beats/min), blood pressure of 166/122 mmHg, and peripheral cyanosis. We used the FloTrac™/EV1000™ system (Edwards Lifesciences, Irvine, CA, USA), a minimally invasive cardiac output monitoring system, to monitor systemic vascular resistance. The systemic vascular resistance index (SVRI) was elevated (4457 dyne.s/cm5/m2; nomal range: 1970-2390 dyne.s/cm5/m2) upon admission and initial treatment with continuous intravenous infusion of phentolamine led to SVRI normalization within 2 h. With the goal of maintaining SVRI normalization, continuous infusion with nicardipine was then started. At 10 h after treatment initiation, the nicardipine dose peaked at 9 mg/h (1.9 µg/kg/min). Treatment was discontinued 8 h later, and the patient was discharged on the fourth day without sequelae. In conclusion, the use of a minimally invasive cardiac output monitoring system to track vascular resistance can effectively guide the dosing of phentolamine or nicardipine in the treatment of naphazoline intoxication.

Association between institutional volume of out-of-hospital cardiac arrest cases and short term outcomes.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a serious condition. The volume-outcome relationship and various post-cardiac arrest care elements are believed to be associated with improved neurological outcomes. Although previous studies have investigated the volume-outcome relationship, adjusting for post-cardiac arrest care, intra-class correlation for each institution, and other covariates may have been insufficient. OBJECTIVE: To investigate the volume-outcome relationships and favorable neurological outcomes among OHCA cases in each institution. METHODS: We conducted a prospective observational study of adult patients with non-traumatic OHCA using the OHCA registry in Japan. The primary outcome was 30-day favorable neurological outcomes, and the secondary outcome was 30-day survival. We set the cutoff values to trisect the number of patients as equally as possible and classified institutions into high-, middle-, and low-volume. Generalized estimating equations (GEE) were performed to adjust for covariates and within-hospital clustering. RESULTS: Among the 9909 registry patients, 7857 were included. These patients were transported to either low- (2679), middle- (2657), or high- (2521) volume institutions. The median number of eligible patients per institution in 19 months of study periods was 82 (range, 1-207), 252 (range, 210-353), and 463 (range, 390-701), respectively. After multivariable GEE using the low-volume institution as a reference, no significant difference in odds ratios and 95% confidence intervals were noted for 30-day favorable neurological outcomes for middle volume [1.22 (0.69-2.17)] and high volume [0.80 (0.47-1.37)] institutions. Moreover, there was no significant difference for 30-day survival for middle volume [1.02 (0.51-2.02)] and high volume [1.09 (0.53-2.23)] institutions. CONCLUSION: The patient volume of each institution was not associated with 30-day favorable neurological outcomes. Although this result needs to be evaluated more comprehensively, there may be no need to set strict requirements for the type of institution when selecting a destination for OHCA cases.

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

OBJECTIVES: Although airway management is important in pediatric resuscitation, the effectiveness of bag-mask ventilation (BMV) and advanced airway management (AAM), such as endotracheal intubation (ETI) and supraglottic airway (SGA) devices, for prehospital resuscitation of pediatric out-of-hospital cardiac arrest (OHCA) remains unclear. We aimed to determine the efficacy of AAM during prehospital resuscitation of pediatric OHCA cases. METHODS: We searched four databases from their inception to November 2022 and included randomized controlled trials and observational studies with appropriate adjustments for confounders that evaluated prehospital AAM for OHCA in children aged <18 years in quantitative synthesis. We compared three interventions (BMV, ETI, and SGA) via network meta-analysis using the GRADE Working Group approach. The outcome measures were survival and favorable neurological outcomes at hospital discharge or 1 month after cardiac arrest. RESULTS: Five studies (including one clinical trial and four cohort studies with rigorous confounding adjustment) involving 4852 patients were analyzed in our quantitative synthesis. Compared with ETI, BMV was associated with survival (relative risk [RR] 0.44 [95% confidence intervals (CI) 0.25-0.77]) (very low certainty). There were no significant association with survival in the other comparisons (SGA vs. BMV: RR 0.62 [95% CI 0.33-1.15] [low certainty], ETI vs. SGA: RR 0.71 [95% CI 0.39-1.32] [very low certainty]). There was no significant association with favorable neurological outcomes in any comparison (ETI vs. BMV: RR 0.33 [95% CI 0.11-1.02]; SGA vs. BMV: RR 0.50 [95% CI 0.14-1.80]; ETI vs. SGA: RR 0.66 [95% CI 0.18-2.46]) (all very low certainty). In the ranking analysis, the hierarches for efficacy for survival and favorable neurological outcome were BMV > SGA > ETI. CONCLUSION: Although the available evidence is from observational studies and its certainty is low to very low, prehospital AAM for pediatric OHCA did not improve outcomes.

