Abstract

BACKGROUND AND AIM The choice of resuscitation fluid in cirrhosis patients with sepsis-induced hypotension (SIH) is unclear. 5% albumin has been superior to normal saline in the FRISC study. We compared the efficacy and safety of 20% albumin, which has greater oncotic properties with plasmalyte in reversing SIH. METHODS Critically-ill cirrhosis(CIC) patients underwent open-label randomization to receive either 20% albumin [0.5-1.0gm/kg over 3 hours; n=50] or plasmalyte (30ml/kg over 3 hours, n=50). The primary end-point of the study was the attainment of mean arterial pressure (MAP) above 65 mmHg at three hours. RESULTS Baseline characteristics were comparable in albumin and plasmalyte groups; arterial lactate(mmol/L) [6.16±3.18 vs. 6.38±4.77; p=0.78), MAP (mmHg) [51.4±6.52 vs. 49.9±4.45; p=0.17] and SOFA score [10.8±2.96 vs. 11.1±4.2; p=0.68] respectively. Most patients were alcoholics (39%) and had pneumonia (40%). In the intention-to-treat (ITT) analysis, albumin was superior to plasmalyte in achieving the primary end-point (62% vs. 22%; p<0.001). A rapid decline in arterial lactate (P=0.03), a lesser proportion of dialysis [48% vs. 62%; p=0.16], and a higher time to initiation of dialysis (in hours) [68.13±47.79 vs. 99.7± 63.4; p=0.06] was seen with albumin. However, the 28-day mortality was not different (58% vs. 62%, p=0.57). Patients in the albumin group required discontinuation of therapy in 11 (22%) patients due to adverse effects compared to none in plasmalyte group. CONCLUSION In patients with cirrhosis and SIH, 20% albumin transiently improves the hemodynamics with early lactate clearance than plasmalyte but needs monitoring as it is more often attended with pulmonary complications. Both fluids provide comparable 28 days survival. NCT02721238 LAY SUMMARY The current randomized controlled trial performed in critically ill patients with cirrhosis and sepsis-induced hypotension highlights that 20% albumin restores hemodynamics but causes more pulmonary complications than plasmalyte. The impact on renal functions was also modest. These effects did not result in improvement in deaths at 28-days. Plasmalyte is safer and well-tolerated and can be considered for volume resuscitation in patients with cirrhosis and sepsis-induced hypotension.

Abstract

OBJECTIVES Neonatal sepsis is one of the leading causes of neonatal deaths in neonatal intensive care units. Hence, it is essential to review the evidence from systematic reviews on interventions for reducing late-onset sepsis (LOS) in neonates. METHODS PubMed and the Cochrane Central were searched from inception through August 2020 without any language restriction. Cochrane reviews of randomized clinical trials (RCTs) assessing any intervention in the neonatal period and including one or more RCTs reporting LOS. Two authors independently performed screening, data extraction, assessed the quality of evidence using Cochrane Grading of Recommendations Assessment, Development and Evaluation, and assessed the quality of reviews using a measurement tool to assess of multiple systematic reviews 2 tool. RESULTS A total of 101 high-quality Cochrane reviews involving 612 RCTs and 193,713 neonates, evaluating 141 interventions were included. High-quality evidence showed a reduction in any or culture-proven LOS using antibiotic lock therapy for neonates with central venous catheters (CVC). Moderate-quality evidence showed a decrease in any LOS with antibiotic prophylaxis or vancomycin prophylaxis for neonates with CVC, chlorhexidine for skin or cord care, and kangaroo care for low birth weight babies. Similarly, moderate-quality evidence showed reduced culture-proven LOS with intravenous immunoglobulin prophylaxis for preterm infants and probiotic supplementation for very low birth weight (VLBW) infants. Lastly, moderate-quality evidence showed a reduction in fungal LOS with the use of systemic antifungal prophylaxis in VLBW infants. CONCLUSIONS The overview summarizes the evidence from the Cochrane reviews assessing interventions for reducing LOS in neonates, and can be utilized by clinicians, researchers, policymakers, and consumers for decision-making and translating evidence into clinical practice.

