Improving Outcomes After Post-Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation.

This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.

Organ Donation After Out-of-Hospital Cardiac Arrest: A Scientific Statement From the International Liaison Committee on Resuscitation.

AIM OF THE REVIEW: Improving rates of organ donation among patients with out-of-hospital cardiac arrest who do not survive is an opportunity to save countless lives. The objectives of this scientific statement were to do the following: define the opportunity for organ donation among patients with out-of-hospital cardiac arrest; identify challenges and opportunities associated with organ donation by patients with cardiac arrest; identify strategies, including a generic protocol for organ donation after cardiac arrest, to increase the rate and consistency of organ donation from this population; and provide rationale for including organ donation as a key clinical outcome for all future cardiac arrest clinical trials and registries. METHODS: The scope of this International Liaison Committee on Resuscitation scientific statement was approved by the International Liaison Committee on Resuscitation board and the American Heart Association, posted on ILCOR.org for public comment, and then assigned by section to primary and secondary authors. A unique literature search was completed and updated for each section. RESULTS: There are a number of defining pathways for patients with out-of-hospital cardiac arrest to become organ donors; however, modifications in the Maastricht classification system need to be made to correctly identify these donors and to report outcomes with consistency. Suggested modifications to the minimum data set for reporting cardiac arrests will increase reporting of organ donation as an important resuscitation outcome. There are a number of challenges with implementing uncontrolled donation after cardiac death protocols, and the greatest impediment is the lack of legislation in most countries to mandate organ donation as the default option. Extracorporeal cardiopulmonary resuscitation has the potential to increase organ donation rates, but more research is needed to derive neuroprognostication rules to guide clinical decision-making about when to stop extracorporeal cardiopulmonary resuscitation and to evaluate cost-effectiveness. CONCLUSIONS: All health systems should develop, implement, and evaluate protocols designed to optimize organ donation opportunities for patients who have an out-of-hospital cardiac arrest and failed attempts at resuscitation.

Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial.

BACKGROUND: The International Liaison Committee on Resuscitation has called for a randomised trial of delivery to a cardiac arrest centre. We aimed to assess whether expedited delivery to a cardiac arrest centre compared with current standard of care following resuscitated cardiac arrest reduces deaths. METHODS: ARREST is a prospective, parallel, multicentre, open-label, randomised superiority trial. Patients (aged ≥18 years) with return of spontaneous circulation following out-of-hospital cardiac arrest without ST elevation were randomly assigned (1:1) at the scene of their cardiac arrest by London Ambulance Service staff using a secure online randomisation system to expedited delivery to the cardiac catheter laboratory at one of seven cardiac arrest centres or standard of care with delivery to the geographically closest emergency department at one of 32 hospitals in London, UK. Masking of the ambulance staff who delivered the interventions and those reporting treatment outcomes in hospital was not possible. The primary outcome was all-cause mortality at 30 days, analysed in the intention-to-treat (ITT) population excluding those with unknown mortality status. Safety outcomes were analysed in the ITT population. The trial was prospectively registered with the International Standard Randomised Controlled Trials Registry, 96585404. FINDINGS: Between Jan 15, 2018, and Dec 1, 2022, 862 patients were enrolled, of whom 431 (50%) were randomly assigned to a cardiac arrest centre and 431 (50%) to standard care. 20 participants withdrew from the cardiac arrest centre group and 19 from the standard care group, due to lack of consent or unknown mortality status, leaving 411 participants in the cardiac arrest centre group and 412 in the standard care group for the primary analysis. Of 822 participants for whom data were available, 560 (68%) were male and 262 (32%) were female. The primary endpoint of 30-day mortality occurred in 258 (63%) of 411 participants in the cardiac arrest centre group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival 1·00, 95% CI 0·90-1·11; p=0·96). Eight (2%) of 414 patients in the cardiac arrest centre group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention. INTERPRETATION: In adult patients without ST elevation, transfer to a cardiac arrest centre following resuscitated cardiac arrest in the community did not reduce deaths. FUNDING: British Heart Foundation.

Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial): A Multicenter, Randomized, Controlled Clinical Trial.

Rationale: Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in coronavirus disease (COVID-19)-related acute respiratory distress syndrome (ARDS). Objectives: We investigated the safety and efficacy of ORBCEL-C (CD362 [cluster of differentiation 362]-enriched, umbilical cord-derived MSCs) in COVID-19-related ARDS. Methods: In this multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial (NCT03042143), patients with moderate to severe COVID-19-related ARDS were randomized to receive ORBCEL-C (400 million cells) or placebo (Plasma-Lyte 148). The primary safety and efficacy outcomes were the incidence of serious adverse events and oxygenation index at Day 7, respectively. Secondary outcomes included respiratory compliance, driving pressure, PaO2:FiO2 ratio, and Sequential Organ Failure Assessment score. Clinical outcomes relating to duration of ventilation, lengths of ICU and hospital stays, and mortality were collected. Long-term follow-up included diagnosis of interstitial lung disease at 1 year and significant medical events and mortality at 2 years. Transcriptomic analysis was performed on whole blood at Days 0, 4, and 7. Measurements and Main Results: Sixty participants were recruited (final analysis: n = 30 received ORBCEL-C, n = 29 received placebo; 1 participant in the placebo group withdrew consent). Six serious adverse events occurred in the ORBCEL-C group and three in the placebo group (risk ratio, 2.9 [95% confidence interval, 0.6-13.2]; P = 0.25). Day 7 mean (SD) oxygenation index did not differ (ORBCEL-C, 98.3 [57.2] cm H2O/kPa; placebo, 96.6 [67.3] cm H2O/kPa). There were no differences in secondary surrogate outcomes or in mortality at Day 28, Day 90, 1 year, or 2 years. There was no difference in the prevalence of interstitial lung disease at 1 year or significant medical events up to 2 years. ORBCEL-C modulated the peripheral blood transcriptome. Conclusion: ORBCEL-C MSCs were safe in subjects with moderate to severe COVID-19-related ARDS but did not improve surrogates of pulmonary organ dysfunction.

Systematic analysis of approaches used in cardiac arrest trials to inform relatives about trial enrolment of non-surviving patients.

BACKGROUND: The recruitment of patients to emergency research studies without the requirement for prior informed consent has furthered the conduct of randomised studies in cardiac arrest. Frameworks enabling this vary around the world depending on local legal or ethical requirements. When an enrolled patient does not survive, researchers may take one of three approaches to inform relatives of their enrolment: a direct (active) approach, providing information indirectly (passively) and inviting relatives to seek further information if they choose, or providing no information about the trial (no attempt). Previous studies have described experiences of US researchers' active approach but there is little known about approaches elsewhere.We aimed to conduct a structured investigation of methods used in cardiac arrest trials to provide information about trial enrolment to relatives of non-surviving patients. METHODS: We systematically searched trial registries to identify randomised clinical trials that recruited cardiac arrest patients. Trials were eligible for inclusion if they recruited adults during cardiac arrest (or within 1 hour of return of spontaneous circulation) between 2010 and 2022 (in the decade prior to study conception). We extracted data from trial registries and, where relevant, published papers and protocols. Investigators were contacted and asked to describe the style, rationale and timing of approach to relatives of non-surviving patients. We present descriptive statistics. RESULTS: Our trial registry search identified 710 unique trials, of which 108 were eligible for inclusion. We obtained information from investigators for 64 (62%) trials. Approximately equal numbers of trials attempted to actively inform relatives of non-survivors (n=28 (44% (95% CI; 31% to 57%))), or made no attempt (n=25 (39% (95% CI; 27% to 52%))). The remaining studies provided general information about the trial to relatives but did not actively inform them (n=11 (17% (95% CI; 8% to 29%))). CONCLUSIONS: There is wide variability in the approach taken to informing relatives of non-surviving patients enrolled in cardiac arrest randomised clinical trials.

Optimizing Outcomes After Out-of-Hospital Cardiac Arrest With Innovative Approaches to Public-Access Defibrillation: A Scientific Statement From the International Liaison Committee on Resuscitation.

