Parth V. Patel

Absolute lactate value vs relative reduction as a predictor of mortality in severe sepsis and septic shock

Purpose: Lactate reduction, a common method of risk stratification, has been variably defined. Among patients with an initial lactate >4 mmol/L, we compared mortality prediction between a subsequent lactate ≥4 mmol/L to a <10% and <20% decrease between initial and subsequent lactate values. Materials and methods: We performed a single‐center retrospective study of patients presenting to the emergency department with an initial lactate ≥4 mmol/L and suspected infection. Patients were stratified by lactate reduction using 3 previously identified definitions (subsequent lactate ≥4 mmol/L, and <10% and <20% relative decrease in lactate) and compared using multivariable logistic regression. Sensitivity and specificity were compared using McNemar test. Results: A subsequent lactate ≥4 mmol/L and a lactate reduction <20% were associated with increased in‐hospital mortality (odds ratio [OR], 3.18; 95% confidence interval [CI], 1.24‐8.16; P = .02 and OR, 3.11; 95% CI, 1.39‐6.96; P = .006, respectively), whereas a lactate reduction <10% was not (OR, 1.13; 95% CI, 0.94‐1.34; P = .11). A subsequent lactate ≥4 mmol/L and a lactate reduction <20% were more sensitive than a lactate reduction <10% (72% vs 41%, P = .002 and 62% vs 41%, P = .008, respectively) but less specific (57% vs 76%, P < .001 and 67% vs 76%, P = .002, respectively). Conclusions: A subsequent lactate ≥4 mmol/L and lactate reduction <20% were associated with increased in‐hospital mortality, whereas a lactate reduction <10% was not. Sensitivity and specificity are different between these parameters.

Quick Sequential Organ Failure Assessment and Systemic Inflammatory Response Syndrome Criteria as Predictors of Critical Care Intervention Among Patients With Suspected Infection

Objectives: The Sepsis III clinical criteria for the diagnosis of sepsis rely on scores derived to predict inhospital mortality. In this study, we introduce the novel outcome of “received critical care intervention” and investigate the related predictive performance of both the quick Sequential Organ Failure Assessment and the Systemic Inflammatory Response Syndrome criteria. Design: This was a single-center, retrospective analysis of electronic health records. Setting: Tertiary care hospital in the United States. Patients: Patients with suspected infection who presented to the emergency department and were admitted to the hospital between January 2010 and December 2014. Interventions: Systemic Inflammatory Response Syndrome and quick Sequential Organ Failure Assessment scores were calculated, and their relationships to the receipt of critical care intervention and inhospital mortality were determined. Measurement and Main Results: A total of 24,164 patients were included of whom 6,693 (27.7%) were admitted to an ICU within 48 hours; 4,453 (66.5%) patients admitted to the ICU received a critical care intervention. Among those with quick Sequential Organ Failure Assessment less than 2, 13.4% received a critical care intervention and 3.5% died compared with 48.2% and 13.4%, respectively, for quick Sequential Organ Failure Assessment greater than or equal to 2. The area under the receiver operating characteristic was similar whether quick Sequential Organ Failure Assessment was used to predict receipt of critical care intervention or inhospital mortality (0.74 [95% CI, 0.73–0.74] vs 0.71 [0.69–0.72]). The area under the receiver operating characteristic of Systemic Inflammatory Response Syndrome for critical care intervention (0.69) and mortality (0.66) was lower than that for quick Sequential Organ Failure Assessment (p < 0.001 for both outcomes). The sensitivity of quick Sequential Organ Failure Assessment for predicting critical care intervention was 38%. Conclusions: Emergency department patients with suspected infection and low quick Sequential Organ Failure Assessment scores frequently receive critical care interventions. The misclassification of these patients as “low risk,” in combination with the low sensitivity of quick Sequential Organ Failure Assessment greater than or equal to 2, may diminish the clinical utility of the quick Sequential Organ Failure Assessment score for patients with suspected infection in the emergency department.

Thiamine as a Renal Protective Agent in Septic Shock. A Secondary Analysis of a Randomized, Double-Blind, Placebo-controlled Trial

Rationale: Acute kidney injury (AKI) is common in patients with sepsis and has been associated with high mortality rates. The provision of thiamine to patients with sepsis may reduce the incidence and severity of sepsis‐related AKI and thereby prevent renal failure requiring renal replacement therapy (RRT). Objectives: To test the hypothesis that thiamine supplementation mitigates kidney injury in septic shock. Methods: This was a secondary analysis of a single‐center, randomized, double‐blind trial comparing thiamine to placebo in patients with septic shock. Renal function, need for RRT, timing of hemodialysis catheter placement, and timing of RRT initiation were abstracted. The baseline creatinine and worst creatinine values between 3 and 24 hours, 24 and 48 hours, and 48 and 72 hours were likewise abstracted. Results: There were 70 patients eligible for analysis after excluding 10 patients in whom hemodialysis was initiated before study drug administration. Baseline serum creatinine in the thiamine group was 1.2 mg/dl (interquartile range, 0.8‐2.5) as compared with 1.8 mg/dl (interquartile range, 1.3‐2.7) in the placebo group (P = 0.3). After initiation of the study drug, more patients in the placebo group than in the thiamine group were started on RRT (eight [21%] vs. one [3%]; P = 0.04). In the repeated measures analysis adjusting for the baseline creatinine level, the worst creatinine levels were higher in the placebo group than in the thiamine group (P = 0.05). Conclusions: In this post hoc analysis of a randomized controlled trial, patients with septic shock randomized to receive thiamine had lower serum creatinine levels and a lower rate of progression to RRT than patients randomized to placebo. These findings should be considered hypothesis generating and can be used as a foundation for further, prospective investigation in this area.

