Tight Blood-Glucose Control without Early Parenteral Nutrition in the ICU.

BACKGROUND: Randomized, controlled trials have shown both benefit and harm from tight blood-glucose control in patients in the intensive care unit (ICU). Variation in the use of early parenteral nutrition and in insulin-induced severe hypoglycemia might explain this inconsistency. METHODS: We randomly assigned patients, on ICU admission, to liberal glucose control (insulin initiated only when the blood-glucose level was >215 mg per deciliter [>11.9 mmol per liter]) or to tight glucose control (blood-glucose level targeted with the use of the LOGIC-Insulin algorithm at 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]); parenteral nutrition was withheld in both groups for 1 week. Protocol adherence was determined according to glucose metrics. The primary outcome was the length of time that ICU care was needed, calculated on the basis of time to discharge alive from the ICU, with death accounted for as a competing risk; 90-day mortality was the safety outcome. RESULTS: Of 9230 patients who underwent randomization, 4622 were assigned to liberal glucose control and 4608 to tight glucose control. The median morning blood-glucose level was 140 mg per deciliter (interquartile range, 122 to 161) with liberal glucose control and 107 mg per deciliter (interquartile range, 98 to 117) with tight glucose control. Severe hypoglycemia occurred in 31 patients (0.7%) in the liberal-control group and 47 patients (1.0%) in the tight-control group. The length of time that ICU care was needed was similar in the two groups (hazard ratio for earlier discharge alive with tight glucose control, 1.00; 95% confidence interval, 0.96 to 1.04; P = 0.94). Mortality at 90 days was also similar (10.1% with liberal glucose control and 10.5% with tight glucose control, P = 0.51). Analyses of eight prespecified secondary outcomes suggested that the incidence of new infections, the duration of respiratory and hemodynamic support, the time to discharge alive from the hospital, and mortality in the ICU and hospital were similar in the two groups, whereas severe acute kidney injury and cholestatic liver dysfunction appeared less prevalent with tight glucose control. CONCLUSIONS: In critically ill patients who were not receiving early parenteral nutrition, tight glucose control did not affect the length of time that ICU care was needed or mortality. (Funded by the Research Foundation-Flanders and others; TGC-Fast ClinicalTrials.gov number, NCT03665207.).

Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial.