Efficacy of different anticoagulant doses for patients with COVID-19: a systematic review and network meta-analysis.

PURPOSE: As no reported randomized control trials (RCTs) directly compare the three administration doses of anticoagulants (prophylactic dose, treatment dose, and no treatment), the most recommended dose to be administered to patients with coronavirus disease 2019 (COVID-19) remains unclear. The purpose of this study was to examine the effects of anticoagulant doses administered to patients with COVID-19, using a network meta-analysis (NMA) including high-quality studies. METHODS: All eligible trials from the Cochrane Central Register of Controlled Trials, MEDLINE, and Clinicaltrials.gov were included. We included RCTs and observational studies adjusted for covariates for patients aged ≥ 18 years and hospitalized due to objectively confirmed COVID-19. The main study outcome was mortality. RESULTS: In patients with moderate COVID-19, the prophylactic (relative risk (RR) 0.64 [95% confidence interval (CI) 0.52-0.80]) and treatment dose (RR 0.57 [95% CI 0.45-0.72] were associated with a lower risk of short-term mortality than that with no anticoagulant treatment. However, the prophylactic and treatment dose groups were not significantly different. The hierarchy for efficacy in reducing short-term mortality was treatment dose (P score 92.4) > prophylactic dose (57.6) > no treatment (0.0). In patients with severe COVID-19, due to the absence of trials with the no-treatment group, NMA could not be conducted. However, pairwise comparison did not show a significant difference between the prophylactic and treatment dose groups. CONCLUSIONS: Treatment and prophylactic doses of anticoagulants showed similar effects on mortality; however, the treatment dose is preferred over the prophylactic dose for patients with both moderate and severe COVID-19. TRIAL REGISTRATION NUMBER AND REGISTRATION DATES: PROSPERO (registration number: CRD42021245308, 05/21/2021).

Comparison of the effects of lidocaine and amiodarone for out-of-hospital cardiac arrest patients with shockable rhythms: a retrospective observational study from a multicenter registry.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) with shockable rhythms, including ventricular fibrillation and pulseless ventricular tachycardia, is associated with better prognosis and neurological outcome than OHCA due to other rhythms. Antiarrhythmic drugs, including lidocaine and amiodarone, are often used for defibrillation. This study aimed to compare the effects of lidocaine and amiodarone on the prognosis and neurological outcome of patients with OHCA due to shockable rhythms in a real-world setting. METHODS: We conducted a retrospective observational study using a multicenter OHCA registry of 91 participating hospitals in Japan. We included adult patients with shockable rhythms, such as ventricular fibrillation and pulseless ventricular tachycardia, who were administered either lidocaine or amiodarone. The primary outcome was 30-day survival, and the secondary outcome was a good neurological outcome at 30 days. We compared the effects of lidocaine and amiodarone for patients with OHCA due to shockable rhythms for these outcomes using logistic regression analysis after propensity score matching (PSM). RESULTS: Of the 51,199 patients registered in the OHCA registry, 1970 patients were analyzed. In total, 105 patients (5.3%) were administered lidocaine, and 1865 (94.7%) were administered amiodarone. After performing PSM with amiodarone used as the reference, the odds ratios and 95% confidence intervals of lidocaine use for 30-day survival and 30-day good neurological outcome were 1.44 (0.58-3.61) and 1.77 (0.59-5.29), respectively. CONCLUSION: The use of lidocaine and amiodarone for patients with OHCA due to shockable rhythms within a real-world setting showed no significant differences in short-term mortality or neurological outcome. There is no evidence that either amiodarone or lidocaine is superior in treatment; thus, either or both drugs could be administered.

Association between short-term neurological outcomes and extreme hyperoxia in patients with out-of-hospital cardiac arrest who underwent extracorporeal cardiopulmonary resuscitation: a retrospective observational study from a multicenter registry.

