Cardiac arrest (CA) is a sudden and devastating disease process resulting in more deaths in the United States than many cancers, metabolic diseases, and even car accidents. Despite such a heavy ...mortality burden, effective treatments have remained elusive. The past century has been productive in establishing the guidelines for resuscitation, known as cardiopulmonary resuscitation (CPR), as well as developing a scientific field whose aim is to elucidate the underlying mechanisms of CA and develop therapies to save lives. CPR has been successful in reinitiating the heart after arrest, enabling a survival rate of approximately 10% in out‐of‐hospital CA. Although current advanced resuscitation methods, including hypothermia and extracorporeal membrane oxygenation, have improved survival in some patients, they are unlikely to significantly improve the national survival rate any further without a paradigm shift. Such a change is possible with sustained efforts in the basic and clinical sciences of resuscitation and their implementation. This review seeks to discuss the current landscape in resuscitation medicine—how we got here and where we are going.
Although current advanced resuscitation methods for cardiac arrest, including hypothermia and extracorporeal membrane oxygenation, have improved survival in some patients, they are unlikely to significantly improve the national survival rate any further without a paradigm shift. Such a change is possible with sustained efforts in the basic and clinical sciences of resuscitation and their implementation. This review discusses the current landscape in resuscitation medicine—how we got here and where we are going.
There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).
To describe the clinical ...characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system.
Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates.
Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission.
Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected.
A total of 5700 patients were included (median age, 63 years interquartile range {IQR}, 52-75; range, 0-107 years; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/min, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years IQR, 56-78; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. As of April 4, 2020, for patients requiring mechanical ventilation (n = 1151, 20.2%), 38 (3.3%) were discharged alive, 282 (24.5%) died, and 831 (72.2%) remained in hospital. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years IQR, 54-75), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1).
This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.
The modern treatment of cardiac arrest is an increasingly complex medical procedure with a rapidly changing array of therapeutic approaches designed to restore life to victims of sudden death. The 2 ...primary goals of providing artificial circulation and defibrillation to halt ventricular fibrillation remain of paramount importance for saving lives. They have undergone significant improvements in technology and dissemination into the community subsequent to their establishment 60 years ago. The evolution of artificial circulation includes efforts to optimize manual cardiopulmonary resuscitation, external mechanical cardiopulmonary resuscitation devices designed to augment circulation, and may soon advance further into the rapid deployment of specially designed internal emergency cardiopulmonary bypass devices. The development of defibrillation technologies has progressed from bulky internal defibrillators paddles applied directly to the heart, to manually controlled external defibrillators, to automatic external defibrillators that can now be obtained over-the-counter for widespread use in the community or home. But the modern treatment of cardiac arrest now involves more than merely providing circulation and defibrillation. As suggested by a 3-phase model of treatment, newer approaches targeting patients who have had a more prolonged cardiac arrest include treatment of the metabolic phase of cardiac arrest with therapeutic hypothermia, agents to treat or prevent reperfusion injury, new strategies specifically focused on pulseless electric activity, which is the presenting rhythm in at least one third of cardiac arrests, and aggressive post resuscitation care. There are discoveries at the cellular and molecular level about ischemia and reperfusion pathobiology that may be translated into future new therapies. On the near horizon is the combination of advanced cardiopulmonary bypass plus a cocktail of multiple agents targeted at restoration of normal metabolism and prevention of reperfusion injury, as this holds the promise of restoring life to many patients for whom our current therapies fail.
The vagus nerve plays an important role in maintaining physiological homeostasis, which includes reflex pathways that regulate cardiac function. The link between vagus nerve activity and the ...high-frequency component of heart rate variability (HRV) has been well established, correlating with vagal tone. Recently, vagus nerve stimulation (VNS) has been investigated as a therapeutic for a multitude of diseases, such as treatment-resistant epilepsy, rheumatoid arthritis, Crohn's disease, and asthma. Because of the vagus nerve's innervation of the heart, VNS has been identified as a potential therapy for cardiovascular disorders, such as cardiac arrest, acute myocardial infarction, and stroke. Here, we review the current state of preclinical and clinical studies, as well as the potential application of VNS in relation to the cardiovascular system.
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.
The incidence and incidence over time of cardiac arrest in hospitalized patients is unknown. We sought to estimate the event rate and temporal trends of adult inhospital cardiac arrest treated with a ...resuscitation response.
