Hemorrhagic Complications of Invasive Intracranial Pressure Monitor Placement in Acute Liver Failure: Outcomes of a Single-Center Protocol and Comprehensive Literature Review.

BACKGROUND: Elevated intracranial pressure due to cerebral edema is associated with very poor survival in patients with acute liver failure (ALF). Placing an intracranial pressure monitor (ICPm) aids in management of intracranial hypertension, but is associated with potentially fatal hemorrhagic complications related to the severe coagulopathy associated with ALF. METHODS: An institutional Acute Liver Failure Clinical Protocol (ALF-CP) was created to correct ALF coagulopathy prior to placing parenchymal ICP monitoring bolts. We aimed to investigate the frequency, severity, and clinical significance of hemorrhagic complications associated with ICPm bolt placement in the setting of an ALF-CP. All assessed patients were managed with the ALF-CP and had rigorous radiologic follow-up allowing assessment of the occurrence and chronology of hemorrhagic complications. We also aimed to compare our outcomes to other studies that were identified through a comprehensive review of the literature. RESULTS: Fourteen ALF patients were included in our analysis. There was no symptomatic hemorrhage after ICP monitor placement though four patients were found to have minor intraparenchymal asymptomatic hemorrhages after liver transplant when the ICP monitor had been removed, making the rate of radiographically identified clinically asymptomatic hemorrhage 28.6%. These results compare favorably to those found in a comprehensive review of the literature which revealed rates as high as 17.5% for symptomatic hemorrhages and 30.4% for asymptomatic hemorrhage. CONCLUSION: This study suggests that an intraparenchymal ICPm can be placed safely in tertiary referral centers which utilize a protocol such as the ALF-CP that aggressively corrects coagulopathy. The ALF-CP led to advantageous outcomes for ICPm placement with a 0% rate of symptomatic and low rate of asymptomatic hemorrhagic complications, which compares well to results reported in other series. A strict ICPm placement protocol in this setting facilitates management of ALF patients with cerebral edema during the wait time to transplantation or spontaneous recovery.

Shock subtypes by left ventricular ejection fraction following out-of-hospital cardiac arrest.

BACKGROUND: Post-resuscitation hemodynamic instability following out-of-hospital cardiac arrest (OHCA) may occur from myocardial dysfunction underlying cardiogenic shock and/or inflammation-mediated distributive shock. Distinguishing the predominant shock subtype with widely available clinical metrics may have prognostic and therapeutic value. METHODS: A two-hospital cohort was assembled of patients in shock following OHCA. Left ventricular ejection fraction (LVEF) was assessed via echocardiography or cardiac ventriculography within 1 day post arrest and used to delineate shock physiology. The study evaluated whether higher LVEF, indicating distributive-predominant shock physiology, was associated with neurocognitive outcome (primary endpoint), survival, and duration of multiple organ failures. The study also investigated whether volume resuscitation exhibited a subtype-specific association with outcome. RESULTS: Of 162 patients with post-resuscitation shock, 48% had normal LVEF (> 40%), consistent with distributive shock physiology. Higher LVEF was associated with less favorable neurocognitive outcome (OR 0.74, 95% CI 0.58-0.94 per 10% increase in LVEF; p = 0.01). Higher LVEF also was associated with worse survival (OR 0.81, 95% CI 0.67-0.97; p = 0.02) and fewer organ failure-free days (ß = - 0.67, 95% CI - 1.28 to - 0.06; p = 0.03). Only 51% of patients received a volume challenge of at least 30 ml/kg body weight in the first 6 h post arrest, and the volume received did not differ by LVEF. Greater volume resuscitation in the first 6 h post arrest was associated with favorable neurocognitive outcome (OR 1.59, 95% CI 0.99-2.55 per liter; p = 0.03) and survival (OR 1.44, 95% CI 1.02-2.04; p = 0.02) among patients with normal LVEF but not low LVEF. CONCLUSIONS: In post-resuscitation shock, higher LVEF-indicating distributive shock physiology-was associated with less favorable neurocognitive outcome, fewer days without organ failure, and higher mortality. Greater early volume resuscitation was associated with more favorable neurocognitive outcome and survival in patients with this shock subtype. Additional studies with repeated measures of complementary hemodynamic parameters are warranted to validate the clinical utility for subtyping post-resuscitation shock.

