Randomized Phase 3 Trial of Ruxolitinib for COVID-19-Associated Acute Respiratory Distress Syndrome.

OBJECTIVES: Evaluate the safety and efficacy of the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib in COVID-19-associated acute respiratory distress syndrome requiring mechanical ventilation. DESIGN: Phase 3 randomized, double-blind, placebo-controlled trial Ruxolitinib in Participants With COVID-19-Associated Acute Respiratory Distress Syndrome Who Require Mechanical Ventilation (RUXCOVID-DEVENT; NCT04377620). SETTING: Hospitals and community-based private or group practices in the United States (29 sites) and Russia (4 sites). PATIENTS: Eligible patients were greater than or equal to 12 years old, hospitalized with severe acute respiratory syndrome coronavirus 2 infection, and mechanically ventilated with a Pa o2 /F io2 of less than or equal to 300 mm Hg within 6 hours of randomization. INTERVENTIONS: Patients were randomized 2:2:1 to receive twice-daily ruxolitinib 15 mg, ruxolitinib 5 mg, or placebo, each plus standard therapy. MEASUREMENTS AND MAIN RESULTS: The primary endpoint, 28-day mortality, was tested for each ruxolitinib group versus placebo using a mixed-effects logistic regression model and one-tailed significance test (significance threshold: p < 0.025); no type 1 error was allocated to secondary endpoints. Between May 24, 2020 and December 15, 2020, 211 patients (age range, 24-87 yr) were randomized (ruxolitinib 15/5 mg, n = 77/87; placebo, n = 47). Acute respiratory distress syndrome was categorized as severe in 27% of patients (58/211) at randomization; 90% (190/211) received concomitant steroids. Day-28 mortality was 51% (39/77; 95% CI, 39-62%) for ruxolitinib 15 mg, 53% (45/85; 95% CI, 42-64%) for ruxolitinib 5 mg, and 70% (33/47; 95% CI, 55-83%) for placebo. Neither ruxolitinib 15 mg (odds ratio, 0.46 [95% CI, 0.201-1.028]; one-sided p = 0.029) nor 5 mg (odds ratio, 0.42 [95% CI, 0.171-1.023]; one-sided p = 0.028) significantly reduced 28-day mortality versus placebo. Numerical improvements with ruxolitinib 15 mg versus placebo were observed in secondary outcomes including ventilator-, ICU-, and vasopressor-free days. Rates of overall and serious treatment-emergent adverse events were similar across treatments. CONCLUSIONS: The observed reduction in 28-day mortality rate between ruxolitinib and placebo in mechanically ventilated patients with COVID-19-associated acute respiratory distress syndrome was not statistically significant; however, the trial was underpowered owing to early termination.

Efficacy of 4-Factor Prothrombin Complex Concentrates in Factor Xa Inhibitor-Associated Intracranial Bleeding.

BACKGROUND/OBJECTIVE: Intracranial bleeding (ICB) is a feared complication of systemic anticoagulation. Factor Xa inhibitors (FXaI) are used frequently due to their improved safety profile and predictable kinetics. Andexanet alfa was recently approved for emergent reversal of FXaI agents but was not compared formally to 4-Factor Prothrombin Complex Concentrates (4FPCC) which are the current standard of care in many centers. The objective of this study is to formally evaluate the hemostatic efficacy of 4FPCC in patients with FXaI-associated ICB. METHODS: We performed a retrospective cohort study of patients receiving 4FPCC for the reversal of a FXaI in the setting of acute ICB. Hemostatic efficacy was adjudicated via evaluation of post-4FPCC CT scan using the criteria closely mirroring those outlined in Annexa-4 (excellent < 20% expansion, good > 20% but ≤ 35% expansion, poor > 35% expansion). Each image was reviewed by two neurointensivist attendings for grading. Mortality was assessed until date of discharge. Charts were screened for thrombotic events out to 30 days post-4FPCC administration. RESULTS: A total of 59 patients were included in the final analysis. The mean age in years was 78.5 ± 10.9 and 56% were male. Apixaban was the most common FXaI prescribed at the time of presentation (67.8%). Most patients were on FXaI therapy for stroke prevention in the setting of atrial fibrillation (81.3%). Median Glasgow Coma Scale at presentation was 15(IQR 12-15), with the most frequently presenting ICB type being intracerebral hemorrhage (52.5%). The mean dose of 4FPCC prescribed was 46.6 (± 8.2) units/kg. Of those receiving 4FPCC for FXaI ICB, 88% were graded as having an excellent or good hemostatic outcome with excellent interrater reliability. Survival was high at 89.8%, and thrombotic events were seen in seven patients (11.9%). CONCLUSION: 4FPCC appears to be an effective and safe option for FXaI-associated ICB with outcomes comparable to andexanet alfa. A formal prospective evaluation of this strategy versus andexanet alpha including cost analysis is warranted.

