Methylprednisolone, venous thromboembolism, and association with heparin to 30 days in hospital survival in severe Covid-19 pneumonia

Background Mortality in severe COVID-19 pneumonia is associated with thrombo-inflammation. Corticosteroids are given to attenuate the inflammation, but they are associated with thrombosis. The aims of this study were to determine the risk of venous thromboembolism between no methylprednisolone and methylprednisolone (dose versus duration) and to evaluate any synergistic dose-dependent association of heparin and methylprednisolone to 30 days in hospital survival. Methods This was a secondary analysis of a retrospective cohort. Patients included in this study were ≥ 18 years of age and admitted for severe COVID-19 pneumonia between March and June 2020 in 13 hospitals in New Jersey, United States. A propensity score analysis between administration of methylprednisolone and no methylprednisolone was fitted for 11 variables and Youden Index Method was used to determine cut-off between low dose and high dose methylprednisolone. Multivariate cox regression was to assess risk. Results In 759 patients, the incidence of venous thromboembolism was 9% of patients who received methylprednisolone and 3% of patients who did not receive methylprednisolone with a [RR 2.92 (95% CI 1.54, 5.55 P < 0.0001)]. There was a higher incidence of mechanical ventilation in the methylprednisolone group. The median d-dimer between patients with venous thromboembolism was higher compared to those without (P < 0.0003). However, the d-dimer was not statistically significant between those who had venous thromboembolism between methylprednisolone and no methylprednisolone groups (P = 0.40). There was no higher risk in high dose versus low dose [RR = 0.524 (95% CI 0.26, 1.06 P 0.4)]; however, the risk for venous thromboembolism between methylprednisolone for > 7 days and ≤ 7 days was statistically significant (RR 5.46 95% CI 2.87, 10.34 P < 0.0001). Patients who received low dose methylprednisolone and therapeutic heparin had a trend towards higher risk of mortality compared to prophylactic heparin (HR 1.81 95% CI 0.994 to 3.294) (P = 0.0522). There was no difference in 30 days in hospital survival between high dose methylprednisolone with prophylactic or therapeutic heparin (HR 0.827 95% CI 0.514 to 1.33) (P = 0.4335). Conclusion Methylprednisolone for > 7 days had a higher association of venous thromboembolism. There was no added benefit of therapeutic heparin to methylprednisolone on mechanically ventilated patients.

Immediate results of surgical treatment of high and intermediate risk pulmonary embolism in elderly and senile patients

The aim of the study: is to analyze the immediate results of surgical treatment of high-and intermediate-risk PE in a group of elderly and senile patients. Material and methods. The study included 43 patients operated on for high-and intermediate-risk pulmonary embolism between 2008 and 2019. In the general group of patients, the number of women prevailed and amounted to 67.4%. The average age was 65.4 ± 4.23 years old. The Miller index in the general group was 29.1 ± 1.42. The Geneva Index was 8.4 ± 1.12. The average pressure in the pulmonary artery at the time of operation was 54 ± 1.4 mm Hg, and the peak pressure was 68 ± 3.43 mm Hg. Results. 5 patients died at the hospital stage. Thus, the hospital survival rate of patients was 88.4%. Among nonlethal complications, cardiovascular and respiratory failure prevailed. According to the statement, the calculated pressure gradient in the pulmonary artery was 29.0 ± 3.1 mm Hg. Conclusion. Surgical treatment is a highly eff ective and reliable method of treatment in the group of older patients.

Diabetic Ketoacidosis Updates: Titratable Insulin Infusions and Long-Acting Insulin Early

Background. To compare a titratable insulin infusion order set (vs. nontitratable) and early administration of long-acting insulin in adult patients with diabetic ketoacidosis (DKA). Methods. Single health system, retrospective study of adult patients admitted to the intensive care unit (ICU) for DKA. The primary outcomes were insulin infusion duration and ICU/hospital length of stays (LoS). Secondary outcomes included ICU/hospital survival, hypoglycemia, and hypokalemia. Results. 151 patients were included in the titratable versus nontitratable insulin infusion comparison. Patients treated with the titratable insulin had shorter hospitalization (6.4 vs. 10.4 days, p = 0.03 ) and reduced the number hypoglycemic events by over half (20.6% vs. 46.0%, p < 0.01 ). 110 patients were identified to compare overlapping a long-acting insulin for more than 4 h with the insulin infusion versus the standard 1-2 h overlap. Patients who received the insulin early spent over 18 h longer on the infusion ( p < 0.01 ). Conclusions. A titratable insulin infusion added to the institutional DKA order set was associated with fewer days in the hospital and a significant reduction in hypoglycemic events. Furthermore, overlapping the long-acting insulin earlier with the insulin infusion early showed no benefit and could potentially be worse than the standard overlap.

