Thiamine for Renal Protection in Septic Shock (TRPSS): A Randomized, Placebo-controlled, Clinical Trial.

Rationale: Kidney injury is common and associated with worse outcomes in patients with septic shock. Mitochondrial resuscitation with thiamine (vitamin B1) may attenuate septic kidney injury. Objectives: To assess whether thiamine supplementation attenuates kidney injury in septic shock. Methods: The TRPSS (Thiamine for Renal Protection in Septic Shock) trial was a multicenter, randomized, placebo-controlled trial of thiamine versus placebo in septic shock. The primary outcome was change in serum creatinine between enrollment and 72 hours after enrollment. Measurements and Main Results: Eighty-eight patients were enrolled (42 patients received the intervention, and 46 received placebo). There was no significant between-groups difference in creatinine at 72 hours (mean difference, -0.57 mg/dl; 95% confidence interval, -1.18, 0.04; P = 0.07). There was no difference in receipt of kidney replacement therapy (14.3% vs. 21.7%, P = 0.34), acute kidney injury (as defined by stage 3 of the Kidney Disease: Improving Global Outcomes acute kidney injury scale; 54.7% vs. 73.9%, P = 0.07), or mortality (35.7% vs. 54.3%, P = 0.14) between the thiamine and placebo groups. Patients who received thiamine had more ICU-free days (median [interquartile range]: 22.5 [0.0-25.0] vs. 0.0 [0.0-23.0], P < 0.01). In the thiamine-deficient cohort (27.4% of patients), there was no difference in rates of kidney failure (57.1% thiamine vs. 81.5% placebo) or in-hospital mortality (28.6% vs. 68.8%) between groups. Conclusions: In the TRPSS trial, there was no statistically significant difference in the primary outcome of change in creatinine over time. Patients who received thiamine had more ICU-free days, but there was no difference in other secondary outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT03550794).

Timing of Transport of Patients with COVID-19.

RATIONALE: The objective of this study was to evaluate the risk of mortality or ECMO cannulation for patients with confirmed or suspected COVID-19 transferred from sending hospitals to receiving tertiary care centers as a function of the duration of time at the sending hospital. OBJECTIVE: To determine outcomes of critically ill patients with COVID-19 who were transferred to tertiary or quarternary care medical centers. MATERIALS AND METHODS: Retrospective cohort study of critical care transports of patients to one of seven consortium tertiary care centers from March 1, 2020, through September 4, 2020. Age 14 years and older with confirmed or suspected COVID-19 transported from a sending hospital to a receiving tertiary care center by the critical care transport organization. RESULTS: Patients transported with confirmed or suspected COVID-19 to tertiary care centers had a mortality rate of 38.0%. Neither the number of days admitted, nor the number of days intubated at the sending hospital correlated with mortality (correlation coefficient 0.051 and -0.007, respectively). Similarly, neither the number of days admitted, nor number of days intubated at the sending hospital correlated with ECMO cannulation (correlation coefficient 0.008 and -0.036, respectively). CONCLUSION: It may be reasonable to transfer a critically ill COVID-19 patient to a tertiary care center even if they have been admitted at the sending hospital for several days.

Critical Care Transport of Patients With COVID-19.

PURPOSE: Critical care transport is associated with a high rate of adverse events, and the risks and outcomes of transporting critically ill patients during the COVID-19 pandemic have not been previously described. MATERIALS AND METHODS: We performed a retrospective review of transports of subjects with suspected or confirmed COVID-19 from sending hospitals to tertiary care hospitals in Boston. Follow-up data were obtained for patients transported between March 1st and April 20th, 2020. RESULTS: Of 254 charts identified, 250 patients were transported. Nine patients (3.5%) had cardiac arrest prior to transport. Twenty-nine (11.6%) had hypotension, 22 (8.8%) had a critical desaturation, and 4 (1.6%) had both en route. Hospital follow-up data were available for 189 patients. Of those intubated during their hospitalization, 44 (25.0%) had died, 59 (33.5%) had been extubated, and 13 (17.6%) had been discharged alive. For the subgroup with prior cardiac arrest, follow-up data available for 6. Of these 6, 2 died and 4 (66.7%) have been discharged alive. CONCLUSIONS: Few patients with COVID-19 had an adverse event in transport. The in-hospital mortality rate was 25%, with a 33.5% extubation rate. Patients resuscitated from cardiac arrest prior to transport had a 66.7% discharge rate among those transported to consortium hospitals.

