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1.
Circulation ; 148(12): 982-988, 2023 09 19.
Article in English | MEDLINE | ID: mdl-37584195

ABSTRACT

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.


Subject(s)
Cardiopulmonary Resuscitation , Hypothermia, Induced , Out-of-Hospital Cardiac Arrest , Humans , Adult , Temperature , American Heart Association , Coma/therapy , Out-of-Hospital Cardiac Arrest/therapy , Survivors
2.
Circulation ; 148(24): e187-e280, 2023 12 12.
Article in English | MEDLINE | ID: mdl-37942682

ABSTRACT

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.


Subject(s)
Cardiopulmonary Resuscitation , Emergency Medical Services , Out-of-Hospital Cardiac Arrest , Premature Birth , Adult , Female , Child , Infant, Newborn , Humans , First Aid , Consensus , Out-of-Hospital Cardiac Arrest/diagnosis , Out-of-Hospital Cardiac Arrest/therapy
3.
Am J Respir Crit Care Med ; 208(5): 570-578, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37364280

ABSTRACT

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).


Subject(s)
Acute Kidney Injury , Shock, Septic , Humans , Thiamine/therapeutic use , Shock, Septic/complications , Shock, Septic/drug therapy , Creatinine , Kidney , Acute Kidney Injury/prevention & control , Acute Kidney Injury/complications
4.
Ann Intern Med ; 175(2): 191-197, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34871057

ABSTRACT

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.


Subject(s)
Alcoholism , Shock, Septic , Substance Withdrawal Syndrome , Adult , Alcoholism/complications , Critical Illness , Dietary Supplements , Humans , Male , Middle Aged , Retrospective Studies , Shock, Septic/drug therapy , Thiamine/therapeutic use
5.
Lancet ; 398(10307): 1257-1268, 2021 10 02.
Article in English | MEDLINE | ID: mdl-34454688

ABSTRACT

Cardiopulmonary resuscitation prioritises treatment for cardiac arrests from a primary cardiac cause, which make up the majority of treated cardiac arrests. Early chest compressions and, when indicated, a defibrillation shock from a bystander give the best chance of survival with a good neurological status. Cardiac arrest can also be caused by special circumstances, such as asphyxia, trauma, pulmonary embolism, accidental hypothermia, anaphylaxis, or COVID-19, and during pregnancy or perioperatively. Cardiac arrests in these circumstances represent an increasing proportion of all treated cardiac arrests, often have a preventable cause, and require additional interventions to correct a reversible cause during resuscitation. The evidence for treating these conditions is mostly of low or very low certainty and further studies are needed. Irrespective of the cause, treatments for cardiac arrest are time sensitive and most effective when given early-every minute counts.


Subject(s)
Anaphylaxis/therapy , Asphyxia/therapy , Cardiopulmonary Resuscitation/methods , Heart Arrest/therapy , Hypothermia/therapy , Pregnancy Complications, Cardiovascular/therapy , Pulmonary Embolism/therapy , Wounds and Injuries/therapy , Anaphylaxis/complications , Asphyxia/complications , COVID-19/complications , COVID-19/therapy , Electric Countershock , Female , Heart Arrest/etiology , Humans , Hypothermia/complications , Intraoperative Complications/therapy , Out-of-Hospital Cardiac Arrest/etiology , Out-of-Hospital Cardiac Arrest/therapy , Personal Protective Equipment , Postoperative Complications/therapy , Practice Guidelines as Topic , Pregnancy , Pulmonary Embolism/complications , Return of Spontaneous Circulation , SARS-CoV-2 , Wounds and Injuries/complications
6.
Circulation ; 142(16_suppl_2): S580-S604, 2020 10 20.
Article in English | MEDLINE | ID: mdl-33081524

ABSTRACT

Survival after cardiac arrest requires an integrated system of people, training, equipment, and organizations working together to achieve a common goal. Part 7 of the 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care focuses on systems of care, with an emphasis on elements that are relevant to a broad range of resuscitation situations. Previous systems of care guidelines have identified a Chain of Survival, beginning with prevention and early identification of cardiac arrest and proceeding through resuscitation to post-cardiac arrest care. This concept is reinforced by the addition of recovery as an important stage in cardiac arrest survival. Debriefing and other quality improvement strategies were previously mentioned and are now emphasized. Specific to out-of-hospital cardiac arrest, this Part contains recommendations about community initiatives to promote cardiac arrest recognition, cardiopulmonary resuscitation, public access defibrillation, mobile phone technologies to summon first responders, and an enhanced role for emergency telecommunicators. Germane to in-hospital cardiac arrest are recommendations about the recognition and stabilization of hospital patients at risk for developing cardiac arrest. This Part also includes recommendations about clinical debriefing, transport to specialized cardiac arrest centers, organ donation, and performance measurement across the continuum of resuscitation situations.


