Association between neuromuscular blocking agents and the development of intensive care unit-acquired weakness (ICU-AW): A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: The present study aims to review the literature and synthesize evidence concerning the effects of the use of neuromuscular blocking agents (NMBA) regarding the development of intensive care unit-acquired weakness (ICU-AW). METHODS: This study was registered in the PROSPERO database CRD42020142916. Systematic review in PubMed, Embase, and the Cochrane Central, Randomized clinical trials (RCTs), and cohort studies with adults that reported the use of NMBA and the development of ICU-AW were included. Pre-specified subgroup analyses were performed for presence of sepsis and type of NMBA used. The quality of evidence for intervention effects was summarized. The certainty of evidence was assessed using the GRADE approach. RESULTS: We included 30 studies, four RCTs, 21 prospective and 5 retrospective cohorts, enrolling a total of 3839 patients. Most of the included studies were observational with high heterogeneity, whereas the RCTs had a high risk of bias. The use of NMBA increased the odds of developing ICU-AW (OR = 2.77 [95% CI 1.98-3.88], I2 = 62%), with low-quality of evidence. A trial sequential analysis showed the need to include 22,330 patients in order to provide evidence for either beneficial or harmful intervention effects. CONCLUSIONS: This meta-analysis suggests that the use of NMBA might be implicated in the development of ICU-AW. However, there is not enough evidence to definitively conclude about the association between the use of NMBA and the development of ICU-AW, as these results are based mostly on observational studies with high heterogeneity.

Association between diabetes and stress-induced hyperglycemia with skeletal muscle gene expression of INSR in critically ill patients: A prospective cohort study.

This study aimed to investigate the association between diabetes and stress-induced hyperglycemia with skeletal muscle gene expression of INSR of critically ill patients. Skeletal muscle biopsies were prospectively taken from the vastus muscle, and the expression level of INSR was analyzed using RT-qPCR. Fifty patients were included from April 2018 to September 2018. No significant differences in skeletal muscle gene expression were found between patients with or without diabetes. Similarly, there were no differences in gene expression between groups according to the presence of hypoglycemia 〈 70 mg/dl or hyperglycemia 〉 140 mg/dl. Patients with glycemic variability ≥ 40 mg/dl exhibited a downregulation of INSR compared to those with glycemic variability < 40 mg/dl (1.3 [0.01-5] vs. 2.1 [0.7 - 3.4] fold-changes, P = 0.045). The same pattern was observed when glycemic gap threshold of 80 mg/dl was used (1.4 [0.25-5] vs 1 [0.01 - 2.3] fold-changes in patients with glycemic gap < 80 mg/dl and glycemic gap ≥ 80 mg/dl respectively, P = 0.015). In conclusion, INSR was downregulated in the skeletal muscle of critically ill patients with stress-induced hyperglycemia.

Diabetes associates with mortality in critically ill patients with SARS-CoV-2 pneumonia: No diabetes paradox in COVID-19.

Background: Diabetes mellitus (DM) is not associated with increased mortality in critically ill patients, a phenomenon known as the "diabetes paradox". However, DM is a risk factor for increased mortality in patients with COVID-19. This study aims to investigate the association of DM and stress-induced hyperglycemia at intensive care unit (ICU) with mortality in this population. Methods: This is a retrospective study. Electronic medical records from patients admitted from March 2020 to September 2020 were reviewed. Primary outcome was mortality. Secondary outcomes were ICU and hospital mortality and stay, and need for mechanical ventilation and renal replacement therapy. Results: 187 patients were included. Overall mortality was 43.2%, higher in patients with DM (55.7% vs. 34%; p = 0.007), even after adjustment for age, hypertension, and disease severity. When patients were separated into groups, named normoglycemia (without DM and glycemia ≤140 mg/dL), stress-induced hyperglycemia (without DM and glycemia >140 mg/dL), and DM (previous diagnosis or HbA1c ≥ 6.5%), the mortality rate was 25.8%, 37.3%, and 55.7%, respectively (p = 0.021). Mortality was higher in patients with higher glycemic variability. No statistical difference related to secondary outcomes was observed. Conclusions: DM, hyperglycemia, and glycemic variability associated with increased mortality in critically ill patients with severe COVID-19, but did not increase the rates of other clinical outcomes. More than stress-induced hyperglycemia, DM was associated with mortality.

Severe hepatopulmonary syndrome with hypoxemia refractory to liver transplant: Recovery after 67 days of ECMO support.

Hepatopulmonary syndrome (HPS) is a complication of end stage liver disease (ESLD) and is manifested by severe hypoxemia, which usually responds to liver transplantation (LT). As compared to patients undergoing LT for other etiologies, patients with HPS present an increased risk of postoperative morbidity and mortality. There is no effective treatment for patients whose hypoxemia does not respond to LT. This subset of patients is at a highly increased risk of death. There are very few reports on the use of extracorporeal membrane oxygenation (ECMO) in this setting with rapid response. However, there is no prior report of ECMO utilization for longer than 4 weeks. We present the case of a 17 year-old male patient who underwent LT for ESLD secondary to chronic portal vein thrombosis and HPS. He received a liver from a deceased donor and presented with severe HPS after LT, requiring ECMO support for 67 days. The patient was discharged home and is breathing in ambient air. He is currently asymptomatic and has a normal liver function.

