Thiamine as a metabolic resuscitator after out-of-hospital cardiac arrest.

INTRODUCTION: Thiamine is a key cofactor for aerobic metabolism, previously shown to improve mortality and neurological outcomes in a mouse model of cardiac arrest. We hypothesized that thiamine would decrease lactate and improve outcomes in post-arrest patients. METHODS: Single center, randomized, blinded, placebo-controlled, Phase II trial of thiamine in adults within 4.5 hours of return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA), with coma and lactate ≥ 3 mmol/L. Participants received 500 mg IV thiamine or placebo twice daily for 2 days. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. The primary outcome of lactate was checked at baseline, 6, 12, and 24 hours, and compared using a linear mixed model to account for repeated measures. Secondary outcomes included SOFA score, pyruvate dehydrogenase, renal injury, neurological outcome, and mortality. RESULTS: Of 93 randomized patients, 76 were enrolled and included in the analysis. There was no difference in lactate over 24 hours (mean difference 0.34 mmol/L (95% CI: -1.82, 2.50), p = 0.43). There was a significant interaction between randomization lactate subgroup and the effect of the intervention on mortality (p = 0.01) such that mortality was higher with thiamine in the lactate > 5 mmol/L group and lower with thiamine in the < 5 mmol/L group. This subgroup difference prompted the Data and Safety Monitoring Board to recommend the study be terminated early. PDH activity increased over 72 hours in the thiamine group. There were no differences in other secondary outcomes. CONCLUSION: In this single-center randomized trial, thiamine did not affect lactate over 24 hours after OHCA.

Thiamine as a metabolic resuscitator after in-hospital cardiac arrest.

INTRODUCTION: Elevated lactate is associated with mortality after cardiac arrest. Thiamine, a cofactor of pyruvate dehydrogenase, is necessary for aerobic metabolism. In a mouse model of cardiac arrest, thiamine improved pyruvate dehydrogenase activity, survival and neurologic outcome. AIM: To determine if thiamine would decrease lactate and increase oxygen consumption after in-hospital cardiac arrest. METHODS: Randomized, double-blind, placebo-controlled phase II trial. Adult patients with arrest within 12 hours, mechanically ventilated, with lactate ≥ 3 mmol/L were included. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. Thiamine 500 mg or placebo was administered every 12 hours for 3 days. The primary outcome of lactate was checked at baseline, 6, 12, 24, and 48 hours, and compared using a linear mixed model, accounting for repeated measures. Secondary outcomes included oxygen consumption, pyruvate dehydrogenase, and mortality. RESULTS: Enrollments stopped after 36 patients due Data Safety and Monitoring Board concern about potential harm in an unplanned subgroup analysis. There was no overall difference in lactate (mean difference at 48 hours 1.5 mmol/L [95% CI -3.1-6.1], global p = 0.88) or any secondary outcomes. In those with randomization lactate > 5 mmol/L, mortality was 92% (11/12) with thiamine and 67% (8/12) with placebo (p = 0.32). In those with randomization lactate ≤ 5 mmol/L mortality was 17% (1/6) with thiamine and 67% (4/6) with placebo (p = 0.24). There was a significant interaction between randomization lactate and the effect of thiamine on survival (p = 0.03). CONCLUSIONS: In this single center trial thiamine had no overall effect on lactate after in-hospital cardiac arrest.

Corticosteroids to Reduce Inflammation in Severe Pancreatitis (CRISP) protocol and statistical analysis plan: a prospective, multicentre, double-blind, randomized, placebo controlled clinical trial.

INTRODUCTION: Acute pancreatitis is a common disease which, in its severe form, is associated with significant morbidity and mortality. Currently, there is no specific therapy known to attenuate organ failure in severe pancreatitis and treatment consists primarily of supportive care. Corticosteroids have been shown to be beneficial in disease processes associated with systemic inflammation and could potentially improve outcomes in severe acute pancreatitis. METHODS: The Corticosteroids to Reduce Inflammation in Severe Pancreatitis (CRISP) trial is a multi-centre, double-blind, randomized, placebo-controlled clinical trial that aims to determine the impact of corticosteroids versus placebo on organ injury in patients with severe acute pancreatitis. Patients are randomized to receive 100 mg of hydrocortisone parenterally versus matching placebo every 8 h for 3 days. Clinical and laboratory data are collected at the time of study enrollment, at 24, 48 and 72 h. The primary end-point for the trial is the difference in 72-h change in the Sequential Organ Failure Assessment (SOFA) score between hydrocortisone and placebo groups. Additional key secondary outcomes include ventilator free days and 28-day mortality. DISCUSSION: This study will add to the evidence base in the treatment of severe acute pancreatitis. The results will inform clinical practice and future studies in the field. Trial registration number The trial is registered on clinicaltrials.gov (NCT05160506). It was posted on December 16th, 2021. The study protocol was approved by the Beth Israel Deaconess Medical Center Committee on Clinical Investigation (CCI) (protocol 2021 P-000803).

