The Discover In-Hospital Cardiac Arrest (Discover IHCA) Study: An Investigation of Hospital Practices After In-Hospital Cardiac Arrest.

IMPORTANCE: In-hospital cardiac arrest (IHCA) is a significant public health burden. Rates of return of spontaneous circulation (ROSC) have been improving, but the best way to care for patients after the initial resuscitation remains poorly understood, and improvements in survival to discharge are stagnant. Existing North American cardiac arrest databases lack comprehensive data on the post-resuscitation period, and we do not know current post-IHCA practice patterns. To address this gap, we developed the Discover In-Hospital Cardiac Arrest (Discover IHCA) study, which will thoroughly evaluate current post-IHCA care practices across a diverse cohort. OBJECTIVES: Our study collects granular data on post-IHCA treatment practices, focusing on temperature control and prognostication, with the objective of describing variation in current post-IHCA practice. DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter, prospectively collected, observational cohort study of patients who have suffered IHCA and have been successfully resuscitated (achieved ROSC). There are 24 enrolling hospital systems (23 in the United States) with 69 individual enrolling hospitals (39 in the United States). We developed a standardized data dictionary, and data collection began in October 2023, with a projected 1000 total enrollments. Discover IHCA is endorsed by the Society of Critical Care Medicine. INTERVENTIONS, OUTCOMES, AND ANALYSIS: The study collects data on patient characteristics including pre-arrest frailty, arrest characteristics, and detailed information on post-arrest practices and outcomes. Data collection on post-IHCA practice was structured around current American Heart Association and European Resuscitation Council guidelines. Among other data elements, the study captures post-arrest temperature control interventions and post-arrest prognostication methods. Analysis will evaluate variations in practice and their association with mortality and neurologic function. CONCLUSIONS: We expect this study, Discover IHCA, to identify variability in practice and outcomes following IHCA, and be a vital resource for future investigations into best-practice for managing patients after IHCA.

Thiamine as a metabolic resuscitator after out-of-hospital cardiac arrest.

INTRODUCTION: Thiamine is a key cofactor for aerobic metabolism, previously shown to improve mortality and neurological outcomes in a mouse model of cardiac arrest. We hypothesized that thiamine would decrease lactate and improve outcomes in post-arrest patients. METHODS: Single center, randomized, blinded, placebo-controlled, Phase II trial of thiamine in adults within 4.5 hours of return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA), with coma and lactate ≥ 3 mmol/L. Participants received 500 mg IV thiamine or placebo twice daily for 2 days. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. The primary outcome of lactate was checked at baseline, 6, 12, and 24 hours, and compared using a linear mixed model to account for repeated measures. Secondary outcomes included SOFA score, pyruvate dehydrogenase, renal injury, neurological outcome, and mortality. RESULTS: Of 93 randomized patients, 76 were enrolled and included in the analysis. There was no difference in lactate over 24 hours (mean difference 0.34 mmol/L (95% CI: -1.82, 2.50), p = 0.43). There was a significant interaction between randomization lactate subgroup and the effect of the intervention on mortality (p = 0.01) such that mortality was higher with thiamine in the lactate > 5 mmol/L group and lower with thiamine in the < 5 mmol/L group. This subgroup difference prompted the Data and Safety Monitoring Board to recommend the study be terminated early. PDH activity increased over 72 hours in the thiamine group. There were no differences in other secondary outcomes. CONCLUSION: In this single-center randomized trial, thiamine did not affect lactate over 24 hours after OHCA.

Corticosteroids to Reduce Inflammation in Severe Pancreatitis (CRISP) protocol and statistical analysis plan: a prospective, multicentre, double-blind, randomized, placebo controlled clinical trial.

INTRODUCTION: Acute pancreatitis is a common disease which, in its severe form, is associated with significant morbidity and mortality. Currently, there is no specific therapy known to attenuate organ failure in severe pancreatitis and treatment consists primarily of supportive care. Corticosteroids have been shown to be beneficial in disease processes associated with systemic inflammation and could potentially improve outcomes in severe acute pancreatitis. METHODS: The Corticosteroids to Reduce Inflammation in Severe Pancreatitis (CRISP) trial is a multi-centre, double-blind, randomized, placebo-controlled clinical trial that aims to determine the impact of corticosteroids versus placebo on organ injury in patients with severe acute pancreatitis. Patients are randomized to receive 100 mg of hydrocortisone parenterally versus matching placebo every 8 h for 3 days. Clinical and laboratory data are collected at the time of study enrollment, at 24, 48 and 72 h. The primary end-point for the trial is the difference in 72-h change in the Sequential Organ Failure Assessment (SOFA) score between hydrocortisone and placebo groups. Additional key secondary outcomes include ventilator free days and 28-day mortality. DISCUSSION: This study will add to the evidence base in the treatment of severe acute pancreatitis. The results will inform clinical practice and future studies in the field. Trial registration number The trial is registered on clinicaltrials.gov (NCT05160506). It was posted on December 16th, 2021. The study protocol was approved by the Beth Israel Deaconess Medical Center Committee on Clinical Investigation (CCI) (protocol 2021 P-000803).

