Objective To determine if intravenous thiamine would reduce lactate in patients with septic shock. Design Randomized, double-blind, placebo-controlled trial. Setting Two US hospitals. Patients Adult patients with septic shock and elevated (> 3 mmol/L) lactate between 2010 and 2014. Interventions Thiamine 200 mg or matching placebo twice daily for 7 days or until hospital discharge. Measurements and Main Results The primary outcome was lactate levels 24 hours after the first study dose. Of 715 patients meeting the inclusion criteria, 88 patients were enrolled and received study drug. There was no difference in the primary outcome of lactate levels at 24 hours after study start between the thiamine and placebo groups (median: 2.5 mmol/L [1.5, 3.4] vs. 2.6 mmol/L [1.6, 5.1], p = 0.40). There was no difference in secondary outcomes including time to shock reversal, severity of illness and mortality. 35% of the patients were thiamine deficient at baseline. In this predefined subgroup, those in the thiamine treatment group had statistically significantly lower lactate levels at 24 hours (median 2.1 mmol/L [1.4, 2.5] vs. 3.1 [1.9, 8.3], p = 0.03). There was a statistically significant decrease in mortality over time in those receiving thiamine in this subgroup (p = 0.047). Conclusion Administration of thiamine did not improve lactate levels or other outcomes in the overall group of patients with septic shock and elevated lactate. In those with baseline thiamine deficiency, patients in the thiamine group had significantly lower lactate levels at 24 hours and a possible decrease in mortality over time.

Introduction Rate of lactate change is associated with in-hospital mortality in post-cardiac arrest patients. This association has not been validated in a prospective multicenter study. Objective To determine the association between percent lactate change and outcomes in post-cardiac arrest patients. Methods Four-center prospective observational study conducted from June 2011 to March 2012. Inclusion criteria consisted of adult out-of-hospital non-traumatic cardiac arrest patients who were comatose after return of spontaneous circulation. The primary outcome was survival to hospital discharge, and secondary outcome was good neurological outcome. We compared the absolute lactate levels and the differences in the percent lactate change over 24-hrs between survivors and non-survivors and between subjects with good and bad neurological outcomes. Results 100 patients were analyzed. The median age was 63 years (IQR: 50 – 75) and 40% were female. 97% received therapeutic hypothermia and overall survival was 46%. Survivors and patients with good neurological outcome had lower lactate levels at 0, 12 and 24 hours (p < 0.01). In adjusted models percent lactate decrease at 12 hours was greater in survivors (OR 2.2 [95% CI 1.1 – 6.2]) and in those with good neurological outcome (OR 2.2 [95% CI 1.1 – 4.4]). Conclusion Lower lactate levels at 0, 12 and 24 hours as well as greater percent decrease in lactate over the first 12-hours post-cardiac arrest are associated with survival and good neurologic outcome.

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Aim Previous studies have examined the association between quantitative computed tomography (CT) measures of cerebral edema and patient outcomes. It has been reported that a calculated gray matter to white matter attenuation ratio (GWR) of < 1.2 indicates a near 100% non-survivable injury post-cardiac arrest. The objective of the current study was to validate whether a GWR < 1.2 reliably indicates poor survival post-cardiac arrest. We also sought to determine the inter-rater variability among reviewers, and examine the utility of a novel GWR measurement to facilitate easier practical use. Methods We performed a retrospective analysis of post-cardiac arrest patients admitted to a single center from 2008 to 2012. Inclusion criteria were age ≥ 18 years, non-traumatic arrest, and available CT imaging within 24 hours after ROSC. Three independent physician reviewers from different specialties measured CT attenuation of pre-specified gray and white matter areas for GWR calculations. Results Out of 171 consecutive patients, 90 met the study inclusion criteria. Thirteen patients were excluded for technical reasons and/or significant additional pathology, leaving 77 head CT scans for evaluation. Median age was 66 years and 63% were male. In-hospital mortality was 65% and 70% of patients received therapeutic hypothermia. For the validation measurement, the intra-class correlation coefficient was 0.70. In our dataset, a GWR below 1.2 did not accurately predict mortality or poor neurological outcome (sensitivity 0.56–0.62 and specificity 0.63–0.81). A score below 1.1 predicted a near 100% mortality but was not a sensitive metric (sensitivity 0.14–0.20 and specificity 0.96–1.00). Similar results were found for the exploratory model. Conclusion A GWR < 1.2 on CT imaging within 24 hours after cardiac arrest was moderately specific for poor neurologic outcome and mortality. Based on our data, a threshold GWR < 1.1 may be a safer cut-off to identify patients with low chance of survival and good neurological outcome. Intra-class correlation among reviewers was moderately good.