Thiamine as adjunctive therapy for diabetic ketoacidosis (DKAT) trial protocol and statistical analysis plan: a prospective, single-centre, double-blind, randomised, placebo-controlled clinical trial in the USA.

INTRODUCTION: Diabetic ketoacidosis (DKA) is a potentially life-threatening diabetic complication. Despite the high prevalence of DKA and the substantial associated healthcare burden, limited research on strategies to improve outcomes currently exists.Thiamine (vitamin B1) is a cofactor of pyruvate dehydrogenase, which plays a key role in aerobic glucose metabolism. Thiamine deficiency is common in patients with DKA, resulting in a shift to anaerobic metabolism and hyperlactatemia, which can prolong and complicate recovery. Therefore, we hypothesise that thiamine administration will improve aerobic metabolism and lead to faster resolution of acidemia in patients with DKA. METHODS AND ANALYSIS: In this single centre, double-blind, randomised, placebo-controlled, parallel group interventional trial, 100 patients admitted to the hospital with DKA will be randomised to receive either intravenous thiamine (200 mg in 50 mL 0.9% saline) or placebo (0.9% saline identical in appearance and volume) two times per day for 2 days. The primary outcome will be the change in bicarbonate level over 24 hours as compared between the two treatment groups. Additional secondary outcomes include the change over time in anion gap, lactate levels, oxygen consumption by circulating mononuclear cells, intensive care unit and hospital length-of-stay and hospital resource usage when comparing the two study arms. ETHICS AND DISSEMINATION: This trial was approved by the Committee on Clinical Investigations, the institutional review board of Beth Israel Deaconess Medical Center (protocol number 2018P000475). Findings will be disseminated through peer-reviewed publications and professional conference presentations. TRIAL REGISTRATION NUMBER: NCT03717896; clinicaltrials.gov.

Shenfu injection as treatment for critical illness: a narrative review of clinical trials.

Background and Objective: Shenfu injection (SFI) is a traditional herbal medicine derived from components of ginseng and aconite and is commonly used in China to treat a variety of conditions. Shenfu has been suggested to have beneficial effects in various critical illnesses, including heart failure, cardiac arrest, and septic shock. In recent years, there have been a number of studies reporting that SFI improves patient outcomes when used concurrently with other treatments, but its use has not been adopted outside of China. This narrative review explored the results of clinical trials that have tested SFI's efficacy in various critical illnesses. Methods: PubMed was searched for clinical trials, systematic reviews and meta-analyses published between 1990 and July 2022 relating to clinical trials using SFI in various critical illnesses. Systematic reviews and meta-analyses were included to enable inclusion of data from trials originally not published in English. The selected articles were then summarized in the following disease categories: heart failure, cardiac arrest, sepsis, and severe pulmonary disease. Key Content and Findings: Clinical trials testing SFI in heart failure, cardiac arrest, sepsis, and pulmonary disease were reviewed. The design, methodology, and key findings of each trial or meta-analysis are summarized and discussed. Key limitations were also highlighted and discussed. Overall, several clinical trials suggest SFI may hold therapeutic potential for the treatment of critical illness, however, additional research is likely still needed. Conclusions: Based on the current body of literature, further research-especially multi-center randomized, double-blind trials with detailed reporting of all methods and results according to international guidelines-is needed to evaluate whether SFI is a useful addition to existing treatments for these conditions.

2023 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates.

2023 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates.

OXYGEN CONSUMPTION AS AN EARLY WARNING SYSTEM IN THE CRITICALLY ILL.

