Amy Uber

Neurologic outcome in comatose patients resuscitated from out-of-hospital cardiac arrest with prolonged downtime and treated with therapeutic hypothermia

BACKGROUND Previous reports have shown that prolonged duration of resuscitation efforts in out-of-hospital cardiac arrest (OHCA) is associated with poor neurologic outcome. This concept has recently been questioned with advancements in post-cardiac arrest care including the use of therapeutic hypothermia (TH). The aim of this study was to determine the rate of good neurologic outcome based on the duration of resuscitation efforts in OHCA patients treated with TH. METHODS This prospective, observational, study was conducted between January 2008 and September 2012. Inclusion criteria consisted of adult non-traumatic OHCA patients who were comatose after return of spontaneous circulation (ROSC) and received TH. The primary endpoint was good neurologic outcome defined as a cerebral performance category score of 1 or 2. Downtime was calculated as the length of time between the patient being recognized as pulseless and ROSC. RESULTS 105 patients were treated with TH and 19 were excluded due to unknown downtime, leaving 86 patients for analysis. The median downtime was 18.5 (10.0-32.3)min and 33 patients (38.0%) had a good neurologic outcome. When downtime was divided into four groups (≤10min, 11-20min, 21-30min, >30min), good neurologic outcomes were 62.5%, 37%, 25%, and 21.7%, respectively (p=0.02). However, even with downtime >20min, 22.9% had a good neurologic outcome, and this percentage increased to 37.5% in patients with an initial shockable rhythm. CONCLUSIONS Although longer downtime is associated with worse outcome in OHCA patients, we found that comatose patients who have been successfully resuscitated and treated with TH have neurologically intact survival rates of 23% even with downtime >20min.

The relationship between lactate and thiamine levels in patients with diabetic ketoacidosis

PURPOSE Thiamine functions as an important cofactor in aerobic metabolism and thiamine deficiency can contribute to lactic acidosis. Although increased rates of thiamine deficiency have been described in diabetic outpatients, this phenomenon has not been studied in relation to diabetic ketoacidosis (DKA). In the present study, we hypothesize that thiamine deficiency is associated with elevated lactate in patients with DKA. MATERIALS AND METHODS This was a prospective observational study of patients presenting to a tertiary care center with DKA. Patient demographics, laboratory results, and outcomes were recorded. A one-time blood draw was performed and analyzed for plasma thiamine levels. RESULTS Thirty-two patients were enrolled. Eight patients (25%) were thiamine deficient, with levels lower than 9 nmol/L. A negative correlation between lactic acid and plasma thiamine levels was found (r = -0.56, P = .002). This relationship remained significant after adjustment for APACHE II scores (P = .009). Thiamine levels were directly related to admission serum bicarbonate (r = 0.44, P = .019), and patients with thiamine deficiency maintained lower bicarbonate levels over the first 24 hours (slopes parallel with a difference of 4.083, P = .002). CONCLUSIONS Patients with DKA had a high prevalence of thiamine deficiency. Thiamine levels were inversely related to lactate levels among patients with DKA. A study of thiamine supplementation in DKA is warranted.

Characterization of mitochondrial injury after cardiac arrest (COMICA)