A Retrospective Review of Angiotensin II Use in Adult Patients With Refractory Distributive Shock.

PURPOSE: Catecholamines are first-line vasopressors for hemodynamic support in distributive shock but are associated with adverse effects, which may be mitigated with noncatecholamine vasopressors. Angiotensin II (ATII) is a noncatecholamine vasopressor recently approved for the management of distributive shock, but limited data support its clinical utility. The purpose of this study was to describe our institution's usage of ATII including patient outcomes (eg, response to therapy, safety profile). MATERIALS AND METHODS: Patients who received ATII at our institution were included. Patient demographics, degree of concordance with institutional ATII use guidelines, safety profile of ATII, and response to therapy (1 and 3 hours after ATII initiation) were collected. RESULTS: A total of 16 patients received ATII for distributive shock. The median Sequential Organ Failure Assessment score at the time of ATII initiation was 16.5 (interquartile range: 15.8-20.0). Fourteen (87.5%) patients met institutional guidelines for ATII use; 10 (62.5%) and 8 (50.0%) patients met our definition for response at 1 and 3 hours, respectively. No patients developed thrombotic or infectious complications after receiving ATII. CONCLUSIONS: In this cohort, ATII appears to be well tolerated in patients with a high predicted mortality. Future studies evaluating the clinical efficacy of ATII are needed to determine its role in the management of distributive shock.

Predicting Outcome After Out-of-Hospital Cardiac Arrest: Lactate, Need for Vasopressors, and Cytochrome c.

BACKGROUND: Outcome prediction after out-of-hospital cardiac arrest (OHCA) is difficult. We hypothesized that lactate and need for vasopressors would predict outcome, and that addition of a mitochondrial biomarker would enhance performance of the tool. METHODS: Prospective observational study of OHCA patients presenting to an academic medical center September 2008 to April 2016. We conducted univariate and multivariate logistic regressions. RESULTS: Patients were divided based on 2 variables: vasopressor status and initial lactate (<5 mmol/L, 5-10, ≥10). Three hundred fifty-two patients were evaluated; 249 had a lactate within 3 hours and were included. Patients on vasopressors had higher mortality (74% vs 40%; P < .001). A stepwise increase in mortality is associated with increasing lactate (45% lactate <5, 66% 5-10, and 83% ≥10; P < 001). Multivariable models with lactate group and vasopressors as predictors demonstrated excellent discrimination (area under the receiver operating curve [AUC]: 0.73 [95% confidence interval, CI: 0.66-0.79]; adjusted for additional covariates: AUC: 0.81 [95% CI: 0.75-0.86]). Thirty-six patients had cytochrome c levels available; among these 36, when comparing models with and without cytochrome c, there was no difference (AUC: 0.88 [95% CI: 0.76-1.00] vs AUC: 0.85 [95% CI: 0.73-0.98], respectively; P = .30). CONCLUSION: In this prospective validation, the combination of lactate and vasopressors in the immediate postarrest period is predictive of mortality. Cytochrome c offered minimal additional predictive power.

ST Segment Elevation Caused by Artifact From Cylindrical Battery Ingestion.

BACKGROUND: Ingestion of cylindrical batteries is uncommon. Management can include removal via upper endoscopy, surgical excision, or observation. This case demonstrates the rare phenomenon of cylindrical battery ingestion causing an electrocardiogram (ECG) artifact that mimics ST segment myocardial infarction (STEMI). CASE REPORT: A 51-year-old man who ingested 13 small pencils and 18 AA batteries was found to have ST segment elevation in the inferior leads of the ECG. Further cardiac workup including cardiac biomarkers and transthoracic echocardiogram was negative, and his ECG changes resolved after extraction of the batteries. The ST segment changes were most likely caused by electrical artifact from battery ingestion. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When faced with an ECG finding that is unexpected and that does not fit the patient's overall clinical picture, emergency physicians should consider artifact as a possible cause. Recognition of artifact as the cause of an ECG abnormality can obviate the need for a prolonged and potentially invasive cardiac workup.

Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial.

IMPORTANCE: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock. OBJECTIVE: To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019. INTERVENTIONS: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102). MAIN OUTCOMES AND MEASURES: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses. RESULTS: Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively). CONCLUSIONS AND RELEVANCE: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03389555.

Case Study: Fatal Exertional Rhabdomyolysis Possibly Related to Drastic Weight Cutting.