ABSTRACT: Introduction: In this study, we assessed whether changes in oxygen consumption (VO 2 ) and other metabolic parameters could be used as an early warning system for detecting clinical deterioration in mechanically ventilated patients. Methods: This was a prospective cohort study of adult patients requiring mechanical ventilation between February 2016 and March 2019. We looked for changes in VO 2 , carbon dioxide production (VCO 2 ), respiratory quotient (RQ), and end-tidal carbon dioxide (EtCO 2 ), occurring prior to clinical deterioration. Clinical deterioration was predefined as a requirement of vasopressor, an increase in serum lactate by 20% where at least one value was above 3 mmol/L, or a decrease in hemoglobin by 20% in the 4 hours prior to clinical deterioration. Results A total of 141 patients were included. There were no detectable changes in VO 2 , VCO 2 , and EtCO 2 within the 4 hours prior to any clinical deterioration. RQ increased significantly within the 4 hours prior to an increase in lactate as compared with no increase in lactate, but there were no detectable changes prior to other clinical deteriorations. Conclusions RQ has the potential to be an early marker of tissue hypoperfusion or mitochondrial dysfunction. However, future studies are necessary to evaluate the use of RQ as a bedside monitor in critical care settings.

Temperature Management for Comatose Adult Survivors of Cardiac Arrest: A Science Advisory From the American Heart Association.

Targeted temperature management has been a cornerstone of post-cardiac arrest care for patients remaining unresponsive after return of spontaneous circulation since the initial trials in 2002 found that mild therapeutic hypothermia improves neurological outcome. The suggested temperature range expanded in 2015 in response to a large trial finding that outcomes were not better with treatment at 33° C compared with 36° C. In 2021, another large trial was published in which outcomes with temperature control at 33° C were not better than those of patients treated with a strategy of strict normothermia. On the basis of these new data, the International Liaison Committee on Resuscitation and other organizations have altered their treatment recommendations for temperature management after cardiac arrest. The new American Heart Association guidelines on this topic will be introduced in a 2023 focused update. To provide guidance to clinicians while this focused update is forthcoming, the American Heart Association's Emergency Cardiovascular Care Committee convened a writing group to review the TTM2 trial (Hypothermia Versus Normothermia After Out-of-Hospital Cardiac Arrest) in the context of other recent evidence and to present an opinion on how this trial may influence clinical practice. This science advisory was informed by review of the TTM2 trial, consideration of other recent influential studies, and discussion between cardiac arrest experts in the fields of cardiology, critical care, emergency medicine, and neurology. Conclusions presented in this advisory statement do not replace current guidelines but are intended to provide an expert opinion on novel literature that will be incorporated into future guidelines and suggest the opportunity for reassessment of current clinical practice.

Pulseless electrical activity and asystole during in-hospital cardiac arrest: Disentangling the 'nonshockable' rhythms.

BACKGROUND: Pulseless electrical activity (PEA) and asystole account for 81% of initial in-hospital cardiac arrest (IHCA) rhythms in the U.S.A. These "non-shockable" rhythms are often grouped together in resuscitation research and practice. We hypothesized that PEA and asystole are distinct initial IHCA rhythms with distinguishing features. METHODS: This was an observational cohort study using the prospectively collected nationwide Get With The Guidelines®-Resuscitation registry. Adult patients with an index IHCA and an initial rhythm of PEA or asystole between the years of 2006 and 2019 were included. Patients with PEA vs. asystole were compared with respect to pre-arrest characteristics, resuscitation practice, and outcomes. RESULTS: We identified 147,377 (64.9%) PEA and 79,720 (35.1%) asystolic IHCA. Asystole had more arrests in non-telemetry wards (20,530/147,377 [13.9%] PEA vs. 17,618/79,720 [22.1%] asystole). Asystole had 3% lower adjusted odds of ROSC (91,007 [61.8%] PEA vs. 44,957 [56.4%] asystole, aOR 0.97, 95%CI 0.96-0.97, P < 0.01); there was no statistically significant difference in survival to discharge (28,075 [19.1%] PEA vs. 14,891 [18.7%] asystole, aOR 1.00, 95%CI 1.00-1.01, P = 0.63). Duration of resuscitation for those without ROSC were shorter for asystole (29.8 [±22.5] minutes in PEA vs. 26.2 [±21.5] minutes in asystole, adjusted mean difference -3.05 95%CI -3.36--2.74, P < 0.01). INTERPRETATION: Patients suffering IHCA with an initial PEA rhythm had patient and resuscitation level differences from those with asystole. PEA arrests were more common in monitored settings and received longer resuscitations. Even though PEA was associated with higher rates of ROSC, there was no difference in survival to discharge.