BACKGROUND: To investigate the impact of hyperoxia that developed immediately after extracorporeal membrane oxygenation (ECMO)-assisted cardiopulmonary resuscitation (ECPR) on patients' short-term neurological outcomes after out-of-hospital cardiac arrest (OHCA). METHODS: This study retrospectively analyzed data from the Japanese OHCA registry from June 2014 to December 2017. We analyzed adult patients (≥ 18 years) who had undergone ECPR. Eligible patients were divided into the following three groups based on their initial partial pressure of oxygen in arterial blood (PaO2) levels after ECMO pump-on: normoxia group, PaO2 ≤ 200 mm Hg; moderate hyperoxia group, 200 mm Hg < PaO2 ≤ 400 mm Hg; and extreme hyperoxia group, PaO2 > 400 mm Hg. The primary and secondary outcomes were 30-day favorable neurological outcomes. Logistic regression statistical analysis model of 30-day favorable neurological outcomes was performed after adjusting for multiple propensity scores calculated using pre-ECPR covariates and for confounding factors post-ECPR. RESULTS: Of the 34,754 patients with OHCA enrolled in the registry, 847 were included. The median PaO2 level was 300 mm Hg (interquartile range: 148-427 mm Hg). Among the eligible patients, 277, 313, and 257 were categorized as normoxic, moderately hyperoxic, and extremely hyperoxic, respectively. Moderate hyperoxia was not significantly associated with 30-day neurologically favorable outcomes compared with normoxia as a reference (adjusted odds ratio, 0.86; 95% confidence interval: 0.55-1.35; p = 0.51). However, extreme hyperoxia was associated with less 30-day neurologically favorable outcomes when compared with normoxia (adjusted odds ratio, 0.48; 95% confidence interval: 0.29-0.82; p = 0.007). CONCLUSIONS: For patients with OHCA who received ECPR, extreme hyperoxia (PaO2 > 400 mm Hg) was associated with 30-day poor neurological outcomes. Avoidance of extreme hyperoxia may improve neurological outcomes in patients with OHCA treated with ECPR.

Post-extubation oxygenation strategies in acute respiratory failure: a systematic review and network meta-analysis.

BACKGROUND: High-flow nasal cannula oxygenation (HFNC) and noninvasive positive-pressure ventilation (NPPV) possibly decrease tracheal reintubation rates better than conventional oxygen therapy (COT); however, few large-scale studies have compared HFNC and NPPV. We conducted a network meta-analysis (NMA) to compare the effectiveness of three post-extubation respiratory support devices (HFNC, NPPV, and COT) in reducing the mortality and reintubation risk. METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Ichushi databases were searched. COT, NPPV, and HFNC use were assessed in patients who were aged ≥ 16 years, underwent invasive mechanical ventilation for > 12 h for acute respiratory failure, and were scheduled for extubation after spontaneous breathing trials. The GRADE Working Group Approach was performed using a frequentist-based approach with multivariate random-effect meta-analysis. Short-term mortality and reintubation and post-extubation respiratory failure rates were compared. RESULTS: After evaluating 4631 records, 15 studies and 2600 patients were included. The main cause of acute hypoxic respiratory failure was pneumonia. Although NPPV/HFNC use did not significantly lower the mortality risk (relative risk [95% confidence interval] 0.75 [0.53-1.06] and 0.92 [0.67-1.27]; low and moderate certainty, respectively), HFNC use significantly lowered the reintubation risk (0.54 [0.32-0.89]; high certainty) compared to COT use. The associations of mortality with NPPV and HFNC use with respect to either outcome did not differ significantly (short-term mortality and reintubation, relative risk [95% confidence interval] 0.81 [0.61-1.08] and 1.02 [0.53-1.97]; moderate and very low certainty, respectively). CONCLUSION: NPPV or HFNC use may not reduce the risk of short-term mortality; however, they may reduce the risk of endotracheal reintubation. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: PROSPERO (registration number: CRD42020139112, 01/21/2020).

Monitoring of gastric residual volume during enteral nutrition.

