Serum Metabolomic Profiles in Critically Ill Patients with Shock on Admission to the Intensive Care Unit.

Inflammatory processes are common in intensive care (ICU) patients and can induce multiple changes in metabolism, leading to increased risks of morbidity and mortality. Metabolomics enables these modifications to be studied and identifies a patient's metabolic profile. The objective is to precise if the use of metabolomics at ICU admission can help in prognostication. This is a prospective ex-vivo study, realized in a university laboratory and a medico-surgical ICU. Metabolic profiles were analyzed by proton nuclear magnetic resonance. Using multivariable analysis, we compared metabolic profiles of volunteers and ICU patients divided into predefined subgroups: sepsis, septic shock, other shock and ICU controls. We also assessed possible correlations between metabolites and mortality. One hundred and eleven patients were included within 24 h of ICU admission, and 19 healthy volunteers. The ICU mortality rate was 15%. Metabolic profiles were different in ICU patients compared to healthy volunteers (p < 0.001). Among the ICU patients, only the subgroup of patients with septic shock had significant differences compared to the ICU control patients in several metabolites: pyruvate, lactate, carnitine, phenylalanine, urea, creatine, creatinine and myo-inositol. However, there was no correlation between these metabolite profiles and mortality. On the first day of ICU admission, we observed changes in some metabolic products in patients with septic shock, suggesting increased anaerobic glycolysis, proteolysis, lipolysis and gluconeogenesis. These changes were not correlated with prognosis.

Cerebro-spinal fluid glucose and lactate concentrations changes in response to therapies in patIents with primary brain injury: the START-TRIP study.

INTRODUCTION: Altered levels of cerebrospinal fluid (CSF) glucose and lactate concentrations are associated with poor outcomes in acute brain injury patients. However, no data on changes in such metabolites consequently to therapeutic interventions are available. The aim of the study was to assess CSF glucose-to-lactate ratio (CGLR) changes related to therapies aimed at reducing intracranial pressure (ICP). METHODS: A multicentric prospective cohort study was conducted in 12 intensive care units (ICUs) from September 2017 to March 2022. Adult (> 18 years) patients admitted after an acute brain injury were included if an external ventricular drain (EVD) for intracranial pressure (ICP) monitoring was inserted within 24 h of admission. During the first 48-72 h from admission, CGLR was measured before and 2 h after any intervention aiming to reduce ICP ("intervention"). Patients with normal ICP were also sampled at the same time points and served as the "control" group. RESULTS: A total of 219 patients were included. In the intervention group (n = 115, 53%), ICP significantly decreased and CPP increased. After 2 h from the intervention, CGLR rose in both the intervention and control groups, although the magnitude was higher in the intervention than in the control group (20.2% vs 1.6%; p = 0.001). In a linear regression model adjusted for several confounders, therapies to manage ICP were independently associated with changes in CGLR. There was a weak inverse correlation between changes in ICP and CGRL in the intervention group. CONCLUSIONS: In this study, CGLR significantly changed over time, regardless of the study group. However, these effects were more significant in those patients receiving interventions to reduce ICP.

Thromboprophylaxis in Critically Ill Coronavirus Disease 2019 Patients.

It is now reported that coronavirus disease 2019 ICU patients are at increased risk of thrombosis. Expert opinion and scientific societies recommend a higher dose of low-molecular-weight heparin, but definitive data is lacking. We report our adapted thromboprophylaxis practice of low-molecular-weight heparin administration in coronavirus disease 2019 ICU patients. One-hundred six measurements in 19 ICU patients were collected. Despite enoxaparin 60 mg once daily, only two measurements of the trough anti-Xa were in the upper end of prophylactic range. Anti-Xa activity peaks increased significantly after administration, but all measurements were under the optimal prophylactic ranges. Despite an adapted protocol, three of the 19 patients (16%) developed venous thromboembolism. We show in coronavirus disease 2019 ICU patients, despite higher prophylactic low-molecular-weight heparin administration due to body mass index, anti-Xa activity was well below peak serum levels in our cohort of critically ill coronavirus disease 2019 patients. This evaluation suggests the need for rapid studies on adequate thromboprophylaxis in these patients.

Near-Continuous Glucose Monitoring Makes Glycemic Control Safer in ICU Patients.