Ascorbic Acid, Thiamine, and Steroids in Septic Shock: Propensity Matched Analysis.

INTRODUCTION: We aimed to study the use of ascorbic acid, thiamine, and steroids (ATS) in patients with septic shock (SS). METHODS: Data on 62 patients with SS were collected from Acute Physiologic and Chronic Health Evaluation (APACHE) Outcome database and medical records. The ATS group received full doses of intravenous (IV) ATS (ascorbic acid [1.5 g every 6 hours for 4 days], hydrocortisone [50 mg every 6 hours for 7 days], and thiamine [200 mg every 12 hours for 4 days]). Data included age, gender, APACHE III, acute physiologic score (APS), mechanical ventilation (MV), lactic acid (LA), serum creatinine (Cr), duration of vasopressors (VP, days, median: interquartile ranges [IQR]: [Q1, Q3]), MV-free days (median: IQR [Q1-Q3]), percentage of patients requiring renal replacement therapy (RRT) for acute kidney injury (AKI), and mortality. Propensity analysis was used to match patients on age, gender, MV, APACHE III, APS, LA, and Cr. RESULTS: The ATS group had longer duration of VP (4.5: 4.0-6.0 vs 2.0: 1.0-2.0, P = .001), similar RRT for AKI (26% vs 29%, P = .8), similar MV-free days (10.2: 5.0-15.0 vs 10.2: 1.6-18.0, P > .9), lower intensive care unit mortality (9.6% vs 42%, P = .004), and a trend toward lower hospital mortality (29% vs 45%, P = .2) compared to the NO ATS group. CONCLUSIONS: The use of IV ascorbic acid, thiamine, and hydrocortisone might be beneficial in patients with SS.

Correction to: Variability in functional outcome and treatment practices by treatment center after out-of-hospital cardiac arrest: analysis of International Cardiac Arrest Registry.

The original version of this article unfortunately contained a mistake.

Angiotensin II in septic shock.

Septic shock is a life threatening condition and a medical emergency. It is associated with organ dysfunction and hypotension despite optimal volume resuscitation. Refractory septic shock carries a very high rate of mortality and is associated with ischemic and arrhythmogenic complications from high dose vasopressors. Angiotensin II (AT-II) is a product of the renin-angiotensin-aldosterone system. It is a vasopressor agent that has been recently approved by FDA to be used in conjunction with other vasopressors (catecholamines) in refractory shock and to reduce catecholamine requirements. We have reviewed the physiology and current literature on AT-II in refractory septic/vasodilatory shock. Larger trials with longer duration of follow-up are warranted to address the questions which are unanswered by the ATHOS-3 trial, especially pertaining to its effects on lungs, brain, microcirculation, inflammation, and venous thromboembolism risk.

Variability in functional outcome and treatment practices by treatment center after out-of-hospital cardiac arrest: analysis of International Cardiac Arrest Registry.

