Vasopressor-free Days Research Articles

Early intravenous high-dose vitamin C in postcardiac arrest shock (VICEPAC): study protocol for a randomised, single-blind, open-label, multicentre, controlled trial

IntroductionThe high incidence of morbidity and mortality associated with the post-cardiac arrest (CA) period highlights the need for novel therapeutic interventions to improve the outcome of out-of-hospital cardiac arrest (OHCA)...

Effects of dexmedetomidine versus propofol on outcomes in critically ill patients with different sedation depths: a propensity score-weighted cohort study

ObjectiveWe explored the effects of dexmedetomidine (DEX) versus propofol on outcomes in critically ill patients and to assess whether these effects are dissimilar under different sedation depths. MethodsA stabilized inverse probability of treatment weighting cohort study was conducted using data from the Medical Information Mart for Intensive Care IV database from 2008 to 2019. Adult intensive care unit (ICU) patients who were administered DEX or propofol as the primary sedative were identified. Various statistical methods were used to evaluate the effects of DEX versus propofol on outcomes. ResultsData on 107 and 2318 patients in DEX and propofol groups, respectively, were analyzed. Compared to the propofol group, the DEX group exhibited longer ventilator-free days on day 28 and a shorter ICU stay. Conversely, it showed null associations of DEX with the risk of 90-day ICU mortality, the odds of persistent organ dysfunction on day 14 and acute kidney injury, and the duration of vasopressor-free days on day 28. Subgroup analyses revealed that DEX positively impacted persistent organ dysfunction on day 14, ventilator-free days on day 28, and ICU stay in the subgroup with a Richmond Agitation Sedation Scale (RASS) score of ≥−2. However, DEX negatively impacted 90-day ICU mortality, persistent organ dysfunction on day 14, and ventilator-free days on day 28 in the subgroup with a RASS score of <−2. ConclusionOur results indicated that, compared with propofol, DEX had beneficial and adverse impacts on certain ICU outcomes in critically ill patients, and these impacts appeared to depend on sedation depths.

Fluid management for sepsis-induced hypotension in patients with advanced chronic kidney disease: a secondary analysis of the CLOVERS trial

BackgroundEarly fluid management in patients with advanced chronic kidney disease (CKD) and sepsis-induced hypotension is challenging with limited evidence to support treatment recommendations. We aimed to compare an early restrictive versus liberal fluid management for sepsis-induced hypotension in patients with advanced CKD.MethodsThis post-hoc analysis included patients with advanced CKD (eGFR of less than 30 mL/min/1.73 m2 or history of end-stage renal disease on chronic dialysis) from the crystalloid liberal or vasopressor early resuscitation in sepsis (CLOVERS) trial. The primary endpoint was death from any cause before discharge home by day 90.ResultsOf 1563 participants enrolled in the CLOVERS trial, 196 participants had advanced CKD (45% on chronic dialysis), with 92 participants randomly assigned to the restrictive treatment group and 104 assigned to the liberal fluid group. Death from any cause before discharge home by day 90 occurred significantly less often in the restrictive fluid group compared with the liberal fluid group (20 [21.7%] vs. 41 [39.4%], HR 0.5, 95% CI 0.29–0.85). Participants in the restrictive fluid group had more vasopressor-free days (19.7 ± 10.4 days vs. 15.4 ± 12.6 days; mean difference 4.3 days, 95% CI, 1.0–7.5) and ventilator-free days by day 28 (21.0 ± 11.8 vs. 16.5 ± 13.6 days; mean difference 4.5 days, 95% CI, 0.9–8.1).ConclusionsIn patients with advanced CKD and sepsis-induced hypotension, an early restrictive fluid strategy, prioritizing vasopressor use, was associated with a lower risk of death from any cause before discharge home by day 90 as compared with an early liberal fluid strategy.Trial RegistrationNCT03434028 (2018-02-09), BioLINCC 14149.

Effect of the 1-h bundle on mortality in patients with suspected sepsis in the emergency department: a stepped wedge cluster randomized clinical trial.