OBJECTIVES: Tight glycemic control using intermittent blood glucose measurements is associated with a risk of hypoglycemia. Glucose concentrations can now be measured near continuously (every 5-15 min). We assessed the quality and safety of glycemic control guided by a near-continuous glucose monitoring system in ICU patients. DESIGN: Prospective, cluster-randomized, crossover study. SETTING: Thirty-five-bed medico-surgical department of intensive care with four separate ICUs. PATIENTS: Adult patients admitted to the department and expected to stay for at least 3 days were considered for inclusion if they had persistent hyperglycemia (blood glucose > 150 mg/dL) up to 6 hours after admission and/or were receiving insulin therapy. INTERVENTIONS: A peripheral venous catheter was inserted in all patients and connected to a continuous glucose monitoring sensor (GlucoClear; Edwards Lifesciences, Irvine, CA). The four ICUs were randomized in pairs in a crossover design to glycemic control using unblinded or blinded continuous glucose monitoring monitors. The insulin infusion rate was adjusted to keep blood glucose between 90 and 150 mg/dL using the blood glucose values displayed on the continuous glucose monitor (continuous glucose monitoring group-unblinded units) or according to intermittent blood glucose readings (intermittent glucose monitoring group-blinded units). MEASUREMENTS AND MAIN RESULTS: The quality and safety of glycemic control were assessed using the proportion of time in range, the frequency of blood glucose less than 70 mg/dL, and the time spent with blood glucose less than 70 mg/dL (TB70), using blood glucose values measured by the continuous glucose monitoring device. Seventy-seven patients were enrolled: 39 in the continuous glucose monitoring group and 38 in the intermittent glucose monitoring group. A total of 43,107 blood glucose values were recorded. The time in range was similar in the two groups. The incidence of hypoglycemia (8/39 [20.5%] vs 15/38 [39.5%]) and the TB70 (0.4% ± 0.9% vs 1.6% ± 3.4%; p < 0.05) was lower in the continuous glucose monitoring than in the intermittent glucose monitoring group. CONCLUSIONS: Use of a continuous glucose monitoring-based strategy decreased the incidence and severity of hypoglycemia, thus improving the safety of glycemic control.

Combination of veno-arterial extracorporeal membrane oxygenation and hypothermia for out-of-hospital cardiac arrest due to Taxus intoxication.

A young woman presented with cardiac arrest following ingestion of yew tree leaves of the Taxus baccata species. The toxin in yew tree leaves has negative inotropic and dromotropic effects. The patient had a cardiac rhythm that alternated between pulseless electrical activity with a prolonged QRS interval and ventricular fibrillation. When standard resuscitation therapy including digoxin immune Fab was ineffective, a combination of extracorporeal membrane oxygenation (ECMO) and hypothermia was initiated. The total duration of low flow/no flow was 82 minutes prior to the initiation of ECMO. After 36 hours of ECMO (including 12 hours of electrical asystole), the patient's electrocardiogram had normalized and the left ventricular ejection fraction was 50%. At this time, dobutamine and the ECMO were stopped. The patient had a full neurologic recovery and was discharged from the intensive care unit after 5 days and from the hospital 1 week later.

Effects of changes in arterial pressure on organ perfusion during septic shock.

INTRODUCTION: Septic shock is characterized by altered tissue perfusion associated with persistent arterial hypotension. Vasopressor therapy is generally required to restore organ perfusion but the optimal mean arterial pressure (MAP) that should be targeted is uncertain. The aim of this study was to assess the effects of increasing MAP using norepinephrine (NE) on hemodynamic and metabolic variables and on microvascular reactivity in patients with septic shock. METHODS: This was a single center, prospective, interventional study conducted in the medico-surgical intensive care unit of a university hospital. Thirteen patients in septic shock for less than 48 hours who required NE administration were included. NE doses were adjusted to obtain MAPs of 65, 75, 85 and (back to) 65 mmHg. In addition to hemodynamic and metabolic variables, we measured thenar muscle oxygen saturation (StO2), using near infrared spectroscopy (NIRS), with serial vaso-occlusive tests (VOTs) on the upper arm. We also evaluated the sublingual microcirculation using sidestream dark field (SDF) imaging in 6 of the patients. RESULTS: Increasing NE dose was associated with an increase in cardiac output (from 6.1 to 6.7 l/min, P<0.05) and mixed venous oxygen saturation (SvO2, from 70.6 to 75.9%, P<0.05). Oxygen consumption (VO2) remained stable, but blood lactate levels decreased. There was a significant increase in the ascending slope of StO2 (from 111 to 177%/min, P<0.05) after VOTs. SDF imaging showed an increase in perfused vessel density (PVD, from 11.0 to 13.2 n/mm, P<0.05) and in microvascular flow index (MFI, from 2.4 to 2.9, P<0.05). CONCLUSIONS: In this series of patients with septic shock, increasing MAP above 65 mmHg with NE was associated with increased cardiac output, improved microvascular function, and decreased blood lactate concentrations. The microvascular response varied among patients suggesting that individualization of blood pressure targets may be warranted.