BACKGROUND: Activation of the triggering receptor expressed on myeloid cells-1 (TREM-1) pathway is associated with septic shock outcomes. Data suggest that modulation of this pathway in patients with activated TREM-1 might improve survival. Soluble TREM-1 (sTREM-1), a potential mechanism-based biomarker, might facilitate enrichment of patient selection in clinical trials of nangibotide, a TREM-1 modulator. In this phase 2b trial, we aimed to confirm the hypothesis that TREM1 inhibition might improve outcomes in patients with septic shock. METHODS: This double-blind, randomised, placebo-controlled, phase 2b trial assessed the efficacy and safety of two different doses of nangibotide compared with placebo, and aimed to identify the optimum treatment population, in patients across 42 hospitals with medical, surgical, or mixed intensive care units (ICUs) in seven countries. Non-COVID-19 patients (18-85 years) meeting the standard definition of septic shock, with documented or suspected infection (lung, abdominal, or urinary [in patients ≥65 years]), were eligible within 24 h of vasopressor initiation for the treatment of septic shock. Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3). Patients and investigators were masked to treatment allocation. Patients were grouped according to sTREM-1 concentrations at baseline (established from sepsis observational studies and from phase 2a change to data) into high sTREM-1 (≥ 400 pg/mL). The primary outcome was the mean difference in total Sequential Organ Failure Assessment (SOFA) score from baseline to day 5 in the low-dose and high-dose groups compared with placebo, measured in the predefined high sTREM-1 (≥ 400 pg/mL) population and in the overall modified intention-to-treat population. Secondary endpoints included all-cause 28-day mortality, safety, pharmacokinetics, and evaluation of the relationship between TREM-1 activation and treatment response. This study is registered with EudraCT, 2018-004827-36, and Clinicaltrials.gov, NCT04055909. FINDINGS: Between Nov 14, 2019, and April 11, 2022, of 402 patients screened, 355 were included in the main analysis (116 in the placebo group, 118 in the low-dose group, and 121 in the high-dose group). In the preliminary high sTREM-1 population (total 253 [71%] of 355; placebo 75 [65%] of 116; low-dose 90 [76%] of 118; high-dose 88 [73%] of 121), the mean difference in SOFA score from baseline to day 5 was 0·21 (95% CI -1·45 to 1·87, p=0·80) in the low-dose group and 1·39 (-0·28 to 3·06, p=0·104) in the high-dose group versus placebo. In the overall population, the difference in SOFA score from baseline to day 5 between the placebo group and low-dose group was 0·20 (-1·09 to 1·50; p=0·76),and between the placebo group and the high-dose group was 1·06 (-0·23 to 2·35, p=0·108). In the predefined high sTREM-1 cutoff population, 23 (31%) patients in the placebo group, 35 (39%) in the low-dose group, and 25 (28%) in the high-dose group had died by day 28. In the overall population, 29 (25%) patients in the placebo, 38 (32%) in the low-dose, and 30 (25%) in the high-dose group had died by day 28. The number of treatment-emergent adverse events (111 [96%] patients in the placebo group, 113 [96%] in the low-dose group, and 115 [95%] in the high-dose group) and serious treatment-emergent adverse events (28 [24%], 26 [22%], and 31 [26%]) was similar between all three groups. High-dose nangibotide led to a clinically relevant improvement in SOFA score (of two points or more) from baseline to day 5 over placebo in those with higher cutoff concentrations (≥532 pg/mL) of sTREM-1 at baseline. Low dose nangibotide displayed a similar pattern with lower magnitude of effect across all cutoff values. INTERPRETATION: This trial did not achieve the primary outcome of improvement in SOFA score at the predefined sTREM-1 value. Future studies are needed to confirm the benefit of nangibotide at higher concentrations of TREM-1 activation. FUNDING: Inotrem.

Foxglove poisoning: diagnostic and therapeutic differences with medicinal digitalis glycosides overdose.

We report a case of a 19-year-old woman who ingested Digitalis purpurea leaves as a suicide attempt. She developed gastro-intestinal symptoms, loss of colour vision, cardiac conduction disturbances as well as an elevated serum potassium. Treatment was initiated in analogy to medicinal digoxin poisoning by means of digoxin-specific Fab-fragments with a good effect. However during the further course we faced difficulties of prolonged intestinal absorption and inability to estimate the ingested dose or half-life of the vegetal cardiac glycoside compounds. To prevent further absorption and interrupt enterohepatic recycling, multi-dose activated charcoal was administered. Because of a relapse of cardiac conduction disturbances and hyperkalemia, two supplementary doses of Fab-fragments were given, up to a total dose of nineteen vials (one vial containing 40 mg). The important diagnostic and therapeutic differences of vegetal digitalis intoxication as compared to medicinal intoxication and the applicability of existing guidelines on medicinal digitalis intoxication in the light of these differences will be discussed here.

Characteristics of Sepsis-2 septic shock patients failing to satisfy the Sepsis-3 septic shock definition: an analysis of real-time collected data.