The efficacy of the 1-h bundle for emergency department (ED) patients with suspected sepsis, which includes lactate measurement, blood culture, broad-spectrum antibiotics administration, administration of 30mL/kg crystalloid fluid for hypotension or lactate ≥ 4mmol/L, remains controversial. We carried out a pragmatic stepped-wedge cluster-randomized trial in 23 EDs in France and Spain. Adult patients with Sepsis-3 criteria or a quick sequential organ failure assessment (SOFA) score ≥ 2 or a lactate > 2mmol/L were eligible. The intervention was theimplementation of the 1-h sepsis bundle.The primary outcome was in-hospital mortality truncated at 28 days. Secondary outcomes included volume of fluid resuscitation at 24h, acute heart failure at 24h, SOFA score at 72h, intensive care unit (ICU) length of stay, number of days on mechanical ventilation or renal replacement therapy, vasopressor free days, unnecessary antibiotic administration, and mortality at 28days. 1148 patients were planned to be analysed; the study period ended after 873 patients were included. 872 patients (mean age 66, 42% female) were analyzed: 387 (44.4%) in the intervention group and 485 (55.6%) in the control group. Median SOFA score was 3 [1-5]. Median time to antibiotic administration was 40min in the intervention group vs 113min in the control group (difference - 73 [95% confidence interval (CI) - 93 to - 53]). There was a significantly higher rate, volume, and shorter time to fluid resuscitation within 3h in the intervention group. There were 47 (12.1%) in-hospital deaths in the intervention group compared to 61 (12.6%) in the control group (difference in percentage - 0.4 [95% CI - 5.1 to 4.2], adjusted relative risk (aRR) 0.81 [95% CI 0.48 to 1.39]). There were no differences between groups for other secondary endpoints. Among patients with suspected sepsis in the ED, the implementation of the 1-h sepsis bundle was not associated with significant difference in in-hospital mortality. However, this study may be underpowered to report a statistically significant difference between groups.

Mortality of Patients With Sepsis Administered Piperacillin-Tazobactam vs Cefepime

Experimental and observational studies have suggested that empirical treatment for bacterial sepsis with antianaerobic antibiotics (eg, piperacillin-tazobactam) is associated with adverse outcomes compared with anaerobe-sparing antibiotics (eg, cefepime). However, a recent pragmatic clinical trial of piperacillin-tazobactam and cefepime showed no difference in short-term outcomes at 14 days. Further studies are needed to help clarify the empirical use of these agents. To examine the use of piperacillin-tazobactam compared with cefepime in 90-day mortality in patients treated empirically for sepsis, using instrumental variable analysis of a 15-month piperacillin-tazobactam shortage. In a retrospective cohort study, hospital admissions at the University of Michigan from July 1, 2014, to December 31, 2018, including a piperacillin-tazobactam shortage period from June 12, 2015, to September 18, 2016, were examined. Adult patients with suspected sepsis treated with vancomycin and either piperacillin-tazobactam or cefepime for conditions with presumed equipoise between piperacillin-tazobactam and cefepime were included in the study. Data analysis was conducted from December 17, 2022, to April 11, 2023. The primary outcome was 90-day mortality. Secondary outcomes included organ failure-free, ventilator-free, and vasopressor-free days. The 15-month piperacillin-tazobactam shortage period was used as an instrumental variable for unmeasured confounding in antibiotic selection. Among 7569 patients (4174 men [55%]; median age, 63 [IQR 52-73] years) with sepsis meeting study eligibility, 4523 were treated with vancomycin and piperacillin-tazobactam and 3046 were treated with vancomycin and cefepime. Of patients who received piperacillin-tazobactam, only 152 (3%) received it during the shortage. Treatment groups did not differ significantly in age, Charlson Comorbidity Index score, Sequential Organ Failure Assessment score, or time to antibiotic administration. In an instrumental variable analysis, piperacillin-tazobactam was associated with an absolute mortality increase of 5.0% at 90 days (95% CI, 1.9%-8.1%) and 2.1 (95% CI, 1.4-2.7) fewer organ failure-free days, 1.1 (95% CI, 0.57-1.62) fewer ventilator-free days, and 1.5 (95% CI, 1.01-2.01) fewer vasopressor-free days. Among patients with suspected sepsis and no clear indication for antianaerobic coverage, administration of piperacillin-tazobactam was associated with higher mortality and increased duration of organ dysfunction compared with cefepime. These findings suggest that the widespread use of empirical antianaerobic antibiotics in sepsis may be harmful.

