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

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

OBJECTIVES The purpose of this research was to determine the effectiveness of Pentaglobin® as adjuvant therapy in the treatment of sepsis in preterm newborns. MATERIALS AND METHODS It was a prospective, observational, randomized study for 272 premature neonates and very low birth weight (VLBW) that were diagnosed with sepsis carried at neonatal intensive care units. The patients randomized into control group who received standard sepsis antibiotic treatments, and an intervention group who received Pentaglobin® 5 ml/kg daily for 3 consecutive days as an adjunct therapy to a standard sepsis antibiotic treatment. RESULTS Multiple organisms that isolated from culture specimens were Gram-negative bacteria, Gram-positive, and candida (56.25%, 42.28%, and 1.47%, respectively). The disease duration was distinctively longer in patients who were treated by the standard antibiotic protocol (mean ± standard deviation [SD]: 30.76 ± 3.97, odds ratio [OR]: 30.76, 95% confidence interval [CI]: 30.051, 31.473) comparing to the patients who received Pentaglobin adjuvant therapy (mean ± SD: 26.48 ± 5.55, OR: 26.48, 95% CI: 25.489, 27.477) (P < 0.000). Patients treated by standard antibiotic protocol were associated to a substantially increased risk of death (11.76%, hazard ratio 4.400, 95% CI: 1.432, 13.529, P = 0.009). CONCLUSION Neonatal sepsis is more common in premature and VLBW newborns, and Pentaglobin® management of newborn nosocomial sepsis might be used in addition to other therapies.

Abstract

BACKGROUND The effect of early vasopressin initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early start of vasopressin support within 6 h after the diagnosis on clinical outcomes in septic shock patients. METHODS We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of February 2021. We included studies involving adult patients (> 16 years)with septic shock. All authors reported our primary outcome of short-term mortality and in the experimental group patients in the studies receiving vasopressin infusion within 6 h after diagnosis of septic shock and in the control group patients in the studies receiving no vasopressin infusion or vasopressin infusion 6 h after diagnosis of septic shock, clearly comparing with clinically relevant secondary outcomes(use of renal replacement therapy(RRT),new onset arrhythmias, ICU length of stay and length of hospitalization). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). RESULTS Five studies including 788 patients were included. The primary outcome of this meta-analysis showed that short-term mortality between the two groups was no difference (odds ratio [OR] = 1.09; 95% CI, 0.8 to 1.48; P = 0.6; χ2 = 0.83; I2 = 0%). Secondary outcomes demonstrated that the use of RRT was less in the experimental group than that of the control group (OR = 0.63; 95% CI, 0.44 to 0.88; P = 0.007; χ2 = 3.15; I2 = 36%).The new onset arrhythmias between the two groups was no statistically significant difference (OR = 0.59; 95% CI, 0.31 to 1.1; P = 0.10; χ2 = 4.7; I2 = 36%). There was no statistically significant difference in the ICU length of stay(mean difference = 0.16; 95% CI, - 0.91 to 1.22; P = 0.77; χ2 = 6.08; I2 = 34%) and length of hospitalization (mean difference = -2.41; 95% CI, -6.61 to 1.78; P = 0.26; χ2 = 8.57; I2 = 53%) between the two groups. CONCLUSIONS Early initiation of vasopressin in patients within 6 h of septic shock onset was not associated with decreased short-term mortality, new onset arrhythmias, shorter ICU length of stay and length of hospitalization, but can reduce the use of RRT. Further large-scale RCTs are still needed to evaluate the benefit of starting vasopressin in the early phase of septic shock.