Subject(s)
Cardiology Service, Hospital/standards , Cardiology/standards , Cardiopulmonary Resuscitation/standards , Delivery of Health Care, Integrated/standards , Emergency Service, Hospital/standards , Heart Arrest/therapy , Patient Care Team/standards , Advanced Cardiac Life Support/standards , American Heart Association , Cardiopulmonary Resuscitation/adverse effects , Consensus , Cooperative Behavior , Emergencies , Evidence-Based Medicine/standards , Heart Arrest/diagnosis , Heart Arrest/physiopathology , Humans , Interdisciplinary Communication , Risk Factors , Treatment Outcome , United States
7.
Circulation ; 142(16_suppl_2): S358-S365, 2020 10 20.
Article in English | MEDLINE | ID: mdl-33081525

ABSTRACT

The 2020 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care is based on the extensive evidence evaluation performed in conjunction with the International Liaison Committee on Resuscitation. The Adult Basic and Advanced Life Support, Pediatric Basic and Advanced Life Support, Neonatal Life Support, Resuscitation Education Science, and Systems of Care Writing Groups drafted, reviewed, and approved recommendations, assigning to each recommendation a Class of Recommendation (ie, strength) and Level of Evidence (ie, quality). The 2020 Guidelines are organized in knowledge chunks that are grouped into discrete modules of information on specific topics or management issues. The 2020 Guidelines underwent blinded peer review by subject matter experts and were also reviewed and approved for publication by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. The AHA has rigorous conflict-of-interest policies and procedures to minimize the risk of bias or improper influence during development of the guidelines. Anyone involved in any part of the guideline development process disclosed all commercial relationships and other potential conflicts of interest.


Subject(s)
Cardiology Service, Hospital/standards , Cardiology/standards , Cardiopulmonary Resuscitation/standards , Emergency Service, Hospital/standards , Heart Arrest/therapy , Advanced Cardiac Life Support/standards , American Heart Association , Cardiopulmonary Resuscitation/adverse effects , Consensus , Emergencies , Evidence-Based Medicine/standards , Heart Arrest/diagnosis , Heart Arrest/physiopathology , Humans , Risk Factors , Treatment Outcome , United States
8.
Circulation ; 142(16_suppl_1): S92-S139, 2020 10 20.
Article in English | MEDLINE | ID: mdl-33084390

ABSTRACT

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations for advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.


Subject(s)
Cardiopulmonary Resuscitation/standards , Cardiovascular Diseases/therapy , Emergency Medical Services/standards , Life Support Care/standards , Adult , Defibrillators , Heart Arrest/therapy , Humans , Vasoconstrictor Agents/administration & dosage , Ventricular Fibrillation/therapy
9.
J Gen Intern Med ; 36(6): 1689-1695, 2021 06.
Article in English | MEDLINE | ID: mdl-33738759

ABSTRACT

BACKGROUND: Widespread reports suggest the characteristics and disease course of coronavirus disease 2019 (COVID-19) and influenza differ, yet detailed comparisons of their clinical manifestations are lacking. OBJECTIVE: Comparison of the epidemiology and clinical characteristics of COVID-19 patients during the pandemic with those of influenza patients in previous influenza seasons at the same hospital DESIGN: Admission rates, clinical measurements, and clinical outcomes from confirmed COVID-19 cases between March 1 and April 30, 2020, were compared with those from confirmed influenza cases in the previous five influenza seasons (8 months each) beginning September 1, 2014. SETTING: Large tertiary care teaching hospital in Boston, MA PARTICIPANTS: Laboratory-confirmed COVID-19 and influenza inpatients MEASUREMENTS: Patient demographics and medical history, mortality, incidence and duration of mechanical ventilation, incidences of vasopressor support and renal replacement therapy, and hospital and intensive care admissions. RESULTS: Data was abstracted from medical records of 1052 influenza patients and 582 COVID-19 patients. An average of 210 hospital admissions for influenza occurred per 8-month season compared to 582 COVID-19 admissions over 2 months. The median weekly number of COVID-19 patients requiring mechanical ventilation was 17 (IQR: 4, 34) compared to a weekly median of 1 (IQR: 0, 2) influenza patient (p=0.001). COVID-19 patients were significantly more likely to require mechanical ventilation (31% vs 8%) and had significantly higher mortality (20% vs. 3%; p<0.001 for all). Relatively more COVID-19 patients on mechanical ventilation lacked pre-existing conditions compared with mechanically ventilated influenza patients (25% vs 4%, p<0.001). Pneumonia/ARDS secondary to the virus was the predominant cause of mechanical ventilation in COVID-19 patients (94%) as opposed to influenza (56%). LIMITATION: This is a single-center study which could limit generalization. CONCLUSION: COVID-19 resulted in more weekly hospitalizations, higher morbidity, and higher mortality than influenza at the same hospital.