Reasons for death in patients with sepsis and septic shock

Purpose: Understanding the underlying cause of mortality in sepsis has broad implications for both clinical care and interventional trial design. However, reasons for death in sepsis remain poorly understood. We sought to characterize reasons for in‐hospital mortality in a population of patients with sepsis or septic shock. Materials and methods: We performed a retrospective review of patients admitted to the intensive care unit with sepsis or septic shock who died during their index admission. Reasons for death were classified into 6 categories determined a priori by group consensus. Interrater reliability was calculated and Fleiss &kgr; reported. The associations between selected patient characteristics (eg, serum lactate) and reason for death were also assessed. Results: One hundred fifteen patients were included. Refractory shock (40%) and comorbid withdrawal of care (44%) were the most common reasons for death. Overall interrater agreement was substantial (&kgr; = 0.61, P < .01). Lactate was higher in patients who died because of refractory shock as compared with those who died for other reasons (4.7 vs 2.8 mmol/L, P < .01). Conclusion: In this retrospective cohort, refractory shock and comorbid withdrawal of care were the most common reasons for death. Following prospective validation, the classification methodology presented here may be useful in the design/interpretation of trials in sepsis. HighlightsReasons for death in sepsis have been incompletely characterized.We present a method for classifying reasons for death among patients with sepsis and septic shock.The most common reasons for death in sepsis were refractory shock and comorbid withdrawal of care.Initial serum lactate may be a useful predictor of death from refractory shock in sepsis.

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.

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.

The association between tidal volume and neurological outcome following in-hospital cardiac arrest

AIMS Prior investigation has found that mechanical ventilation with lower tidal volumes (Vt) following out-of-hospital cardiac arrest is associated with better neurologic outcomes. The relationship between Vt and neurologic outcome following in-hospital cardiac arrest (IHCA) has not previously been explored. In the present study, we investigate the association between Vt and neurologic outcome following IHCA. METHODS This was an observational study using a prospectively collected database of IHCA patients at a tertiary care hospital in the United States. The relationship between time-weighted average Vt per predicted body weight (PBW) over the first 6- and 48 h after cardiac arrest and neurologic outcome were assessed using propensity-score adjusted logistic regression. MEASUREMENTS AND MAIN RESULTS Of 185 IHCA patients who received invasive mechanical ventilation within 6 h of return of spontaneous circulation (ROSC), the average Vt over the first 6 h was 7.7 ± 2.0 ml/kg and 68 (36.8%) patients received an average Vt > 8.0 ml/kg. Of 121 patients who received mechanical ventilation for at least 48 h post-ROSC, the average Vt was 7.6 ± 1.5 ml/kg and 46 (38.0%) patients received an average Vt > 8.0 ml/kg. There was no relationship between Vt/PBW over the first 6- or 48 h post-ROSC and neurologic outcome (OR 0.99; 95%CI 0.84-1.16; p = 0.89; OR 1.03; 95%CI 0.78-1.37; p = 0.83 respectively). CONCLUSIONS This study did not identify a relationship between Vt and neurologic outcome following IHCA. This contrasts with results in OHCA, where higher Vt has been associated with worse neurologic outcome. Additional investigation is needed with respect to other potential benefits of low-Vt post IHCA.

Performance of the CURB-65 Score in Predicting Critical Care Interventions in Patients Admitted With Community-Acquired Pneumonia

STUDY OBJECTIVE Confusion, uremia, elevated respiratory rate, hypotension, and aged 65 years or older (CURB-65) is a clinical prediction rule intended to stratify patients with pneumonia by expected mortality. We assess the predictive performance of CURB-65 for the proximal endpoint of receipt of critical care intervention in emergency department (ED) patients admitted with community-acquired pneumonia. METHODS We performed a retrospective analysis of electronic health records from a single tertiary center for ED patients admitted as inpatients with a primary diagnosis of pneumonia from 2010 to 2014. Patients with a history of malignancy, tuberculosis, bronchiectasis, HIV, or readmission within 14 days were excluded. We assessed the predictive accuracy of CURB-65 for receipt of critical care interventions (ie, vasopressors, large-volume intravenous fluids, invasive catheters, assisted ventilation, insulin infusions, or renal replacement therapy) and inhospital mortality. Logistic regression was performed to assess the increase in odds of critical care intervention or inhospital mortality by increasing CURB-65 score. RESULTS There were 2,322 patients admitted with community-acquired pneumonia in the study cohort; 630 (27.1%) were admitted to the ICU within 48 hours of ED triage and 343 (14.8%) received a critical care intervention. Of patients with a CURB-65 score of 0 to 1, 181 (15.6%) were admitted to the ICU, 74 (6.4%) received a critical care intervention, and 7 (0.6%) died. Of patients with a CURB-65 score of 2, 223 (27.0%) were admitted to the ICU, 127 (15.4%) received a critical care intervention, and 47 (5.7%) died. Among patients with CURB-65 score greater than or equal to 3, 226 (67.0%) were admitted to the ICU, 142 (42.1%) received a critical care intervention, and 43 (12.8%) died. The areas under the receiver operating characteristic for CURB-65 as a predictor of critical care intervention and mortality were 0.73 and 0.77, whereas sensitivity of CURB-65 score greater than or equal to 2 in predicting critical care intervention was 78.4%; for mortality, 92.8%. CONCLUSION Patients with CURB-65 score less than or equal to 2 were often admitted to the ICU and received critical care interventions. Given this finding and the relatively low sensitivity of CURB-65 for critical care intervention, clinicians should exercise caution when using CURB-65 to guide disposition. Future ED-based clinical prediction rules may benefit from calibration to proximal endpoints.