Blood Pressure Coefficient of Variation and Its Association With Cardiac Surgical Outcomes.

BACKGROUND: Multiple studies completed in the ambulatory nonsurgical setting show a significant association between short- and long-term blood pressure variability and poor outcomes. However, perioperative blood pressure variability outcomes have not been well studied, especially in the cardiac surgical setting. In this study, we sought to assess whether systolic and mean arterial blood pressure variability were associated with 30-day mortality and in-hospital renal failure in patients undergoing cardiac surgery requiring cardiopulmonary bypass. Furthermore, blood pressure variability has not been evaluated specifically during each phase of surgery, namely in the pre-, intra- and postbypass phases; thus, we aimed also to assess whether outcomes were associated with phase-specific systolic and mean arterial blood pressure variability. METHODS: All patients undergoing cardiac surgery from January 2008 to June 2014 were enrolled in this retrospective, single-center study. Demographic, intraoperative, and postoperative outcome data were obtained from the institution's Society of Thoracic Surgery database and Anesthesia Information Management System. Systolic and mean arterial blood pressure variability were assessed using the coefficient of variation (CV). The primary outcomes were 30-day mortality and in-hospital renal failure in relation to the entire duration of a case, while the secondary outcomes assessed phase-specific surgical periods. In an effort to control the family-wise error rate, P values <.0125 were considered significant for the primary outcomes. RESULTS: Of the 3687 patients analyzed, 2.7% of patients died within 30 days of surgery and 2.8% experienced in-hospital renal failure. After adjusting for significant covariates, we found a statistically significant association between increasing CV for systolic blood pressure (CVSBP) and 30-day mortality and in-hospital renal failure. For every 0.10 increase in CVSBP, there was a 150% increase in the odds of death (odds ratio, 2.50; 95% confidence interval, 1.60-3.92; P < .0001) and there was a 104% increase in odds of experiencing renal failure (odds ratio, 2.04; 95% confidence interval, 1.33-3.14; P = .001). The association with mortality was driven primarily by the prebypass period, because the association between CVSBP and mortality during the prebypass phase was significant (P = .01), and not during the postbypass phase (P = .08). There was no significant association between CV for mean arterial blood pressure and either death or renal failure during any period of surgery, including the bypass phase. CONCLUSIONS: Increasing systolic blood pressure variability was associated with 30-day mortality and development of renal failure, with surgery phase-specific relationships observed. Further research is required to determine how to prospectively detect blood pressure variability and elucidate opportunities for intervention.

Favorable Neurocognitive Outcome with Low Tidal Volume Ventilation after Cardiac Arrest.

RATIONALE: Neurocognitive outcome after out-of-hospital cardiac arrest (OHCA) is often poor, even when initial resuscitation succeeds. Lower tidal volumes (Vts) attenuate extrapulmonary organ injury in other disease states and are neuroprotective in preclinical models of critical illness. OBJECTIVE: To evaluate the association between Vt and neurocognitive outcome after OHCA. METHODS: We performed a propensity-adjusted analysis of a two-center retrospective cohort of patients experiencing OHCA who received mechanical ventilation for at least the first 48 hours of hospitalization. Vt was calculated as the time-weighted average over the first 48 hours, in milliliters per kilogram of predicted body weight (PBW). The primary endpoint was favorable neurocognitive outcome (cerebral performance category of 1 or 2) at discharge. MEASUREMENTS AND MAIN RESULTS: Of 256 included patients, 38% received time-weighted average Vt greater than 8 ml/kg PBW during the first 48 hours. Lower Vt was independently associated with favorable neurocognitive outcome in propensity-adjusted analysis (odds ratio, 1.61; 95% confidence interval [CI], 1.13-2.28 per 1-ml/kg PBW decrease in Vt; P = 0.008). This finding was robust to several sensitivity analyses. Lower Vt also was associated with more ventilator-free days (ß = 1.78; 95% CI, 0.39-3.16 per 1-ml/kg PBW decrease; P = 0.012) and shock-free days (ß = 1.31; 95% CI, 0.10-2.51; P = 0.034). Vt was not associated with hypercapnia (P = 1.00). Although the propensity score incorporated several biologically relevant covariates, only height, weight, and admitting hospital were independent predictors of Vt less than or equal to 8 ml/kg PBW. CONCLUSIONS: Lower Vt after OHCA is independently associated with favorable neurocognitive outcome, more ventilator-free days, and more shock-free days. These findings suggest a role for low-Vt ventilation after cardiac arrest.