Psychophysiologic Symptom Relief Therapy (PSRT) for Post-acute Sequelae of COVID-19.

Objective: To determine if psychophysiologic symptom relief therapy (PSRT) will reduce symptom burden in patients suffering from post-acute sequelae of COVID-19 (PASC) who had mild/moderate acute COVID-19 disease without objective evidence of organ injury. Patients and Methods: Twenty-three adults under the age of 60 with PASC for at least 12 weeks following COVID-19 infection were enrolled in an interventional cohort study conducted via virtual platform between May 18, 2021 and August 7, 2022. Participants received PSRT during a 13 week (approximately 44 hour) course. Participants were administered validated questionnaires at baseline and at 4, 8, and 13 weeks. The primary outcome was change in somatic symptoms from baseline, measured using the Somatic Symptom Scale-8 (SSS-8), at 13 weeks. Results: The median duration of symptoms prior to joining the study was 267 days (IQR: 144, 460). The mean SSS-8 score of the cohort decreased from baseline by 8.5 (95% CI: 5.7-11.4), 9.4 (95% CI: 6.9-11.9), and 10.9 (95% CI: 8.3-13.5) at 4, 8, and 13 weeks respectively (all p<.001). Participants also experienced statistically significant improvements across other secondary outcomes including changes in dyspnea, fatigue, and pain (all p<.001). Conclusion: PSRT may effectively decrease symptom burden in patients suffering from PASC without evidence of organ injury. The study was registered on clinicaltrials.gov (NCT04854772).

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).

Single-cell transcriptomics reveal a hyperacute cytokine and immune checkpoint axis after cardiac arrest in patients with poor neurological outcome.

BACKGROUND: Most patients hospitalized after cardiac arrest (CA) die because of neurological injury. The systemic inflammatory response after CA is associated with neurological injury and mortality but remains poorly defined. METHODS: We determine the innate immune network induced by clinical CA at single-cell resolution. FINDINGS: Immune cell states diverge as early as 6 h post-CA between patients with good or poor neurological outcomes 30 days after CA. Nectin-2+ monocyte and Tim-3+ natural killer (NK) cell subpopulations are associated with poor outcomes, and interactome analysis highlights their crosstalk via cytokines and immune checkpoints. Ex vivo studies of peripheral blood cells from CA patients demonstrate that immune checkpoints are a compensatory mechanism against inflammation after CA. Interferon γ (IFNγ)/interleukin-10 (IL-10) induced Nectin-2 on monocytes; in a negative feedback loop, Nectin-2 suppresses IFNγ production by NK cells. CONCLUSIONS: The initial hours after CA may represent a window for therapeutic intervention in the resolution of inflammation via immune checkpoints. FUNDING: This work was supported by funding from the American Heart Association, Brigham and Women's Hospital Department of Medicine, the Evergreen Innovation Fund, and the National Institutes of Health.

Calcium during cardiac arrest: A systematic review.

Aim: To perform a systematic review of administration of calcium compared to no calcium during cardiac arrest. Methods: The search included Medline (PubMed), Embase, Cochrane, Web of Science, and CINAHL Plus and was conducted on September 30, 2022. The population included adults and children in any setting with cardiac arrest. The outcomes included return of spontaneous circulation, survival, survival with favourable neurologic outcome to hospital discharge and 30 days or longer, and quality of life outcome. Cochrane Risk of Bias 2 and ROBINS-I were performed to assess risk of bias for controlled and observational studies, respectively. Results: The systematic review identified 4 studies on 3 randomised controlled trials on 554 adult out-of-hospital cardiac arrest (OHCA) patients, 8 observational studies on 2,731 adult cardiac arrest patients, and 3 observational studies on 17,449 paediatric in-hospital cardiac arrest (IHCA) patients. The randomised controlled and observational studies showed that routine calcium administration during cardiac arrest did not improve the outcome of adult OHCA or IHCA or paediatric IHCA. The risk of bias for the adult trials was low for one recent trial and high for two earlier trials, with randomization as the primary source of bias. The risk of bias for the individual observational studies was assessed to be critical due to confounding. The certainty of evidence was assessed to be moderate for adult OHCA and low for adult and paediatric IHCA. Heterogeneity across studies precluded any meaningful meta-analyses. Conclusions: This systematic review found no evidence that routine calcium administration improves the outcomes of cardiac arrest in adults or children.PROSPERO Registration: CRD42022349641.