PURPOSE: Functional outcomes vary between centers after out-of-hospital cardiac arrest (OHCA) and are partially explained by pre-existing health status and arrest characteristics, while the effects of in-hospital treatments on functional outcome are less understood. We examined variation in functional outcomes by center after adjusting for patient- and arrest-specific characteristics and evaluated how in-hospital management differs between high- and low-performing centers. METHODS: Analysis of observational registry data within the International Cardiac Arrest Registry was used to perform a hierarchical model of center-specific risk standardized rates for good outcome, adjusted for demographics, pre-existing functional status, and arrest-related factors with treatment center as a random effect variable. We described the variability in treatments and diagnostic tests that may influence outcome at centers with adjusted rates significantly above and below registry average. RESULTS: A total of 3855 patients were admitted to an ICU following cardiac arrest with return of spontaneous circulation. The overall prevalence of good outcome was 11-63% among centers. After adjustment, center-specific risk standardized rates for good functional outcome ranged from 0.47 (0.37-0.58) to 0.20 (0.12-0.26). High-performing centers had faster time to goal temperature, were more likely to have goal temperature of 33 °C, more likely to perform unconscious cardiac catheterization and percutaneous coronary intervention, and had differing prognostication practices than low-performing centers. CONCLUSIONS: Center-specific differences in outcomes after OHCA after adjusting for patient-specific factors exist. This variation could partially be explained by in-hospital management differences. Future research should address the contribution of these factors to the differences in outcomes after resuscitation.

Thrombocytopenia: A possible side effect of apixaban.

Apixaban is becoming more frequently prescribed for stroke prevention in patients with atrial fibrillation, and even rare side effects such as thrombocytopenia should be considered and monitored closely.

Intrathoracic pressure regulation therapy applied to ventilated patients for treatment of compromised cerebral perfusion from brain injury.

BACKGROUND: Reducing intrathoracic pressure in the setting of compromised cerebral perfusion due to acute brain injury has been associated with reduced intracranial pressure and enhanced cerebral perfusion pressure and blood flow in animals. Noninvasive active intrathoracic pressure regulation lowers intrathoracic pressure, increases preload, reduces the volume of venous blood and cerebral spinal fluid in the skull, and enhances cerebral blood flow. We examined the feasibility of active intrathoracic pressure regulation therapy in patients with brain injury. We hypothesized that active intrathoracic pressure regulation therapy would be associated with lowered intracranial pressure and increased cerebral perfusion pressure in these patients. METHODS: At three institutions, active intrathoracic pressure regulation therapy (CirQlator™, ZOLL) was utilized for 2 consecutive hours in five mechanically ventilated patients with brain injury. A 30-minute interval was used to collect baseline data and determine persistence of effects after device use. End-tidal carbon dioxide was controlled by respiratory rate changes during device use. The intracranial pressure, mean arterial pressure, and cerebral perfusion pressure were recorded at 5-minute intervals throughout all three periods of the protocol. Results for each interval are reported as mean and standard deviation. RESULTS: Intracranial pressure was decreased in all five patients by an average of 21% during (15 ± 4 mmHg) compared to before active intrathoracic pressure regulation (19 ± 4) (p = 0.005). This effect on intracranial pressure (15 ± 6) was still present in four of the five patients 30 minutes after therapy was discontinued (p = 0.89). As a result, cerebral perfusion pressure was 16% higher during (81 ± 10) compared to before active intrathoracic pressure regulation (70 ± 14) (p = 0.04) and this effect remained present 30 minutes after therapy was discontinued. No adverse events were reported. CONCLUSIONS: These data support the notion that active intrathoracic pressure regulation, in this limited evaluation, can successfully augment cerebral perfusion by lowering intracranial pressure and increasing mean arterial pressure in patients with mild brain injury. The measured effects were immediate on administration of the therapy and persisted to some degree after the therapy was terminated.

Do All Acute Stroke Patients Receiving tPA Require ICU Admission?

