Emergency research without prior consent in the United States, Canada, European Union and United Kingdom: How regulatory differences affect study design and implementation in cardiac arrest trials.

Aim: A major barrier to performing cardiac arrest trials is the requirement for prospective informed consent, which is often infeasible during individual medical emergencies. In an effort to improve outcomes, some governments have adopted legislation permitting research without prior consent (RWPC) in these circumstances. We aimed to outline key differences between legislation in four Western locations and explore the effects of these differences on trial design and implementation in cardiac arrest research. Data sources: We performed a narrative review of RWPC legislation in the United States (US), Canada, the European Union (EU) and the United Kingdom (UK). Results: The primary criteria required to perform RWPC was similar across locations: the study must involve an individual medical emergency during which neither the prospective subject nor their authorized representative can provide informed consent. The US regulations were unique in their requirements for performing Community Consultation and Public Disclosure in the communities in which the research takes place. Another major difference was the requirement for consent for ongoing participation in Canada, the EU and the UK, while only notification of enrollment and the opportunity to discontinue participation are required in the US. Additionally, only Canada and the EU explicitly state that the subject or their representative may request withdrawal of their data. Conclusion: Regulations governing RWPC in the US, Canada, the EU and the UK have similar goals and protections for vulnerable populations during medical emergencies. Differences in the qualifying criteria and implementation procedures exist across locations and may affect study design.

Community consultation in the pediatric intensive care unit for an exception from informed consent Trial: A survey of patient caregivers.

Aim: To explore perspectives of families in the pediatric intensive care unit (PICU) about an emergency interventional trial on peri-arrest bolus epinephrine for acute hypotension using Exception From Informed Consent (EFIC). Methods: We performed face-to-face interviews with families whose children were hospitalized in the PICU. A research team member provided an educational presentation about the planned trial and administered a survey with open- and closed-ended items. Analyses included descriptive statistics for quantitative data and thematic analysis for qualitative data. Results: Sixty-seven participants contributed to 60 survey responses (53 individuals and 7 families for whom 2 family members participated). Most participants answered favorably toward the planned trial: 55/58 (95%) reported that the trial seemed "somewhat" or "very important"; 52/57 (91%) felt the use of EFIC was "somewhat" or "completely acceptable"; and 43/58 (74%) said they would be "somewhat" or "very likely" to allow their child to participate. Five themes emerged supporting participation in the planned trial: 1) trust in the clinical team; 2) familiarity with the study intervention (epinephrine); 3) study protocol being similar to standard care; 4) informed consent during an emergency was not feasible; and 5) importance of research. Barriers to potential participation included requests for additional time to decide about participating and misconceptions about study elements, especially eligibility. Conclusions: Families of PICU patients generally supported plans for an emergency interventional trial using EFIC. Future inpatient EFIC studies may benefit from highlighting the themes identified here in their educational materials.

In-Hospital Cardiac Arrest in Adult Patients Admitted to a Quaternary Children's Center.

OBJECTIVE: This study aimed to describe baseline and event characteristics and outcomes for adult patients who experience in-hospital cardiac arrest (IHCA) in a quaternary children's hospital and compare IHCA outcomes in younger (18-24 years) versus older (≥25 years) adults. We hypothesized that the rate of survival to hospital discharge would be lower in the older adult group. METHODS: We performed a retrospective single-center cohort study of inpatient areas of a quaternary children's center. Adult patients (≥18 years of age) with an index pulseless IHCA requiring at least 1 minute of cardiopulmonary resuscitation or defibrillation were included. RESULTS: Thirty-three events met the inclusion criteria with a median patient age of 23.9 years (interquartile range, 20.2-33.3 years). Twenty-one (64%) patients had congenital heart disease, and 25 (76%) patients had comorbidities involving ≥2 organ systems. The most common prearrest interventions were invasive mechanical ventilation (76%) and vasoactive infusions (55%). Seventeen patients (52%) survived to hospital discharge.Survival to discharge was lower in patients 25 years or older compared with patients aged 18 to 24 years old (3 of 15 [20%] vs 14 of 18 [78%], respectively; P = 0.002). CONCLUSIONS: The majority of adult patients with IHCA in our pediatric hospital had preexisting multisystem comorbidities, the most common of which was congenital heart disease. Overall survival to discharge after IHCA was 52%, similar to that reported for the general pediatric population. Survival to discharge was significantly lower in the subgroup of patients 25 years or older when compared with those between the ages of 18 and 24 years.

