Hyperoxemia in postsurgical sepsis/septic shock patients is associated with reduced mortality

Background Despite growing interest in treatment strategies that limit oxygen exposure in ICU patients, no studies have compared conservative oxygen with standard oxygen in postsurgical patients with sepsis/septic shock, although there are indications that it may improve outcomes. It has been proven that high partial pressure of oxygen in arterial blood (PaO2) reduces the rate of surgical-wound infections and mortality in patients under major surgery. The aim of this study is to examine whether PaO2 is associated with risk of death in adult patients with sepsis/septic shock after major surgery. Methods We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups whether they had hyperoxemia, defined as PaO2 > 100 mmHg (n = 216), or PaO2 ≤ 100 mmHg (n = 238) at the day of sepsis/septic shock onset according to SEPSIS-3 criteria maintained during 48 h. Primary end-point was 90-day mortality after diagnosis of sepsis. Secondary endpoints were ICU length of stay and time to extubation. Results In patients with PaO2 ≤ 100 mmHg, we found prolonged mechanical ventilation (2 [8] vs. 1 [4] days, p < 0.001), higher ICU stay (8 [13] vs. 5 [9] days, p < 0.001), higher organ dysfunction as assessed by SOFA score (9 [3] vs. 7 [5], p < 0.001), higher prevalence of septic shock (200/238, 84.0% vs 145/216) 67.1%, p < 0.001), and higher 90-day mortality (37.0% [88] vs. 25.5% [55], p = 0.008). Hyperoxemia was associated with higher probability of 90-day survival in a multivariate analysis (OR 0.61, 95%CI: 0.39–0.95, p = 0.029), independent of age, chronic renal failure, procalcitonin levels, and APACHE II score > 19. These findings were confirmed when patients with severe hypoxemia at the time of study inclusion were excluded. Conclusions Oxygenation with a PaO2 above 100 mmHg was independently associated with lower 90-day mortality, shorter ICU stay and intubation time in critically ill postsurgical sepsis/septic shock patients. Our findings open a new venue for designing clinical trials to evaluate the boundaries of PaO2 in postsurgical patients with severe infections.

Azithromycin and Septic Shock Outcomes

Introduction: Although there is evidence describing the immunomodulatory effects of macrolide antibiotics, there is little literature exploring the clinical effects these properties may have and their impact on measurable outcomes. Objective: The purpose of this study was to determine if empiric antimicrobial regimens containing azithromycin shorten time to shock resolution. Methods: A retrospective study was performed in adults with septic shock admitted to intensive care units (ICUs) of 3 university-affiliated, urban teaching hospitals between June 2012 and June 2016. Eligible patients with septic shock required treatment with norepinephrine as the first-line vasopressor for a minimum of 4 hours and received at least 48 hours of antimicrobial treatment from the time of shock onset. Propensity scores were utilized to match patients who received azithromycin to those who did not. Results: A total of 3116 patients met initial inclusion criteria. After propensity score matching, 258 patients were included, with 124 and 134 patients in the azithromycin and control groups, respectively. Median shock duration was similar in patients treated with or without azithromycin (45.6 hr vs 59.7 hr, P = .44). In-hospital mortality was also similar (37.9% vs 38.1%, P = .979). There were no significant differences in mechanical ventilation duration, ICU length of stay (LOS), or hospital LOS. Conclusions: In patients admitted to the ICU with septic shock, empiric azithromycin did not have a significant effect on shock duration, mechanical ventilation duration, ICU LOS, hospital LOS, or in-hospital mortality.

Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock

Background Disruption of the endothelial glycocalyx (eGC) is observed in septic patients and its injury is associated with multiple-organ failure and inferior outcomes. Besides this biomarker function, increased blood concentrations of shedded eGC constituents might play a mechanistic role in septic organ failure. We hypothesized that therapeutic plasma exchange (TPE) using fresh frozen plasma might influence eGC-related pathology by removing injurious mediators of eGC breakdown while at the time replacing eGC protective factors. Methods We enrolled 20 norepinephrine-dependent (NE > 0.4 μg/kg/min) patients with early septic shock (onset < 12 h). Sublingual assessment of the eGC via sublingual sidestream darkfield (SDF) imaging was performed. Plasma eGC degradation products, such as heparan sulfate (HS) and the eGC-regulating enzymes, heparanase (Hpa)-1 and Hpa-2, were obtained before and after TPE. A 3D microfluidic flow assay was performed to examine the effect of TPE on eGC ex vivo. Results were compared to healthy controls. Results SDF demonstrated a decrease in eGC thickness in septic patients compared to healthy individuals (p = 0.001). Circulating HS levels were increased more than sixfold compared to controls and decreased significantly following TPE [controls: 16.9 (8–18.6) vs. septic patients before TPE: 105.8 (30.8–143.4) μg/ml, p < 0.001; vs. after TPE: 70.7 (36.9–109.5) μg/ml, p < 0.001]. The Hpa-2 /Hpa-1 ratio was reduced in septic patients before TPE but normalized after TPE [controls: 13.6 (6.2–21.2) vs. septic patients at inclusion: 2.9 (2.1–5.7), p = 0.001; vs. septic patients after TPE: 13.2 (11.2–31.8), p < 0.001]. Ex vivo stimulation of endothelial cells with serum from a septic patient induced eGC damage that could be attenuated with serum from the same patient following TPE. Conclusions Septic shock results in profound degradation of the eGC and an acquired deficiency of the protective regulator Hpa-2. TPE removed potentially injurious eGC degradation products and partially attenuated Hpa-2 deficiency. Trial registration clinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020

Antihypertensive Medications Prior to Shock Onset Do Not Impact Initial Vasopressor Requirements in Patients With Shock

Purpose: The effect of the use of antihypertensive agents in patients prior to the development of shock is unclear. The purpose of this study was to determine the impact of antihypertensive agents on vasopressor dose and duration in shock. Materials and Methods: This retrospective, single-center study included patients with shock who received at least one vasopressor for at least 24 hours after shock onset from January 1 to June 30, 2017. Patients taking an antihypertensive agent(s) were compared to those who were not. The primary outcome was the number of vasopressor-free hours at 72 hours. Secondary outcomes included maximum and cumulative vasopressor doses, intensive care unit length of stay, and 30-day mortality. Results: One hundred and sixty-eight patients were included and 99 (59%) were on antihypertensives. Distributive shock was the most common type of shock (75.5%) and more patients taking antihypertensives had hypertension, coronary artery disease, and dyslipidemia at baseline. There was no difference in the number of vasopressor-free hours at 72 hours between patients taking an antihypertensive medication(s) and the control group (2 hours vs 1 hour; P = .11). No difference was found between any of the secondary outcomes. Conclusion: Patients taking antihypertensive agents prior to shock onset did not require increased vasopressor doses or duration.

Features of Patients Receiving Extracorporeal Membrane Oxygenation Relative to Cardiogenic Shock Onset: A Single-Centre Experience

Background and Objectives: Extracorporeal membrane oxygenation (ECMO) can be helpful in patients with cardiogenic shock associated with myocardial infarction, and its early use can improve the patient survival rate. In this study, we report a mortality rate-difference analysis that examined the time and location of shock occurrence. Materials and Methods: We enrolled patients who underwent ECMO due to cardiogenic shock related to myocardial infarction and assigned them to either a pre- or post-admission shock group. The primary outcome was the 1-month mortality rate; a subgroup analysis was conducted to assess the effect of bailout ECMO. Results: Of the 113 patients enrolled, 67 (38 with pre-admission shock, 29 with post-admission shock) were analysed. Asystole was more frequently detected in the pre-admission shock group than in the post-admission group. In both groups, the commonest culprit lesion location was in the left anterior descending artery. Cardiopulmonary resuscitation was performed significantly more frequently and earlier in the pre-admission group. The 1-month mortality rate was significantly lower in the pre-admission group than in the post-admission group. Male sex and ECMO duration (≥6 days) were factors significantly related to the reduced mortality rate in the pre-admission group. In the subgroup analysis, the mortality rate was lower in patients receiving bailout ECMO than in those not receiving it; the difference was not statistically significant. Conclusions: ECMO application resulted in lower short-term mortality rate among patients with out-of-hospital cardiogenic shock onset than with in-hospital shock onset; early cardiopulmonary resuscitation and ECMO might be helpful in select patients.