Comparison of Low-Versus High-Dose Steroids in the Clinical Outcome of Hospitalized COVID-19 Patients

(1) Objectives: Patients with COVID-19 infection have been given various formulations and dosages of steroids over the last year and a half. This study aims to compare the effects of different formulations and doses of steroids on the 30 day in-hospital clinical outcome of patients with severe COVID-19 infection. (2) Material and Methods: An analysis of a retrospective cohort was carried out on patients with severe COVID-19 infection in a high-dependency unit (HDU) between February and July 2021. In total, 557 patients were included in this study. Patients who did not receive steroids (124) were excluded. Patients were divided into three groups based on dosages of steroids (Dexamethasone = 6 mg/day, Dexamethasone > 6 mg/day, and Methylprednisolone = 500 mg/day), given for 10 days. First, clinical outcome was evaluated on the 10th day of steroid administration in relation to mode of oxygen delivery. Then, Kaplan–Meier analysis was employed to determine 30 day in-hospital survival in relation to the use of steroid. (3) Results: Three groups were statistically equal according to biochemical characteristics. After 10 days of Methylprednisolone = 500 mg/day vs. Dexamethasone = 6 mg/day, 10.9% vs. 6.2% of patients required invasive ventilation (p = 0.01). The 30 day in-hospital mortality was lowest, 3%, in individuals receiving Dexamethasone = 6 mg/day, compared to 3.9% in individuals receiving Dexamethasone > 6 mg/day and 9.9% in individuals receiving Methylprednisolone = 500 mg/day, respectively. The median elapsed time was longer than 28 days between admission and outcome for Dexamethasone = 6 mg/day, compared to 18 days for Dexamethasone > 6 mg/day and 17 days for Methylprednisolone = 500 mg/day (p = < 0.0001). Dexamethasone = 6 mg/day was found to be a positive predictor of clinical outcome in COVID-19 patients on regression analysis. (4) Conclusions: Low-dose Dexamethasone (6 mg/day) is more effective than high-dose Dexamethasone and Methylprednisolone in improving the survival outcome of severe COVID-19 cases.

Abstract 13607: Correlation in Hospital Survival Following Out-of-Hospital Cardiac Arrest With Variation in Post-Arrest Inpatient Intervention Rates in Michigan

Introduction: Wide variations in rates of survival to hospital discharge exist for survivors of out-of-hospital cardiac arrest (OHCA). The potential influence of variation in post-OHCA hospital care has not been adequately explored. We hypothesized that variation of in hospital survival rates may be influenced by variation of in-hospital care in Michigan. Methods: We performed a secondary analysis of a statewide cardiac arrest database constructed from two probabilistically-linked cardiac arrest registries [Cardiac Arrest Registry to Enhance Survival (CARES) and Michigan Inpatient Database (MIDB)] from 2014 - 2017. A novel composite rank score was created to characterize post-arrest in-hospital care, incorporating four specific interventions: left heart catheterization within 24 hours (LHC), emergent mechanical circulatory support (EMCS), targeted temperature management (TTM), and do-not-resuscitate order placed within 72 hours of arrival (DNR). The highest score (1 of 38) was given to the hospital with highest procedure rate (LHC, TTM, LHC) and the lowest rate of early DNR. Spearman’s correlation coefficients assessed the relationship between the equal weight composite rank score and rate of hospital survivors. Results: We included 3,644 patients admitted to 38 hospitals who treated >30 OHCA patients during the study period. Patient mean age was 62.4 years, and 59.3% were male. Survival, rank scores and correlation coefficients are listed below: We observed four-fold variation in survival for all patients and witnessed arrest, with a non-significant correlation with care provision. However, we identified a sixteen-fold variation in survival among unwitnessed arrests, which was significantly correlated with a higher rank of care provided. Conclusions: In Michigan, the greatest variation in survival was identified among unwitnessed arrests. This variation was robustly associated with a composite rank of in-hospital post-arrest interventions.