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.

Aim Neuromuscular blockade may improve outcome in patients with acute respiratory distress syndrome. In post-cardiac arrest patients receiving therapeutic hypothermia, neuromuscular blockade is often used to prevent shivering. Our objective was to determine whether neuromuscular blockade is associated with improved outcomes after out-of-hospital cardiac arrest. Methods A post-hoc analysis of a prospective observational study of comatose adult (> 18 years) out-of-hospital cardiac arrest at 4 tertiary cardiac arrest centers. The primary exposure of interest was neuromuscular blockade for 24 hours following return of spontaneous circulation and primary outcomes were in-hospital survival and neurologically intact survival. Secondary outcomes were evolution of oxygenation (PaO2:FiO2), and change in lactate. We tested the primary outcomes of in-hospital survival and neurologically intact survival with multivariable logistic regression. Secondary outcomes were tested with multivariable linear mixed-models. Results A total of 111 patients were analyzed. In patients with 24 hours of sustained neuromuscular blockade, the crude survival rate was 14/18 (78%) compared to 38/93 (41%) in patients without sustained neuromuscular blockade (p = 0.004). After multivariable adjustment, neuromuscular blockade was associated with survival (adjusted OR: 7.23, 95% CI: 1.56 –33.38). There was a trend toward improved functional outcome with neuromuscular blockade (50% vs. 28%; p = 0.07). Sustained neuromuscular blockade was associated with improved lactate clearance (adjusted p = 0.01). Conclusions We found that early neuromuscular blockade for a 24-hour period is associated with an increased probability of survival. Secondarily, we found that early, sustained neuromuscular blockade is associated with improved lactate clearance.

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) minutes and 33 patients (38.0%) had a good neurologic outcome. When downtime was divided into four groups (≤10 min, 11-20 min, 21-30 min, > 30 min), good neurologic outcomes were 62.5%, 37%, 25%, and 21.7%, respectively (p=0.02). However, even with downtime >20 minutes, 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 > 20 minutes.

Aim We hypothesized that microcirculatory dysfunction, similar to that seen in sepsis, occurs in post-cardiac arrest patients and that better microcirculatory flow will be associated with improved outcome. We also assessed the association between microcirculatory dysfunction and inflammatory markers in the post-cardiac arrest state. Methods We prospectively evaluated the sublingual microcirculation in post-cardiac arrest patients, severe sepsis/septic shock patients, and healthy control patients using Sidestream Darkfield Microscopy. Microcirculatory flow was assessed using the Microcirculation flow index (MFI) at 6 and 24 hours in the cardiac arrest patients, and within 6 hours of Emergency Department admission in the sepsis and control patients. Results We evaluated 30 post-cardiac arrest patients, 16 severe sepsis/septic shock patients, and 9 healthy control patients. Sublingual microcirculatory blood flow was significantly impaired in post-cardiac arrest patients at 6 hours (MFI 2.6 [IQR: 2 - 2.9]) and 24 hours (2.7 [IQR: 2.3 - 2.9]) compared to controls (3.0 [IQR: 2.9 - 3.0]; p < 0.01 and 0.02, respectively). After adjustment for initial APACHE II score, post-cardiac arrest patients had significantly lower MFI at 6-hours compared to sepsis patients (p < 0.03). In the post-cardiac arrest group, patients with good neurologic outcome had better microcirculatory blood flow as compared to patients with poor neurologic outcome (2.9 [IQR: 2.4 – 3.0] vs. 2.6 [IQR: 1.9 – 2.8]; p < 0.03). There was a trend toward higher median MFI at 24 hours in survivors vs. non-survivors (2.8 [IQR: 2.4 – 3.0] vs. 2.6 [IQR: 2.1-2.8] respectively; p < 0.09). We found a negative correlation between MFI-6 and vascular endothelial growth factor (VEGF) (r= −0.49, P= 0.038). However, after Bonferroni adjustment for multiple comparisons, this correlation was statistically non-significant. Conclusion Microcirculatory dysfunction occurs early in post-cardiac arrest patients. Better microcirculatory function at 24 hours may be associated with good neurologic outcome.