BACKGROUND: Limited resources warrant investigating models for predicting which stroke tissue-type plasminogen activator (tPA) patients benefit from admission to neurologic intensive care unit (neuroICU). METHODS: This model classifies patients who on day 1 of their ICU admission are predicted to receive one or more of 30 subsequent active life supporting treatments. Two groups of patients were compared: low risk monitor (LRM) (patients who did not receive active treatment (AT) on the first day and whose risk of ever receiving active treatment was ≤ 10%) and AT (patients who received at least one treatment on any day of their ICU admission). RESULTS: Compared to LRM group (21 patients), AT group (59 patients) had similar age (75 ± 13 vs. 72 ± 17, P = 0.4), similar gender (male: 56% vs. 52%, P = 0.8), similar National Institutes of Health stroke scale (NIHSS, 16 ± 9 vs. 14 ± 8, P = 0.4), and higher Acute Physiologic and Chronic Health Evaluation (APACHE) III scores (62 ± 26 vs. 41 ± 15, P = 0.0008). Compared to LRM group, AT group had longer ICU length of stay (4.5 ± 4.4 vs. 2.5 ± 1.3, P = 0.04), higher ICU mortality (22% vs. 4.7% (one patient DNR/hospice); OR: 5.6; 95% CI: 0.7 - 46.0; P = 0.1), and higher hospital mortality (36% vs. 4.7%; OR: 11; 95% CI: 1.4 - 88.0; P = 0.02). CONCLUSION: The outcome of LRM patients with stroke post-tPA suggests that they may not require admission to a formal neuroICU, improving resource use and reducing costs.

Is it possible to recover from traumatic brain injury and a Glasgow coma scale score of 3 at emergency department presentation?

INTRODUCTION: A Glasgow Coma Scale (GCS) score of 3 on presentation in patients with traumatic brain injury (TBI) portends a poor prognosis. Consequently, there is often a tendency to treat these patients less aggressively because of low expectations for a good outcome. METHODS AND RESULTS: We performed a retrospective review of patients with TBI and a GCS score of 3. Patients were divided into 2 groups based on Glasgow Outcome Scale (GOS): Group 1 (GOS=1-3) and Group 2 (GOS=4-5). A total of 62 patients were included. The overall mortality rate was 80.6%. At 6-month, 9 patients (14.5%) achieved a GOS 4-5. Compared to Group 2 (n=9), Group 1 (n=53) had higher average APACHE IV score (104±19 vs 89±27, p=0.04), more patients with bilateral fixed pupils (59% vs 22%, p=0.04), and higher ICP burden (50±34 vs 0±0, p=0.0001). Using the CRASH calculator, the estimated mortality at 14days was 66% compared to actual mortality of 81%; difference of 15%, (p=0.05), and the estimated GOS 1-3 was 85.5% compared to actual of 85.5%, (p=1.0). CONCLUSIONS: 14.5% of patients with TBI and a GCS of 3 at presentation achieved a good outcome at 6months, and 6.9% of patients with GCS of 3 and bilateral fixed pupils on presentation to the ED achieved a good outcome at 6months.

Does Red Cell Distribution Width Predict Outcome in Traumatic Brain Injury: Comparison to Corticosteroid Randomization After Significant Head Injury.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability. The role of red cell distribution width (RDW) as a prognostic biomarker for outcome in TBI patients is unknown. Based on the corticosteroid randomization after significant head injury (CRASH) trial database, a prognosis calculator (CRASH) has been developed for outcome prediction in TBI. The objectives of this study are to investigate the association between RDW on day 1 of TBI and outcome, and to compare outcome prediction from RDW to that from CRASH. METHODS: We performed a retrospective review of patients with TBI and a Glasgow coma scale (GCS) score of 14 or less. Day 1 RDW and CRASH data were extracted. CRASH was calculated for each patient. Outcome was defined as mortality at 14 days and GOS at 6 months, with poor outcome defined as GOS of 1 - 3. Patients were stratified according to RDW values into six groups, and according to CRASH values into six groups. RESULTS: A total of 416 patients with TBI were included, with 339 survivors (S) and 77 non-survivors (NS). Compared to survivors, non-survivors were of similar age in years (58 ± 23 vs. 58 ± 23, P = 1.0), had lower GCS scores (5 ± 3 vs. 12 ± 3, P = 0.0001), similar RDW (14.0 ± 1.2 vs. 13.9 ± 1.5, P = 0.6), and higher CRASH values (68 ± 26 vs. 24 ± 22, P = 0.0001). Estimating the receiver-operating characteristic (ROC) area under the curve (AUC) showed that CRASH was a significantly better predictor of mortality compared to RDW (AUC = 0.91 ± 0.01 for CRASH compared to 0.66 ± 0.03 for RDW; P < 0.0001). In addition, CRASH was a better predictor of neurologic outcome compared to RDW (AUC = 0.85 ± 0.02 for CRASH compared to 0.76 ± 0.03 for RDW; P = 0.005). CONCLUSIONS: CRASH calculator was a strong predictor of mortality in patients with TBI. RDW on day 1 did not differ between survivors and non-survivors, and was a poor predictor of mortality. Both RDW on day 1 and CRASH calculator are good predictors of 6-month outcome in TBI patients, although CRASH calculator remains a better predictor.