Abstract

BACKGROUND Discordance with well-known sepsis resuscitation guidelines is often attributed to rational assessments of patients at the point of care. Conversely, we sought to explore the impact of choice architecture (i.e., the environment, manner, and behavioral psychology within which options are presented and decisions are made) on decisions to prescribe guideline-discordant fluid volumes. DESIGN We conducted an electronic, survey-based study using a septic shock clinical vignette. Physicians from multiple specialties and training levels at an academic tertiary-care hospital and academic safety-net hospital were randomized to distinct answer sets: control (6 fluid options), time constraint (6 fluid options with a 10-s limit to answer), or choice overload (25 fluid options). The primary outcome was discordance with Surviving Sepsis Campaign fluid resuscitation guidelines. We also measured response times and examined the relationship between each choice architecture intervention group, response time, and guideline discordance. RESULTS A total of 189 of 624 (30.3%) physicians completed the survey. Time spent answering the vignette was reduced in time constraint (9.5 s, interquartile range [IQR] 7.3 s to 10.0 s, P < 0.001) and increased in choice overload (56.8 s, IQR 35.9 s to 86.7 s, P < 0.001) groups compared with control (28.3 s, IQR 20.0 s to 44.6 s). In contrast, the relative risk of guideline discordance was higher in time constraint (2.07, 1.33 to 3.23, P = 0.001) and lower in choice overload (0.75, 0.60, to 0.95, P =0.02) groups. After controlling for time spent reading the vignette, the overall odds of choosing guideline-discordant fluid volumes were reduced for every additional second spent answering the vignette (OR 0.98, 0.97, to 0.99, P < 0.001). CONCLUSIONS Choice architecture may affect fluid resuscitation decisions in sepsis regardless of patient conditions, warranting further investigation in real-world contexts. These effects should be considered when implementing practice guidelines. HIGHLIGHTS Time constrained clinical decision making was associated with increased proportion of guideline-discordant responses and relative risk of failure to prescribe guideline-recommended intravenous fluids using a sepsis clinical vignette.Choice overload increased response times and was associated with decreased proportion of guideline-discordant responses and relative risk of guideline discordance.Physician odds of choosing to prescribe guideline-discordant fluid volumes were reduced with increased deliberation as measured by response times.Clinicians, researchers, policy makers, and administrators should consider the effect of choice architecture on clinical decision making and guideline discordance when implementing guidelines for sepsis and other acute care conditions.

Abstract

OBJECTIVE To explore the clinical effects of albumin supplements on the basis of crystalloid solution in patients with sepsis or septic shock. METHODS The online databases including PubMed, Web of Science, Cochrane Library, and EMBASE were comprehensively searched from inception to June 28, 2021, with the keywords including "albumin," "sepsis," or "septic shock." Retrospective cohort (RC) and randomized controlled trials (RCT) were included for analysis. Two authors independently searched and analyzed the literature. The in-hospital mortality at 7 days and 28 days, duration of mechanical ventilation, renal replacement therapy, length of ICU stay, and length of hospital stay were compared between patients with albumin supplements and crystalloid solution and those with crystalloid alone. RESULTS A total of 10 studies with 6463 patients were eventually included for meta-analysis. The in-hospital mortality of patients at 7 days (OR = 1.00, 95% CI: 0.81-1.23) and 28 days (OR = 1.02, 95% CI: 0.91-1.13) did not show a significant difference between the two groups of patients. Also, the pooled results demonstrated no significant differences in duration of mechanical ventilation (OR = 0.29, 95% CI: -0.05-0.63), renal replacement therapy (WMD = 1.15, 95% CI: 0.98-1.35), length of ICU stay (WMD = -0.07, 95% CI: -0.62-0.48), and length of hospital stay (WMD = -0.09, 95% CI: -0.70-0.52) between patients receiving albumin plus crystalloid solution and those with crystalloid solution alone. CONCLUSION Albumin supplements on the basis of crystalloid solution did not improve the 7-day and 28-dayin-hospital mortality in patients with sepsis or septic shock compared with those with crystalloid solution alone.