Thiamine as adjunctive therapy for diabetic ketoacidosis (DKAT) trial protocol and statistical analysis plan: a prospective, single-centre, double-blind, randomised, placebo-controlled clinical trial in the USA.

INTRODUCTION: Diabetic ketoacidosis (DKA) is a potentially life-threatening diabetic complication. Despite the high prevalence of DKA and the substantial associated healthcare burden, limited research on strategies to improve outcomes currently exists.Thiamine (vitamin B1) is a cofactor of pyruvate dehydrogenase, which plays a key role in aerobic glucose metabolism. Thiamine deficiency is common in patients with DKA, resulting in a shift to anaerobic metabolism and hyperlactatemia, which can prolong and complicate recovery. Therefore, we hypothesise that thiamine administration will improve aerobic metabolism and lead to faster resolution of acidemia in patients with DKA. METHODS AND ANALYSIS: In this single centre, double-blind, randomised, placebo-controlled, parallel group interventional trial, 100 patients admitted to the hospital with DKA will be randomised to receive either intravenous thiamine (200 mg in 50 mL 0.9% saline) or placebo (0.9% saline identical in appearance and volume) two times per day for 2 days. The primary outcome will be the change in bicarbonate level over 24 hours as compared between the two treatment groups. Additional secondary outcomes include the change over time in anion gap, lactate levels, oxygen consumption by circulating mononuclear cells, intensive care unit and hospital length-of-stay and hospital resource usage when comparing the two study arms. ETHICS AND DISSEMINATION: This trial was approved by the Committee on Clinical Investigations, the institutional review board of Beth Israel Deaconess Medical Center (protocol number 2018P000475). Findings will be disseminated through peer-reviewed publications and professional conference presentations. TRIAL REGISTRATION NUMBER: NCT03717896; clinicaltrials.gov.

Thiamine administration in septic shock: a post hoc analysis of two randomized trials.

BACKGROUND: This is a post hoc analysis of combined cohorts from two previous Phase II clinical trials to assess the effect of thiamine administration on kidney protection and mortality in patients with septic shock. METHODS: Patient-level data from the Thiamine in Septic Shock Trial (NCT01070810) and the Thiamine for Renal Protection in Septic Shock Trial (NCT03550794) were combined in this analysis. The primary outcome for the current study was survival without the receipt of renal replacement therapy (RRT). Analyses were performed on the overall cohort and the thiamine-deficient cohort (thiamine < 8 nmol/L). RESULTS: Totally, 158 patients were included. Overall, thiamine administration was associated with higher odds of being alive and RRT-free (adjusted odds ratio [aOR]: 2.05 [95% confidence interval (CI) 1.08-3.90]) and not needing RRT (aOR: 2.59 [95% CI 1.01-6.62]). In the thiamine-deficient group, thiamine administration was associated with higher odds of being alive and RRT-free (aOR: 8.17 [95% CI 1.79-37.22]) and surviving to hospital discharge (aOR: 6.84 [95% CI 1.54-30.36]). There was a significant effect modification by baseline thiamine deficiency for alive and RRT-free (interaction, p = 0.016) and surviving to hospital discharge (p = 0.019). CONCLUSION: In the combined analysis of two previous randomized trials, thiamine administration was associated with higher odds of being alive and RRT-free at hospital discharge in patients with septic shock. This signal was stronger in patients with thiamine deficiency.

Central catheter tip migration in critically ill patients.

OBJECTIVES: Chest X-ray (CXR) is routinely required for assessing Central Venous Catheter (CVC) tip position after insertion, but there is limited data as to the movement of the tip location during hospitalization. We aimed to assess the migration of Central Venous Catheter (CVC) position, as a significant movement of catheter tip location may challenge some of the daily practice after insertion. DESIGN AND SETTINGS: Retrospective, single-center study, conducted in the Intensive Care and Cardiovascular Intensive Care Units in Tel Aviv Sourasky Medical Center 'Ichilov', Israel, between January and June 2019. PATIENTS: We identified 101 patients with a CVC in the Right Internal Jugular (RIJ) with at least two CXRs during hospitalization. MEASUREMENTS AND RESULTS: For each patient, we measured the CVC tip position below the carina level in the first and all consecutive CXRs. The average initial tip position was 1.52 (±1.9) cm (mean±SD) below the carina. The maximal migration distance from the initial insertion position was 1.9 (±1) cm (mean±SD). During follow-up of 2 to 5 days, 92% of all subject's CVCs remained within the range of the Superior Vena Cava to the top of the right atrium, regardless of the initial positioning. CONCLUSIONS: CVC tip position can migrate significantly during a patient's early hospitalization period regardless of primary location, although for most patients it will remain within a wide range of the top of the right atrium and the middle of the Superior Vena Cava (SVC), if accepted as well-positioned.