Characteristics and Outcomes of Cardiac Arrest in Adult Patients Admitted to Pediatric Services: A Descriptive Analysis of the American Heart Association's Get With The Guidelines-Resuscitation Data.

OBJECTIVES: Differences between adult and pediatric in-hospital cardiac arrest (IHCA) are well-described. Although most adults are cared for on adult services, pediatric services often admit adults, particularly those with chronic conditions. The objective of this study is to describe IHCA in adults admitted to pediatric services. DESIGN: Retrospective cohort analysis from the American Heart Association's Get With The Guidelines-Resuscitation registry of a subpopulation of adults with IHCA while admitted to pediatric services. Multivariable logistic regression was used to evaluate adjusted survival outcomes and compare outcomes between age groups (18-21, 22-25, and ≥26 yr old). SETTING: Hospitals contributing to the Get With The Guidelines-Resuscitation registry. PATIENTS: Adult-aged patients (≥ 18 yr) with an index pulseless IHCA while admitted to a pediatric service from 2000 to 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 491 adult IHCAs were recorded on pediatric services at 17 sites, during the 19 years of review, and these events represented 0.1% of all adult IHCAs. In total, 221 cases met inclusion criteria with 139 events excluded due to an initial rhythm of bradycardia with poor perfusion. Median patient age was 22 years (interquartile range, 19-28 yr). Ninety-eight percent of patients had at least one pre-existing condition. Return of spontaneous circulation occurred in 63% of events and 30% of the patients survived to discharge. All age groups had similar rates of survival to discharge (range 26-37%; p = 0.37), and survival did not change over the study period (range 26-37%; p = 0.23 for adjusted survival to discharge). CONCLUSIONS: In this cohort of adults with IHCA while admitted to a pediatric service, we failed to find an association between survival outcomes and age. Additional research is needed to better understand resuscitation in this population.

Trends in Disease Severity Among Critically Ill Children With Severe Acute Respiratory Syndrome Coronavirus 2: A Retrospective Multicenter Cohort Study in the United States.

OBJECTIVES: To describe trends in critical illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children over the course of the COVID-19 pandemic. We hypothesized that PICU admission rates were higher in the Omicron period compared with the original outbreak but that fewer patients needed endotracheal intubation. DESIGN: Retrospective cohort study. SETTING: This study took place in nine U.S. PICUs over 3 weeks in January 2022 (Omicron period) compared with 3 weeks in March 2020 (original period). PATIENTS: Patients less than or equal to 21 years old who screened positive for SARS-CoV-2 infection by polymerase chain reaction or hospital-based rapid antigen test and were admitted to a PICU or intermediate care unit were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 267 patients (239 Omicron and 28 original) were reviewed. Forty-five patients in the Omicron cohort had incidental SARS-CoV-2 and were excluded from analysis. The Omicron cohort patients were younger compared with the original cohort patients (median [interquartile range], 6 yr [1.3-13.3 yr] vs 14 yr [8.3-17.3 yr]; p = 0.001). The Omicron period, compared with the original period, was associated with an average increase in COVID-19-related PICU admissions of 13 patients per institution (95% CI, 6-36; p = 0.008), which represents a seven-fold increase in the absolute number admissions. We failed to identify an association between cohort period (Omicron vs original) and odds of intubation (odds ratio, 0.7; 95% CI, 0.3-1.7). However, we cannot exclude the possibility of up to 70% reduction in intubation. CONCLUSIONS: COVID-19-related PICU admissions were seven times higher in the Omicron wave compared with the original outbreak. We could not exclude the possibility of up to 70% reduction in use of intubation in the Omicron versus original epoch, which may represent differences in PICU/hospital admission policy in the later period, or pattern of disease, or possibly the impact of vaccination.

Peri-arrest bolus epinephrine practices amongst pediatric resuscitation experts.