Out-of-hospital cardiac arrest is a global public health issue experienced by ≈3.8 million people annually. Only 8% to 12% survive to hospital discharge. Early defibrillation of shockable rhythms is associated with improved survival, but ensuring timely access to defibrillators has been a significant challenge. To date, the development of public-access defibrillation programs, involving the deployment of automated external defibrillators into the public space, has been the main strategy to address this challenge. Public-access defibrillator programs have been associated with improved outcomes for out-of-hospital cardiac arrest; however, the devices are used in <3% of episodes of out-of-hospital cardiac arrest. This scientific statement was commissioned by the International Liaison Committee on Resuscitation with 3 objectives: (1) identify known barriers to public-access defibrillator use and early defibrillation, (2) discuss established and novel strategies to address those barriers, and (3) identify high-priority knowledge gaps for future research to address. The writing group undertook systematic searches of the literature to inform this statement. Innovative strategies were identified that relate to enhanced public outreach, behavior change approaches, optimization of static public-access defibrillator deployment and housing, evolved automated external defibrillator technology and functionality, improved integration of public-access defibrillation with existing emergency dispatch protocols, and exploration of novel automated external defibrillator delivery vectors. We provide evidence- and consensus-based policy suggestions to enhance public-access defibrillation and guidance for future research in this area.

Traumatic cardiac arrest.

PURPOSE OF REVIEW: This review considers the latest evidence relating to the epidemiology and outcomes, treatment guidelines, diagnostic and therapeutic interventions in traumatic cardiac arrest. RECENT FINDINGS: There is variation in the incidence and outcomes of traumatic cardiac arrest which is influenced in part by case definitions. Irrespective of case definitions outcomes from traumatic cardiac arrest are typically worse than those seen from cardiac arrest due to medical causes but not so poor as to consider that treatment is futile. Clinical guidelines focus on the prompt treatment of reversible causes, although evidence that this improves outcomes is limited. Point of care ultrasound to assist with the identification of reversible causes should be limited to experienced operators where there is thought to be a high likelihood of a reversible cause being present. Care should be taken to minimize interruptions in chest compressions during scanning. There is little recent evidence to support specific therapeutic interventions. The role of Resuscitative Endovascular Balloon Occlusion of the Aorta during traumatic cardiac arrest remains to be determined in on-going research. CONCLUSION: Trauma related cardiac arrest differs from cardiac arrest due to medical causes. Whilst the core principles of treatment are similar, a higher priority is placed on identifying and treating reversible causes.

Improving vasopressor use in cardiac arrest.

The Chain of Survival highlights the effectiveness of early recognition of cardiac arrest and call for help, early cardiopulmonary resuscitation and early defibrillation. Most patients, however, remain in cardiac arrest despite these interventions. Drug treatments, particularly the use of vasopressors, have been included in resuscitation algorithms since their inception. This narrative review describes the current evidence base for vasopressors and reports that adrenaline (1 mg) is highly effective at achieving return of spontaneous circulation (number needed to treat 4) but is less effective on long-term outcomes (survival to 30 days, number needed to treat 111) with uncertain effects on survival with a favourable neurological outcome. Randomised trials evaluating vasopressin, either as an alternative to or in addition to adrenaline, and high-dose adrenaline have failed to find evidence of improved long-term outcomes. There is a need for future trials to evaluate the interaction between steroids and vasopressin. Evidence for other vasopressors (e.g. noradrenaline, phenylephedrine) is insufficient to support or refute their use. The use of intravenous calcium chloride as a routine intervention in out of hospital cardiac arrest is not associated with benefit and may cause harm. The optimal route for vascular access between peripheral intravenous versus intraosseous routes is currently the subject of two large randomised trials. Intracardiac, endobronchial, and intramuscular routes are not recommended. Central venous administration should be limited to patients where an existing central venous catheter is in situ and patent.

Prehospital early warning scores for adults with suspected sepsis: retrospective diagnostic cohort study.