INTRODUCTION Mitochondrial injury post-cardiac arrest has been described in pre-clinical settings but the extent to which this injury occurs in humans remains largely unknown. We hypothesized that increased levels of mitochondrial biomarkers would be associated with mortality and neurological morbidity in post-cardiac arrest subjects. METHODS We performed a prospective multicenter study of post-cardiac arrest subjects. Inclusion criteria were comatose adults who suffered an out-of-hospital cardiac arrest. Mitochondrial biomarkers were measured at 0, 12, 24, 36 and 48h after return of spontaneous circulation as well as in healthy controls. RESULTS Out of 111 subjects enrolled, 102 had evaluable samples at 0h. Cardiac arrest subjects had higher baseline cytochrome c levels compared to controls (2.18ng/mL [0.74, 7.74] vs. 0.16ng/mL [0.03, 0.91], p<0.001), and subjects who died had higher 0h cytochrome c levels compared to survivors (3.66ng/mL [1.40, 14.9] vs. 1.27ng/mL [0.16, 2.37], p<0.001). There were significantly higher Ribonuclease P (RNaseP) (3.3 [1.2, 5.7] vs. 1.2 [0.8, 1.2], p<0.001) and Beta-2microglobulin (B2M) (12.0 [1.0, 22.9], vs. 0.6 [0.6, 1.3], p<0.001) levels in cardiac arrest subjects at baseline compared to the control subjects. There were no differences between survivors and non-survivors for mitochondrial DNA, nuclear DNA, or cell free DNA. CONCLUSIONS Cytochrome c was increased in post- cardiac arrest subjects compared to controls, and in post-cardiac arrest non-survivors compared to survivors. Nuclear DNA and cell free DNA was increased in plasma of post-cardiac arrest subjects. There were no differences in mitochondrial DNA, nuclear DNA, or cell free DNA between survivors and non-survivors. Mitochondrial injury markers showed mixed results in the post-cardiac arrest period. Future research needs to investigate these differences.

Thiamine in septic shock patients with alcohol use disorders: An observational pilot study

Purpose: Alcohol‐use disorders (AUDs) have been associated with increased sepsis‐related mortality. As patients with AUDs are often thiamine deficient, we investigated practice patterns relating to thiamine administration in patients with AUDs presenting with septic shock and explored the association between receipt of thiamine and mortality. Materials: We performed a retrospective cohort study of patients presenting with septic shock between 2008 and 2014 at a single tertiary care center. We identified patients with an AUD diagnosis, orders for microbial cultures and use of antibiotics, vasopressor dependency, and lactate levels ≥ 4 mmol/L. We excluded those who received thiamine later than 48 h of sepsis onset. Results: We included 53 patients. Thirty‐four (64%) patients received thiamine. Five patients (15%) received their first thiamine dose in the emergency department. The median time to thiamine administration was 9 (quartiles: 4, 18) hours. The first thiamine dose was most often given parenterally (68%) and for 100 mg (88%). In those receiving thiamine, 15/34 (44%) died, compared to 15/19 (79%) of those not receiving thiamine, p = 0.02. Conclusions: A considerable proportion of patients with AUDs admitted for septic shock do not receive thiamine. Thiamine administration in this patient population was associated with decreased mortality. Highlights:Many patients with alcohol‐use‐disorders and septic shock do not receive thiamine.Thiamine was most often given in the ICU, rather than the emergency department.Failure to receive thiamine may be associated with increased mortality.

Intubation is not a marker for coma after in-hospital cardiac arrest: A retrospective study

INTRODUCTION In-hospital cardiac arrest (IHCA) strikes over 200,000 people in the United States annually. Targeted temperature management (TTM) is considered beneficial in other settings, but there is no prospective data for IHCA. Recent work on TTM and IHCA found an association between TTM and worse outcome. However, the authors used intubation as a marker for coma to determine eligibility for TTM. The validity of this approach is unexplored. METHODS Retrospective, single center study of adult patients with IHCA occurring in an intensive care unit, intubated prior to or during the event, or immediately after ROSC. We evaluated the percentage of patients documented as comatose after arrest, defined as Glasgow Comas Score (GCS) <8 for the primary analysis. We also evaluated the difference in hospital survival in patients with GCS <8 versus ≥8. Two sensitivity analyses using different methods for defining coma using post-ROSC GCS were conducted. RESULTS 29/102 (28%) intubated patients had a post-ROSC GCS≥8, and 22 (22%) were documented as following commands. Survival in patients with GCS≥8 vs.<8 was 62% (18/29) vs. 37% (27/73) in unadjusted analysis (p=0.02). The adjusted odds ratio for survival to hospital discharge was 3.81 (95%CI: 1.37-10.61, p=0.01). Results were similar in both sensitivity analyses. CONCLUSIONS Intubation prior to or during IHCA was not a valid marker of coma after ROSC. Post-ROSC mental status was associated with hospital survival, and thus could be an important confounder when conducting observational studies on the association of TTM with outcomes in this patient population.