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

BACKGROUND Aggressive fluid administration is recommended in the resuscitation of septic patients. However, the delivery of a rapid fluid bolus might cause harm by inducing degradation of the endothelial glycocalyx. This research aimed to examine the effects of the limited infusion rate of fluid on glycocalyx shedding as measured by syndecan-1 in patients with sepsis-induced hypoperfusion. METHODS A prospective, randomized, controlled, open-label trial was conducted between November 2018 and February 2020 in an urban academic emergency department. Patients with sepsis-induced hypoperfusion, defined as hypotension or hyperlactatemia, were randomized to receive either the standard rate (30 ml/kg/h) or limited rate (10 ml/kg/h) of fluid for the first 30 ml/kg fluid resuscitation. Subsequently, the fluid rate was adjusted according to the physician's discretion but not more than that of the designated fluid rate for the total of 6 h. The primary outcome was differences in change of syndecan-1 levels at 6 h compared to baseline between standard and limited rate groups. Secondary outcomes included adverse events, organ failure, and 90-day mortality. RESULTS We included 96 patients in the intention-to-treat analysis, with 48 assigned to the standard-rate strategy and 48 to the limited-rate strategy. The median fluid volume in 6 h in the limited-rate group was 39 ml/kg (interquartile range [IQR] 35-52 ml/kg) vs. 53 ml/kg (IQR 46-64 ml/kg) in the standard-rate group (p < 0.001). Patients in the limited-rate group were less likely to received vasopressors (17% vs 42%; p = 0.007) and mechanical ventilation (20% vs 41%; p = 0.049) during the first 6 h. There were no significantly different changes in syndecan-1 levels at 6 h between the two groups (geometric mean ratio [GMR] in the limited-rate group, 0.82; 95% confidence interval [CI], 0.66-1.02; p = 0.07). There were no significant differences in adverse events, organ failure outcomes, or mortality between the two groups. CONCLUSIONS In sepsis resuscitation, the limited rate of fluid resuscitation compared to the standard rate did not significantly reduce changes in syndecan-1 at 6 h. TRIAL REGISTRATION Thai Clinical Trials Registry number: TCTR20181010001. Registered 8 October 2018, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=4064.

Abstract

Red blood cell transfusion is thought to improve cell respiration during septic shock. Nevertheless, its acute impact on oxygen transport and metabolism in this condition remains highly debatable. The objective of this study was to evaluate the impact of red blood cell transfusion on microcirculation and oxygen metabolism in patients with sepsis and septic shock. We conducted a search in the MEDLINE®, Elsevier and Scopus databases. We included studies conducted in adult humans with sepsis and septic shock. A systematic review and meta-analysis were performed using the DerSimonian and Laird random-effects model. A p value < 0.05 was considered significant. Nineteen manuscripts with 428 patients were included in the analysis. Red blood cell transfusions were associated with an increase in the pooled mean venous oxygen saturation of 3.7% (p < 0.001), a decrease in oxygen extraction ratio of -6.98 (p < 0.001) and had no significant effect on the cardiac index (0.02L/minute; p = 0,96). Similar results were obtained in studies including simultaneous measurements of venous oxygen saturation, oxygen extraction ratio, and cardiac index. Red blood cell transfusions led to a significant increase in the proportion of perfused small vessels (2.85%; p = 0.553), while tissue oxygenation parameters revealed a significant increase in the tissue hemoglobin index (1.66; p = 0.018). Individual studies reported significant improvements in tissue oxygenation and sublingual microcirculatory parameters in patients with deranged microcirculation at baseline. Red blood cell transfusions seemed to improve systemic oxygen metabolism with apparent independence from cardiac index variations. Some beneficial effects have been observed for tissue oxygenation and microcirculation parameters, particularly in patients with more severe alterations at baseline. More studies are necessary to evaluate their clinical impact and to individualize transfusion decisions.

Abstract

The mortality rate of sepsis-associated disseminated intravascular coagulation (DIC) is high. This study aimed to explore the efficacy of therapeutic plasma exchange (TPE) in sepsis-associated DIC patients by improving endothelial function. A total of 112 sepsis-associated DIC patients were randomly divided into the TPE group (n = 40), the heparin (HP) group (n = 36), and the SHAM group (n = 36). The SHAM group received conventional treatment; the HP group was treated with HP based on conventional treatment; and the TPE group received conventional treatment plus TPE. The differences in thromboelastogram (TEG), platelet (PLT), coagulation function, and the endothelial cell (EC) injury biomarkers at 6 h, 24 h, 48 h, 72 h, and 7 days after TPE were compared among the three groups, and the three groups were compared in terms of Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sepsis-Related Organ Failure Assessment (SOFA) score, the length of intensive care unit (ICU) hospitalization, 28-day mortality rate, 28-day cumulative survival rate, the incidence of bleeding events, the incidence of acute kidney injury (AKI), and acute respiratory distress syndrome (ARDS). The efficacy of TPE is superior to the HP in increasing PLT, improving coagulation function, increasing the 28-day cumulative survival rate, and reducing the length of ICU hospitalization, 28-day mortality, and the incidence of bleeding events, AKI, and ARDS with statistically significant differences (P < .05). Moreover, the effect of TPE outperforms HP on the EC injury biomarkers with statistically significant differences (P < .05). Our results suggest that TPE may be more effective than HP in the treatment of patients with sepsis-associated DIC. The possible mechanism is via improving endothelial function.