Hyperchloremia, not Concomitant Hypernatremia, Independently Predicts Early Mortality in Critically Ill Moderate-Severe Traumatic Brain Injury Patients.

BACKGROUND: Hypernatremia has been associated with mortality in neurocritically ill patients, with and without traumatic brain injury (TBI). These studies, however, lack concomitant adjustment for hyperchloremia as a physiologically co-occurring finding despite the associations with hyperchloremia and worse outcomes after trauma, sepsis, and intracerebral hemorrhage. The objective of our study was to examine the association of concomitant hypernatremia and hyperchloremia with in-hospital mortality in moderate-severe TBI (msTBI) patients. METHODS: We retrospectively analyzed prospectively collected data from the OPTIMISM-study and included all msTBI patients consecutively enrolled between 11/2009 and 1/2017. Time-weighted average (TWA) sodium and chloride values were calculated for all patients to examine the unadjusted mortality rates associated with the burden of hypernatremia and hyperchloremia over the entire duration of the intensive care unit stay. Multivariable logistic regression modeling predicting in-hospital mortality adjusted for validated confounders of msTBI mortality was applied to evaluate the concomitant effects of hypernatremia and hyperchloremia. Internal bootstrap validation was performed. RESULTS: Of the 458 patients included for analysis, 202 (44%) died during the index hospitalization. Fifty-five patients (12%) were excluded due to missing data. Unadjusted mortality rates were nearly linearly increasing for both TWA sodium and TWA chloride, and were highest for patients with a TWA sodium > 160 mmol/L (100% mortality) and TWA chloride > 125 mmol/L (94% mortality). When evaluated separately in the multivariable analysis, TWA sodium (per 10 mmol/L change: adjusted OR 4.0 [95% CI 2.1-7.5]) and TWA chloride (per 10 mmol/L change: adjusted OR 3.9 [95% CI 2.2-7.1]) independently predicted in-hospital mortality. When evaluated in combination, TWA chloride remained independently associated with in-hospital mortality (per 10 mmol/L change: adjusted OR 2.9 [95% CI 1.1-7.8]), while this association was no longer observed with TWA sodium values (per 10 mmol/L change: adjusted OR 1.5 [95% CI 0.51-4.4]). CONCLUSIONS: When concomitantly adjusting for the burden of hyperchloremia and hypernatremia, only hyperchloremia was independently associated with in-hospital mortality in our msTBI cohort. Pending validation, our findings may provide the rationale for future studies with targeted interventions to reduce hyperchloremia and improve outcomes in msTBI patients.

Carbapenem Treatment and Outcomes Among Patients With Culture-Positive Complicated Intra-abdominal Infections in US Hospitals: A Retrospective Cohort Study.

BACKGROUND: Carbapenems are a frequent firstline therapy in complicated intra-abdominal infections (cIAIs). We examined the microbiology, epidemiology, and outcomes among patients hospitalized in the United States with culture-positive cIAIs in the context of their exposure to empiric carbapenem treatment (ECT). METHODS: We performed a multicenter retrospective cohort study of Premier database of ~180 hospitals, 2013-2017. Using an International Classification of Diseases (ICD)-9/10-based algorithm, we identified all culture-positive adult patients hospitalized with cIAI and examined their microbiology, epidemiology, and outcomes. RESULTS: Among 4453 patients with cIAIs, 3771 (84.7%) had a gram-negative (GN) and 1782 (40.0%) a gram-positive organism; 1185 (26.6%) received ECT. Compared with those on non-ECT, patients on ECT were less frequently admitted from home (82.5% vs 86.0%) or emergently (76.0% vs 81.4%; P < .05 for each); E. coli were less frequent, whereas P. aeruginosa and Enterococcus spp. were more prevalent and resistance to third-generation cephalosporins (C3R; 10.1% vs 5.1%; P < .001) and carbapenems (CR; 3.6% vs 1.2%; P < .001) was more common. In adjusted analyses, ECT was associated with no rise in mortality, shorter postinfection length of stay (-0.59 days; 95% confidence interval [CI], -1.15 to -0.03), but higher postinfection costs ($3844; 95% CI, $1921 to $5767) and risk of Clostridioides difficile (odds ratio, 2.15; 95% CI, 1.02 to 4.50). CONCLUSIONS: Among patients hospitalized with cIAI, the majority were gram-negative. Despite a 10% prevalence of C3R, fully one-quarter of all empiric regimens contained a carbapenem. ECT was a marker for slightly lower postinfection length of stay, but higher costs and risk of hospital complications.

Use of Nebulized Heparin, Nebulized N-Acetylcysteine, and Nebulized Epoprostenol in a Patient With Smoke Inhalational Injury and Acute Respiratory Distress Syndrome.

Smoke inhalation injury (SIJ) is associated with an increase in morbidity and mortality in patients with burns. SIJ causes airway damage, inflammation, and bronchial obstruction, resulting in decreased oxygenation and perfusion status in these patients. Retrospective studies have compared the use of nebulized heparin (NH) plus nebulized N-acetylcysteine (NAC) and albuterol in patients with SIJ to those who received standard ventilator support with bronchodilator therapy. These studies are associated with a decrease in mortality when NH and nebulized NAC are administered to patients with SIJ. Approximately 20% of patients who develop SIJ will also develop acute respiratory distress syndrome (ARDS). Epoprostenol, a selective pulmonary vasodilator, has been utilized in the treatment of ARDS with mixed results for improving gas exchange. To our knowledge, this is the first case report of the concomitant administration of NH, nebulized NAC, and nebulized epoprostenol following SIJ in a burn patient with ARDS.

Idarucizumab for Reversal of Dabigatran-Associated Anticoagulation.