Acute respiratory distress syndrome after in-hospital cardiac arrest.

OBJECTIVE: Acute respiratory distress syndrome (ARDS) after out-of-hospital cardiac arrest is common and associated with worse outcomes. In the hospital setting, there are many potential risk factors for post-arrest ARDS, such as aspiration, sepsis, and shock. ARDS after in-hospital cardiac arrest (IHCA) has not been characterized. METHODS: We performed a single-center retrospective study of adult patients admitted to the hospital between 2014-2018 who suffered an IHCA, achieved return of spontaneous circulation (ROSC), and were either already intubated at the time of arrest or within 2 hours of ROSC. Post-IHCA ARDS was defined as meeting the Berlin criteria in the first 3 days following ROSC. Outcomes included alive-and-ventilator free days across 28 days, hospital length-of-stay, hospital mortality, and hospital disposition. RESULTS: Of 203 patients included, 146 (71.9%) developed ARDS. In unadjusted analysis, patients with ARDS had fewer alive-and-ventilator-free days over 28 days with a median of 1 (IQR: 0, 21) day, compared to 18 (IQR: 0, 25) days in patients without ARDS (p = 0.03). However, this association was not significant after multivariate adjustment. There was also a non-significant longer hospital length-of-stay (15 [IQR: 7, 26] vs 10 [IQR: 7, 22] days, p = 0.25; median adjusted increase in ARDS patients: 3 [95% CI: -2 to 8] days, p = 0.27) and higher hospital mortality (53% vs 44%, p = 0.26; aOR 1.6 [95% CI: 0.8-2.9], p = 0.17) in the ARDS group. CONCLUSION: Among IHCA patients, almost three-quarters developed ARDS within 3 days of ROSC. As in out of hospital cardiac arrest, post-IHCA ARDS is common.

Thiamine Supplementation in Patients With Alcohol Use Disorder Presenting With Acute Critical Illness : A Nationwide Retrospective Observational Study.

BACKGROUND: Thiamine supplementation is recommended for patients with alcohol use disorder (AUD). The authors hypothesize that critically ill patients with AUD are commonly not given thiamine supplementation. OBJECTIVE: To describe thiamine supplementation incidence in patients with AUD and various critical illnesses (alcohol withdrawal, septic shock, traumatic brain injury [TBI], and diabetic ketoacidosis [DKA]) in the United States. DESIGN: Retrospective observational study. SETTING: Cerner Health Facts database. PATIENTS: Adult patients with a diagnosis of AUD who were admitted to the intensive care unit with alcohol withdrawal, septic shock, TBI, or DKA between 2010 and 2017. MEASUREMENTS: Incidence and predicted probability of thiamine supplementation in alcohol withdrawal and other critical illnesses. RESULTS: The study included 14 998 patients with AUD. Mean age was 52.2 years, 77% of participants were male, and in-hospital mortality was 9%. Overall, 7689 patients (51%) received thiamine supplementation. The incidence of thiamine supplementation was 59% for alcohol withdrawal, 26% for septic shock, 41% for TBI, and 24% for DKA. Most of those receiving thiamine (n = 3957 [52%]) received it within 12 hours of presentation in the emergency department. The predominant route of thiamine administration was enteral (n = 3119 [41%]). LIMITATION: Specific dosing and duration were not completely captured. CONCLUSION: Thiamine supplementation was not provided to almost half of all patients with AUD, raising a quality-of-care issue for this cohort. Supplementation was numerically less frequent in patients with septic shock, DKA, or TBI than in those with alcohol withdrawal. These data will be important for the design of quality improvement studies in critically ill patients with AUD. PRIMARY FUNDING SOURCE: National Institutes of Health.

Cardiopulmonary resuscitation and defibrillation for cardiac arrest when patients are in the prone position: A systematic review.