Copeptin and stress-induced hyperglycemia in critically ill patients: A prospective study.

OBJECTIVES: Copeptin, an equimolar indicator of serum antidiuretic hormone levels, has been associated with higher mortality in critically ill patients and with the development of diabetes in the general population. The aim of the present study was to investigate the association of copeptin levels with glycemic parameters in critically ill patients and to compare the time-course of copeptin in survivors and non-survivors. DESIGN: Prospective cohort study. PATIENTS: From June to October 2019, critically ill patients were prospectively enrolled and followed for 90 days. MEASUREMENTS: Plasma copeptin levels were determined at intensive care unit (ICU) admission (copeptin T1), 24 h (copeptin T2), and 48 h (copeptin T3) after study entry. Blood glucose and glycated hemoglobin levels were measured. ICU, in-hospital, and 90-day mortality, and length of stay in the ICU and hospital were evaluated. RESULTS: 104 patients were included. No significant correlation was detected between copeptin levels and blood glucose (r = -0.17, p = 0.09), HbA1c (r = 0.01, p = 0.9), glycemic gap (r = -0.16, p = 0.11), and stress hyperglycemia ratio (r = -0.14, p = 0.16). Copeptin T3 levels were significantly higher in survivors than in non-survivors at hospital discharge (561 [370-856] vs 300 [231-693] pg/mL, p = 0.015) and at 90 days (571 [380-884] vs 300 [232-698] pg/mL, p = 0.03). CONCLUSIONS: No significant correlations were found between copeptin levels and glycemic parameters, suggesting that copeptin is not a relevant factor in the induction of hyperglycemia during critical illness. Copeptin levels at ICU day 3 were higher in survivors than in non-survivors.

Effect of adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure: a randomized clinical trial.

Acute decompensated heart failure (ADHF) is the leading cause of hospitalization in patients aged 65 years or older, and most of them present with congestion. The use of hydrochlorothiazide (HCTZ) may increase the response to loop diuretics. To evaluate the effect of adding HCTZ to furosemide on congestion and symptoms in patients with ADHF. This randomized clinical trial compared HCTZ 50 mg versus placebo for 3 days in patients with ADHF and signs of congestion. The primary outcome of the study was daily weight reduction. Secondary outcomes were change in creatinine, need for vasoactive drugs, change in natriuretic peptides, congestion score, dyspnea, thirst, and length of stay. Fifty-one patients were randomized-26 to the HCTZ group and 25 to the placebo group. There was an increment of 0.73 kg/day towards additional weight reduction in the HCTZ group (HCTZ: - 1.78 ± 1.08 kg/day vs placebo: - 1.05 ± 1.51 kg/day; p = 0.062). In post hoc analysis, the HCTZ group demonstrated significant weight reduction for every 40 mg of intravenous furosemide (HCTZ: - 0.74 ± 0.47 kg/40 mg vs placebo: - 0.33 ± 0.80 kg/40 mg; p = 0.032). There was a trend to increase in creatinine in the HCTZ group (HCTZ: 0.50 ± 0.37 vs placebo: 0.27 ± 0.40; p = 0.05) but no significant difference in onset of acute renal failure (HCTZ: 58% vs placebo: 41%; p = 0.38). No differences were found in the remaining outcomes. Adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure did not cause significant difference in daily body weight reduction compared to placebo. In analysis adjusted to the dose of intravenous furosemide, adding HCTZ 50 mg to furosemide resulted in a significant synergistic effect on weight loss.Trial registration: The Brazilian Clinical Trials Registry (ReBEC), a publically accessible primary register that participates in the World Health Organization International Clinical Trial Registry Platform; number RBR-5qkn8h. Registered in 23/07/2019 (retrospectively), http://www.ensaiosclinicos.gov.br/rg/RBR-5qkn8h/ .

Association of multiple glycemic parameters at intensive care unit admission with mortality and clinical outcomes in critically ill patients.

The aim of the present study was to investigate the association of multiple glycemic parameters at intensive care unit (ICU) admission with outcomes in critically ill patients. Critically ill adults admitted to ICU were included prospectively in the study and followed for 180 days until hospital discharge or death. Patients were assessed for glycemic gap, hypoglycemia, hyperglycemia, glycemic variability, and stress hyperglycemia ratio (SHR). A total of 542 patients were enrolled (30% with preexisting diabetes). Patients with glycemic gap >80 mg/dL had increased need for renal replacement therapy (RRT; 37.7% vs. 23.7%, p = 0.025) and shock incidence (54.7% vs. 37.4%, p = 0.014). Hypoglycemia was associated with increased mortality (54.8% vs. 35.8%, p = 0.004), need for RRT (45.1% vs. 22.3%, p < 0.001), mechanical ventilation (MV; 72.6% vs. 57.5%, p = 0.024), and shock incidence (62.9% vs. 35.8%, p < 0.001). Hyperglycemia increased mortality (44.3% vs. 34.9%, p = 0.031). Glycemic variability >40 mg/dL was associated with increased need for RRT (28.3% vs. 14.4%, p = 0.002) and shock incidence (41.4% vs.31.2%, p = 0.039). In this mixed sample of critically ill subjects, including patients with and without preexisting diabetes, glycemic gap, glycemic variability, and SHR were associated with worse outcomes, but not with mortality. Hypoglycemia and hyperglycemia were independently associated with increased mortality.