Subject(s)
COVID-19 , Influenza, Human , Hospitalization , Humans , Influenza, Human/epidemiology , Influenza, Human/therapy , Pandemics , SARS-CoV-2 , Tertiary Care Centers
10.
Curr Opin Crit Care ; 27(6): 637-641, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34535001

ABSTRACT

PURPOSE OF REVIEW: This review discusses potential reasons why many recent large trials in advanced cardiac life support have failed to demonstrate a difference in outcomes and suggests some points for consideration in planning future trials. RECENT FINDINGS: The ARREST trial, a small controlled trial studying the effect of intra-arrest extracorporeal membrane oxygenation (ECMO, or E-CPR) on survival and functional outcome in patients with refractory ventricular fibrillation cardiac arrest, was stopped after 30 patients for benefit. This stands in contrast to several recent trials enrolling up to several thousand patients and finding no difference. Three ways in which the ARREST trial approach differed from that of other recent trials, and how those differences may contribute to the possibility of detecting the benefit of an intervention, are discussed. SUMMARY: Refining our ability to select patients with potential to benefit from an intervention, providing those interventions earlier, and tailoring the specifics of an intervention to the individual patient all may be important in design of cardiac arrest trials, as illustrated by the large effect seen in the ARREST trial.


Subject(s)
Cardiopulmonary Resuscitation , Extracorporeal Membrane Oxygenation , Heart Arrest , Heart Arrest/therapy , Humans
11.
Circulation ; 140(24): e881-e894, 2019 12 10.
Article in English | MEDLINE | ID: mdl-31722552

ABSTRACT

The fundamentals of cardiac resuscitation include the immediate provision of high-quality cardiopulmonary resuscitation combined with rapid defibrillation (as appropriate). These mainstays of therapy set the groundwork for other possible interventions such as medications, advanced airways, extracorporeal cardiopulmonary resuscitation, and post-cardiac arrest care, including targeted temperature management, cardiorespiratory support, and percutaneous coronary intervention. Since 2015, an increased number of studies have been published evaluating some of these interventions, requiring a reassessment of their use and impact on survival from cardiac arrest. This 2019 focused update to the American Heart Association advanced cardiovascular life support guidelines summarizes the most recent published evidence for and recommendations on the use of advanced airways, vasopressors, and extracorporeal cardiopulmonary resuscitation during cardiac arrest. It includes revised recommendations for all 3 areas, including the choice of advanced airway devices and strategies during cardiac arrest (eg, bag-mask ventilation, supraglottic airway, or endotracheal intubation), the training and retraining required, the administration of standard-dose epinephrine, and the decisions involved in the application of extracorporeal cardiopulmonary resuscitation and its potential impact on cardiac arrest survival.


Subject(s)
Cardiopulmonary Resuscitation/standards , Emergency Medical Services/standards , Emergency Service, Hospital/standards , Guidelines as Topic , Heart Arrest/therapy , American Heart Association , Humans , Respiration, Artificial/standards , United States
12.
Circulation ; 140(24): e895-e903, 2019 12 10.
Article in English | MEDLINE | ID: mdl-31722563

ABSTRACT

Survival after out-of-hospital cardiac arrest requires an integrated system of care (chain of survival) between the community elements responding to an event and the healthcare professionals who continue to care for and transport the patient for appropriate interventions. As a result of the dynamic nature of the prehospital setting, coordination and communication can be challenging, and identification of methods to optimize care is essential. This 2019 focused update to the American Heart Association systems of care guidelines summarizes the most recent published evidence for and recommendations on the use of dispatcher-assisted cardiopulmonary resuscitation and cardiac arrest centers. This article includes the revised recommendations that emergency dispatch centers should offer and instruct bystanders in cardiopulmonary resuscitation during out-of-hospital cardiac arrest and that a regionalized approach to post-cardiac arrest care may be reasonable when comprehensive postarrest care is not available at local facilities.