AIM: To perform a systematic review of cardiopulmonary resuscitation (CPR) and/or defibrillation in the prone position compared to turning the patient supine prior to starting CPR and/or defibrillation. METHODS: The search included PubMed, Embase, Web of Science, Cochrane, CINAHL Plus, and medRxiv on December 9, 2020. The population included adults and children in any setting with cardiac arrest while in the prone position. The outcomes included arterial blood pressure and end-tidal capnography during CPR, time to start CPR and defibrillation, return of spontaneous circulation, survival and survival with favorable neurologic outcome to discharge, 30 days or longer. ROBINS-I was performed to assess risk of bias for observational studies. RESULTS: The systematic review identified 29 case reports (32 individual cases), two prospective observational studies, and two simulation studies. The observational studies enrolled 17 patients who were declared dead in the supine position and reported higher mean systolic blood pressure from CPR in prone position (72 mmHg vs 48 mmHg, p < 0.005; 79 ± 20 mmHg vs 55 ± 20 mmHg, p = 0.028). One simulation study reported a faster time to defibrillation in the prone position. Return of spontaneous circulation, survival to discharge or 30 days were reported in adult and paediatric case reports. Critical risk of bias limited our ability to perform pooled analyses. CONCLUSIONS: We identified a limited number of observational studies and case reports comparing prone versus supine CPR and/or defibrillation. Prone CPR may be a reasonable option if immediate supination is difficult or poses unacceptable risks to the patient.

The Effect of a Single Dose of Thiamine on Oxygen Consumption in Patients Requiring Mechanical Ventilation for Acute Illness: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial.

Lower oxygen consumption is associated with worse survival in septic shock and in other forms of critical illness. No treatment that increases oxygen extraction, a key determinant of oxygen consumption, has been found. Thiamine is required for aerobic metabolism, and deficiency is common in the critically ill. OBJECTIVES: We evaluated the effect of thiamine on oxygen consumption in patients requiring mechanical ventilation for an acute illness. DESIGN: Phase II, randomized, double-blind, and placebo-controlled trial. SETTING AND PARTICIPANTS: ICUs in a tertiary care hospital in the United States. Patients admitted to the ICU and requiring mechanical ventilation were screened for enrollment. INTERVENTIONS: After enrollment, baseline measurement of oxygen consumption and baseline laboratories including lactate, central venous oxygen saturation, and pyruvate dehydrogenase, a single dose of 200 mg IV thiamine or placebo was administered. Oxygen consumption was then monitored for 6 additional hours and repeat laboratories were drawn at the end of the protocol. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in oxygen consumption. Analysis was done using linear regression with a first-order autoregressive variance-covariance structure to account for repeated measures within subjects. Secondary outcomes included change in lactate, central venous oxygen saturation, and pyruvate dehydrogenase quantity and activity. RESULTS: Sixty-seven patients were enrolled. After excluding 11 patients due to inadequate quantity or quality of oxygen consumption data, 56 patients were included. There was no difference in change in oxygen consumption in the 6 hours after study drug. Results for secondary outcomes were similarly negative. In the prespecified subgroup of 18 thiamine deficient patients, there was a difference in the two oxygen consumption curves (p = 0.006), although no difference in median oxygen consumption or area under the curve. CONCLUSIONS AND RELEVANCE: A single dose of IV thiamine did not alter oxygen consumption in patients requiring mechanical ventilation for acute illness.

A Trigger and Response System for Preventing Cardiac Arrest in the ICU.

Although patients in the ICU are closely monitored, some ICU cardiac arrest events may be preventable. In this study, we sought to reduce the rate of cardiac arrests occurring in the ICU through a quality improvement initiative. DESIGN: Prospective, observational study. SETTING: ICUs of a single tertiary care center. PATIENTS: Patients hospitalized in the ICUs between August 2017 and November 2019. INTERVENTIONS: A comprehensive trigger and response tool. MEASUREMENT AND MAIN RESULTS: Forty-three patients experienced an ICU cardiac arrest in the preintervention epoch (6.79 arrests per 1,000 discharges), and 59 patients experienced an ICU cardiac arrest in the intervention epoch (7.91 arrests per 1,000 discharges). In the intervention epoch, the clinical trigger and response tool was activated 106 times over a 1-year period, most commonly due to unexpected new/worsening hypotension. There was no step change in arrest rate (2.24 arrests/1,000 patients; 95% CI, -1.82 to 6.28; p = 0.28) or slope change (-0.02 slope of arrest rate; 95% CI, -0.14 to 0.11; p = 0.79) comparing the preintervention and intervention time epochs. Cardiac arrests in the preintervention epoch were more likely to be "potentially preventable" than that in the intervention epoch (25.6% vs 12.3%, respectively; odds ratio, 0.58; 95% CI, 0.20-0.88; p < 0.01). CONCLUSIONS: A novel trigger-and-response tool did not reduce the frequency of ICU cardiac arrest. Additional investigation is needed into the optimal approach for ICU cardiac arrest prevention.