BACKGROUND: The main goal of enteral nutrition (EN) is to manage malnutrition in order to improve clinical outcomes. However, EN may increase the risks of vomiting or aspiration pneumonia during gastrointestinal dysfunction. Consequently, monitoring of gastric residual volume (GRV), that is, to measure GRV periodically and modulate the speed of enteral feeding according to GRV, has been recommended as a management goal in many intensive care units. Yet, there is a lack of robust evidence that GRV monitoring reduces the level of complications during EN. The best protocol of GRV monitoring is currently unknown, and thus the precise efficacy and safety profiles of GRV monitoring remain to be ascertained. OBJECTIVES: To investigate the efficacy and safety of GRV monitoring during EN. SEARCH METHODS: We searched electronic databases including CENTRAL, MEDLINE, Embase, and CINAHL for relevant studies on 3 May 2021. We also checked reference lists of included studies for additional information and contacted experts in the field. SELECTION CRITERIA: We included randomized controlled trials (RCTs), randomized cross-over trials, and cluster-RCTs investigating the effects of GRV monitoring during EN. We imposed no restrictions on the language of publication. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results for eligible studies and extracted trial-level information from each included study, including methodology and design, characteristics of study participants, interventions, and outcome measures. We assessed risk of bias for each study using Cochrane's risk of bias tool. We followed guidance from the GRADE framework to assess the overall certainty of evidence across outcomes. We used a random-effects analytical model to perform quantitative synthesis of the evidence. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous and mean difference (MD) with 95% CIs for continuous outcomes. MAIN RESULTS: We included eight studies involving 1585 participants. All studies were RCTs conducted in ICU settings. Two studies (417 participants) compared less-frequent (less than eight hours) monitoring of GRV against a regimen of more-frequent (eight hours or greater) monitoring. The evidence is very uncertain about the effect of frequent monitoring of GRV on mortality rate (RR 0.91, 95% CI 0.60 to 1.37; I² = 8%; very low-certainty evidence), incidence of pneumonia (RR 1.08, 95% CI 0.64 to 1.83; heterogeneity not applicable; very low-certainty evidence), length of hospital stay (MD 2.00 days, 95% CI -2.15 to 6.15; heterogeneity not applicable; very low-certainty evidence), and incidence of vomiting (RR 0.14, 95% CI 0.02 to 1.09; heterogeneity not applicable; very low-certainty evidence). Two studies (500 participants) compared no GRV monitoring with frequent (12 hours or less) monitoring. Similarly, the evidence is very uncertain about the effect of no monitoring of GRV on mortality rate (RR 0.87, 95% CI 0.62 to 1.23; I² = 51%; very low-certainty evidence), incidence of pneumonia (RR 0.70, 95% CI 0.43 to 1.13; heterogeneity not applicable; very low-certainty evidence), length of hospital stay (MD -1.53 days, 95% CI -4.47 to 1.40; I² = 0%; very low-certainty evidence), and incidence of vomiting (RR 1.47, 95% CI 1.13 to 1.93; I² = 0%; very low-certainty evidence). One study (322 participants) assessed the impact of GRV threshold (500 mL per six hours) on clinical outcomes. The evidence is very uncertain about the effect of the threshold for GRV at time of aspiration on mortality rate (RR 1.01, 95% CI 0.74 to 1.38; heterogeneity not applicable; very low-certainty evidence), incidence of pneumonia (RR 1.03, 95% CI 0.72 to 1.46; heterogeneity not applicable; very low-certainty evidence), and length of hospital stay (MD -0.90 days, 95% CI -2.60 to 4.40; heterogeneity not applicable; very low-certainty evidence). Two studies (140 participants) explored the effects of returning or discarding the aspirated/drained GRV. The evidence is uncertain about the effect of discarding or returning the aspirated/drained GRV on the incidence of vomiting (RR 1.00, 95% CI 0.06 to 15.63; heterogeneity not applicable; very low-certainty evidence) and volume aspirated from the stomach (MD -7.30 mL, 95% CI -26.67 to 12.06, I² = 0%; very low-certainty evidence) We found no studies comparing the effects of protocol-based EN strategies that included GRV-related criteria against strategies that did not include such criteria. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effect of GRV on clinical outcomes including mortality, pneumonia, vomiting, and length of hospital stay.

Non-pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy.