Rapid weight loss or "weight cutting" is a dangerous practice that is ubiquitous in modern combat sports yet underrepresented in the medical literature. We present a case of exertional rhabdomyolysis in a mixed martial artist with sickle cell trait to illustrate the hazards of weight cutting and ensuing critical illness. Sickle cell trait is known to predispose patients to exertional rhabdomyolysis, and multiple fatal cases have been reported in the setting of strenuous exercise. Dehydration and consequent electrolyte abnormalities make combat sport athletes with sickle cell trait particularly vulnerable to this entity. This case suggests a potential role for sickle cell trait screening in this population and underscores the need for safer weight-control practices and monitoring among all combat sport athletes.

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.

Factors associated with performing urgent coronary angiography in out-of-hospital cardiac arrest patients.

OBJECTIVES: Factors associated with performing urgent coronary angiography (UCA) in patients with out-of-hospital cardiac arrest (OHCA) were identified. BACKGROUND: Current guidelines for resuscitated OHCA patients recommend UCA if there is ST-elevation on post-arrest electrocardiogram or high suspicion of acute myocardial infarction. Some have advocated for UCA in all OHCA regardless of suspected etiology. The reasons for variations in performing UCA are not well understood. METHODS: A retrospective analysis of subjects presenting with resuscitated OHCA to a single academic medical center from 12/15/2007 to 8/31/2014 was conducted. Demographic and clinical characteristics of patients undergoing UCA, defined as angiography within 6 hr of presentation, were compared with those not undergoing UCA. Logistic regression was used to determine predictors of UCA. RESULTS: A total of 323 resuscitated OHCA patients (mean age, 64 years; women, 35%) were included in the analysis; 107 (33.1%) underwent coronary angiography during their hospitalization and 66 (20.4%) underwent UCA. Multivariable adjusted factors associated with UCA were ST-elevation [odds ratio (OR) 14.66, 95% confidence interval (CI) 6.28-34.24, P < 0.001], initial shockable rhythm (OR 3.69, 95% CI 1.52-8.97, P = 0.004), and history of coronary artery disease (CAD) (OR 3.37, 95% CI 1.43-7.95, P = 0.005). Higher age (OR 0.71 per decade, 95% CI 0.55-0.92, P = 0.01) and obvious non-cardiac cause of arrest (OR 0.08, 95% CI 0.02-0.38, P = 0.001) were negatively associated with UCA. CONCLUSIONS: In resuscitated out-of-hospital cardiac arrest patients, ST-elevation, shockable rhythm, and history of CAD were associated with performing urgent coronary angiography; older patients and those with obvious non-cardiac causes of arrest were negatively associated.

Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation.

The combination of thiamine, ascorbic acid, and hydrocortisone has recently emerged as a potential adjunctive therapy to antibiotics, infectious source control, and supportive care for patients with sepsis and septic shock. In the present manuscript, we provide a comprehensive review of the pathophysiologic basis and supporting research for each element of the thiamine, ascorbic acid, and hydrocortisone drug combination in sepsis. In addition, we describe potential areas of synergy between these therapies and discuss the strengths/weaknesses of the two studies to date which have evaluated the drug combination in patients with severe infection. Finally, we describe the current state of current clinical practice as it relates to the thiamine, ascorbic acid, and hydrocortisone combination and present an overview of the randomized, placebo-controlled, multi-center Ascorbic acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial and other planned/ongoing randomized clinical trials.

Mortality and Resource Utilization After Critical Care Transport of Patients With Hypoxemic Respiratory Failure.

INTRODUCTION: We performed this study to quantify resources required by mechanically ventilated patients with hypoxemia after critical care transport (CCT) and to assess short-term clinical outcomes. METHODS: We performed a retrospective review of transports of patients with severe hypoxemic respiratory failure from referring hospitals to 3 tertiary care hospitals to assess the outcomes including in-hospital mortality, ventilator days, intensive care unit length of stay (LOS), hospital LOS, disposition, and reported neurologic status on hospital discharge as well as medical interventions specific to acute respiratory failure and critical care. RESULTS: Of 230 patients transported with hypoxemic respiratory failure, 152 survived to hospital discharge, for a mortality rate of 34.5%, despite a predicted mortality of 64% by Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Twenty-five percent of patients were treated with neuromuscular blockade, 10.1% received inhaled pulmonary vasodilators, and extracorporeal membrane oxygenation was initiated in 2.6%. CONCLUSIONS: In this cohort with hypoxemic respiratory failure transported to tertiary care facilities, patients had a mortality rate comparable to patients with acute respiratory distress syndrome treated with best practices and a mortality rate lower than predicted based on APACHE-II score. The risks of CCT are outweighed by the benefits of transfer to a tertiary care facility, and pretransport hypoxemia should not be used as an absolute contraindication to transport.