Three approaches were used to estimate the inhospital cardiac arrest event rate. First approach: calculate the inhospital cardiac arrest event rate at hospitals (n = 433) in the Get With The Guidelines-Resuscitation registry, years 2003-2007, and multiply this by U.S. annual bed days. Second approach: use the Get With The Guidelines-Resuscitation inhospital cardiac arrest event rate to develop a regression model (including hospital demographic, geographic, and organizational factors), and use the model coefficients to calculate predicted event rates for acute care hospitals (n = 5445) responding to the American Hospital Association survey. Third approach: classify acute care hospitals into groups based on academic, urban, and bed size characteristics, and determine the average event rate for Get With The Guidelines-Resuscitation hospitals in each group, and use weighted averages to calculate the national inhospital cardiac arrest rate. Annual event rates were calculated to estimate temporal trends.
Get With The Guidelines-Resuscitation registry.
Adult inhospital cardiac arrest with a resuscitation response.
The mean adult treated inhospital cardiac arrest event rate at Get With The Guidelines-Resuscitation hospitals was 0.92/1000 bed days (interquartile range 0.58 to 1.2/1000). In hospitals (n = 150) contributing data for all years of the study period, the event rate increased from 2003 to 2007. With 2.09 million annual U.S. bed days, we estimated 192,000 inhospital cardiac arrests throughout the United States annually. Based on the regression model, extrapolating Get With The Guidelines-Resuscitation hospitals to hospitals participating in the American Hospital Association survey projected 211,000 annual inhospital cardiac arrests. Using weighted averages projected 209,000 annual U.S. inhospital cardiac arrests.
There are approximately 200,000 treated cardiac arrests among U.S. hospitalized patients annually, and this rate may be increasing. This is important for understanding the burden of inhospital cardiac arrest and developing strategies to improve care for hospitalized patients.
Historically, hypothermia was induced prior to surgery to enable procedures with prolonged ischemia, such as open heart surgery and organ transplant. Within the past decade, the efficacy of ...hypothermia to treat emergency cases of ongoing ischemia such as stroke, myocardial infarction, and cardiac arrest has been studied. Although the exact role of ischemia/reperfusion is unclear clinically, hypothermia holds significant promise for improving outcomes for patients suffering from reperfusion after ischemia. Research has elucidated two distinct windows of opportunity for clinical use of hypothermia. In the early intra-ischemia window, hypothermia modulates abnormal cellular free radical production, poor calcium management, and poor pH management. In the more delayed post-reperfusion window, hypothermia modulates the downstream necrotic, apoptotic, and inflammatory pathways that cause delayed cell death. Improved cooling and monitoring technologies are required to realize the full potential of this therapy. Herein we discuss the current state of clinical practice, clinical trials, recommendations for cooling, and ongoing research on therapeutic hypothermia.
The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock.
To determine whether the combination of ascorbic acid, corticosteroids, ...and thiamine attenuates organ injury in patients with septic shock.
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.
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).
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.
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).
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.
ClinicalTrials.gov Identifier: NCT03389555.
Increasingly complex behavior of free radicals and reactive oxygen species (ROS) are noted within biological systems. Classically free radicals and ROS were considered injurious, however current ...mechanisms describe both protective and deleterious effects. A burst of ROS has been well described with the first moments of reperfusion and is associated with injury. However ROS can also be protective as signal preconditioning protection and induce stress responses that lead to survival. ROS generation is appreciated to occur during ischemia despite the low oxygen tension, from a likely mitochondria source, and ROS-induced ROS release may amplify its signal. The burst of ROS seen during reperfusion may originate from a different cellular source than during ischemia and is not yet fully identified. ROS and cellular redox conditions regulate a large number of vital pathways (energy metabolism, survival/stress responses, apoptosis, inflammatory response, oxygen sensing, etc). While cellular systems may demonstrate reperfusion injury, whole organ and animal models continue to report contradictory results on reperfusion injury and the role of antioxidants as a therapy. Collectively, these data may offer insight into why clinical trials of antioxidants have had such mixed and mostly negative results. Future antioxidant therapies are likely to be effective but they must become: more specific for site of action, not have deleterious effects on other signaling pathways, be targeted to a specific reactive oxygen species or cellular compartment, and be "time sensitive" so they deliver the correct therapy at precisely the correct time in ischemia and reperfusion.
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