BACKGROUND: Acute kidney injury (AKI) is a common complication amongst people who are critically ill, and it is associated with an increased risk of death. For people with severe AKI, continuous kidney replacement therapy (CKRT), which is delivered over 24 hours, is needed when they become haemodynamically unstable. When CKRT is interrupted due to clotting of the extracorporeal circuit, the delivered dose is decreased and thus leading to undertreatment. OBJECTIVES: This review assessed the efficacy of non-pharmacological measures to maintain circuit patency in CKRT. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 25 January 2021 which includes records identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) (parallel-group and cross-over studies), cluster RCTs and quasi-RCTs that examined non-pharmacological interventions to prevent clotting of extracorporeal circuits during CKRT.  DATA COLLECTION AND ANALYSIS: Three pairs of review authors independently extracted information including participants, interventions/comparators, outcomes, study methods, and risk of bias. The primary outcomes were circuit lifespan and death due to any cause at day 28. We used a random-effects model to perform quantitative synthesis (meta-analysis). We assessed risk of bias in included studies using the Cochrane Collaboration's tool for assessing risk of bias. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: A total of 20 studies involving 1143 randomised participants were included in the review. The methodological quality of the included studies was low, mainly due to the unclear randomisation process and blinding of the intervention. We found evidence on the following 11 comparisons: (i) continuous venovenous haemodialysis (CVVHD) versus continuous venovenous haemofiltration (CVVH) or continuous venovenous haemodiafiltration (CVVHDF); (ii) CVVHDF versus CVVH; (iii) higher blood flow (≥ 250 mL/minute) versus standard blood flow (< 250 mL/minute); (iv) AN69 membrane (AN69ST) versus other membranes; (v) pre-dilution versus post-dilution; (vi) a longer catheter (> 20 cm) placing the tip targeting the right atrium versus a shorter catheter (≤ 20 cm) placing the tip in the superior vena cava; (vii) surface-modified double-lumen catheter versus standard double-lumen catheter with identical geometry and flow design; (viii) single-site infusion anticoagulation versus double-site infusion anticoagulation; (ix) flat plate filter versus hollow fibre filter of the same membrane type; (x) a filter with a larger membrane surface area versus a smaller one; and (xi) a filter with more and shorter hollow fibre versus a standard filter of the same membrane type. Circuit lifespan was reported in 9 comparisons. Low certainty evidence indicated that CVVHDF (versus CVVH: MD 10.15 hours, 95% CI 5.15 to 15.15; 1 study, 62 circuits), pre-dilution haemofiltration (versus post-dilution haemofiltration: MD 9.34 hours, 95% CI -2.60 to 21.29; 2 studies, 47 circuits; I² = 13%), placing the tip of a longer catheter targeting the right atrium (versus placing a shorter catheter targeting the tip in the superior vena cava: MD 6.50 hours, 95% CI 1.48 to 11.52; 1 study, 420 circuits), and surface-modified double-lumen catheter (versus standard double-lumen catheter: MD 16.00 hours, 95% CI 13.49 to 18.51; 1 study, 262 circuits) may prolong circuit lifespan. However, higher blood flow may not increase circuit lifespan (versus standard blood flow: MD 0.64, 95% CI -3.37 to 4.64; 2 studies, 499 circuits; I² = 70%). More and shorter hollow fibre filters (versus standard filters: MD -5.87 hours, 95% CI -10.18 to -1.56; 1 study, 6 circuits) may reduce circuit lifespan. Death from any cause was reported in four comparisons We are uncertain whether CVVHDF versus CVVH, CVVHD versus CVVH or CVVHDF, longer versus a shorter catheter, or surface-modified double-lumen catheters versus standard double-lumen catheters reduced death due to any cause, in very low certainty evidence. Recovery of kidney function was reported in three comparisons. We are uncertain whether CVVHDF versus CVVH, CVVHDF versus CVVH, or surface-modified double-lumen catheters versus standard double-lumen catheters increased recovery of kidney function. Vascular access complications were reported in two comparisons. Low certainty evidence indicated using a longer catheter (versus a shorter catheter: RR 0.40, 95% CI 0.22 to 0.74) may reduce vascular access complications, however the use of surface-modified double lumen catheters versus standard double-lumen catheters may make little or no difference to vascular access complications. AUTHORS' CONCLUSIONS: The use of CVVHDF as compared with CVVH, pre-dilution haemofiltration, a longer catheter, and surface-modified double-lumen catheter may be useful in prolonging the circuit lifespan, while higher blood flow and more and shorter hollow fibre filter may reduce circuit life. The Overall, the certainty of evidence was assessed to be low to very low due to the small sample size of the included studies. Data from future rigorous and transparent research are much needed in order to fully understand the effects of non-pharmacological interventions in preventing circuit coagulation amongst people with AKI receiving CKRT.

Etiology and mortality in severe acute pancreatitis: A multicenter study in Japan.