The Effect of Positive End-Expiratory Pressure on Intracranial Pressure and Cerebral Hemodynamics.

BACKGROUND: Lung protective ventilation has not been evaluated in patients with brain injury. It is unclear whether applying positive end-expiratory pressure (PEEP) adversely affects intracranial pressure (ICP) and cerebral perfusion pressure (CPP). We aimed to evaluate the effect of PEEP on ICP and CPP in a large population of patients with acute brain injury and varying categories of acute lung injury, defined by PaO2/FiO2. METHOD: Retrospective data were collected from 341 patients with severe acute brain injury admitted to the ICU between 2008 and 2015. These patients experienced a total of 28,644 paired PEEP and ICP observations. Demographic, hemodynamic, physiologic, and ventilator data at the time of the paired PEEP and ICP observations were recorded. RESULTS: In the adjusted analysis, a statistically significant relationship between PEEP and ICP and PEEP and CPP was found only among observations occurring during periods of severe lung injury. For every centimeter H2O increase in PEEP, there was a 0.31 mmHg increase in ICP (p = 0.04; 95 % CI [0.07, 0.54]) and a 0.85 mmHg decrease in CPP (p = 0.02; 95 % CI [-1.48, -0.22]). CONCLUSION: Our results suggest that PEEP can be applied safely in patients with acute brain injury as it does not have a clinically significant effect on ICP or CPP. Further prospective studies are required to assess the safety of applying a lung protective ventilation strategy in brain-injured patients with lung injury.

Close surveillance imaging is unnecessary for patients with grade I blunt thoracic aortic injury.

BACKGROUND: No evidence-based recommendations exist for imaging surveillance of grade I blunt thoracic aortic injuries (BTAI). We aimed to evaluate the natural history of these injuries to provide guidance for follow-up imaging. METHODS: Patients that presented to our trauma center from 2008 to 2021 with grade I BTAI were retrospectively evaluated. CT angiography images were assessed for initial injury grade and subsequent stability, improvement, worsening, or resolution. RESULTS: Of 83 patients who had grade I injuries and repeat imaging, 57.8% had complete resolution, 20.5% had improvement, and 18.1% had stability of their injury. Only seven patients (8.4%) demonstrated worsening of their injury. Six patients had eventual resolution and one underwent endovascular repair that would not have been performed under current practice patterns. CONCLUSIONS: Since grade I injuries do not worsen to require later surgical intervention, early surveillance imaging is not necessary and further imaging may not be necessary at all.

The Effect of Anticoagulation and Antiplatelet Use in Trauma Patients on Mortality and Length of Stay.

BACKGROUND: Though many trauma patients are on anticoagulation or antiplatelet therapy (AAT), there are few generalizable data on the risks for these patients. The purpose of this study was to analyze the impact of anticoagulation (AC) and antiplatelet (AP) therapy on mortality and length of stay (LOS) in general trauma patients. METHODS: A retrospective review was performed of patients in the institutional trauma registry during 2019 to determine AAT use on admission and discharge. Outcomes were compared using standard statistics. RESULTS: Of 2261 patients who met the inclusion criteria, 2 were excluded due to an incomplete medication reconciliation, resulting in 2259 patients. Patients on AAT had a higher mortality (4.5% vs 2.1%). On multivariable analysis, preadmission AC (odds ratio OR, 3.325, P = .001), age (OR 1.040, P < .001), and injury severity score ((ISS) 1.094, P < .001) were associated with mortality. Anticoagulation use was also associated with longer LOS on multivariable analysis (OR: 1.626, P = .005). Antiplatelet use was not associated with higher mortality or longer LOS. More patients on AAT were unable to be discharged home. However, patients on AAT did not have a greater blood transfusion requirement or need more hemorrhage control procedures. Lastly, 23.7% of patients on preadmission AAT were not discharged on any AAT. DISCUSSION: These data demonstrate that patients on AC, but not AP, have greater mortality and longer hospital LOS. This may provide guidance for those being newly started on AAT. Further work to determine which patients benefit most from restarting AAT would lead to improvement in the care of trauma patients.