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis.

BACKGROUND: Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. METHODS: This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) < 2.6. MFI is a semiquantitative score ranging from 0 (no flow) to 3 (continuous flow). Associations between microcirculatory flow abnormalities, single-spot lactate measurements, and outcome were analyzed. RESULTS: In 338 of 501 patients, lactate levels were available. For this substudy, all 257 patients with lactate levels ≤ 2 mmol/L (median [IQR] 1.04 [0.80-1.40] mmol/L) were included. Crude ICU mortality increased with each lactate quartile. In a multivariable analysis, a lactate level > 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). CONCLUSIONS: In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01179243 . Registered on August 3, 2010.

Predicting Mortality of Patients With Sepsis: A Comparison of APACHE II and APACHE III Scoring Systems.

BACKGROUND: Acute Physiology, Age and Chronic Health Evaluation (APACHE) II and III scores were developed in 1985 and 1991, respectively, and are used mainly for critically ill patients of all disease categories admitted to the intensive care unit (ICU). They differ in how chronic health status is assessed, in the number of physiologic variables included (12 vs. 17), and in the total score. These two scoring systems have not been compared in predicting hospital mortality in patients with sepsis. METHODS: We retrospectively identified all septic patients admitted to our 54-bed medical-surgical ICU between June 2009 and February 2014 using the APACHE outcomes database. We calculated correlation coefficients for APACHE II and APACHE III scores in predicting hospital mortality. Receiver-operating characteristic (ROC) curves were also used to assess the mortality predictions. RESULTS: We identified a total of 2,054 septic patients. Average APACHE II score was 19 ± 7, and average APACHE III score was 68 ± 28. ICU mortality was 11.8% and hospital mortality was 18.3%. Both APACHE II (r = 0.41) and APACHE III scores (r = 0.44) had good correlations with hospital mortality. There was no statistically significant difference between the two correlations (P = 0.1). ROC area under the curve (AUC) was 0.80 (95% confidence interval (CI): 0.78 - 0.82) for APACHE II, and 0.83 (95% CI: 0.81 - 0.85) for APACHE III, suggesting that both scores have very good discriminative powers for predicting hospital mortality. CONCLUSIONS: This study shows that both APACHE II and APACHE III scores in septic patients were very strong predictors of hospital mortality. APACHE II was as good as APACHE III in predicting hospital mortality in septic patients.

A Model for Identifying Patients Who May Not Need Neurologic Intensive Care Unit Admission: Resource Utilization Study.

PURPOSE: Limited resources, neurointensivists, and neurologic intensive care unit (neuro-ICU) beds warrant investigating models for predicting who will benefit from admission to neuro-ICU. This study presents a possible model for identifying patients who might be too well to benefit from admission to a neuro-ICU. METHODS: We retrospectively identified all patients admitted to our 16-bed neuro-ICU between November 2009 and February 2013. We used the Acute Physiology and Chronic Health Evaluation (APACHE) outcomes database to identify patients who on day 1 of neuro-ICU admission received 1 or more of 30 subsequent active life-supporting treatments. We compared 2 groups of patients: low-risk monitor (LRM; patients who did not receive active treatment [AT] on the first day and whose risk of ever receiving AT was ≤ 10%) and AT (patients who received at least 1 of the 30 ICU treatments on any day of their ICU admission). RESULTS: There were 873 (46%) admissions in the LRM group and 1006 (54%) admissions in the AT group. The ICU length of stay in days was 1.7 (± 1.9) for the LRM group versus 4.5 (± 5.5) for the AT group. The ICU mortality was 0.8% for the LRM group compared to 14% for the AT group (odds ratio [OR] = 17.6; 95% confidence interval [CI], 8.2-37.8, P < .0001). Hospital mortality was 1.9% for the LRM group compared to 19% for the AT group (OR = 9.7; 95% CI, 5.8-16.1, P < .0001). CONCLUSION: The outcome for LRM patients in our neuro-ICU suggests they may not require admission to neurologic intensive care. This may provide a measure of neuro-ICU resource use. Improved resource use and reduced costs might be achieved by strategies to provide care for these patients on floors or intermediate care units. This model will need to be validated in other neuro-ICUs and prospectively studied before it can be adopted for triaging admissions to neuro-ICUs.

