Ubiquinol (Reduced Coenzyme Q10) and Cellular Oxygen Consumption in Patients Undergoing Coronary Artery Bypass Grafting.

Ubiquinol is a fundamental component of cellular metabolism. Low ubiquinol levels have been associated with mortality. This was a substudy of a randomized trial in patients undergoing coronary artery bypass grafting. We drew blood before and after surgery. Ubiquinol or placebo was added to peripheral blood mononuclear cells for oxygen consumption (OCR) measurements. In vivo ubiquinol levels were lower postsurgery compared to presurgery (0.16 µmol/L [quartiles: 0.02-0.39], P = .01), although the difference disappeared when adjusting for hemoglobin levels (P = .30). There was no difference in presurgical basal (1.0 mL/min/mg [95% confidence interval [CI]: -0.9 to 2.2], P = .08) and maximal (0.5 mL/min/mg [95% CI: -4.3 to 7.3], P = .56) OCR in cells receiving ubiquinol or placebo. There was a difference in postsurgical basal (1.1 mL/min/mg [95% CI: 0.9-1.6], P < .001) and maximal (4.2 mL/min/mg [95% CI: 0.3-7.0], P = .01) OCR between the groups. We found no association between ubiquinol and OCR levels (all P > .05).

Increased Heat Generation in Postcardiac Arrest Patients During Targeted Temperature Management Is Associated With Better Outcomes.

OBJECTIVES: Assess if amount of heat generated by postcardiac arrest patients to reach target temperature (Ttarget) during targeted temperature management is associated with outcomes by serving as a proxy for thermoregulatory ability, and whether it modifies the relationship between time to Ttarget and outcomes. DESIGN: Retrospective cohort study. SETTING: Urban tertiary-care hospital. PATIENTS: Successfully resuscitated targeted temperature management-treated adult postarrest patients between 2008 and 2015 with serial temperature data and Ttarget less than or equal to 34°C. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Time to Ttarget was defined as time from targeted temperature management initiation to first recorded patient temperature less than or equal to 34°C. Patient heat generation ("heat units") was calculated as inverse of average water temperature × hours between initiation and Ttarget × 100. Primary outcome was neurologic status measured by Cerebral Performance Category score; secondary outcome was survival, both at hospital discharge. Univariate analyses were performed using Wilcoxon rank-sum tests; multivariate analyses used logistic regression. Of 203 patients included, those with Cerebral Performance Category score 3-5 generated less heat before reaching Ttarget (median, 8.1 heat units [interquartile range, 3.6-21.6 heat units] vs median, 20.0 heat units [interquartile range, 9.0-33.5 heat units]; p = 0.001) and reached Ttarget quicker (median, 2.3 hr [interquartile range, 1.5-4.0 hr] vs median, 3.6 hr [interquartile range, 2.0-5.0 hr]; p = 0.01) than patients with Cerebral Performance Category score 1-2. Nonsurvivors generated less heat than survivors (median, 8.1 heat units [interquartile range, 3.6-20.8 heat units] vs median, 19.0 heat units [interquartile range, 6.5-33.5 heat units]; p = 0.001) and reached Ttarget quicker (median, 2.2 hr [interquartile range, 1.5-3.8 hr] vs median, 3.6 hr [interquartile range, 2.0-5.0 hr]; p = 0.01). Controlling for average water temperature between initiation and Ttarget, the relationship between outcomes and time to Ttarget was no longer significant. Controlling for location, witnessed arrest, age, initial rhythm, and neuromuscular blockade use, increased heat generation was associated with better neurologic (adjusted odds ratio, 1.01 [95% CI, 1.00-1.03]; p = 0.039) and survival (adjusted odds ratio, 1.01 [95% CI, 1.00-1.03]; p = 0.045) outcomes. CONCLUSIONS: Increased heat generation during targeted temperature management initiation is associated with better outcomes at hospital discharge and may affect the relationship between time to Ttarget and outcomes.

Does Non-Targeted Community CPR Training Increase Bystander CPR Frequency?