When to Stop CPR and When to Perform Rhythm Analysis Potential Confusion Among ACLS Providers

Background: Health care providers nationwide are routinely trained in Advanced Cardiac Life Support (ACLS), an American Heart Association program that teaches cardiac arrest management. Recent changes in the ACLS approach have de-emphasized routine pulse checks in an effort to promote uninterrupted chest compressions. We hypothesized that this new ACLS algorithm may lead to uncertainty regarding the appropriate action following detection of a pulse during a cardiac arrest. Methods: We conducted an observational study in which a Web-based survey was sent to ACLS-trained medical providers at 4 major urban tertiary care centers in the United States. The survey consisted of 5 multiple-choice, scenario-based ACLS questions, including our question of interest. Adult staff members with a valid ACLS certification were included. Results: A total of 347 surveys were analyzed. The response rate was 28.1%. The majority (53.6%) of responders were between 18 and 32 years old, and 59.9% were female. The majority (54.2%) of responders incorrectly stated that they would continue CPR and possibly administer additional therapies when a team member detects a pulse immediately following defibrillation. Secondarily, only 51.9% of respondents correctly chose to perform a rhythm check following 2 minutes of CPR. The other 3 survey questions were correctly answered an average of 89.1% of the time. Conclusion: Confusion exists regarding whether or not CPR and cardiac medications should be continued in the presence of a pulse. Education may be warranted to emphasize avoiding compressions and medications when a palpable pulse is detected.

Immunocapture and microplate-based activity and quantity measurement of pyruvate dehydrogenase in human peripheral blood mononuclear cells.

BACKGROUND Pyruvate dehydrogenase (PDH) activity is altered in many human disorders. Current methods require tissue samples and yield inconsistent results. We describe a modified method for measuring PDH activity from isolated human peripheral blood mononuclear cells (PBMCs). RESULTS/METHODOLOGY: We found that PDH activity and quantity can be successfully measured in human PBMCs. Freeze-thaw cycles cannot efficiently disrupt the mitochondrial membrane. Processing time of up to 20 h does not affect PDH activity with proteinase inhibitor addition and a detergent concentration of 3.3% showed maximum yield. Sample protein concentration is correlated to PDH activity and quantity in human PBMCs from healthy subjects. CONCLUSION Measuring PDH activity from PBMCs is a novel, easy and less invasive way to further understand the role of PDH in human disease.

Preliminary observations in systemic oxygen consumption during targeted temperature management after cardiac arrest

AIM Limited data suggests low oxygen consumption (VO2), driven by mitochondrial injury, is associated with mortality after cardiac arrest. Due to the challenges of measurement in the critically ill, post-arrest metabolism remains poorly characterized. We monitored VO2, carbon dioxide production (VCO2) and the respiratory quotient (RQ) in post-arrest patients and explored associations with outcome. METHODS Using a gas exchange monitor, we measured continuous VO2 and VCO2 in post- arrest patients treated with targeted temperature management. We used area under the curve and medians over time to evaluate the association between VO2, VCO2, RQ and the VO2:lactate ratio with survival. RESULTS In 17 patients, VO2 in the first 12 h after return of spontaneous circulation (ROSC) was associated with survival (median in survivors 3.35 mL/kg/min [2.98,3.88] vs. non-survivors 2.61 mL/kg/min [2.21,2.94], p = .039). This did not persist over 24 h. The VO2:lactate ratio was associated with survival (median in survivors 1.4 [IQR: 1.1,1.7] vs. non-survivors 0.8 [IQR: 0.6,1.2] p < 0.001). Median RQ was 0.66 (IQR 0.63,0.70) and 71% of RQ measurements were <0.7. Patients with initial RQ < 0.7 had 17% survival versus 64% with initial RQ > 0.7 (p = .131). VCO2 was not associated with survival. CONCLUSIONS There was a significant association between VO2 and mortality in the first 12 h after ROSC, but not over 24 h. Lower VO2: lactate ratio was associated with mortality. A large percentage of patients had RQs below physiologic norms. Further research is needed to explore whether these parameters could have true prognostic value or be a potential treatment target.