Sepsis in the neurologic intensive care unit: epidemiology and outcome.

BACKGROUND: Sepsis is a major contributor to mortality in patients admitted to a general intensive care unit (ICU). Early recognition and treatment of sepsis is key in improving outcomes. The epidemiology and outcome of sepsis in neurologic ICU (NeuroICU) has not been evaluated. METHODS: We retrospectively identified all patients admitted to our 16-bed NeuroICU between June 2009 and December 2013 using the acute physiologic and chronic health evaluation (APACHE) outcomes database. We excluded patients admitted with an infection, such as meningitis, encephalitis, brain or spinal abscess, or with any other infection. We compared NeuroICU patients who did to NeuroICU patients who did not develop sepsis after ICU admission. The diagnosis of sepsis was based on the SCCM/ACCP consensus conference definition. RESULTS: There were a total of 2,025 patients, out of which 29 patients (1.4%) developed sepsis. Patients who developed sepsis had a trend towards older age (67 ± 13 vs. 61 ± 11 years, P = 0.07), a trend towards more male gender (69.0% vs. 51.5%, P = 0.07), significantly higher APACHE III scores (58 ± 17 vs. 43 ± 21, P = 0.0001), and significantly higher acute physiologic scores (APS) (43 ± 16 vs. 32 ± 18, P = 0.001) than patients who did not develop sepsis. Patients who developed sepsis had higher ICU mortality (41.4% vs. 5.1%, odds ratio (OR) = 13.1; 95% confidence interval (CI), 6.1 - 28.2, P < 0.0001), and higher hospital mortality (44.8% vs. 8.2%, OR = 9.0; 95% CI, 4.3 - 19.0, P < 0.0001). CONCLUSIONS: Sepsis developed in 1.4% of patients admitted to a NeuroICU. Predictors of sepsis development were comorbidities and worsening acute physiologic variables. Patients who developed sepsis had significantly higher mortality. Vigilance to development of sepsis in NeuroICU is paramount, especially in this era when early recognition and intervention of sepsis significantly improves outcomes.

Comparison of the Full Outline of UnResponsiveness score and the Glasgow Coma Scale in predicting mortality in critically ill patients*.

OBJECTIVE: Impaired consciousness has been incorporated in prediction models that are used in the ICU. The Glasgow Coma Scale has value but is incomplete and cannot be assessed in intubated patients accurately. The Full Outline of UnResponsiveness score may be a better predictor of mortality in critically ill patients. SETTING: Thirteen ICUs at five U.S. hospitals. SUBJECTS: One thousand six hundred ninety-five consecutive unselected ICU admissions during a six-month period in 2012. DESIGN: Glasgow Coma Scale and Full Outline of UnResponsiveness score were recorded within 1 hour of admission. Baseline characteristics and physiologic components of the Acute Physiology and Chronic Health Evaluation system, as well as mortality were linked to Glasgow Coma Scale/Full Outline of UnResponsiveness score information. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We recruited 1,695 critically ill patients, of which 1,645 with complete data could be linked to data in the Acute Physiology and Chronic Health Evaluation system. The area under the receiver operating characteristic curve of predicting ICU mortality using the Glasgow Coma Scale was 0.715 (95% CI, 0.663-0.768) and using the Full Outline of UnResponsiveness score was 0.742 (95% CI, 0.694-0.790), statistically different (p = 0.001). A similar but nonsignificant difference was found for predicting hospital mortality (p = 0.078). The respiratory and brainstem reflex components of the Full Outline of UnResponsiveness score showed a much wider range of mortality than the verbal component of Glasgow Coma Scale. In multivariable models, the Full Outline of UnResponsiveness score was more useful than the Glasgow Coma Scale for predicting mortality. CONCLUSIONS: The Full Outline of UnResponsiveness score might be a better prognostic tool of ICU mortality than the Glasgow Coma Scale in critically ill patients, most likely a result of incorporating brainstem reflexes and respiration into the Full Outline of UnResponsiveness score.