Intensive or liberal glucose control in intensive care units for septic patients? A meta-analysis of randomized controlled trials

ObjectiveTo compare the clinical outcomes of intensive glucose control and liberal glucose control for septic patients in intensive care unit. MethodsThe databases of PubMed, Cochrane Library, Embase and Web of Science were searched systematically from inception to November 27, 2023 to identify trials involving a randomized comparison between intensive and liberal glucose control for septic patients in intensive care unit. ResultsA total of 14 randomized controlled trials involving 6226 patients were finally included. There was no statistically significant difference observed between intensive glucose control and liberal glucose control in terms of all-cause mortality, the need for renal replacement, vasopressor-free and mechanical ventilation-free days, and length of hospital stay. However, it is noteworthy that intensive glucose control exhibited a statistically higher risk of severe hypoglycemia (RR 2.66; 95%CI 1.85 to 3.83), need for blood transfusion (RR 1.12; 95%CI 1.01 to 1.23), and statistically prolonged length of stay in the ICU (MD 1.67; 95%CI 0.22 to 3.12) compared to liberal glucose control. Nevertheless, sensitivity analysis revealed that the need for blood transfusion and length of stay in the intensive care unit were not robust. ConclusionsBoth intensive and liberal glucose control had comparable effects on improving patient outcomes, but intensive glucose control carried a higher risk of severe hypoglycemia.

Effect of acyclovir therapy on the outcome of mechanically ventilated patients with lower respiratory tract infection and detection of herpes simplex virus in bronchoalveolar lavage: protocol for a multicentre, randomised controlled trial (HerpMV)

IntroductionHerpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients and is associated with a worse outcome. The aim of this study is to determine...

The Effect of Albumin Replacement on Vasopressor Duration in Septic Shock in Patients With Hypoalbuminemia.

The use of albumin resuscitation in septic shock is only recommended in patients who have received large volumes of crystalloid resuscitation regardless of serum albumin concentration. The role of albumin is still largely debated and evidence to support its use still lacking. The objective of this study was to evaluate whether albumin replacement increases the number of vasopressor-free days in patients with septic shock and hypoalbuminemia. A retrospective analysis was conducted to assess the effect of albumin replacement in septic shock. Hypoalbuminemic patients with septic shock who received albumin were retrospectively compared with a cohort who did not. The primary outcome was number of vasopressor-free days at day 14 from shock presentation, which was analyzed using an adjusted linear regression model to adjust for confounders. There was no difference in vasopressor-free days at day 14 in patients who received albumin versus those who did not, after adjusting for confounders of exposure (0.50, 95% CI = -0.97 to 1.97; P = 0.502). There also was no difference in secondary outcomes except for need for invasive mechanical ventilation (MV), which was significantly lower in patients who received albumin (61 [54.4%] vs 88 [67.7%]; P = 0.035). We observed no difference in vasopressor-free days at day 14 in patients with hypoalbuminemia who received albumin compared with those who did not. However, patients who received albumin required significantly less MV although further studies are warranted to assess this effect.

Ketamine versus etomidate as an induction agent for tracheal intubation in critically ill adults: a Bayesian meta-analysis

BackgroundTracheal intubation is a high-risk intervention commonly performed in critically ill patients. Due to its favorable cardiovascular profile, ketamine is considered less likely to compromise clinical outcomes. This meta-analysis aimed to assess whether ketamine, compared with other agents, reduces mortality in critically ill patients undergoing intubation.MethodsWe searched MEDLINE, Embase, and the Cochrane Library from inception until April 27, 2023, for randomized controlled trials and matched observational studies comparing ketamine with any control in critically ill patients as an induction agent. The primary outcome was mortality at the longest follow-up available, and the secondary outcomes included Sequential Organ Failure Assessment score, ventilator-free days at day 28, vasopressor-free days at day 28, post-induction mean arterial pressure, and successful intubation on the first attempt. For the primary outcome, we used a Bayesian random-effects meta-analysis on the risk ratio (RR) scale with a weakly informative neutral prior corresponding to a mean estimate of no difference with 95% probability; the estimated effect size will fall between a relative risk of 0.25 and 4. The RR and 95% credible interval (CrI) were used to estimate the probability of mortality reduction (RR < 1). The secondary outcomes were assessed with a frequentist random-effects model. We registered this study in Open Science Framework (https://osf.io/2vf79/).ResultsWe included seven randomized trials and one propensity-matched study totaling 2978 patients. Etomidate was the comparator in all the identified studies. The probability that ketamine reduced mortality was 83.2% (376/1475 [25%] vs. 411/1503 [27%]; RR, 0.93; 95% CrI, 0.79–1.08), which was confirmed by a subgroup analysis excluding studies with a high risk of bias. No significant difference was observed in any secondary outcomes.ConclusionsAll of the included studies evaluated ketamine versus etomidate among critically ill adults requiring tracheal intubation. This meta-analysis showed a moderate probability that induction with ketamine is associated with a reduced risk of mortality.Graphical abstract