BACKGROUND: Baseline characteristics and disease severity of patients with septic shock according to the new Sepsis-3 definition may differ from patients that only comply with the Sepsis-2 definition. We conducted a retrospective cohort study on the ICU of a Belgian tertiary care facility to seek out differences between these two patient groups and to identify variables associated with no longer satisfying the latest definition of septic shock. RESULTS: Of 1198 patients with septic shock according to the Sepsis-2 consensus definition, 233 (19.4%) did not have septic shock according to the Sepsis-3 shock definition. These patients more often had medical admission reasons and a respiratory infection as cause for the septic shock. They less often had surgery on admission and were less likely to have chronic liver disease (5.6% vs 16.2%, absolute difference 10.6% (95% CI 6.4-14.1%). Patients with septic shock only according to the old definition had significant lower APACHE II and SOFA scores and lower hospital mortality (31.6% vs 55.3%, p < 0.001). In a multivariate analysis, following variables were associated with Sepsis-2 shock patients no longer being defined as such by the Sepsis-3 definition: respiratory infection (OR 1.485 (95% CI 1.56-2.089), p = 0.023), a medical admission reason (OR 1.977 (95% CI 1.396-2.800) and chronic liver disease (OR 0.345 (95% CI 0.181-0.660), p < 0.001). CONCLUSIONS: One in five patients with septic shock according to the Sepsis-2 consensus definition is no longer considered as such when the Sepsis-3 shock criteria are applied. A medical admission reason, a respiratory infection and absence of chronic liver disease are independently associated with no longer being identified as having septic shock by the Sepsis-3 criteria.

Microbleed patterns in critical illness and COVID-19.

BACKGROUND: Cerebral microbleeds are increasingly reported in critical ill patients with respiratory failure in need of mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO). Typically, these critical illness-associated microbleeds involve the juxtacortical white matter and corpus callosum. Recently, this pattern was reported in patients with respiratory failure, suffering from COVID-19. MATERIALS AND METHODS: In this retrospective single-center study, we listed patients from March 11, 2020 to September 2, 2020, with laboratory-confirmed COVID-19, critical illness and cerebral microbleeds. Literature research was conducted through a methodical search on Pubmed databases on critical illness-associated microbleeds and cerebral microbleeds described in patients with COVID-19. RESULTS AND DISCUSSION: On 279 COVID-19 admissions, two cases of cerebral microbleeds were detected in critical ill patients with respiratory failure due to COVID-19. Based on review of existing literature critical illness-associated microbleeds tend to predominate in subcortical white matter and corpus callosum. Cerebral microbleeds in patients with COVID-19 tend to follow similar patterns as reported in critical illness-associated microbleeds. Hence, one patient with typical critical illness-associated microbleeds and COVID-19 is reported. However, a new pattern of widespread cortico-juxtacortical microbleeds, predominantly in the anterior vascular territory with relative sparing of deep gray matter, corpus callosum and infratentorial structures is documented in a second case. The possible etiologies of these microbleeds include hypoxia, hemorrhagic diathesis, brain endothelial erythrophagocytosis and/or cytokinopathies. An association with COVID-19 remains to be determined. CONCLUSION: Further systematic investigation of microbleed patterns in patients with neurological impairment and COVID-19 is necessary.

Discharge from hospital with newly administered antipsychotics after intensive care unit delirium - Incidence and contributing factors.

PURPOSE: Delirium in the intensive care unit (ICU) is often treated with haloperidol or atypical antipsychotics. Antipsychotic treatment can lead to severe adverse effects and excess mortality. After initiation in the ICU, patients are at risk of having their antipsychotics continued unnecessarily at ICU and hospital discharge. This study aims to determine the incidence of, and risk factors for antipsychotic continuation at hospital discharge after ICU delirium. METHODS: This retrospective observational study was performed in a tertiary care center. Adult patients who received antipsychotics for ICU delirium during 2016 were included. Data was extracted from patient records. After univariate testing, a multivariate binary logistic regression model was used to identify independent risk factors for antipsychotic continuation. RESULTS: A total of 196 patients were included, of which 104 (53.1%) and 41 (20.9%) had their antipsychotics continued at ICU and hospital discharge respectively. Medical ICU admission (odds ratio [95% confidence interval] 2.97 [1.37-6.41]) and quetiapine treatment (5.81 [1.63-20.83]) were independently associated with antipsychotic continuation at hospital discharge. CONCLUSIONS: Approximately one in five patients were discharged from the hospital with continued antipsychotics. Hospital policies should implement strategies for systematic antipsychotic tapering and better follow-up of antipsychotics at transitions of care.