OBJECTIVE: Only 37% of out-of-hospital cardiac arrests (OHCA) receive bystander Cardiopulmonary resuscitation (CPR) in Kent County, MI. In May 2014, prehospital providers offered one-time, point-of-contact compression-only CPR training to 2,253 passersby at 7 public locations in Grand Rapids, Michigan. To assess the impact of this intervention, we compared bystander CPR frequency and clinical outcomes in regions surrounding training sites before and after the intervention, adjusting for prehospital covariates. We aimed to assess the effect of this broad, non-targeted intervention on bystander CPR frequency, type of CPR utilized, and clinical outcomes. We also tested for differences in geospatial variation of bystander CPR and clinical outcomes clustered around training sites. METHODS: Retrospective, observational, before-after study of adult, EMS-treated OHCA in Kent County from January 1, 2010 to December 31, 2015. We generated a 5-kilometer radius surrounding each training site to estimate any geospatial influence that training sites might have on bystander CPR frequency in nearby OHCA cases. Chi-squared, Fisher's exact, and t-tests assessed differences in subject features. Difference-in-differences analysis with generalized estimating equation (GEE) modeling assessed bystander CPR frequency, adjusting for training site, covariates (age, sex, witnessed, shockable rhythm, public location), and clustering around training sites. Similar modeling tested for changes in bystander CPR type, return of spontaneous circulation (ROSC), survival to hospital discharge, and cerebral performance category (CPC) of 1-2 at hospital discharge. RESULTS: We included 899 cases before and 587 cases post-intervention. Overall, we observed no increase in the frequency of bystander CPR or favorable clinical outcomes. We did observe an increase in compression-only CPR, but this was paradoxically restricted to OHCA cases falling outside radii around training sites. In adjusted modeling, the bystander CPR training intervention was not associated with bystander CPR frequency (ß -0.002; 95% CI -0.16, 0.15), compression-only CPR (ß -0.06; 95% CI -0.15, 0.02), ROSC (ß -0.06; 95% CI -0.21, 0.25), survival (ß -0.02; 95% CI -0.11, 0.06), or favorable neurologic outcome (ß -0.01; 95% CI -0.07, 0.09). CONCLUSIONS: We observed no impact in bystander CPR performance or outcomes from a blanket, non-targeted approach to community CPR education. The effect of targeted CPR education in locales with known low bystander CPR rates should be tested in this region.

The Effects of Thiamine on Breast Cancer Cells.

(1) Background: Thiamine is an important cofactor for multiple metabolic processes. Its role in cancer has been debated for years. Our aim is to determine if thiamine can convert the cellular metabolic state of breast cancer cells from anaerobic to aerobic, thus reducing their growth. (2) Methods: Breast cancer (MCF7) and non-tumorigenic (MCF10A) cell lines were treated with various doses of thiamine and assessed for changes in cell growth. The mechanism of this relationship was identified through the measurement of enzymatic activity and metabolic changes. (3) Results: A high dose of thiamine reduced cell proliferation in MCF7 (63% decrease, p < 0.0001), but didn't affect apoptosis and the cell-cycle profile. Thiamine had a number of effects in MCF7; it (1) reduced extracellular lactate levels in growth media, (2) increased cellular pyruvate dehydrogenase (PDH) activities and the baseline and maximum cellular oxygen consumption rates, and (3) decreased non-glycolytic acidification, glycolysis, and glycolytic capacity. MCF10A cells preferred mitochondrial respiration instead of glycolysis. In contrast, MCF7 cells were more resistant to mitochondrial respiration, which may explain the inhibitory effect of thiamine on their proliferation. (4) Conclusions: The treatment of MCF7 breast cancer cells with 1 µg/mL and 2 µg/mL of thiamine for 24 h significantly reduced their proliferation. This reduction is associated with a reduction in glycolysis and activation of the PDH complex in breast cancer cells.

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.

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.

Psychiatric and Substance Use Disorders and Their Association With Clinical Outcomes in Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic Syndrome.