Muscle wasting assessed by ultrasound versus scoring systems as early predictor of outcomes of intensive care unit stay in critically ill patients

ABSTRACT Background A lot of outcome predictive tools are already in use in critical care setting with different degrees of reliability aiming for possible prevention or minimization of bad outcome and better resource management. Some critical illness sequelae significantly affect patient’s outcome and currently not included in the in-use predictive scoring system. Muscle wasting/weakness is one of these sequelae, and it was found to be an independent risk factor of poor outcomes. Objective This study was conducted to evaluate the degree of muscle wasting estimated by ultrasonography during ICU stay as a predictor of mortality, successful weaning of mechanical ventilation, ICU stay and hospital stay. Patients and Methods A prospective observational study was conducted in critical care units in Ain Shams University Hospitals, Cairo, Egypt over a period of 12 months. Results Decrease in muscle measurements was found to correlated to mortality in ICU with cutoff points from area under the curve for right QMT, left QMT, right RFCSA, left RFCSA, IEDT and EEDT were supposed to be:>9.77,>15, >16.67, >12.5, >12.63, >12.5, respectively, with best specificity and positive predictive value was found in right RFCSA (95.45, 87.5, respectively) while best sensitivity and negative predictive value was found in left RFCSA (65.38, 82, respectively). Significant negative correlation between vasoactive agent free period and maximum daily reduction in RFCSA, QMT, EIDT, and EEDT (P value = 0.001). Conclusion Daily reduction of the RFCSA and to lesser extent the QMT has significant correlation to mortality, prolongation of mechanical ventilation days and reduction in the vasopressor free days but has a poor correlation to the ICU and hospital stay. Pneumonia and renal disease had significant correlation with the muscle mass reduction. The left RFCSA found to be comparable to SOFA score as mortality predictor.

RESTRICTIVE FLUID RESUSCITATION IN SEPTIC SHOCK PATIENTS HAS LOWER MORTALITY AND ORGAN DYSFUNCTION RATES THAN STANDARD THERAPY.

Background : The influence of restrictive fluid resuscitation and the early administration of vasopressors on the clinical outcomes in patients with septic shock are not fully understood. The purpose of this study was to evaluate the effects of restrictive fluid management on mortality and organ dysfunction in patients with septic shock. Methods : This study included consecutive patients with septic shock in need of fluid resuscitation. Based on the fluid management provided in the initial resuscitation phase, a comparison was made between a restrictive group and a standard fluid management group. The primary outcome was in-hospital death, whereas secondary outcomes included organ dysfunction and other adverse events. Results : A total of 238 patients were included in this study. Restrictive fluid management was administered to 59.2% of patients, whereas 40.8% received standard fluid management. Restrictive resuscitation was associated with a lower in-hospital mortality rate (24.8% vs. 52.6%), as well as a shorter median intensive care unit stay (8.0 vs. 11.0 days). The restrictive strategy was associated with a significantly lower prevalence of new-onset acute kidney injury (25.5% vs. 51.5%) and a decrease in the incidence of renal replacement therapy (20.6% vs. 40.2%). The standard group had a higher risk of the need for mechanical ventilation and a significantly lower median number of days without a ventilator than the restrictive group. The median duration of vasopressor-free days in the restrictive group was significantly longer than that in the standard group (25.0 vs. 18.0). The administration rate of inotropes in the restrictive group was significantly lower than that in the standard group. A multivariate logistic regression model showed that restrictive fluid management (odds ratio [OR], 0.312; 95% confidence interval [CI], 0.098-0.994) and vasopressor-free days (OR, 0.807; 95% CI, 0.765-0.851) protect against in-hospital death, whereas Acute Physiology and Chronic Health Evaluation II scores (OR, 1.121; 95% CI, 1.018-1.234) were independent risk factors for in-hospital death. Conclusions : Restrictive fluid resuscitation and early vasopressor protocol in patients with septic shock are associated with better outcomes, indicating that this regimen is feasible and safe.

Restrictive Versus Liberal Fluid Regimen in Refractory Sepsis and Septic Shock: A Systematic Review and Meta-Analysis.