Subject(s)
Cardiopulmonary Resuscitation/standards , Emergency Medical Services/standards , Emergency Service, Hospital/standards , Out-of-Hospital Cardiac Arrest/therapy , American Heart Association , Emergency Treatment/standards , Humans , Out-of-Hospital Cardiac Arrest/mortality , United States
13.
Circulation ; 140(24): e826-e880, 2019 12 10.
Article in English | MEDLINE | ID: mdl-31722543

ABSTRACT

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the 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. The task forces also listed priority knowledge gaps for further research.


Subject(s)
Cardiopulmonary Resuscitation/standards , Emergency Medical Services/standards , Emergency Treatment , Hypothermia, Induced/standards , Child , Emergency Service, Hospital/standards , Emergency Treatment/standards , Humans , Out-of-Hospital Cardiac Arrest/therapy
14.
Curr Opin Crit Care ; 26(6): 617-621, 2020 12.
Article in English | MEDLINE | ID: mdl-33109950

ABSTRACT

PURPOSE OF REVIEW: Cardiac arrest is one of the most challenging disease processes to study with clinical trials due to the emergent and unpredictable nature of these events and complexity of the patient population. In recent years, there has been a major push to complete more large, multicentre trials. In many cases, however, there remains little certainty on what treatments are most efficacious, in spite of the recent increase in evidence. This review was undertaken to address some of the unique barriers to address answering research questions in cardiac arrest with clinical trials. RECENT FINDINGS: Multiple examples of trials that have failed to reach definitive conclusions, and potential reasons for this, are discussed. SUMMARY: Trials on multiple major cardiac arrest interventions, including temperature management, drugs during cardiopulmonary resuscitation (CPR) and airway management, now have high-quality randomized trials, but significant questions on efficacy and best practices remain. Common pitfalls and reasons for this are explored, including heterogeneity of patients and providers, variability in exact interventions studied, delay in starting research interventions and lack of consistency across systems in decision making around appropriateness for resuscitation.


Subject(s)
Cardiopulmonary Resuscitation , Heart Arrest , Out-of-Hospital Cardiac Arrest , Airway Management , Heart Arrest/therapy , Humans , Out-of-Hospital Cardiac Arrest/therapy
15.
Crit Care ; 24(1): 398, 2020 07 08.
Article in English | MEDLINE | ID: mdl-32641148

ABSTRACT

BACKGROUND: Prescribing pharmacologic therapies for critically ill patients requires a careful balancing of risks and benefits. Defining, monitoring, and reporting harms that occur in clinical trials conducted in critically ill populations, however, is challenging given that the natural history of most critical illnesses includes progressive multiple organ failure and death. In this study, we assessed harms reporting in clinical trials performed in critically ill populations. METHODS: Randomized, non-industry-sponsored, human clinical trials of pharmacologic interventions in adult critically ill populations published between 2015 and 2018 in high-impact journals were included in this systematic review. Harms data, adherence to Consolidated Standards of Reporting Trials (CONSORT) harms reporting guidelines, and restrictions on harms reporting were recorded. RESULTS: A total of 707 abstracts were screened with 40 trials ultimately being included in the analysis. Included trials represent 28,636 randomized patients with a median of 292 (IQR 100-546) patients per trial. The most common disease states were general critical care (33%) and sepsis (28%). Of 18 included CONSORT items, the median number met was 12 (IQR 9, 14). The most commonly missed items were adverse event (AE) severity grading definitions and AE attribution (relationship of AE to study drug), which were only reported in 35 and 38% of manuscripts, respectively. Half of the manuscripts (48%) provided definitions for recorded AEs. There were 5 studies investigating the effects of corticosteroids in sepsis, with the number of AEs reported per analyzed patient ranging from 0.01 to 1.89. AE definitions in studies of similar/equivalent interventions often varied substantially. Study protocols were available for 30/40 (75%) of studies, with 13 (43%) of those not providing any guidance regarding AE attribution. CONCLUSIONS: Randomized trials of pharmacologic interventions conducted in critically ill populations and published in high impact journals often fail to adequately describe AE definitions, severity, attribution, and collection procedures. Among trials of similar interventions in comparable populations, variation in AE collection and reporting procedures is substantial. These factors may limit a clinician's ability to accurately balance the potential benefits and harms of an intervention.