Effects of Therapeutic Plasma Exchange on the Endothelial Glycocalyx in Septic Shock

Background: Disruption of the endothelial glycocalyx (eGC) is observed in septic patients and its injury is associated with multiple-organ failure and inferior outcomes. Besides this biomarker function, increased blood concentrations of shedded eGC constituents might play a mechanistic role in septic organ failure. We hypothesized that therapeutic plasma exchange (TPE) against fresh frozen plasma might influence eGC related pathology.Methods: We enrolled 20 norepinephrine dependent (NE > 0.4mg/kg/min) patients with early septic shock (onset < 12h). Sublingual assessment of the eGC via sublingual sidestream darkfield (SDF) imaging was performed. Plasma eGC degradation products such as heparan-sulfate (HS) and the eGC regulating enzymes, heparanase (Hpa)-1 and Hpa-2, were obtained before and after TPE. A 3D microfluidic flow assay was performed to examine the effect of TPE on eGC ex vivo. Results were compared to healthy controls. Results: SDF demonstrated a decrease in eGC thickness in septic patients compared to healthy individuals (p=0.001). Circulating HS levels were increased more than six-fold compared to controls and decreased significantly following TPE (controls: 16.9 (8-18.6) vs. septic patients before TPE: 105.8 (30.8-143.4) μg/ml, p<0.001; vs. after TPE: 70.7 (36.9-109.5) μg/ml, p<0.001). The Hpa-2 /Hpa-1 ratio was reduced in septic patients before TPE but normalized after TPE (controls: 13.6 (6.2-21.2) vs. septic patients at inclusion: 2.9 (2.1-5.7), p=0.001; vs. septic patients after TPE: 13.2 (11.2-31.8), p<0.001). Ex vivo stimulation of endothelial cells with serum from a septic patient induced eGC damage that could be attenuated with serum from the same patient following TPE.Conclusions: Septic shock results in profound degradation of the eGC and an acquired deficiency of the protective regulator Hpa-2. TPE removed potentially injurious eGC degradation products and partially attenuated Hpa-2 deficiency. Trial registration: clinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020

Effects of Therapeutic Plasma Exchange on the Endothelial Glycocalyx in Septic Shock

BackgroundDisruption of the endothelial glycocalyx (eGC) is observed in septic patients and its injury is associated with multiple-organ failure and inferior outcomes. Besides this biomarker function, increased blood concentrations of shedded eGC constituents might play a mechanistic role in septic organ failure. We hypothesized that therapeutic plasma exchange (TPE) against fresh frozen plasma might influence eGC related pathology.MethodsWe enrolled 20 norepinephrine dependent (NE > 0.4μg/kg/min) patients with early septic shock (onset < 12h). Sublingual assessment of the eGC via sublingual sidestream darkfield (SDF) imaging was performed. Plasma eGC degradation products such as heparan-sulfate (HS) and the eGC regulating enzymes, heparanase (Hpa)-1 and Hpa-2, were obtained before and after TPE. A 3D microfluidic flow assay was performed to examine the effect of TPE on eGC ex vivo. Results were compared to healthy controls.ResultsSDF demonstrated a marked decrease in eGC thickness in septic patients compared to healthy individuals (p=0.001). Circulating HS levels were increased more than six-fold compared to controls and decreased significantly following TPE (controls: 16.9 (8-18.6) vs. septic patients before TPE: 105.8 (30.8-143.4) μg/ml, p<0.001; vs. after TPE: 70.7 (36.9-109.5) μg/ml, p<0.001). The Hpa-2 /Hpa-1 ratio was markedly reduced in septic patients before TPE but normalized after TPE (controls: 13.6 (6.2-21.2) vs. septic patients at inclusion: 2.9 (2.1-5.7), p=0.001; vs. septic patients after TPE: 13.2 (11.2-31.8), p<0.001). Ex vivo stimulation of endothelial cells with serum from septic patients induced eGC damage that could be attenuated with serum post TPE.ConclusionsSeptic shock results in profound degradation of the eGC and an acquired deficiency of the protective regulator Hpa-2. TPE removed potentially injurious eGC degradation products and partially attenuated Hpa-2 deficiency.Trial registrationclinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020

Circulatory collapse during wound closure in spine surgery with an unknown cause: a possible adverse effect of topical application of vancomycin?