The optimal fluid management strategy for patients with sepsis remains a topic of debate. This meta-analysis aims to evaluate the impact of restrictive versus liberal fluid regimens on mortality, adverse events, and other clinical outcomes in patients with sepsis. We systematically reviewed 11 randomized controlled trials published between 2008 and 2023, comprising a total of 4,121 participants. The studies assessed 90-day mortality, 30-day mortality, adverse events, hospital length of stay, ICU admission rate, mechanical ventilation, ventilator-free days, ICU-free days, and vasopressor-free days. Quality assessments indicated minimal bias across the studies. The meta-analysis showed no statistically significant difference in 90-day mortality between restrictive and liberal fluid regimens (OR, 0.93; 95% CI, 0.80 to 1.70; P=0.30). Similar results were observed for 30-day mortality (OR, 0.73; 95% CI, 0.30 to 1.80; P=0.50). Adverse events were comparable between the two groups (OR, 0.81; 95% CI, 0.55 to 1.19; P=0.28). Furthermore, there were no significant differences in hospital length of stay (OR, 0.47; 95% CI, -0.85 to 1.80; P=0.48) or ICU admission rate (OR, 1.09; 95% CI, 0.66 to 1.77; P=0.75) between the restrictive and liberal fluid regimens. Regarding mechanical ventilation and ventilator-free days, no significant distinctions were observed (OR, 0.87; 95% CI, 0.65 to 1.17; P=0.48; OR, 0.99; 95% CI, -0.17 to 2.15; P=0.09, respectively). ICU-free days and vasopressor-free days also showed no significant differences between the two groups (OR, 0.97; 95% CI, -0.28 to 2.21; P=0.13; OR, -0.38; 95% CI, -1.14 to 0.37; P=0.32, respectively). This comprehensive meta-analysis of clinical trials suggests that restrictive and liberal fluid management strategies have comparable outcomes in patients with sepsis, including mortality, adverse events, and various clinical parameters. However, most studies favored restrictive fluid regimen over liberal approach regarding the number of vasopressor-free days, need for mechanical ventilation, adverse events, 30-day mortality, and 90-day mortality in sepsis patients.

Anisodamine hydrobromide in the treatment of critically ill patients with septic shock: a multicenter randomized controlled trial

Background Septic shock is the development of sepsis to refractory circulatory collapse and metabolic derangements, characterized by persistent hypotension and increased lactate levels. Anisodamine hydrobromide (Ani HBr) is a Chinese medicine used to improve blood flow in circulatory disorders. The purpose of this study was to determine the therapeutic efficacy of Ani HBr in the treatment of patients with septic shock. Methods This was a prospective, multicenter, randomized controlled trial focusing on patients with septic shock in 16 hospitals in China. Patients were randomly assigned in a 1:1 ratio to either the treatment group or the control group. The primary endpoint was 28-day mortality. The secondary outcomes included 7-day mortality, hospital mortality, hospital length of stay, vasopressor-free days within 7 days, etc. These indicators were measured and collected at 0, 6h, 24h, 48h, 72h and 7d after the diagnosis. Results Between September 2017 and March 2021, 404 subjects were enrolled. 203 subjects received Ani HBr and 201 subjects were assigned to the control group. The treated group showed lower 28-day mortality than the control group. Stratified analysis further showed significant differences in 28-day mortality between the two groups for patients with a high level of illness severity. We also observed significant differences in 7-day mortality, hospital mortality and some other clinical indicators between the two groups. Conclusion Ani HBr might be an important adjuvant to conventional treatment to reduce 28-day mortality in patients with septic shock. A large-scale prospective randomized multicenter trial is warranted to confirm our results.

Can Use of Intravenous Methylene Blue Improve the Hemodynamics and Outcome of the Patients with Refractory Septic Shock? An Observational Study.