OBJECTIVE: To review clinical data on idarucizumab for the reversal of dabigatran-associated anticoagulation. DATA SOURCES: Articles for this review were identified via PubMed using the MeSH term dabigatran combined with the keyword idarucizumab Additional online searches via PubMed and Google Scholar were conducted for both prescribing and cost information. STUDY SELECTION AND DATA EXTRACTION: English-language clinical trials published between 1946 and May 2016 were included for review. Bibliographies of selected articles were also manually reviewed for relevant publications that focused on reversal strategies for dabigatran-associated anticoagulation. DATA SYNTHESIS: The safety and tolerability of idarucizumab has been evaluated in 3 phase I clinical trials. The use of idarucizumab for reversing dabigatran-associated anticoagulation is also being evaluated in the phase III RE-VERSE AD study. Interim results of the RE-VERSE AD study have been published. CONCLUSIONS: Idarucizumab rapidly neutralizes the anticoagulant effect of dabigatran in healthy volunteers, in patients with life-threatening bleeding, and in patients requiring urgent surgery that cannot be delayed. These observations are largely based on laboratory assessments rather than clinical outcomes. Idarucizumab is well tolerated, and it does not appear to induce procoagulant or immunogenic adverse effects.

The Impact of Liver and Renal Dysfunction on the Pharmacokinetics and Pharmacodynamics of Sedative and Analgesic Drugs in Critically Ill Adult Patients.

The use of sedative and analgesic drug therapy is often necessary for the care of critically ill patients. Renal and hepatic dysfunction, which occurs frequently in this patient population, can significantly alter drugs' pharmacokinetic and pharmacodynamics properties. By anticipating how these medications may be affected by liver or kidney dysfunction, health care practitioners may be able to provide tailored dosing regimens that ensure optimal comfort while minimizing the risk of adverse events.

Clinical experience of life-threatening dabigatran-related bleeding at a large, tertiary care, academic medical center: a case series.

INTRODUCTION: Dabigatran, an oral direct thrombin inhibitor, is FDA approved for the prevention of stroke in patients with nonvalvular atrial fibrillation. No agent exists for the reversal of dabigatran-related major bleeding. Prothrombin complex concentrate (PCC) has been studied in reversal but was not shown to affect the surrogate markers of bleeding such as the thrombin time, ecarin clotting time, or activated partial thromboplastin time (aPTT). Recombinant factor VIIa (rFVIIa) may provide benefit in patients with life-threatening or major bleeding; however, it has not been studied in dabigatran-related bleeding. PCC and rFVIIa are agents utilized at our institution for major bleeding in patients receiving anticoagulant therapy. Due to the high cost and thrombogenic risk of both rVIIa and PCC and lack of a clear reversal strategy, we reviewed the management of all reported cases of dabigatran-related bleeding. METHODS: This was a retrospective chart review of patients admitted to UMass Memorial Medical Center with a bleeding event and also receiving dabigatran therapy. RESULTS: Eleven patients on dabigatran admitted for bleeding were identified. Seven were admitted for an intracranial hemorrhage (ICH) and four for a gastrointestinal hemorrhage (GIH). The baseline characteristics are as follows: mean age was 74.55 years (range, 63-89), and seven were male. Admission mean hemoglobin was 11.88 g/dl (range, 6.1-18), mean international normalized ratio (INR) was 2.2 (range, 1.1-7.1), and mean aPTT was 42.21 s (range, 36-81.4). Interventions received included fresh frozen plasma (n = 6), platelets (n = 3), packed red blood cells (n = 4), rFVIIa (n = 2), intravenous fluids (n = 10), surgical intervention (n = 3), and dialysis (n = 2). No patients received PCC. Four patients survived in the ICH group, and four patients survived in the GIH group. CONCLUSION: Reversal strategies for dabigatran-related bleeding events at our institution are highly variable. Intracranial hemorrhage in patients on dabigatran was associated with 43 % mortality. Patients with severe dabigatran-related bleeding may benefit from a standardized approach to treatment.

Comparison of a low, fixed dose and a high, weight-based dose of recombinant factor VIIa in the treatment of warfarin-associated intracranial hemorrhage.

BACKGROUND: Recombinant activated Factor VII (rFVIIa) can be used for rapid INR normalization in patients with warfarin-associated intracranial hemorrhage (WA-ICH); however, the optimal dose to normalize INR has not been established. METHODS: This is a retrospective review comparing two rFVIIa hospital protocols for WA-ICH [weight-based dose (80 mcg/kg) or fixed dose (2 mg)]. Primary endpoint was the percentage of patients with INR reversal (INR <1.3) at the next INR draw and the need for further doses of rFVIIa. Secondary endpoints included time to documented INR reversal and sustained INR normalization, morbidity, mortality, change in hematoma size, cost, and adverse drug reactions. RESULTS: Twenty-nine patients were included in each group. The weight-based group received a mean dose of 78.9 ± 21 mcg/kg versus 26.6 ± 8 mcg/kg in the fixed dose group. More patients in the fixed dose protocol achieved documented INR reversal than those in the weight-based group (92.6 vs 72.4 %, p = 0.19). The weight-based group achieved INR normalization in 229.5 [102, 331] minutes versus 165 [83, 447] minutes in the fixed dose group (p=0.02). Time to sustained INR normalization was similar in both groups. Four patients in the fixed dose group received an additional dose of 1 mg per hospital protocol. With the exception of medication acquisition cost savings of about $4,300 per patient who received fixed dose protocol, all other endpoints were similar between groups. CONCLUSIONS: A low, fixed dose of rFVIIa appears to be as effective as a high, weight-based dose in achieving INR normalization in patients with WA-ICH.