Background Vancomycin (VCM) is effective in fighting Gram-positive bacteria related severe infections, and topical application of VCM powder is widely used in orthopedic surgery to prevent wound infection. However, VCM could lead to infusion rate-dependent antibody-and complement-independent anaphylaxis reaction by inducing direct release of histamine. Case presentation We retrospectively analyzed seven cases of severe hypotension and shock during wound closure or immediately after orthopedic surgery with unidentifiable reasons. We found that these cases were all associated with local application of VCM powder during wound closure process. Two patients experienced sudden cardiac arrest. Most of the cases (6/7) with circulatory collapse were discharged without severe sequelae. While one case with application of 3 g VCM developed cardiac arrest and remained in a coma due to hypoxic-hypoxic encephalopathy. The clinical presentations and the time of the shock onset were considered to be related with a VCM induced anaphylaxis reaction. However, as this was a retrospective study, and there was no laboratory examination performed, the conclusion was made upon differential diagnosis based on clinical manifestations and the timing of the shock. Conclusions Local application of VCM may not be as safe as was once believed and may lead to a related anaphylaxis. As VCM induced infusion-rate dependent, non-IgE mediated anaphylaxis is characterized by delayed occurrence, severe hypotension and even circulatory collapse, surgeons and anesthesiologists should be extra vigilant during and after VCM application.

Machine learning and artificial intelligence: applications in healthcare epidemiology

Artificial intelligence (AI) refers to the performance of tasks by machines ordinarily associated with human intelligence. Machine learning (ML) is a subtype of AI; it refers to the ability of computers to draw conclusions (ie, learn) from data without being directly programmed. ML builds from traditional statistical methods and has drawn significant interest in healthcare epidemiology due to its potential for improving disease prediction and patient care. This review provides an overview of ML in healthcare epidemiology and practical examples of ML tools used to support healthcare decision making at 4 stages of hospital-based care: triage, diagnosis, treatment, and discharge. Examples include model-building efforts to assist emergency department triage, predicting time before septic shock onset, detecting community-acquired pneumonia, and classifying COVID-19 disposition risk level. Increasing availability and quality of electronic health record (EHR) data as well as computing power provides opportunities for ML to increase patient safety, improve the efficiency of clinical management, and reduce healthcare costs.

Efficacy of Early Administration of Liposomal Amphotericin B in Patients with Septic Shock: A Nationwide Observational Study

To determine the most suitable time to initiate liposomal amphotericin B (L-AMB) treatment in patients with invasive fungal infections, patients with septic shock treated with L-AMB were identified from the Japanese Diagnosis Procedure Combination national database to determine their survival rates following septic shock onset, mortality during shock, and shock cessation period. We identified 141 patients administered L-AMB: 60 patients received treatment on the day of septic shock onset (early L-AMB group), whereas 81 patients received treatment after the onset (delayed L-AMB group). Survival rates after septic shock onset were higher in the early L-AMB group than in the delayed L-AMB group (4 weeks: 68.4% vs 57.9%, P=0.197; 6 weeks: 62.2% vs 44.5%, P=0.061; 12 weeks: 43.4% vs 35.0%, P=0.168, respectively). Mortality during septic shock was significantly lower in the early L-AMB group than in the delayed L-AMB group (13% vs 42%, P<0.001), with a significant difference confirmed after adjusting for confounding factors (odds ratio: 0.240, 95% confidence interval: 0.096-0.601, P=0.002). Septic shock cessation period was shorter in the early L-AMB group than in the delayed L-AMB group (7.0±7.0 days vs 16.5±15.4 days, P<0.001). L-AMB administration at septic shock onset could be associated with early shock cessation and decreased mortality.