AIM: To describe current practices of peri-arrest bolus epinephrine use amongst pediatric resuscitation experts in a multinational survey. METHODS: A 9-question survey was developed and electronically distributed to pediatric critical care physicians who are site investigators for the Pediatric Resuscitation Quality Collaborative (pediRES-Q) network. Institutional demographics were collected through the American Hospital Association 2018 Annual Survey and linked to responses. Descriptive statistics were used to characterize closed-ended responses, and qualitative content analysis to analyze open-ended responses. RESULTS: Of the 63 collaborative members invited to participate, 49 (78%) responded, representing 35 institutions in 9 countries. Forty-six of the 49 respondents (94%) reported that they would consider using peri-arrest bolus epinephrine during critical situations in patients not requiring cardiopulmonary resuscitation. Initial dosing strategies ranged from 0.1mcg/kg to 10mcg/kg, with the most commonly reported initial dose of 1mcg/kg by 25 of the 37 (68%) respondents who answered this question. Three of the 49 (6%) participants indicated that they would generally avoid using peri-arrest bolus epinephrine, citing lack of evidence to support its use. CONCLUSIONS: In this multinational survey of pediatric resuscitation experts, endorsement of peri-arrest bolus epinephrine use was nearly universal, though a few clinicians cited lack of evidence to support this practice. There was a 100-fold difference in the range of initial weight-based doses reported, as well as a minority of clinicians who reported using non-weight-based dosing. Further research is needed to determine best practices, standardization of initial dosing, clinical factors that may warrant dosing modifications and associations with clinically important outcomes.

Trends over time in drug administration during pediatric in-hospital cardiac arrest in the United States.

AIMS: To describe trends in pediatric in-hospital cardiac arrest drug administration and to assess temporal associations of the Pediatric Advanced Life Support (PALS) guideline changes with drug usage. METHODS: Pediatric patients <18 years old with in-hospital cardiac arrest recorded in the American Heart Association Get With The Guidelines-Resuscitation database between 2002 and 2018 were included. The annual adjusted odds of receiving each intra-arrest medication was determined. The association between changes in the PALS Guidelines and medication use over time was assessed interrupted time series analyses. RESULTS: A total of 6107 patients were analyzed. The adjusted odds of receiving lidocaine (0.33; 95% CI, 0.18, 0.61; p < 0.001), atropine (0.19; 95% CI 0.12, 0.30; p < 0.001) and bicarbonate (0.54; 95% CI 0.35, 0.86; p = 0.009) were lower in 2018 compared to 2002. For lidocaine, there were no significant changes in the step (-2.1%; 95% CI, -5.9%, 1.6%; p = 0.27) after the 2010 or 2015 (Step: -1.5%; 95% CI, -8.0%, 5.0; p = 0.65) guideline releases. There were no significant changes in the step for bicarbonate (-2.3%; 95% CI, -7.6%, 3.0%; p = 0.39) after the 2010 updates. For atropine, there was a downward step change after the 2010 guideline release (-5.9%; 95% CI, -10.5%, -1.3%; p = 0.01). CONCLUSIONS: Changes to the PALS guidelines for lidocaine and bicarbonate were not temporally associated with acute changes in the use of these medications; however, better alignment with these updates was observed over time. A minor update to the language surrounding atropine in the PALS text was associated with a modest acute change in the observed use of atropine. Future studies exploring other factors that influence prescribers in pediatric IHCA are needed.

Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units.

IMPORTANCE: The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs). OBJECTIVE: To provide an early description and characterization of COVID-19 infection in North American PICUs, focusing on mode of presentation, presence of comorbidities, severity of disease, therapeutic interventions, clinical trajectory, and early outcomes. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included children positive for COVID-19 admitted to 46 North American PICUs between March 14 and April 3, 2020. with follow-up to April 10, 2020. MAIN OUTCOMES AND MEASURES: Prehospital characteristics, clinical trajectory, and hospital outcomes of children admitted to PICUs with confirmed COVID-19 infection. RESULTS: Of the 48 children with COVID-19 admitted to participating PICUs, 25 (52%) were male, and the median (range) age was 13 (4.2-16.6) years. Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation. Eleven patients (23%) had failure of 2 or more organ systems. Extracorporeal membrane oxygenation was required for 1 patient (2%). Targeted therapies were used in 28 patients (61%), with hydroxychloroquine being the most commonly used agent either alone (11 patients) or in combination (10 patients). At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively. CONCLUSIONS AND RELEVANCE: This early report describes the burden of COVID-19 infection in North American PICUs and confirms that severe illness in children is significant but far less frequent than in adults. Prehospital comorbidities appear to be an important factor in children. These preliminary observations provide an important platform for larger and more extensive studies of children with COVID-19 infection.

Pediatric Massive and Submassive Pulmonary Embolism: A Single-Center Experience.