Subject(s)
Drug-Related Side Effects and Adverse Reactions/diagnosis , Pharmacological Phenomena , Randomized Controlled Trials as Topic/statistics & numerical data , Adrenal Cortex Hormones/adverse effects , Antipsychotic Agents/adverse effects , Critical Illness/epidemiology , Critical Illness/therapy , Dexmedetomidine/adverse effects , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/etiology , Haloperidol/adverse effects , Humans , Hypnotics and Sedatives/adverse effects , Randomized Controlled Trials as Topic/standards
16.
JAMA ; 324(7): 642-650, 2020 Aug 18.
Article in English | MEDLINE | ID: mdl-32809003

ABSTRACT

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.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Ascorbic Acid/therapeutic use , Multiple Organ Failure/prevention & control , Shock, Septic/drug therapy , Thiamine/therapeutic use , Adrenal Cortex Hormones/adverse effects , Adult , Aged , Ascorbic Acid/adverse effects , Cross Infection , Drug Therapy, Combination , Female , Humans , Hyperglycemia/chemically induced , Hypernatremia/chemically induced , Male , Middle Aged , Multiple Organ Failure/etiology , Organ Dysfunction Scores , Proportional Hazards Models , Shock, Septic/complications , Thiamine/adverse effects , Treatment Failure
17.
Circulation ; 138(23): e740-e749, 2018 12 04.
Article in English | MEDLINE | ID: mdl-30571262

ABSTRACT

Antiarrhythmic medications are commonly administered during and immediately after a ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. However, it is unclear whether these medications improve patient outcomes. This 2018 American Heart Association focused update on advanced cardiovascular life support guidelines summarizes the most recent published evidence for and recommendations on the use of antiarrhythmic drugs during and immediately after shock-refractory ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. This article includes the revised recommendation that providers may consider either amiodarone or lidocaine to treat shock-refractory ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest.


Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Cardiopulmonary Resuscitation/methods , Heart Arrest/drug therapy , American Heart Association , Amiodarone/therapeutic use , Emergency Medical Services , Heart Arrest/etiology , Humans , Lidocaine/therapeutic use , Magnesium/therapeutic use , Tachycardia, Ventricular/complications , Tachycardia, Ventricular/pathology , United States , Ventricular Fibrillation/complications , Ventricular Fibrillation/pathology
18.
Circulation ; 138(23): e714-e730, 2018 12 04.
Article in English | MEDLINE | ID: mdl-30571263

ABSTRACT

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the second annual summary of International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations that includes the most recent cardiopulmonary resuscitation science reviewed by the International Liaison Committee on Resuscitation. This summary addresses the role of antiarrhythmic drugs in adults and children and includes the Advanced Life Support Task Force and Pediatric Task Force consensus statements, which summarize the most recent published evidence and an assessment of the quality of the evidence based on Grading of Recommendations, Assessment, Development, and Evaluation criteria. The statements include consensus treatment recommendations approved by members of the relevant task forces. Insights into the deliberations of each task force are provided in the Values and Preferences and Task Force Insights sections. Finally, the task force members have listed the top knowledge gaps for further research.


Subject(s)
Cardiopulmonary Resuscitation , Out-of-Hospital Cardiac Arrest/therapy , Amiodarone/therapeutic use , Anti-Arrhythmia Agents/therapeutic use , Consensus , Emergency Medical Services , Humans , Lidocaine/therapeutic use , Magnesium/therapeutic use , Out-of-Hospital Cardiac Arrest/drug therapy
19.
Crit Care Med ; 47(2): 194-200, 2019 02.
Article in English | MEDLINE | ID: mdl-30407950