Continuous Electroencephalogram in Comatose Postcardiac Arrest Syndrome Patients Treated With Therapeutic Hypothermia: Outcome Prediction Study.

PURPOSE: Therapeutic Hypothermia (TH) is the only therapeutic intervention proven to significantly improve survival and neurologic outcome in comatose postcardiac arrest patients and is now considered standard of care. When we discuss prognostication with regard to comatose survivors postcardiac arrest, we should look for tools that are both reliable and accurate and that achieve a false-positive rate (FPR) equal to or very closely approaching zero. METHODS: We retrospectively reviewed data that were prospectively collected on all cardiac arrest patients admitted to our ICU. Continuous electroencephalogram (cEEG) monitoring was performed as part of our protocol for therapeutic hypothermia in comatose postcardiac arrest patients. The primary outcome measure was the best score on hospital discharge on the 5-point Glasgow-Pittsburgh cerebral performance category (CPC) scores. RESULTS: A total of 58 patients were included in this study. Twenty five (43%) patients had a good neurologic outcome (CPC score of 1-2). Three (5.2%) patients had nonconvulsive status epilepticus, all of whom had poor outcome (CPC = 5). Seventeen (29%) patients had burst suppression (BS); all had poor outcome. Both nonconvuslsive seizures (NCS) and BS had a specificity of 100% (95% confidence interval [CI], 84%-100%), positive predictive values of 100% (95% CI, 31%-100%), and 100% (95% CI, 77%-100%), respectively. Both NCS and BS had FPRs of zero (95% CI, 0.0-0.69, and 0.0-0.23, respectively). CONCLUSIONS: In comatose postcardiac arrest patients treated with hypothermia, EEG during the maintenance and rewarming phase of hypothermia can contribute to prediction of neurologic outcome. Pending large multicenter prospective studies evaluating the role of cEEG in prognostication, our study adds to the existing evidence that cEEG can play a potential role in prediction of outcome in postcardiac arrest patients treated with hypothermia.

International study on microcirculatory shock occurrence in acutely ill patients.

OBJECTIVES: Microcirculatory alterations are associated with adverse outcome in subsets of critically ill patients. The prevalence and significance of microcirculatory alterations in the general ICU population are unknown. We studied the prevalence of microcirculatory alterations in a heterogeneous ICU population and its predictive value in an integrative model of macro- and microcirculatory variables. DESIGN: Multicenter observational point prevalence study. SETTING: The Microcirculatory Shock Occurrence in Acutely ill Patients study was conducted in 36 ICUs worldwide. PATIENTS: A heterogeneous ICU population consisting of 501 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic, hemodynamic, and laboratory data were collected in all ICU patients who were 18 years old or older. Sublingual Sidestream Dark Field imaging was performed to determine the prevalence of an abnormal capillary microvascular flow index (< 2.6) and its additional value in predicting hospital mortality. In 501 patients with a median Acute Physiology and Chronic Health Evaluation II score of 15 (10-21), a Sequential Organ Failure Assessment score of 5 (2-8), and a hospital mortality of 28.4%, 17% exhibited an abnormal capillary microvascular flow index. Tachycardia (heart rate > 90 beats/min) (odds ratio, 2.71; 95% CI, 1.67-4.39; p < 0.001), mean arterial pressure (odds ratio, 0.979; 95% CI, 0.963-0.996; p = 0.013), vasopressor use (odds ratio, 1.84; 95% CI, 1.11-3.07; p = 0.019), and lactate level more than 1.5 mEq/L (odds ratio, 2.15; 95% CI, 1.28-3.62; p = 0.004) were independent risk factors for hospital mortality, but not abnormal microvascular flow index. In reference to microvascular flow index, a significant interaction was observed with tachycardia. In patients with tachycardia, the presence of an abnormal microvascular flow index was an independent, additive predictor for in-hospital mortality (odds ratio, 3.24; 95% CI, 1.30-8.06; p = 0.011). This was not true for nontachycardic patients nor for the total group of patients. CONCLUSIONS: In a heterogeneous ICU population, an abnormal microvascular flow index was present in 17% of patients. This was not associated with mortality. However, in patients with tachycardia, an abnormal microvascular flow index was independently associated with an increased risk of hospital death.