Identifying early-measured variables associated with APACHE IVa providing incorrect in-hospital mortality predictions for critical care patients

APACHE IVa provides typically useful and accurate predictions on in-hospital mortality and length of stay for patients in critical care. However, there are factors which may preclude APACHE IVa from reaching its ceiling of predictive accuracy. Our primary aim was to determine which variables available within the first 24 h of a patient’s ICU stay may be indicative of the APACHE IVa scoring system making occasional but potentially illuminating errors in predicting in-hospital mortality. We utilized the publicly available multi-institutional ICU database, eICU, available since 2018, to identify a large observational cohort for our investigation. APACHE IVa scores are provided by eICU for each patient’s ICU stay. We used Lasso logistic regression in an aim to build parsimonious final models, using cross-validation to select the penalization parameter, separately for each of our two responses, i.e., errors, of interest, which are APACHE falsely predicting in-hospital death (Type I error), and APACHE falsely predicting in-hospital survival (Type II error). We then assessed the performance of the models with a random holdout validation sample. While the extremeness of the APACHE prediction led to dependable predictions for preventing either type of error, distinct variables were identified as being strongly associated with the two different types of errors occurring. These included a primary set of predictors consisting of mean SpO2 and worst lactate for predicting Type I errors, and worst albumin and mean heart rate for Type II. In addition, a secondary set of predictors including changes recorded in care limitations for the patient’s treatment plan, worst pH, whether cardiac arrest occurred at admission, and whether vasopressor was provided for predicting Type I error; age, whether the patient was ventilated in day 1, mean respiratory rate, worst lactate, worst blood urea nitrogen test, and mean aperiodic vitals for Type II. The two models also differed in their performance metrics in their holdout validation samples, in large part due to the lower prevalence of Type II errors compared to Type I. The eICU database was a good resource for evaluating our objective, and important recommendations are provided, particularly identifying key variables that could lead to APACHE prediction errors when APACHE scores are sufficiently low to predict in-hospital survival.

Impact of temporary mechanical circulatory support on mortality in cardiogenic shock: an emulated target trial with a prospective, multicenter, French cohort study

Background The field of temporary mechanical circulatory support (TMCS) has advanced in last decade justifying that TMCS is increasingly used for treatment of refractory cardiogenic shock (CS). Nevertheless, the efficacy of TMCS (extracorporeal life support (ECLS) and Impella) in CS remains controversial due to the lack of high-quality evidence. The aim of this prospective multicenter observational study simulating a randomized trial was to assess the impact of TMCS on the hospital mortality in patients with CS. Methods This study (ClinicalTrials.gov ID: NCT03528291) was conducted at 3 TMCS centers organized in a cardiac assistance network, one as a level 1 TMCS center (expert center), and 2 as level 2 centers (hub centers). The study was designed and led by the heart team of the expert center with input from the hub centers. All patients admitted to an intensive care unit between July 2017 and May 2020 either directly at the TMCS centers or after transfer from a non-specialized hospital, were screened for TMCS indication provided they were admitted for CS. CS was defined according to the European Society of Cardiology criteria. Were excluded patients younger than 18 years, CS after cardiac surgery, or after cardiac arrest if it was refractory or with a no flow &gt;3 min and/or out-of-hospital cardiac arrest with non-shockable rhythm, or CS in the context of myocardial infarction complications, massive pulmonary embolism, and if TMCS was contraindicated TMCS indication was decided after a multidisciplinary discussion carried out by the “heart team”. Implantation of TMCS resulted from an agreement of the heart team within the first 24 hours after admission mainly based on the initial severity of the CS, or if CS was refractory to the medical treatment. The primary outcome was in-hospital survival. A propensity score-weighted analysis was done for treatment-effect estimation. This method, which weights each patient according to their propensity score, includes all participants in the analysis. Results 246 patients with CS were included in the study: 121 in TMCS group (72% ECLS, 14% Impella, 14% both ECLS and Impella) and 125 in control group. After adjustment by a propensity score, hospital mortality was comparable in the two groups (32% TMCS group vs 27% control group; Odds ratio with TMCS, 1.28; 95% confidence interval, 0.87 to 1.88; p=0.21). Mortality at D180 was also similar in the two group (33% vs 30% respectively; p=0.51). Thromboembolic events were significantly higher in the TCMS group (14% vs 4%; p&lt;0.01) as well as the transfusion rate ((median (IQR); 4.0 (0.0; 9.0) vs 0.0 (0.0; 0.0); p&lt;0.01). Conclusion In our study, the use of TMCS does not seem to improve hospital survival in patients with cardiogenic shock. Thus, TMCS, which are iatrogenic side effects providers, should be reserved for the most severe patient and discussed by a multidisciplinary team. FUNDunding Acknowledgement Type of funding sources: None. Flow chart