Abstract

BACKGROUND Recently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock. Prediction of clinical efficacy in specific sepsis treatments is fundamental for individualized sepsis therapy. METHODS In the original RCT, patients with septic shock of < 24 h duration and norepinephrine (NE) requirement ≥ 0.4 μg/kg/min received standard of care (SOC) or SOC + one single TPE. Here, we report all clinical and biological endpoints of this study. Multivariate mixed-effects modeling of NE reduction was performed to investigate characteristics that could be associated with clinical response to TPE. RESULTS A continuous effect of TPE on the reduction in NE doses over the initial 24 h was observed (SOC group: estimated NE dose reduction of 0.005 µg/kg/min per hour; TPE group: 0.018 µg/kg/min per hour, p = 0.004). Similarly, under TPE, serum lactate levels, continuously decreased over the initial 24 h in the TPE group, whereas lactate levels increased under SOC (p = 0.001). A reduction in biomarkers and disease mediators (such as PCT (p = 0.037), vWF:Ag (p < 0.001), Angpt-2 (p = 0.009), sTie-2 (p = 0.005)) along with a repletion of exhausted protective factors (such as AT-III (p = 0.026), Protein C (p = 0.012), ADAMTS-13 (p = 0.008)) could be observed in the TPE but not in the SOC group. In a multivariate mixed effects model, increasing baseline lactate levels led to greater NE dose reduction effects with TPE as opposed to SOC (p = 0.004). CONCLUSIONS Adjunctive TPE is associated with the removal of injurious mediators and repletion of consumed protective factors altogether leading to preserved hemodynamic stabilization in refractory septic shock. We identified that baseline lactate concentration as a potential response predictor might guide future designing of large RCTs that will further evaluate TPE with regard to hard endpoints. Trial registration Retrospectively registered 18th January 2020 at clinicaltrials.gov (Identifier: NCT04231994 ).

Abstract

The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive meta-analysis to compare the effect of balanced crystalloids (BC) vs. normal saline (NS) in adults with sepsis. A systematic search of PubMed, EMBASE, and Web of Sciences databases through 22 January 2022, was performed for studies that compared BC vs. NS in adults with sepsis. Our outcomes included mortality and acute kidney injury (AKI), need for renal replacement therapy (RRT), and ICU length of stay (LOS). Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were obtained using a random-effect model. Fifteen studies involving 20,329 patients were included. Overall, BC showed a significant reduction in the overall mortality (RR 0.88, 95% CI 0.81-0.96), 28/30-day mortality (RR 0.87, 95% CI 0.79-0.95), and AKI (RR 0.85, 95% CI 0.77-0.93) but similar 90-day mortality (RR 0.96, 95% CI 0.90-1.03), need for RRT (RR 0.91, 95% CI 0.76-1.08), and ICU LOS (MD -0.25 days, 95% CI -3.44, 2.95), were observed between the two groups. However, subgroup analysis of randomized controlled trials (RCTs) showed no statistically significant differences in overall mortality (RR 0.92, 95% CI 0.82-1.02), AKI (RR 0.71, 95% CI 0.47-1.06), and need for RRT (RR 0.71, 95% CI 0.36-1.41). Our meta-analysis demonstrates that overall BC was associated with reduced mortality and AKI in sepsis compared to NS among patients with sepsis. However, subgroup analysis of RCTs showed no significant differences in both overall mortality and AKI between the groups. There was no significant difference in the need for RRT or ICU LOS between BC and NS. Pending further data, our study supports using BC over NS for fluid resuscitation in adults with sepsis. Further large-scale RCTs are necessary to validate our findings.

Abstract

BACKGROUND Refractory septic shock in neonates is still associated with high mortality, necessitating an alternative therapy, despite all currently available treatments. This study aims to assess the vasopressor effect of methylene blue (MB) in comparison to terlipressin (TP) as adjuvant therapy for refractory septic shock in the preterm neonate. METHODS A double-blinded randomized controlled trial was conducted in the Neonatal Intensive Care Units at Ain Shams University, Egypt. Thirty preterm neonates with refractory septic shock were randomized to receive either MB or TP as an adjuvant to conventional therapy. Both MB and TP were administered as an intravenous loading dose followed by continuous intravenous infusion. The hemodynamic variables, functional echocardiographic variables, and oxidant stress marker were assessed over a 24 h period together with the side effects of MB. RESULTS MB causes significant improvement in mean arterial blood pressure with a significant decrease of the norepinephrine requirements (1.15±0.21μm/kg/min at baseline vs. 0.55±0.15μm/kg/min at 24 h). MB infusion causes an increase of the pulmonary pressure (44.73±8.53 mmHg at baseline vs. 47.27±7.91 mmHg after 24 h) without affecting the cardiac output. Serum malonaldehyde decreased from 5.45±1.30 nmol/mL at baseline to 4.40±0.90 nmol/mL at 24 h in the MB group. CONCLUSION Administration of MB to preterm infants with refractory septic shock showed rapid increases in systemic vascular resistance and arterial blood pressure with minimal side effects.