Correction to: Lung ultrasound predicts clinical course and outcomes in COVID-19 patients.

The original article can be found online.

Lung ultrasound predicts clinical course and outcomes in COVID-19 patients.

PURPOSE: Information regarding the use of lung ultrasound (LUS) in patients with Coronavirus disease 2019 (COVID-19) is quickly accumulating, but its use for risk stratification and outcome prediction has yet to be described. We performed the first systematic and comprehensive LUS evaluation of consecutive patients hospitalized with COVID-19 infection, in order to describe LUS findings and their association with clinical course and outcome. METHODS: Between 21/03/2020 and 04/05/2020, 120 consecutive patients admitted to the Tel Aviv Medical Center due to COVID-19, underwent complete LUS within 24 h of admission. A second exam was performed in case of clinical deterioration. LUS score of 0 (best)-36 (worst) was assigned to each patient. LUS findings were compared with clinical data. RESULTS: The median baseline total LUS score was 15, IQR [7-20]. Baseline LUS score was 0-18 in 80 (67%) patients, and 19-36 in 40 (33%) patients. The majority had patchy pleural thickening (n = 100; 83%), or patchy subpleural consolidations (n = 93; 78%) in at least one zone. The prevalence of pleural thickening, subpleural consolidations and the total LUS score were all correlated with severity of illness on admission. Clinical deterioration was associated with increased follow-up LUS scores (p = 0.0009), mostly due to loss of aeration in anterior lung segments. The optimal cutoff point for LUS score was 18 (sensitivity = 62%, specificity = 74%). Both mortality and need for invasive mechanical ventilation were increased with baseline LUS score > 18 compared to baseline LUS score 0-18. Unadjusted hazard ratio of death for LUS score was 1.08 per point [1.02-1.16], p = 0.008; Unadjusted hazard ratio of the composite endpoint (death or need for invasive mechanical ventilation) for LUS score was 1.12 per point [1.05-1.2], p = 0.0008. CONCLUSION: Hospitalized patients with COVID-19, at all clinical grades, present with pathological LUS findings. Baseline LUS score strongly correlates with the eventual need for invasive mechanical ventilation and is a strong predictor of mortality. Routine use of LUS may guide patients' management strategies, as well as resource allocation in case of surge capacity.

Spontaneous Hemopericardium in a Patient Receiving Apixaban Therapy: First Case Report.

Apixaban, a direct factor Xa inhibitor, is a novel oral anticoagulant (NOAC) indicated for prevention of embolic events in patients with nonvalvular atrial fibrillation. The agent is associated with a lower risk of bleeding compared with vitamin K antagonists such as warfarin. Hemopericardium is a life-threatening bleeding event that is rarely caused by anticoagulants. We describe the case of a 76-year-old woman who was diagnosed with nonvalvular atrial fibrillation and treated with apixaban. Six weeks later, she was hospitalized after complaints of weakness and dizziness, and a chest radiograph revealed cardiomegaly. Further imaging, including a computed tomography scan and transthoracic echocardiogram, confirmed a diagnosis of hemopericardium. To our knowledge, this is the first case report of hemopericardium associated with apixaban therapy. This report, along with two previous cases reports of hemopericardium associated with dabigatran and rivaroxaban, emphasizes the need for careful use of NOACs and for further research to identify an antidote or other method for controlling hemorrhage secondary to NOACs in an acute setting. Furthermore, clinicians should consider hemopericardium in the differential diagnosis of patients treated with anticoagulants, including NOACs, who present with cardiomegaly.

Polymorphisms in the human organic cation transporter and the multidrug resistance gene: correlation with imatinib levels and clinical course in patients with chronic myeloid leukemia.

The optimal tyrosine kinase inhibitor for any individual patient with chronic myeloid leukemia (CML) is not predictable. Pharmacogenetic parameters and trough levels of imatinib (IM) have each been independently correlated with response. We therefore studied the human organic cation transporter (hOCT1) and multidrug resistance (MDR1) single nucleotide polymorphisms (SNPs) and correlated these with IM levels and major molecular response (MMR) (3-log reduction) in 84 patients with CML, the first such study performed in Caucasians. We studied MDR1 G2677T and C3435T, and for hOCT1, C480G and A1222G. IM levels varied significantly with dose (< or > 400 mg/day) (p = 0.038) and were significantly lower in 20 patients who lost MMR (p = 0.042). Adjusting for dose, trough IM levels were not significantly correlated with SNPs. Patients with MDR1 3435 TT had significantly longer times to MMR compared to CC/CT genotypes (p = 0.047). Genotypes did not predict treatment failure when controlling for IM levels. We conclude that IM levels, but not the SNPs studied here, determine IM failure.