ABSTRACT

OBJECTIVES: Clinical providers have access to a number of pharmacologic agents during in-hospital cardiac arrest. Few studies have explored medication administration patterns during in-hospital cardiac arrest. Herein, we examine trends in use of pharmacologic interventions during in-hospital cardiac arrest both over time and with respect to the American Heart Association Advanced Cardiac Life Support guideline updates. DESIGN: Observational cohort study. SETTING: Hospitals contributing data to the American Heart Association Get With The Guidelines-Resuscitation database between 2001 and 2016. PATIENTS: Adult in-hospital cardiac arrest patients. INTERVENTIONS: The percentage of patients receiving epinephrine, vasopressin, amiodarone, lidocaine, atropine, bicarbonate, calcium, magnesium, and dextrose each year were calculated in patients with shockable and nonshockable initial rhythms. Hierarchical multivariable logistic regression was used to determine the annual adjusted odds of medication administration. An interrupted time series analysis was performed to assess change in atropine use after the 2010 American Heart Association guideline update. MEASUREMENTS AND MAIN RESULTS: A total of 268,031 index in-hospital cardiac arrests were included. As compared to 2001, the adjusted odds ratio of receiving each medication in 2016 were epinephrine (adjusted odds ratio, 1.5; 95% CI, 1.3-1.8), vasopressin (adjusted odds ratio, 1.5; 95% CI, 1.1-2.1), amiodarone (adjusted odds ratio, 3.4; 95% CI, 2.9-4.0), lidocaine (adjusted odds ratio, 0.2; 95% CI, 0.2-0.2), atropine (adjusted odds ratio, 0.07; 95% CI, 0.06-0.08), bicarbonate (adjusted odds ratio, 2.0; 95% CI, 1.8-2.3), calcium (adjusted odds ratio, 2.0; 95% CI, 1.7-2.3), magnesium (adjusted odds ratio, 2.2; 95% CI, 1.9-2.7; p < 0.0001), and dextrose (adjusted odds ratio, 2.8; 95% CI, 2.3-3.4). Following the 2010 American Heart Association guideline update, there was a downward step change in the intercept and slope change in atropine use (p < 0.0001). CONCLUSIONS: Prescribing patterns during in-hospital cardiac arrest have changed significantly over time. Changes to American Heart Association Advanced Cardiac Life Support guidelines have had a rapid and substantial effect on the use of a number of commonly used in-hospital cardiac arrest medications.


Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Heart Arrest/drug therapy , Vasoconstrictor Agents/therapeutic use , Aged , Amiodarone/therapeutic use , Atropine/therapeutic use , Bicarbonates/therapeutic use , Calcium/therapeutic use , Epinephrine/therapeutic use , Female , Glucose/therapeutic use , Guideline Adherence/statistics & numerical data , Hospitalization , Humans , Lidocaine/therapeutic use , Logistic Models , Magnesium/therapeutic use , Male , Middle Aged , Odds Ratio , Practice Guidelines as Topic , Practice Patterns, Physicians'/statistics & numerical data , Vasopressins/therapeutic use
20.
JAMA ; 321(12): 1200-1210, 2019 Mar 26.
Article in English | MEDLINE | ID: mdl-30912843

ABSTRACT

IMPORTANCE: In-hospital cardiac arrest is common and associated with a high mortality rate. Despite this, in-hospital cardiac arrest has received little attention compared with other high-risk cardiovascular conditions, such as stroke, myocardial infarction, and out-of-hospital cardiac arrest. OBSERVATIONS: In-hospital cardiac arrest occurs in over 290 000 adults each year in the United States. Cohort data from the United States indicate that the mean age of patients with in-hospital cardiac arrest is 66 years, 58% are men, and the presenting rhythm is most often (81%) nonshockable (ie, asystole or pulseless electrical activity). The cause of the cardiac arrest is most often cardiac (50%-60%), followed by respiratory insufficiency (15%-40%). Efforts to prevent in-hospital cardiac arrest require both a system for identifying deteriorating patients and an appropriate interventional response (eg, rapid response teams). The key elements of treatment during cardiac arrest include chest compressions, ventilation, early defibrillation, when applicable, and immediate attention to potentially reversible causes, such as hyperkalemia or hypoxia. There is limited evidence to support more advanced treatments. Post-cardiac arrest care is focused on identification and treatment of the underlying cause, hemodynamic and respiratory support, and potentially employing neuroprotective strategies (eg, targeted temperature management). Although multiple individual factors are associated with outcomes (eg, age, initial rhythm, duration of the cardiac arrest), a multifaceted approach considering both potential for neurological recovery and ongoing multiorgan failure is warranted for prognostication and clinical decision-making in the post-cardiac arrest period. Withdrawal of care in the absence of definite prognostic signs both during and after cardiac arrest should be avoided. Hospitals are encouraged to participate in national quality-improvement initiatives. CONCLUSIONS AND RELEVANCE: An estimated 290 000 in-hospital cardiac arrests occur each year in the United States. However, there is limited evidence to support clinical decision making. An increased awareness with regard to optimizing clinical care and new research might improve outcomes.


Subject(s)
Electric Countershock , Heart Arrest/therapy , Hospitalization , Resuscitation , Adult , Aged , Clinical Decision-Making , Female , Heart Arrest/epidemiology , Heart Arrest/etiology , Heart Arrest/mortality , Humans , Male , Practice Guidelines as Topic , Prognosis , Quality Improvement , Resuscitation/standards , Survival Rate , United States/epidemiology
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