OBJECTIVES: To describe and compare patient and event characteristics and outcomes in pediatric massive pulmonary embolism (MPE) and submassive pulmonary embolism (SMPE). METHODS: A retrospective cohort study at a quaternary-care pediatric hospital was conducted. Patients age <19 years with MPE (acute pulmonary embolism [PE] with cardiac arrest, hypotension, or compensated shock due to PE) or SMPE (right ventricular strain due to acute PE) between January 1997 and June 2019 were included. RESULTS: Thirty-three patients were identified, including 9 (27%) patients with MPE and 24 (73%) patients with SMPE. The most commonly identified risk factor was use of oral contraceptive pills in 16 (49%) patients. Six (18%) patients died, 3 (9%) of which were PE-related deaths. Before PE, patients with MPE were more likely to be hospitalized (89% vs 13%, P < .001), have major comorbidities (89% vs 25%, P = .002), central venous catheters (67% vs 17%, P = .01), critical illness (56% vs 8%, P = .009), immobility (67% vs 13%, P = .005), and be postoperative (44% vs 4%, P = .01). MPE patients were also more likely to die before discharge (56% vs 4%, P = .003). Both groups were equally likely to have primary reperfusion attempts (78% of MPE versus 67% of SMPE, P = .69). CONCLUSIONS: Pediatric MPE and SMPE differed in presentation, comorbidities, and risk factors, many of which were associated with hospitalization status. Pediatric-specific studies are warranted to determine risk assessment and management strategies, which may differ from adult guidelines.

Epinephrine in children receiving cardiopulmonary resuscitation for bradycardia with poor perfusion.

AIM: To determine whether the use of epinephrine in pediatric patients receiving cardiopulmonary resuscitation for bradycardia and poor perfusion was associated with improved clinical outcomes. METHODS: Using the Get With The Guidelines-Resuscitation registry, we included pediatric patients (≤18 years) who received in-hospital cardiopulmonary resuscitation for bradycardia with poor perfusion (non-pulseless event) between January 2000 and December 2018. Time-dependent propensity score matching was used to match patients receiving epinephrine within the first 10 min of resuscitation to patients at risk of receiving epinephrine within the same minute. RESULTS: In the full cohort, 55% of patients were male and 39% were neonates. A higher number of patients receiving epinephrine required vasopressors and mechanical ventilation prior to the event compared to those not receiving epinephrine. A total of 3528 patients who received epinephrine were matched to 3528 patients at risk of receiving epinephrine based on the propensity score. Epinephrine was associated with decreased survival to hospital discharge (RR, 0.79 [95% CI, 0.74-0.85]; p < 0.001), return of spontaneous circulation (RR, 0.94 [95% CI, 0,91-0.96]; p < 0.001), 24-h survival (RR, 0.85 [95% CI, 0.81-0.90]; p < 0.001), and favorable neurological outcome (RR, 0.76 [95% CI, 0.68-0.84]; p < 0.001). Epinephrine was also associated with an increased risk of progression to pulselessness (RR, 1.17 [95% CI, 1.06-1.28]; p < 0.001). CONCLUSION: In children receiving cardiopulmonary resuscitation for bradycardia with poor perfusion, epinephrine was associated with worse outcomes, although the study does not eliminate the potential for confounding.

Lidocaine versus amiodarone for pediatric in-hospital cardiac arrest: An observational study.

BACKGROUND: Lidocaine and amiodarone are both included in the pediatric cardiac arrest guidelines as treatments of shock-refractory ventricular fibrillation or pulseless ventricular tachycardia, although there is limited evidence to support this recommendation. METHODS: In this cohort study from the Get With The Guidelines - Resuscitation registry, we included pediatric patients (≤18 years) with an in-hospital cardiac arrest between 2000 and 2018, who presented with an initial or subsequent shockable rhythm (ventricular fibrillation and pulseless ventricular tachycardia). Patients receiving amiodarone were matched to patients receiving lidocaine based on a propensity score, calculated from multiple patient, event, and hospital characteristics. RESULTS: A total of 365 patients were available for the analysis, of which 180 (49%) patients were matched on the propensity score. The median age in the raw cohort was 6 (quartiles, 0.5-14) years, 164 (45%) patients were female, and 238 (65%) patients received an antiarrhythmic for an initial shockable rhythm. In the matched cohort, there were no statistically significant differences between patients receiving lidocaine compared to amiodarone in return of spontaneous circulation (RR, 0.99 [95%CI, 0.82-1.19]; p = 0.88), survival to 24 h (RR, 1.02 [95%CI, 0.76-1.38]; p = 0.88), survival to hospital discharge (RR, 1.01 [95%CI, 0.63-1.63]; p = 0.96), and favorable neurological outcome (RR, 0.65 [95%CI, 0.35-1.21]; p = 0.17). The results remained consistent in multiple sensitivity analyses. CONCLUSIONS: In children with cardiac arrest receiving antiarrhythmics for a shockable rhythm, there was no significant difference in clinical outcomes between those receiving lidocaine compared to amiodarone.