Transfusion of red blood cells is associated with improved central venous oxygen saturation but not mortality in septic shock patients.

BACKGROUND: Although the optimum hemoglobin (H) concentration for patients with septic shock (SS) has not been specifically investigated, current guidelines suggest that H of 7 - 9 g/dL, compared with 10 - 12 g/dL, was not associated with increased mortality in critically ill adults. This contrasts with early goal-directed resuscitation protocols that use a target hematocrit of 30% in patients with low central venous oxygen saturation (ScvO2) during the first 6 hours of resuscitation of SS. METHODS: Data elements were prospectively collected on all patients with SS patients (lactic acid (LA) > 4 mmol/L, or hypotension). Out of a total of 396 SS patients, 46 patients received red blood cell (RBC) transfusion for ScvO2 < 70% (RBC group). We then matched 71 SS patients that did not receive RBC transfusion (NRBC group) on the following goals (G): LA obtained within 6 hours (G1), antibiotics given within 3 hours (G2), 20 mL/kg fluid bolus followed by vasopressors (VP) if needed to keep mean arterial pressure > 65 mm Hg (G3), central venous pressure > 8 mm Hg within 6 hours (G4) and ScvO2 > 70% within 6 hours (G5). RESULTS: In the RBC group, after one unit of RBC transfusion, ScvO2 improved from average of 63% (± 12%) to 68% (± 10%) (P = 0.02). Sixteen patients required another unit of RBC, and this resulted in increase of ScvO2 to 78% (± 11%) (P < 0.01). The RBC and NRBC groups were matched on sequential organ failure assessment (SOFA) scores and all five goals. There was no difference in mortality between the two groups: 41% vs. 39.4% (OR: 0.8, 95% CI: 0.4 - 1.7, P = 0.6). CONCLUSIONS: In our study, transfusion of RBC was not associated with decreased mortality in SS patients.

Fluid resuscitation in septic shock: the effect of increasing fluid balance on mortality.

PURPOSE: To determine whether progressively increasing fluid balance after initial fluid resuscitation for septic shock is associated with increased mortality. METHODS: A retrospective review of the use of intravenous fluids in patients with septic shock in a large university affiliated hospital with 56 medical-surgical intensive care unit beds. We analyzed the data of 350 patients with septic shock who were managed according to the Surviving Sepsis Campaign guidelines. Based on net fluid balance at 24 hours, we examined the results of increase in positive fluid balance on the risk of in-hospital mortality. Patients were divided into 4 groups based on the amount of fluid balance by 24 hours, based on 6-L aliquots. RESULTS: At 24 hours, the average fluid balance was +6.5 L. After correcting for age and sequential organ failure assessment score, a more positive fluid balance at 24 hours significantly increased the risk of in-hospital mortality. Using Cox proportional hazard analysis, excess 12-, 18-, and 24-L positive fluid balance had higher risk of mortality than those patients with a neutral to positive 6-L fluid balance (reference group). Adjusted hazard ratios, 1.519 (95% confidence interval [CI], 1.353-1.685), 1.740 (95% CI, 1.467-2.013), and 1.620 (95% CI, 1.197-2.043), respectively, P < .05. CONCLUSION: In patients with septic shock resuscitated according to current guidelines, a more positive fluid balance at 24 hours is associated with an increase in the risk of mortality. Optimal survival occurred at neutral fluid balance and up to 6-L positive fluid balance at 24 hours after the development of septic shock.