BACKGROUND: Ambulance services need to identify and prioritise patients with sepsis for early hospital assessment. We aimed to determine the accuracy of early warning scores alongside paramedic diagnostic impression to identify sepsis that required urgent treatment. METHODS: We undertook a retrospective diagnostic cohort study involving adult emergency medical cases transported to Sheffield Teaching Hospitals ED by Yorkshire Ambulance Service in 2019. We used routine ambulance service data to calculate 21 early warning scores and categorise paramedic diagnostic impressions as sepsis, infection, non-specific presentation or other presentation. We linked cases to hospital records and identified those meeting the sepsis-3 definition who received urgent hospital treatment for sepsis (reference standard). Analysis determined the accuracy of strategies that combined early warning scores at varying thresholds for positivity with paramedic diagnostic impression. RESULTS: We linked 12 870/24 955 (51.6%) cases and identified 348/12 870 (2.7%) with a positive reference standard. None of the strategies provided sensitivity greater than 0.80 with positive predictive value greater than 0.15. The area under the receiver operating characteristic curve for the National Early Warning Score, version 2 (NEWS2) applied to patients with a diagnostic impression of sepsis or infection was 0.756 (95% CI 0.729, 0.783). No other early warning score provided clearly superior accuracy to NEWS2. Paramedic impression of sepsis or infection had sensitivity of 0.572 (0.519, 0.623) and positive predictive value of 0.156 (0.137, 0.176). NEWS2 thresholds of >4, >6 and >8 applied to patients with a diagnostic impression of sepsis or infection, respectively, provided sensitivities and positive predictive values of 0.522 (0.469, 0.574) and 0.216 (0.189, 0.245), 0.447 (0.395, 0.499) and 0.274 (0.239, 0.313), and 0.314 (0.268, 0.365) and 0.333 (0.284, 0.386). CONCLUSION: No strategy is ideal but using NEWS2 alongside paramedic diagnostic impression of infection or sepsis could identify one-third to half of sepsis cases without prioritising unmanageable numbers. No other score provided clearly superior accuracy to NEWS2. TRIAL REGISTRATION NUMBER: researchregistry5268, https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/5de7bbd97ca5b50015041c33/.

Landiolol and Organ Failure in Patients With Septic Shock: The STRESS-L Randomized Clinical Trial.

Importance: Patients with septic shock undergo adrenergic stress, which affects cardiac, immune, inflammatory, and metabolic pathways. ß-Blockade may attenuate the adverse effects of catecholamine exposure and has been associated with reduced mortality. Objectives: To assess the efficacy and safety of landiolol in patients with tachycardia and established septic shock requiring prolonged (>24 hours) vasopressor support. Design, Setting, and Participants: An open-label, multicenter, randomized trial involving 126 adults (≥18 years) with tachycardia (heart rate ≥95/min) and established septic shock treated for at least 24 hours with continuous norepinephrine (≥0.1 µg/kg/min) in 40 UK National Health Service intensive care units. The trial ran from April 2018 to December 2021, with early termination in December 2021 due to a signal of possible harm. Intervention: Sixty-three patients were randomized to receive standard care and 63 to receive landiolol infusion. Main Outcomes and Measures: The primary outcome was the mean Sequential Organ Failure Assessment (SOFA) score from randomization through 14 days. Secondary outcomes included mortality at days 28 and 90 and the number of adverse events in each group. Results: The trial was stopped prematurely on the advice of the independent data monitoring committee because it was unlikely to demonstrate benefit and because of possible harm. Of a planned 340 participants, 126 (37%) were enrolled (mean age, 55.6 years [95% CI, 52.7 to 58.5 years]; 58.7% male). The mean (SD) SOFA score in the landiolol group was 8.8 (3.9) compared with 8.1 (3.2) in the standard care group (mean difference [MD], 0.75 [95% CI, -0.49 to 2.0]; P = .24). Mortality at day 28 after randomization in the landiolol group was 37.1% (23 of 62) and 25.4% (16 of 63) in the standard care group (absolute difference, 11.7% [95% CI, -4.4% to 27.8%]; P = .16). Mortality at day 90 after randomization was 43.5% (27 of 62) in the landiolol group and 28.6% (18 of 63) in the standard care group (absolute difference, 15% [95% CI, -1.7% to 31.6%]; P = .08). There were no differences in the number of patients having at least one adverse event. Conclusion and Relevance: Among patients with septic shock with tachycardia and treated with norepinephrine for more than 24 hours, an infusion of landiolol did not reduce organ failure measured by the SOFA score over 14 days from randomization. These results do not support the use of landiolol for managing tachycardia among patients treated with norepinephrine for established septic shock. Trial Registration: EU Clinical Trials Register Eudra CT: 2017-001785-14; isrctn.org Identifier: ISRCTN12600919.