Abstract

BACKGROUND Whether to use limited fluid resuscitation (LFR) in patients with hemorrhagic shock or septic shock remains controversial. This research was aimed to assess the pros and cons of utilizing LFR in hemorrhagic shock or septic shock patients. METHODS PubMed, Cochrane Library, Embase, Web of science, CNKI, VIP, and Wan Fang database searches included for articles published before December 15, 2020. Randomized controlled trials of LFR or adequate fluid resuscitation in hemorrhagic shock or septic shock patients were selected. RESULT This meta-analysis including 28 randomized controlled trials (RCTs) and registered 3288 patients. The 7 of 27 RCTs were the patients with septic shock. Others were traumatic hemorrhagic shock patients. Comparing LFR or adequate fluid resuscitation in hemorrhagic shock or septic shock patients, the summary odds ratio (OR) was 0.50 (95% confidence interval [CI] 0.42-0.60, P < .00001) for mortality, 0.46 (95% CI 0.31-0.70, P = .0002) for multiple organ dysfunction syndrome (MODS), 0.35 (95% CI 0.25-0.47) for acute respiratory distress syndrome (ARDS), and 0.33 (95% CI 0.20-0.56) for disseminated intravascular coagulation (DIC). CONCLUSION Limited fluid resuscitation is the benefit of both traumatic hemorrhagic shock patients and septic shock patients.

Abstract

INTRODUCTION The ultrasound measurement of inferior vena cava (IVC) diameter change during respiratory phase to guide fluid resuscitation in shock patients is widely performed, but the benefit on reducing the mortality of sepsis patients is questionable. The study objective was to evaluate the 30-day mortality rate of patients with sepsis-induced tissue hypoperfusion (SITH) and septic shock (SS) treated with ultrasound-guided fluid management (UGFM) using ultrasonographic change of the IVC diameter during respiration compared with those treated with the usual-care strategy. METHODS This was a randomized controlled trial conducted in an urban, university-affiliated tertiary-care hospital. Adult patients with SITH/SS were randomized to receive treatment with UGFM using respiratory change of the IVC (UGFM strategy) or with the usual-care strategy during the first six hours after emergency department (ED) arrival. We compared the 30-day mortality rate and other clinical outcomes between the two groups. RESULTS A total of 202 patients were enrolled, 101 in each group (UGFM vs usual-care strategy) for intention-to-treat analysis. There was no significant difference in 30-day overall mortality between the two groups (18.8% and 19.8% in the usual-care and UGFM strategy, respectively; p > 0.05 by log rank test). Neither was there a difference in six-hour lactate clearance, a change in the sequential organ failure assessment score, or length of hospital stay. However, the cumulative fluid amount given in 24 hours was significantly lower in the UGFM arm. CONCLUSION In our ED setting, the use of respiratory change of IVC diameter determined by point-of-care ultrasound to guide initial fluid resuscitation in SITH/SS ED patients did not improve the 30-day survival probability or other clinical parameters compared to the usual-care strategy. However, the IVC ultrasound-guided resuscitation was associated with less amount of fluid used.

Abstract

Current evidences in resuscitation of adult sepsis have pointed to the importance of types of crystalloid fluid-related complications on resuscitation outcomes, but evidences are lacking in pediatric populations. In this study, the authors aimed to compare outcomes of pediatric sepsis resuscitation with different types of crystalloid. They randomly assigned pediatric sepsis patients requiring fluid bolus into three groups to receive either normal saline solution (NSS), Ringer lactate solution (RLS), or Sterofundin as fluid bolus therapy. Forty-two patients were included in the study. Median age was 29 mo and, weight 13 kg. After fluid bolus, the complications were not different among groups. However, in the RLS group, the patients who received large dose of the fluid showed significant reduction in urinary neutrophil gelatinase-associated lipocalin (uNGAL) level. It is concluded that fluid bolus therapy with different types of crystalloid solution did not result in different outcomes but large dose of RLS was associated with greater reduction of uNGAL level, compared to other fluids.Trial Registration: Thai Clinical Trial Registry (TCTR) identification number TCTR20170605001 (retrospectively registered on 1st June 2017). https://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task20=search&task2=view1&id=2576.