Refractory shock, which fails to respond to conventional vasopressor therapy, is a common complication of sepsis. Methylene blue has emerged as a potential adjunctive treatment option for reversing refractory shock in sepsis. The aim of this study was to evaluate the impact of intravenous methylene blue infusion on hemodynamic improvement and mortality in patients with refractory shock. This was an observational prospective study for the duration of six months conducted at intensive care a medical college and teaching hospital including 76 patients with a diagnosis of septic shock requiring vasopressor therapy. Intravenous (IV) methylene blue was infused as a bolus dose with 2 mg/kg dose in 20 minutes and its response to mean arterial blood pressure, decrease in vasopressor therapy, lactate level, and urine output was recorded in next 2 hours. Patients with improvement in mean arterial pressure (MAP) by 10% or decrease in vasopressor therapy in the next 2 hours were leveled as responder. The length of intensive care unit (ICU) stay, duration of mechanical ventilation, incidence of acute kidney injury (AKI), and mortality were compared between responder and non-responder. A total of 76 patients with refractory shock were included in the study. With the use of IV methylene blue, 41 (53.9%) patients showed significant improvement in MAP within 2 hours (70.17 ± 8.30 vs 64.28 ± 11.84, p = 0.005). Responders were 4.019 times more likely to have vasopressor-free time within 24 hours (18.4% vs 5.3%, p = 0.020, odds ratio 4.019, 95% confidence interval, 1.180-13.682). However, there was no significant difference in terms of mortality, length of ICU stay, ventilator free days, and incidence of AKI. In the responder group, there was a significant increase in the MAP and decrease in vasopressor requirement pre- and post-infusion of methylene blue (p < 0.05). Responder had shorter vasopressor-free days as compared with non-responder (5.34 vs 6.79, p = 0.008) while the mean survival time was longer with responders (21.97 vs 15.93 days, p = 0.024). The use of IV methylene blue in refractory shock as an adjuvant therapy significantly improved the mean arterial blood pressure and decreased the requirement of vasopressor therapy as well as improvement in the survival time. However, there was no change in the mortality, length of ICU stay, ventilator-free days, or incidence of AKI in the patients. Rajbanshi LK, Bajracharya A, Arjyal B, Devkota D. Can Use of Intravenous Methylene Blue Improve the Hemodynamics and Outcome of the Patients with Refractory Septic Shock? An Observational Study. Indian J Crit Care Med 2023;27(9):669-674.

Intraoperative Versus Postoperative Hydroxocobalamin for Vasoplegic Shock in Cardiothoracic Surgery

Hydroxocobalamin inhibits nitric oxide pathways contributing to vasoplegic shock in patients undergoing cardiopulmonary bypass (CPB). The objective of this study was to evaluate the effect of intraoperative versus postoperative application of hydroxocobalamin for vasoplegic shock in patients undergoing CPB. This was a historic cohort study. The study was conducted at a quaternary academic cardiovascular surgery program. Adults undergoing cardiac surgery using CPB were participants in the study. Hydroxocobalamin (5 g) intravenously over 15 minutes. The treatment groups were assigned based on the receipt location of hydroxocobalamin (ie, intensive care unit [ICU] versus operating room [OR]). The primary outcome was vasopressor-free days in the first 14 days after CPB. Of the 112 patients included, 37 patients received hydroxocobalamin in the OR and 75 in the ICU. Patients in the OR group were younger than those in the ICU group (57.5 v 63.9 years, p=0.007), with statistically similar American Society of Anesthesiologists scores. The mean CPB duration was 3.4 hours in the OR group and 2.9 hours in the ICU group (p=0.09). In both groups, the norepinephrine-equivalent dose of vasopressors at hydroxocobalamin was 0.27 µg/kg/min. Days alive and free of vasopressors were not different between the OR and ICU groups (hazard ratio 0.48 [95% CI 1.76-2.72], p=0.67). The odds of postoperative renal failure, mesenteric ischemia, ICU, hospital length of stay, and in-hospital mortality were also similar between groups. A difference in vasopressor-free days after CPB was not found between patients who received hydroxocobalamin intraoperatively versus postoperatively for vasoplegic shock.

Acute kidney injury in pediatric toxic shock syndrome is associated with worse clinical course in the intensive care unit.