BACKGROUND/OBJECTIVES: Severe acute pancreatitis (SAP) has a high mortality rate despite ongoing attempts to improve prognosis through a various therapeutic modalities. This study aimed to delineate etiology-based routes that may guide clinical decisions for the treatment of SAP. METHODS: Using data from a recent retrospective multicenter study in Japan, we analyzed the association between clinical outcomes, mainly in-hospital mortality and pancreatic infection, and various etiologies while considering confounding factors. We performed additional multivariate analyses and built decision tree models. RESULTS: The 1097 participating patients were classified into the following groups by etiology: alcohol (n = 436, 39.7%); cholelithiasis (n = 230, 21.0%); idiopathic (n = 227, 20.7%); and others (n = 204, 18.6%). Mortality at hospital discharge was 8.4%, 12.2%, 16.7%, and 16.2% in the alcohol, cholelithiasis, idiopathic, and others groups, respectively. According to multivariable analysis, early enteral nutrition (EN) was significantly associated with reduced in-hospital mortality only in the cholelithiasis group. However, there was a consistent association between age and the need for mechanical ventilation and increased mortality, regardless of etiology. Our decision tree models presented different contributing factors depending on the etiology and patient background. Interaction analysis showed that EN and the use of prophylactic antibiotics may influence these results differently according to etiology. CONCLUSIONS: No study has yet used comprehensive models to investigate etiology-related prognostic factors for SAP; our results can, therefore, be used as a reference for improving clinical decisions.

Large Volume Fluid Resuscitation for Severe Acute Pancreatitis is Associated With Reduced Mortality: A Multicenter Retrospective Study.

BACKGROUND AND AIMS: Although fluid resuscitation is critical in acute pancreatitis, the optimal fluid volume is unknown. The aim of this study is to evaluate the association between the volume of fluid administered and clinical outcomes in patients with severe acute pancreatitis (SAP). METHODS: We conducted a multicenter retrospective study at 44 institutions in Japan. Inclusion criteria were age 18 years or older, and diagnosed with SAP from 2009 to 2013. Patients were stratified into 2 groups: administered fluid volume <6000 and ≥6000 mL in the first 24 hours. We evaluated the association between the 2 groups and clinical outcomes using multivariable logistic regression analysis. The primary outcome was in-hospital mortality. Secondary outcomes included the incidence of pancreatic infection and the need for surgical intervention. RESULTS: We analyzed 1097 patients, and the mean fluid volume administered was 5618±3018 mL (mean±SD), with 708 and 389 patients stratified into the fluid <6000 mL and fluid ≥6000 mL groups, respectively. Overall in-hospital mortality was 12.3%. The fluid ≥6000 mL group had significantly higher mortality than the fluid <6000 mL group (univariable analysis, 15.9% vs. 10.3%; P<0.05). In multivariable logistic regression analysis, administration of ≥6000 mL of fluid within the first 24 hours was significantly associated with reduced mortality (odds ratio, 0.58; P<0.05). No significant association was found between the administered fluid volume and pancreatic infection, or between the volume administered and the need for surgical intervention. CONCLUSIONS: In patients with SAP, administration of a large fluid volume within the first 24 hours is associated with decreased mortality.

Comparison of the efficacy of three topical antiseptic solutions for the prevention of catheter colonization: a multicenter randomized controlled study.

BACKGROUND: To compare the efficacy of three antiseptic solutions [0.5%, and 1.0% alcohol/chlorhexidine gluconate (CHG), and 10% aqueous povidone-iodine (PVI)] for the prevention of intravascular catheter colonization, we conducted a randomized controlled trial in patients from 16 intensive care units in Japan. METHODS: Adult patients undergoing central venous or arterial catheter insertions were randomized to have one of three antiseptic solutions applied during catheter insertion and dressing changes. The primary endpoint was the incidence of catheter colonization, and the secondary endpoint was the incidence of catheter-related bloodstream infections (CRBSI). RESULTS: Of 1132 catheters randomized, 796 (70%) were included in the full analysis set. Catheter-tip colonization incidence was 3.7, 3.9, and 10.5 events per 1000 catheter-days in 0.5% CHG, 1% CHG, and PVI groups, respectively (p = 0.03). Pairwise comparisons of catheter colonization between groups showed a significantly higher catheter colonization risk in the PVI group (0.5% CHG vs. PVI: hazard ratio, HR 0.33 [95% confidence interval, CI 0.12-0.95], p = 0.04; 1.0% CHG vs. PVI: HR 0.35 [95% CI 0.13-0.93], p = 0.04). Sensitivity analyses including all patients by multiple imputations showed consistent quantitative conclusions (0.5% CHG vs. PVI: HR 0.34, p = 0.03; 1.0% CHG vs. PVI: HR 0.35, p = 0.04). No significant differences were observed in the incidence of CRBSI between groups. CONCLUSIONS: Both 0.5% and 1.0% alcohol CHG are superior to 10% aqueous PVI for the prevention of intravascular catheter colonization. TRIAL REGISTRATION: Japanese Primary Registries Network; No.: UMIN000008725 Registered on 1 September 2012.