An effective multi-modality model for single-session cricothyroidotomy training for trainees.

BACKGROUND: We piloted a curriculum combining a flipped classroom with two-stage narration, role-play, and partial task trainer simulation to teach this critical skill to trainees. METHODS: This "flipped classroom" module (2012-2018) for open and percutaneous cricothyroidotomy (OC and PC) required participants to watch two 4 min training videos for OC and PC. The simulation session consisted of a 45-min hands-on simulation of OC and PC in which participants rotated between the roles of operator, narrator, and critiquer. Median performance scores were calculated. RESULTS: 103 trainees were evaluated. The median performance score was 14 out of maximum 14 (range: 9-14) across all trainees for OC. The median performance score was 13 out of maximum 13 (range: 3-13) across all trainees for PC. CONCLUSION: A multi-modality approach including the flipped classroom, role-play, and partial task trainer simulation is an efficient and effective method for teaching trainees proficiency in short, single operator procedures.

The organizational structure of an intensive care unit influences treatment of hypotension among critically ill patients: A retrospective cohort study.

PURPOSE: Prior studies report that weekend admission to an intensive care unit is associated with increased mortality, potentially attributed to the organizational structure of the unit. This study aims to determine whether treatment of hypotension, a risk factor for mortality, differs according to level of staffing. METHODS: Using the Multiparameter Intelligent Monitoring in Intensive Care database, we conducted a retrospective study of patients admitted to an intensive care unit at Beth Israel Deaconess Medical Center who experienced one or more episodes of hypotension. Episodes were categorized according to the staffing level, defined as high during weekday daytime (7 am-7 pm) and low during weekends or nighttime (7 pm-7 am). RESULTS: Patients with a hypotensive event on a weekend were less likely to be treated compared with those that occurred during the weekday daytime (P = .02). No association between weekday daytime vs weekday nighttime staffing levels and treatment of hypotension was found (risk ratio, 1.02; 95% confidence interval, 0.98-1.07). CONCLUSION: Patients with a hypotensive event on a weekend were less likely to be treated than patients with an event during high-staffing periods. No association between weekday nighttime staffing and hypotension treatment was observed. We conclude that treatment of a hypotensive episode relies on more than solely staffing levels.

Cofactor binding and enzymatic activity in an unevolved superfamily of de novo designed 4-helix bundle proteins.

To probe the potential for enzymatic activity in unevolved amino acid sequence space, we created a combinatorial library of de novo 4-helix bundle proteins. This collection of novel proteins can be considered an "artificial superfamily" of helical bundles. The superfamily of 102-residue proteins was designed using binary patterning of polar and nonpolar residues, and expressed in Escherichia coli from a library of synthetic genes. Sequences from the library were screened for a range of biological functions including heme binding and peroxidase, esterase, and lipase activities. Proteins exhibiting these functions were purified and characterized biochemically. The majority of de novo proteins from this superfamily bound the heme cofactor, and a sizable fraction of the proteins showed activity significantly above background for at least one of the tested enzymatic activities. Moreover, several of the designed 4-helix bundles proteins showed activity in all of the assays, thereby demonstrating the functional promiscuity of unevolved proteins. These studies reveal that de novo proteins-which have neither been designed for function, nor subjected to evolutionary pressure (either in vivo or in vitro)-can provide rudimentary activities and serve as a "feedstock" for evolution.