To explore the prevalence, severity, nature, and significance of acute kidney injury (AKI) among children admitted to the pediatric intensive care unit (PICU) with toxic shock syndrome (TSS). Bi-center, retrospective observational study. Children admitted for TSS to two intensive care units from 2009-2022 were included. We identified 41 children (median age 5years, 46% females) who met the Centers for Disease Control and Prevention (CDC) definitions of TSS. Staphylococcal TSS accounted for 63% of the patients and Streptococcal TSS accounted for the remaining 37%. AKI was diagnosed in 24 (59%) (stage 1: n = 6 [15% of total], stage 2: n = 10 [24%], and stage 3: n = 8 [20%]). The worst creatinine level was measured during the first day of admission in 34 (83%) patients. The median duration of AKI was 2days. Creatinine normalized by hospital discharge in all cases. Patients with AKI had a longer intensive care unit stay than those without AKI (6 vs. 3days, respectively, p = 0.01), needed more respiratory support (87% vs. 47%, p = 0.002), had fewer 28 ventilation-free days (25 vs. 28, p = 0.01), fewer vasopressor-free days (25 vs. 28, p = 0.001), and received more blood products (p = 0.03). Conclusion: Children admitted to the PICU with TSS, show a high prevalence of AKI at presentation. Creatinine levels and clearance normalize by hospital discharge in most cases. AKI in the setting of TSS could be used as an early marker for illness severity and a predictor of a more complex course. What is Known: • TSS is characterized according to the CDC by specific sets of clinical signs and symptoms in conjunction with specific laboratory findings one of which is AKI. • AKI is associated with worse outcomes in critically ill patients in general and in septic patients in particular. What is New: • AKI is found in about 60% of all patients admitted to the PICU with a diagnosis of TSS and hence is an important defining criteria. • AKI in the setting of TSS is associated with a more complex illness course and can serve as an early marker predicting such a course.

Patient-Level Meta-Analysis of Low-Dose Hydrocortisone in Adults with Septic Shock

BackgroundTrials and study-level meta-analyses have failed to resolve the role of corticosteroids in the management of patients with septic shock. Patient-level meta-analyses may provide more precise estimates of treatment effects, particularly subgroup effects.MethodsWe pooled individual patient data from septic shock trials investigating the adjunctive use of intravenous hydrocortisone. The primary outcome was 90-day all-cause mortality, and it was also analyzed across predefined subgroups. Secondary outcomes included mortality at intensive care unit and hospital discharge, at 28 and 180 days, and vasopressor-, ventilator-, and organ failure–free days. Adverse events included superinfection, muscle weakness, hyperglycemia, hypernatremia, and gastroduodenal bleeding.ResultsOf 24 eligible trials (n=8528), 17 (n=7882) provided individual patient data, and 7 (n=5929) provided 90-day mortality. The marginal relative risk (RR) for 90-day mortality of hydrocortisone versus placebo was 0.93 (95% confidence interval [CI], 0.82 to 1.04; P=0.22; moderate certainty). It was 0.86 (9% CI, 0.79 to 0.92) for hydrocortisone with fludrocortisone and 0.96 (95% CI, 0.82 to 1.12) without fludrocortisone. There was no significant differential treatment effect across subgroups. Hydrocortisone was associated with little to no difference in any of the secondary outcomes except vasopressor-free days (mean difference, 1.24 days; 95% CI, 0.74 to 1.73; high certainty). Hydrocortisone may not be associated with an increase in the risk of superinfection (RR, 1.04; 95% CI, 0.95 to 1.15; low certainty), hyperglycemia (RR, 1.05; 95% CI, 0.98 to 1.12; low certainty), or gastroduodenal bleeding (RR, 1.11; 95% CI, 0.83 to 1.48; low certainty). Hydrocortisone may be associated with an increase in the risk of hypernatremia (RR, 2.01; 95% CI, 1.56 to 2.60; low certainty) and muscle weakness (n=2647; RR, 1.73; 95% CI, 1.49 to 1.99; low certainty).ConclusionsIn this patient-level meta-analysis, hydrocortisone compared with placebo was not associated with reduced mortality for patients with septic shock. (Funded by “Programme d’Investissements d’Avenir,” a research Professorship from the National Institute of Health and Care Research, Leadership Fellowships from the National Health and Medical Research Council of Australia, and Emerging Leaders Fellowship from the National Health and Medical Research Council of Australia; PROSPERO registration number, CRD42017062198.)

The effect of meropenem versus piperacillin-tazobactam in critically ill patients with sepsis and septic shock

BackgroundAntibiotics are a popular and efficient treatment for sepsis and septic shock. However, there is presently little proof of Meropenem with piperacillin-therapeutic tazobactam's benefits. MethodsFrom January 1, 2010 to January 1, 2021, we treated a total of 1244 patients with sepsis and septic shock using either Meropenem (n = 622, 1 g every 8 h) or piperacillin-tazobactam (n = 622, 3.375 g or 4.5 g every 8 h). The intervention was administered for 7 days following randomization and continued for up to 14 days thereafter, or until the patient was discharged from the critical care unit or passed away, whichever occurred first. ResultsFirst, we discovered that there were no significant changes in the duration of stay in ICU, Cardiovascular in SOFA, Coagulation in SOFA, Hepatic in SOFA, or Central Nervous System in SOFA between the meropenem alone group and the piperacillin-tazobactam group. In addition, WBC beyond the standard limit was 68.00% in the meropenem alone group against 61.89% in the piperacillin-tazobactam group (P = 0.03). However, Meropenem had a lower mortality rate on ventilator-free days, vasopressor-free days, and hospital-free days. ConclusionThis procedure may offer clinical evidence for the safety and efficacy of meropenem with piperacillin-tazobactam in critically sick patients with sepsis and septic shock.