External Validation for Acute Kidney Injury Severity Scores: A Multicenter Retrospective Study in 14 Japanese ICUs.

BACKGROUND/AIMS: Acute kidney injury (AKI) is associated with high mortality. Multiple AKI severity scores have been derived to predict patient outcome. We externally validated new AKI severity scores using the Japanese Society for Physicians and Trainees in Intensive Care (JSEPTIC) database. METHODS: New AKI severity scores published in the 21st century (Mehta, Stuivenberg Hospital Acute Renal Failure (SHARF) II, Program to Improve Care in Acute Renal Disease (PICARD), Vellore and Demirjian), Liano, Simplified Acute Physiology Score (SAPS) II and lactate were compared using the JSEPTIC database that collected retrospectively 343 patients with AKI who required continuous renal replacement therapy (CRRT) in 14 intensive care units. Accuracy of the severity scores was assessed by the area under the receiver-operator characteristic curve (AUROC, discrimination) and Hosmer-Lemeshow test (H-L test, calibration). RESULTS: The median age was 69 years and 65.8% were male. The median SAPS II score was 53 and the hospital mortality was 58.6%. The AUROC curves revealed low discrimination ability of the new AKI severity scores (Mehta 0.65, SHARF II 0.64, PICARD 0.64, Vellore 0.64, Demirjian 0.69), similar to Liano 0.67, SAPS II 0.67 and lactate 0.64. The H-L test also demonstrated that all assessed scores except for Liano had significantly low calibration ability. CONCLUSIONS: Using a multicenter database of AKI patients requiring CRRT, this study externally validated new AKI severity scores. While the Demirjian's score and Liano's score showed a better performance, further research will be required to confirm these findings.

The lower limit of intensity to control uremia during continuous renal replacement therapy.

INTRODUCTION: The recommended lower limit of intensity during continuous renal replacement therapy (CRRT) is 20 or 25 mL/kg/h. However, limited information is available to support this threshold. We aimed to evaluate the impact of different intensities of CRRT on the clearance of creatinine and urea in critically ill patients with severe acute kidney injury (AKI). METHODS: This is a multicenter retrospective study conducted in 14 Japanese ICUs in 12 centers. All patients older than 18 years and treated with CRRT due to AKI were eligible. We evaluated the effect of CRRT intensity by two different definitions: daily intensity (the mean intensity over each 24-h period) and average intensity (the mean of daily intensity during the period while CRRT was performed). To study the effect of different CRRT intensity on clearance of urea and creatinine, all patients/daily observations were arbitrarily allocated to one of 4 groups based on the average intensity and daily intensity: <10, 10-15, 15-20, and >20 mL/kg/h. RESULTS: Total 316 patients were included and divided into the four groups according to average CRRT intensity. The groups comprised 64 (20.3%), 138 (43.7%), 68 (21.5%), and 46 patients (14.6%), respectively. Decreases in creatinine and urea increased as the average intensity increased over the first 7 days of CRRT. The relative changes of serum creatinine and urea levels remained close to 1 over the 7 days in the "<10" group. Total 1,101 daily observations were included and divided into the four groups according to daily CRRT intensity. The groups comprised 254 (23.1%), 470 (42.7%), 239 (21.7%), and 138 observations (12.5%), respectively. Creatinine and urea increased (negative daily change) only in the "<10" group and decreased with the increasing daily intensity in the other groups. CONCLUSIONS: The lower limit of delivered intensity to control uremia during CRRT was approximately between 10 and 15 mL/kg/h in our cohort. A prescribed intensity of approximately 15 mL/kg/h might be adequate to control uremia for patients with severe AKI in the ICU. However, considering the limitations due to the retrospective nature of this study, prospective studies are required to confirm our findings.

Early versus late advanced airway management for adult patients with out-of-hospital cardiac arrest: A time-dependent propensity score-matched analysis.