Redesigning Rounds in the ICU: Standardizing Key Elements Improves Interdisciplinary Communication.

BACKGROUND: Daily multidisciplinary rounds (MDR) in the ICU represent a mechanism by which health care professionals from different disciplines and specialties can meet to synthesize data, think collectively, and form complete patient care plans. It was hypothesized that providing a standardized, structured approach to the daily rounds process would improve communication and collaboration in seven distinct ICUs in a single academic medical center. METHODS: Lean-inspired methodology and information provided by frontline staff regarding inefficiencies and barriers to optimal team functioning were used in designing a toolkit for standardization of rounds in the ICUs. Staff perceptions about communication were measured, and direct observations of rounds were conducted before and after implementation of the intervention. RESULTS: After implementation of the intervention, nurse participation during presentation of patient data increased from 17/47 (36.2%) to 56/78 (71.8%) (p < 0.0002) in the surgical ICUs and from 8/23 (34.8%) to 107/107 (100%) (p <0.0001) in the medical ICUs. Nurse participation during generation of the daily plan increased in the surgical ICUs from 24/47 (51.1%) to 63/78 (80.8%) (p = 0.0005) and from 7/23 (30.4%) to 106/107 (99.1%) (p < 0.0001) in the medical ICUs. Miscommunications and errors were corrected in nearly half of the rounding episodes observed. CONCLUSION: This study demonstrated that the implementation of a simple toolkit that can be incorporated into existing work flow and rounding culture in several different types of ICUs can result in improvements in engagement of nursing staff and in overall communication.

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.

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.

Acute Respiratory Compromise in the Emergency Department: A Description and Analysis of 3571 Events from the Get With the Guidelines-Resuscitation® Registry.

BACKGROUND: Respiratory events requiring the use of assisted ventilation are relatively common in the emergency department (ED), and can be associated with substantial morbidity and mortality. OBJECTIVE: The aim of this study was to describe and elucidate patient and event characteristics associated with mortality and progression to cardiac arrest in ED patients with acute respiratory compromise. METHODS: Data were obtained from the multicenter Get With the Guidelines-Resuscitation® registry. We included patients with acute respiratory compromise defined as absent, agonal, or inadequate respiration that required emergency assisted ventilation. All adult patients between January 2005 and December 2014 with an index event in the ED were included. We used multivariable logistic regression models to assess the association between patient and event characteristics and in-hospital mortality, with cardiac arrest during the event as a secondary outcome. RESULTS: A total of 3571 events were included. The in-hospital mortality was 34%. Twelve percent of events progressed to cardiac arrest, with a subsequent 82% in-hospital mortality. When adjusting for patient and event characteristics, we found no temporal changes in in-hospital mortality from 2005 to 2014. Several characteristics were associated with increased mortality, such as pre-event hypotension, septicemia, and acute stroke. Similarly, multiple characteristics, including pre-event hypotension, were associated with progression to cardiac arrest. CONCLUSIONS: Patient with acute respiratory compromise in the ED had an in-hospital mortality of 34% in the current study. These patients also have a high risk of progressing to cardiac arrest, with a subsequent increase in in-hospital mortality to 82%. Potentially reversible characteristics, such as hypotension before the event, showed a strong association to in-hospital mortality, along with multiple other patient and event characteristics.

Temperature Management After Cardiac Arrest: An Advisory Statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation.