BACKGROUND AND OBJECTIVE: Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are life-threatening conditions that send nearly 180,000 patients to the intensive care unit each year, with mortality rates up to 5-10%. Little is known about the impact of concurrent psychiatric disorders on specific DKA/HHS outcomes. Identifying these relationships offers opportunities to improve clinical management, treatment planning, and mitigate associated morbidity and mortality. METHODS: We conducted a retrospective review including adult DKA/HHS admissions within a large Massachusetts hospital system from 2010 to 2019. We identified patients admitted inpatient for DKA or HHS, then filtered by International Classification of Disease-9-CM and International Classification of Disease-10-CM codes for psychiatric diagnoses that were present in patients electronic medical record at any point in this observational period. Outcomes included the number of inpatient admissions for DKA/HHS, age of death, rates of discharging against medical advice (AMA) from any inpatient admission, and end-stage renal disease/dialysis status. Multivariate regression was conducted using R software to control for variables across patients and evaluate relationships between outcomes and concurrent psychiatric disorders. Significance was set at P < 0.05. RESULTS: Seven thousand seven hundred fifty-six patients were admitted for DKA or HHS, 66.9% of whom had a concurrent psychiatric disorder. Of these patients, 54.5% were male, 70.4% were White, and they had an average age of 61.6 years. This compares with 26.1% with concurrent psychiatric condition within the general diabetes population, 52.1% of whom were male, 72.1% were White, and an average age of 68.2 years. A concurrent psychiatric disorder was associated with increased odds of rehospitalization (adjusted odds ratio [aOR] = 1.62 95% confidence interval [CI] 1.35-1.95, P < 0.001), of being diagnosed with end-stage renal disease and on dialysis (aOR = 1.02 95% CI 1.002-1.035, P = 0.02), and of leaving AMA (aOR = 6.44 95% CI 4.46-9.63, P < 0.001). The average age of death for those with a concurrent psychiatric disorder had an adjusted mean difference in years of -7.5 years (95% CI -9.3 to 5.8) compared to those without a psychiatric disorder. CONCLUSIONS: Of patients with DKA/HHS, 66.9% have a concurrent psychiatric disorder. Patients with a concurrent psychiatric disorder admitted for DKA/HHS were more likely to have multiple admissions, to leave AMA, to be on renal dialysis, and to have a lower age of mortality.

Symptom Overlap of Acute Mountain Sickness and Lithium Toxicity: A Case Report.

Uber, Amy, and Claire Twark. Symptom overlap of acute mountain sickness and lithium toxicity: a case report. High Alt Med Biol. 23:291-293, 2022.-Mild lithium toxicity and acute mountain sickness share multiple overlapping features. We report a case of a patient with bipolar disorder on lithium who hiked to altitude and experienced symptoms that are shared by both conditions. We review the literature on lithium fluctuations under similar conditions showing that acute altitude exposure may elevate serum lithium levels and excess sweating may lower lithium levels, despite the prevailing thought that fluid loss concentrates serum lithium levels. We advise individualized testing of athletes' lithium levels in response to exercise and altitude, and we recommend physicians counsel their patients on ways to maintain therapeutic lithium levels during their athletic pursuits, including the importance of hydration and avoidance of nonsteroidal anti-inflammatory drugs. Further research is needed on lithium pharmacokinetics in conditions of exercise and altitude exposure.

Infections in out-of-hospital and in-hospital post-cardiac arrest patients.

This study aims to describe infectious complications in both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) patients with sustained return of spontaneous circulation (ROSC) and to compare differences in antimicrobial treatment and outcomes between the two groups. This was a retrospective, single-center, observational study. Adult patients (≥ 18 years) with OHCA or IHCA who had sustained ROSC between December 2007 to March 2015 were included. Blood, urine, sputum, and other fluid cultures, as well as radiologic imaging, were obtained at the discretion of the treating clinical teams. 275 IHCA and 318 OHCA patients were included in the analysis. We found evidence of infection in 181 IHCA and 168 OHCA patients. Significant differences were found between the IHCA and OHCA group in terms of initial rhythm, duration of arrest (10 min vs. 20, p = < 0.001), targeted temperature management (30% vs. 73%, p = < 0.001), and post-arrest infection rates (66% vs 53%, p = 0.001). 95% of IHCA and 82% of OHCA patients received antimicrobial treatment in the post-cardiac arrest period. The source of infection in both groups was largely respiratory, followed by urinary. Gram-positive cocci and gram-negative rods were the most common organisms identified among subjects with culture-proven bacteremia. Infections in the post-arrest period were common in both OHCA and IHCA. We found significantly more infections in IHCA compared to OHCA patients. The most common infection category was respiratory and the most common organism isolated from sputum cultures was Staphylococcus aureus coagulase-positive. The incidence of culture-positive bacteremia was similar in both OHCA and IHCA cohorts but overall lower than previously reported.

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.

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≥4mmol/L. We excluded those who received thiamine later than 48h 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 100mg (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.

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 Moran's 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.

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.

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.

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.

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.