Acute Type A Aortic Dissection Complicated by COVID-19 Infection.

A patient underwent surgery for acute type A aortic dissection. Testing for SARS-CoV-2 was positive. The postoperative course was complicated by a mixed viral and bacterial pneumonia with bilateral infiltration, treated with antibiotics and hydroxychloroquine, without any need for reintubation. The patient recovered and finally could be discharged. This report shows the feasibility for surgical treatment of acute aortic disease in patients with COVID-19.

Automated screening of natural language in electronic health records for the diagnosis septic shock is feasible and outperforms an approach based on explicit administrative codes.

PURPOSE: Identification of patients for epidemiologic research through administrative coding has important limitations. We investigated the feasibility of a search based on natural language processing (NLP) on the text sections of electronic health records for identification of patients with septic shock. MATERIALS AND METHODS: Results of an explicit search strategy (using explicit concept retrieval) and a combined search strategy (using both explicit and implicit concept retrieval) were compared to hospital ICD-9 based administrative coding and to our department's own prospectively compiled infection database. RESULTS: Of 8911 patients admitted to the medical or surgical ICU, 1023 (11.5%) suffered from septic shock according to the combined search strategy. This was significantly more than those identified by the explicit strategy (518, 5.8%), by hospital administrative coding (549, 5.8%) or by our own prospectively compiled database (609, 6.8%) (p < .001). Sensitivity and specificity of the automated combined search strategy were 72.7% (95%CI 69.0%-76.2%) and 93.0% (95%CI 92.4%-93.6%), compared to 56.0% (95%CI 52.0%-60.0%) and 97.5% (95%CI 97.1%-97.8%) for hospital administrative coding. CONCLUSIONS: An automated search strategy based on a combination of explicit and implicit concept retrieval is feasible to screen electronic health records for septic shock and outperforms an administrative coding based explicit approach.

Critically ill octogenarians and nonagenarians: evaluation of long-term outcomes, posthospital trajectories and quality of life one year and seven years after ICU discharge.

BACKGROUND: The aim of this study was to investigate long-term outcomes, posthospital trajectories, and quality of life (QOL) in patients ≥80 years admitted to the Intensive Care Unit (ICU) of a tertiary care hospital. METHODS: A 1-year prospective observational cohort analysis was performed. All consecutive patients ≥80 years admitted to the ICU were screened for inclusion. Demographics, comorbidity, organ failures, and outcomes were analyzed. QOL before admission, 3 months, 1 year, and 7 years after ICU discharge was assessed using EuroQoL-5D (EQ-5D) and Medical Outcomes Study 36-item Short Form Health Survey (SF-36) questionnaires. Statistical significance was attained at P<0.05. RESULTS: In the study 131 patients with a median age of 83 years (IQR 81-85), a Charlson Comorbidity Index of 2 (IQR 0-4), a SOFA Score of 4 (3-8) upon ICU admission and an APACHE II Score of 20 (IQR 15-24) were included. ICU, hospital, 3 months, 1-year, and 7-year mortality rates were 17%, 29%, 39%, 50%, and 84% respectively. QOL decreased significantly over time. Most elderly considered QOL as acceptable and perceived only a worsening in physical functioning and self-care at long-term. Of the 1-year and 7-year survivors, 21% and 39% (P=0.122) lived in nursing homes, and 81% and 72% (P=0.423) preferred to be readmitted to an ICU department if necessarily. CONCLUSIONS: Most critically ill long-term elderly survivors lived at home, perceived their QOL as acceptable, and wanted to be readmitted to the ICU if necessary. In older patients, age alone is a poor indicator of the possible value to be gained from an ICU admission.