Effects of digging by a native and introduced ecosystem engineer on soil physical and chemical properties in temperate grassy woodland.

Temperate grasslands and woodlands are the focus of extensive restoration efforts worldwide. Reintroduction of locally extinct soil-foraging and burrowing animals has been suggested as a means to restore soil function in these ecosystems. Yet little is known about the physical and chemical effects of digging on soil over time and how these effects differ between species of digging animal, vegetation types or ecosystems. We compared foraging pits of a native reintroduced marsupial, the eastern bettong (Bettongia gaimardi) and that of the exotic European rabbit (Oryctolagus cuniculus). We simulated pits of these animals and measured pit dimensions and soil chemical properties over a period of 2 years. We showed that bettong and rabbit pits differed in their morphology and longevity, and that pits had a strong moderating effect on soil surface temperatures. Over 75% of the simulated pits were still visible after 2 years, and bettong pits infilled faster than rabbit pits. Bettong pits reduced diurnal temperature range by up to 25 °C compared to the soil surface. We did not find any effects of digging on soil chemistry that were consistent across vegetation types, between bettong and rabbit pits, and with time since digging, which is contrary to studies conducted in arid biomes. Our findings show that animal foraging pits in temperate ecosystems cause physical alteration of the soil surface and microclimatic conditions rather than nutrient changes often observed in arid areas.

Trends in Survival After Pediatric In-Hospital Cardiac Arrest in the United States.

BACKGROUND: Cardiac arrest in hospitalized children is associated with poor outcomes, but no contemporary study has reported whether the trends in survival have changed over time. In this study, we examined temporal trends in survival for pediatric patients with an in-hospital pulseless cardiac arrest and pediatric patients with a nonpulseless cardiopulmonary resuscitation event from 2000 to 2018. METHODS: This was an observational study of hospitalized pediatric patients (≤18 years of age) who received cardiopulmonary resuscitation from January 2000 to December 2018 and were included in the Get With The Guidelines-Resuscitation registry, a United States-based in-hospital cardiac arrest registry. The primary outcome was survival to hospital discharge, and the secondary outcome was return of spontaneous circulation (binary outcomes). Generalized estimation equations were used to obtain unadjusted trends in outcomes over time. Separate analyses were performed for patients with a pulseless cardiac arrest and patients with a nonpulseless event (bradycardia with poor perfusion) requiring cardiopulmonary resuscitation. A subgroup analysis was conducted for shockable versus nonshockable initial rhythms in pulseless events. RESULTS: A total of 7433 patients with a pulseless cardiac arrest and 5751 patients with a nonpulseless event were included for the analyses. For pulseless cardiac arrests, survival was 19% (95% CI, 11%-29%) in 2000 and 38% (95% CI, 34%-43%) in 2018, with an absolute change of 0.67% (95% CI, 0.40%-0.95%; P<0.001) per year, although the increase in survival appeared to stagnate following 2010. Return of spontaneous circulation also increased over time, with an absolute change of 0.83% (95% CI, 0.53%-1.14%; P<0.001) per year. We found no interaction between survival to hospital discharge and the initial rhythm. For nonpulseless events, survival was 57% (95% CI, 39%-75%) in 2000 and 66% (95% CI, 61%-72%) in 2018, with an absolute change of 0.80% (95% CI, 0.32%-1.27%; P=0.001) per year. CONCLUSIONS: Survival has improved for pediatric events requiring cardiopulmonary resuscitation in the United States, with a 19% absolute increase in survival for in-hospital pulseless cardiac arrests and a 9% absolute increase in survival for nonpulseless events between 2000 and 2018. However, survival from pulseless cardiac arrests appeared to have reached a plateau following 2010.