Bystander Cardiopulmonary Resuscitation Is Clustered and Associated With Neighborhood Socioeconomic Characteristics: A Geospatial Analysis of Kent County, Michigan

OBJECTIVES Geographic clustering of bystander cardiopulmonary resuscitation (CPR) is associated with demographic and socioeconomic features of the community where out-of-hospital cardiac arrest (OHCA) occurred, although this association remains largely untested in rural areas. With a significant rural component and relative racial homogeneity, Kent County, Michigan, provides a unique setting to externally validate or identify new community features associated with bystander CPR. Using a large, countywide data set, we tested for geographic clustering of bystander CPR and its associations with community socioeconomic features. METHODS Secondary analysis of adult OHCA subjects (2010-2015) in the Cardiac Arrest Registry to Enhance Survival (CARES) data set for Kent County, Michigan. After linking geocoded OHCA cases to U.S. census data, we used Morans I-test to assess for spatial autocorrelation of population-weighted cardiac arrest rate by census block group. Getis-Ord Gi statistic assessed for spatial clustering of bystander CPR and mixed-effects hierarchical logistic regression estimated adjusted associations between community features and bystander CPR. RESULTS Of 1,592 subjects, 1,465 met inclusion criteria. Geospatial analysis revealed significant clustering of OHCA in more populated/urban areas. Conversely, bystander CPR was less likely in these areas (99% confidence) and more likely in suburban and rural areas (99% confidence). Adjusting for clinical, demographic, and socioeconomic covariates, bystander CPR was associated with public location (odds ratio [OR] = 1.19; 95% confidence interval [CI] = 1.03-1.39), initially shockable rhythms (OR = 1.48; 95% CI = 1.12-1.96), and those in urban neighborhoods (OR = 0.54; 95% CI = 0.38-0.77). CONCLUSIONS Out-of-hospital cardiac arrest and bystander CPR are geographically clustered in Kent County, Michigan, but bystander CPR is inversely associated with urban designation. These results offer new insight into bystander CPR patterns in mixed urban and rural regions and afford the opportunity for targeted community CPR education in areas of low bystander CPR prevalence.

Outcomes in variceal hemorrhage following the use of a balloon tamponade device

Background: Variceal hemorrhage is associated with high morbidity and mortality. A balloon tamponade device (BTD), such as the Sengstaken‐Blakemore or Minnesota tube, may be used in cases of variceal hemorrhage. While these devices may be effective at controlling acute bleeding, the effect on patient outcomes remains less clear. We sought to describe the number of patients with variceal hemorrhage and a BTD who survive to discharge, survive to one‐year, and develop complications related to a BTD. Methods: In this retrospective study, we identified patients at a single, tertiary care center who underwent placement of a BTD for upper gastrointestinal hemorrhage between 2003 and 2014. Patient characteristics and outcomes were summarized using descriptive statistics. Results: 34 patients with a BTD were identified. Median age was 57.5 (IQR 47–63) and 76% (26/34) were male. Approximately 59% (20/34) of patients survived to discharge, and 41% (13/32) were alive after one year. Two patients were lost to follow‐up. Of those surviving to discharge, 95% (19/20) had undergone transjugular intrahepatic portosystemic shunt (TIPS), while 36% (5/14) of patients who did not survive to discharge had TIPS (p < 0.01). One complication, an esophageal perforation, was identified and managed conservatively. Conclusion: In this cohort of patients undergoing BTD placement for variceal hemorrhage, approximately 59% of patients were alive at discharge and 41% were alive after one year. Placement of a BTD as a temporizing measure in the management of acute variceal hemorrhage may be helpful, particularly when utilized as a bridge to more definitive therapy.