Effect of early vasopressin combined with norepinephrine on short-term mortality in septic shock: A retrospective study based on the MIMIC-IV database

BackgroundSeptic shock is a leading cause of death in intensive care units (ICUs), with short-term mortality rates of 35–40%. Vasopressin (AVP) is a second-line vasoactive agent for septic shock, and recent studies suggest that early AVP use can be beneficial. However, differences between early initiation of AVP combined with norepinephrine (NE) and nonearly AVP with NE are unclear. A retrospective cohort research was designed to explore the effects of early AVP initiation versus nonearly AVP initiation. MethodsThis retrospective single-center cohort study included adult patients with septic shock from the MIMIC (Medical Information Mart for Intensive Care)-IV database. According to whether AVP was used early in the ICU (intensive care unit), patients were assigned to the early- (within 6 h of septic shock onset) and non-early-AVP (at least 6 h after septic shock onset) groups. The primary outcome was 28-day mortality. The secondary outcomes were ICU and hospital mortality, the numbers of vasopressor-free and ventilation-free days at 28 days, ICU length of stay (LOS), hospital LOS, sequential organ failure assessment (SOFA) score on days 2 and 3, and renal replacement therapy (RRT) use on days 2 and 3. Univariate and multivariate cox proportional-hazards regression, propensity-score matching were used to analyze the differences between the groups. ResultsThe study included 531 patients with septic shock: 331 (62.5%) in the early-AVP group and 200 (37.5%) in the non-early-AVP group. For 1:1 matching, 158 patients in the early-AVP group were matched with the same number of patients with nonearly AVP. Regarding the primary outcome, there was no significant difference between the early- and non-early-AVP groups in 28-day mortality (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.68–1.24). For the secondary outcomes, there were no differences between the early- and non-early-AVP groups in ICU mortality (HR = 0.95, 95% CI = 0.67–1.35), hospital mortality (HR = 0.95, 95% CI = 0.69–1.31), the numbers of vasopressor-free and ventilation-free days at 28 days, ICU LOS, hospital LOS, SOFA score on days 2 and 3, and RRT use on days 2 and 3. ConclusionsThere was no difference in short-term mortality between early AVP combined with NE and nonearly AVP with NE in septic shock.

Safety, tolerability, pharmacokinetics, and efficacy of kukoamine B in patients with sepsis: A randomized phase IIa trial

PurposeTo evaluate the safety, tolerability, pharmacokinetics, and efficacy of kukoamine B (KB), an alkaloid compound with high affinity for both lipopolysaccharide (LPS) and oligodeoxynucle-otides containing CpG motifs (CpG DNA), in patients with sepsis-induced organ failure. Materials and methodsThis was a multicenter, randomized, double-blind, placebo-controlled phase IIa trial. Patients with sepsis-induced organ failure were randomized to receive either KB (0.06, 0.12, or 0.24 mg/kg) or placebo, every 8 h for 7 days. Primary endpoint was safety, and secondary endpoints included pharmacokinetic (PK) parameters, changes in inflammatory mediators' level, and prognostic parameters. ResultsOf 44 patients enrolled, adverse events occurred in 28 patients [n = 20, 66.7% (KB pooled); n = 8, 57.1% (placebo)], while treatment emergent adverse events were reported in 14 patients [n = 10, 33.3% (KB pooled); n = 4, 28.6% (placebo)]. Seven patients died at 28-day follow-up [n = 4, 13.3% (KB pooled); n = 3, 21.4% (placebo)], none was related to study drug. PK parameters suggested dose-dependent drug exposure and no drug accumulation. KB did not affect clinical outcomes such as ΔSOFA score, vasopressor-free days or ventilator-free days. ConclusionsIn patients with sepsis-induced organ failure, KB was safe and well tolerated. Further investigation is warranted. Trial registrationhttp://ClinicalTrials.gov, NCT03237728.