Annual Incidence of Adult and Pediatric In-Hospital Cardiac Arrest in the United States

BACKGROUND: Previous incidence estimates may no longer reflect the current public health burden of cardiac arrest in hospitalized adult and pediatric patients across the United States. The aim of this study was to estimate the contemporary annual incidence of in-hospital cardiac arrest in adults and children across the United States and to describe trends in incidence between 2008 and 2017. METHODS AND RESULTS: Using the Get With The Guidelines­ Resuscitation registry, we developed a negative binomial regression model to estimate the incidence of index pulseless in-hospital cardiac arrest based on hospital-level characteristics. The model was used to predict the number of in-hospital cardiac arrests in all US hospitals, using data from the American Hospital Association Annual Survey. We performed separate analyses for adult (≥18 years) and pediatric (<18 years) cardiac arrests. Additional analyses were performed for recurrent cardiac arrests and pediatric patients requiring cardiopulmonary resuscitation for poor perfusion (nonpulseless events). The average annual incidence of in-hospital cardiac arrest in the United States was estimated at 292 000 (95% prediction interval, 217 600­503 500) adult and 15 200 pediatric cases, of which 7100 (95% prediction interval, 4400­9900) cases were pulseless cardiac arrests and 8100 (95% prediction interval, 4700­11 500) cases were nonpulseless events. The rate of adult cardiac arrests increased over time, while pediatric events remained more stable. When including both index and recurrent inhospital cardiac arrests, the average annual incidence was estimated at 357 900 (95% prediction interval, 247 100­598 400) adult and 19 900 pediatric cases, of which 8300 (95% prediction interval, 4900­11 200) cases were pulseless cardiac arrests and 11 600 (95% prediction interval, 6400­16 700) cases were nonpulseless events. CONCLUSIONS: There are ≈292 000 adult in-hospital cardiac arrests and 15 200 pediatric in-hospital events in the United States each year. This study provides contemporary estimates of the public health burden of cardiac arrest among hospitalized patients.

Trends Over Time in Drug Administration During Adult In-Hospital Cardiac Arrest.

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.

Physiology-directed cardiopulmonary resuscitation: advances in precision monitoring during cardiac arrest.

PURPOSE OF REVIEW: We review the recent advances in physiologic monitoring during cardiac arrest and offer an evidence-based framework for prioritizing physiologic targets during cardiopulmonary resuscitation (CPR). RECENT FINDINGS: Current CPR guidelines recommend a uniform approach for all patients in cardiac arrest, but newer data support a precision strategy that uses the individual patient's physiology to guide resuscitation. Coronary perfusion pressure and arterial DBP are associated with survival outcomes in recent animal and human studies. End-tidal carbon dioxide is a reasonable noninvasive alternative, but may be inferior to invasive hemodynamic endpoints. Cerebral oximetry and cardiac ultrasound are emerging physiologic indicators of CPR effectiveness. SUMMARY: Physiologic monitoring can and should be used to deliver precision CPR whenever possible and may improve outcomes after cardiac arrest.

Preliminary observations in systemic oxygen consumption during targeted temperature management after cardiac arrest.

AIM: Limited data suggests low oxygen consumption (VO2), driven by mitochondrial injury, is associated with mortality after cardiac arrest. Due to the challenges of measurement in the critically ill, post-arrest metabolism remains poorly characterized. We monitored VO2, carbon dioxide production (VCO2) and the respiratory quotient (RQ) in post-arrest patients and explored associations with outcome. METHODS: Using a gas exchange monitor, we measured continuous VO2 and VCO2 in post- arrest patients treated with targeted temperature management. We used area under the curve and medians over time to evaluate the association between VO2, VCO2, RQ and the VO2:lactate ratio with survival. RESULTS: In 17 patients, VO2 in the first 12 h after return of spontaneous circulation (ROSC) was associated with survival (median in survivors 3.35 mL/kg/min [2.98,3.88] vs. non-survivors 2.61 mL/kg/min [2.21,2.94], p = .039). This did not persist over 24 h. The VO2:lactate ratio was associated with survival (median in survivors 1.4 [IQR: 1.1,1.7] vs. non-survivors 0.8 [IQR: 0.6,1.2] p < 0.001). Median RQ was 0.66 (IQR 0.63,0.70) and 71% of RQ measurements were <0.7. Patients with initial RQ < 0.7 had 17% survival versus 64% with initial RQ > 0.7 (p = .131). VCO2 was not associated with survival. CONCLUSIONS: There was a significant association between VO2 and mortality in the first 12 h after ROSC, but not over 24 h. Lower VO2: lactate ratio was associated with mortality. A large percentage of patients had RQs below physiologic norms. Further research is needed to explore whether these parameters could have true prognostic value or be a potential treatment target.