OBJECTIVE: The objective was to investigate whether early advanced airway management during the entire resuscitation period is associated with favorable neurological outcomes and survival in patients with out-of-hospital cardiac arrest (OHCA). METHODS: We performed a retrospective cohort study of patients with OHCA aged ≥18 years enrolled in OHCA registry in Japan who received advanced airway management during cardiac arrest between June 2014 and December 2020. To address resuscitation time bias, we performed risk set matching analyses in which patients who did and did not receive advanced airway management were matched at the same time point (min) using the time-dependent propensity score; further, we compared early (≤10 min) and late (>10 min) advanced airway management. The primary and secondary outcome measures were favorable neurological outcomes using Cerebral Performance Category scores and survival at 1 month after cardiac arrest. RESULTS: Of the 41,101 eligible patients, 21,446 patients received early advanced airway management. Thus, risk set matching was performed with a total of 42,866 patients. In the main analysis, early advanced airway management was significantly associated with favorable neurological outcomes (risk ratio [RR] 0.997, 95% confidence interval [CI] 0.995-0.999) and survival (RR 0.990, 95% CI 0.986-0.994) at 1 month after cardiac arrest. In the sensitivity analysis with early advanced airway management defined as ≤5 min and ≤20 min, the results were comparable. CONCLUSIONS: Although early advanced airway management was statistically significant for improved neurological outcomes and survival at 1 month after cardiac arrest, the RR was very close to 1, indicating that the timing of advanced airway management has minimal impact on clinical outcomes, and decisions should be made based on the individual needs of the patient.

Follow-up computed tomography and unexpected hemostasis in non-operative management of pediatric blunt liver and spleen injury.

PURPOSE: While follow-up CT and prophylactic embolization with angiography are often conducted during non-operative management (NOM) for BLSI, particularly in a high-grade injury, the utility of early repeated CT for preventing unexpected hemorrhage remains unclear. This study aimed to elucidate whether early follow-up computerized tomography (CT) within 7 days after admission would decrease unexpected hemostatic procedures on pediatric blunt liver and spleen injury (BLSI). METHODS: A post-hoc analysis of a multicenter observational cohort study on pediatric patients with BLSI (2008-2019) was conducted on those who underwent NOM, in whom the timing of follow-up CT were decided by treating physicians. The incidence of unexpected hemostatic procedure (laparotomy and/or emergency angiography for ruptured pseudoaneurysm) and complications related to BLSI were compared between patients with and without early follow-up CT within 7 days. Inverse probability weighting with propensity scores adjusted patient demographics, comorbidities, mechanism and severity of injury, initial resuscitation, and institutional characteristics. RESULTS: Among 1320 included patients, 552 underwent early follow-up CT. Approximately 25% of patients underwent angiography on the day of admission. The incidence of unexpected hemostasis was similar between patients with and without early repeat CT (8 [1.4%] vs. 6 [0.8%]; adjusted OR, 1.44 [0.62-3.34]; p = 0.40). Patients with repeat CT scans more frequently underwent multiple angiographies (OR, 2.79 [1.32-5.88]) and had more complications related to BLSI, particularly bile leak (OR, 1.73 [1.04-2.87]). CONCLUSION: Follow-up CT scans within 7 days was not associated with reduced unexpected hemostasis in NOM for pediatric BLSI.

Steroid therapy for patients with septic shock: A multicenter observational study conducted in Japan.

Objectives The Clinical Practice Guidelines for the Management of Sepsis and Septic Shock weakly recommend steroids for septic shock resistant to fluid resuscitation and vasopressors. This study aimed to describe the clinical practices for septic shock in the real world and to compare the association between the intermittent or continuous infusion of steroids and the prognosis. Methods This was a retrospective cohort study based on the AMOR-VENUS, in which Japanese intensive care unit (ICU) inpatients were enrolled between January and March 2018. Adult patients with sepsis who received vasopressors within 72 h of ICU admission were included. The patients were divided into non-steroid and steroid groups, which were further divided into intermittent and continuous infusion groups. The patient characteristics and details of the steroids are described. To investigate the association between intermittent or continuous infusion, shock reversal, and mortality, logistic regression analyses were performed after adjusting for possible confounding factors. Results A total of180 patients with septic shock from 18 ICUs were enrolled. The mean age was 69.6 (SD, 14.3) years. Sixty-three patients (35.0%) received steroids (26 intermittently, 37 continuously). In the steroid group, hydrocortisone was used in 85.7%, the median daily dose was 192 mg, and the steroids were administered within 6 h of initiating vasopressor in 71.4%. The adjusted odds ratios of shock reversal on the 7th day and the ICU mortality for continuous versus intermittent infusion were 1.90 (95%CI, 0.43-8.40) and 0.61 (0.10-3.85), respectively. Conclusions There was considerable variation in the criteria for the selection of patients and in the decision to use continuous or intermittent steroid infusion.