For more than a decade, mild induced hypothermia (32 °C-34 °C) has been standard of care for patients remaining comatose after resuscitation from out-of-hospital cardiac arrest with an initial shockable rhythm, and this has been extrapolated to survivors of cardiac arrest with initially nonshockable rhythms and to patients with in-hospital cardiac arrest. Two randomized trials published in 2002 reported a survival and neurological benefit with mild induced hypothermia. One recent randomized trial reported similar outcomes in patients treated with targeted temperature management at either 33 °C or 36 °C. In response to these new data, the International Liaison Committee on Resuscitation Advanced Life Support Task Force performed a systematic review to evaluate 3 key questions: (1) Should mild induced hypothermia (or some form of targeted temperature management) be used in comatose post-cardiac arrest patients? (2) If used, what is the ideal timing of the intervention? (3) If used, what is the ideal duration of the intervention? The task force used Grading of Recommendations Assessment, Development and Evaluation methodology to assess and summarize the evidence and to provide a consensus on science statement and treatment recommendations. The task force recommends targeted temperature management for adults with out-of-hospital cardiac arrest with an initial shockable rhythm at a constant temperature between 32 °C and 36 °C for at least 24 hours. Similar suggestions are made for out-of-hospital cardiac arrest with a nonshockable rhythm and in-hospital cardiac arrest. The task force recommends against prehospital cooling with rapid infusion of large volumes of cold intravenous fluid. Additional and specific recommendations are provided in the document.

Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study.

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.

Corticosteroid therapy in refractory shock following cardiac arrest: a randomized, double-blind, placebo-controlled, trial.

BACKGROUND: The purpose of this study was to determine whether the provision of corticosteroids improves time to shock reversal and outcomes in patients with post-cardiac arrest shock. METHODS: We conducted a randomized, double-blind trial of post-cardiac arrest patients in shock, defined as vasopressor support for a minimum of 1 hour. Patients were randomized to intravenous hydrocortisone 100 mg or placebo every 8 hours for 7 days or until shock reversal. The primary endpoint was time to shock reversal. RESULTS: Fifty patients were included with 25 in each group. There was no difference in time to shock reversal between groups (hazard ratio: 0.83 [95% CI: 0.40-1.75], p = 0.63). We found no difference in secondary outcomes including shock reversal (52% vs. 60%, p = 0.57), good neurological outcome (24% vs. 32%, p = 0.53) or survival to discharge (28% vs. 36%, p = 0.54) between the hydrocortisone and placebo groups. Of the patients with a baseline cortisol < 15 ug/dL, 100% (6/6) in the hydrocortisone group achieved shock reversal compared to 33% (1/3) in the placebo group (p = 0.08). All patients in the placebo group died (100%; 3/3) whereas 50% (3/6) died in the hydrocortisone group (p = 0.43). CONCLUSIONS: In a population of cardiac arrest patients with vasopressor-dependent shock, treatment with hydrocortisone did not improve time to shock reversal, rate of shock reversal, or clinical outcomes when compared to placebo. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT00676585, registration date: May 9, 2008.

Thiamine as an adjunctive therapy in cardiac surgery: a randomized, double-blind, placebo-controlled, phase II trial.

BACKGROUND: Thiamine is a vitamin that is essential for adequate aerobic metabolism. The objective of this study was to determine if thiamine administration prior to coronary artery bypass grafting would decrease post-operative lactate levels as a measure of increased aerobic metabolism. METHODS: We performed a randomized, double-blind, placebo-controlled trial of patients undergoing coronary artery bypass grafting. Patients were randomized to receive either intravenous thiamine (200 mg) or placebo both immediately before and again after the surgery. Our primary endpoint was post-operative lactate levels. Additional endpoints included pyruvate dehydrogenase activity, global and cellular oxygen consumption, post-operative complications, and hospital and intensive care unit length of stay. RESULTS: Sixty-four patients were included. Thiamine levels were significantly higher in the thiamine group as compared to the placebo group immediately after surgery (1200 [683, 1200] nmol/L vs. 9 [8, 13] nmol/L, p < 0.001). There was no difference between the groups in the primary endpoint of lactate levels immediately after the surgery (2.0 [1.5, 2.6] mmol/L vs. 2.0 [1.7, 2.4], p = 0.75). Relative pyruvate dehydrogenase activity was lower immediately after the surgery in the thiamine group as compared to the placebo group (15% [11, 37] vs. 28% [15, 84], p = 0.02). Patients receiving thiamine had higher post-operative global oxygen consumption 1 hour after the surgery (difference: 0.37 mL/min/kg [95% CI: 0.03, 0.71], p = 0.03) as well as cellular oxygen consumption. We found no differences in clinical outcomes. CONCLUSIONS: There were no differences in post-operative lactate levels or clinical outcomes between patients receiving thiamine or placebo. Post-operative oxygen consumption was significantly increased among patients receiving thiamine. TRIAL REGISTRATION: clinicaltrials.gov NCT02322892, December 14, 2014.