Brain injury after cardiac arrest.

As more people are surviving cardiac arrest, focus needs to shift towards improving neurological outcomes and quality of life in survivors. Brain injury after resuscitation, a common sequela following cardiac arrest, ranges in severity from mild impairment to devastating brain injury and brainstem death. Effective strategies to minimise brain injury after resuscitation include early intervention with cardiopulmonary resuscitation and defibrillation, restoration of normal physiology, and targeted temperature management. It is important to identify people who might have a poor outcome, to enable informed choices about continuation or withdrawal of life-sustaining treatments. Multimodal prediction guidelines seek to avoid premature withdrawal in those who might survive with a good neurological outcome, or prolonging treatment that might result in survival with severe disability. Approximately one in three admitted to intensive care will survive, many of whom will need intensive, tailored rehabilitation after discharge to have the best outcomes.

SARS-CoV-2 environmental contamination from hospitalised patients with COVID-19 receiving aerosol-generating procedures.

BACKGROUND: Continuous positive airways pressure (CPAP) and high-flow nasal oxygen (HFNO) are considered 'aerosol-generating procedures' in the treatment of COVID-19. OBJECTIVE: To measure air and surface environmental contamination with SARS-CoV-2 virus when CPAP and HFNO are used, compared with supplemental oxygen, to investigate the potential risks of viral transmission to healthcare workers and patients. METHODS: 30 hospitalised patients with COVID-19 requiring supplemental oxygen, with a fraction of inspired oxygen ≥0.4 to maintain oxygen saturation ≥94%, were prospectively enrolled into an observational environmental sampling study. Participants received either supplemental oxygen, CPAP or HFNO (n=10 in each group). A nasopharyngeal swab, three air and three surface samples were collected from each participant and the clinical environment. Real-time quantitative polymerase chain reaction analyses were performed for viral and human RNA, and positive/suspected-positive samples were cultured for the presence of biologically viable virus. RESULTS: Overall 21/30 (70%) participants tested positive for SARS-CoV-2 RNA in the nasopharynx. In contrast, only 4/90 (4%) and 6/90 (7%) of all air and surface samples tested positive (positive for E and ORF1a) for viral RNA respectively, although there were an additional 10 suspected-positive samples in both air and surfaces samples (positive for E or ORF1a). CPAP/HFNO use or coughing was not associated with significantly more environmental contamination than supplemental oxygen use. Only one nasopharyngeal sample was culture positive. CONCLUSIONS: The use of CPAP and HFNO to treat moderate/severe COVID-19 did not appear to be associated with substantially higher levels of air or surface viral contamination in the immediate care environment, compared with the use of supplemental oxygen.

RAND appropriateness panel to determine the applicability of UK guidelines on the management of acute respiratory distress syndrome (ARDS) and other strategies in the context of the COVID-19 pandemic.

BACKGROUND: COVID-19 has become the most common cause of acute respiratory distress syndrome (ARDS) worldwide. Features of the pathophysiology and clinical presentation partially distinguish it from 'classical' ARDS. A Research and Development (RAND) analysis gauged the opinion of an expert panel about the management of ARDS with and without COVID-19 as the precipitating cause, using recent UK guidelines as a template. METHODS: An 11-person panel comprising intensive care practitioners rated the appropriateness of ARDS management options at different times during hospital admission, in the presence or absence of, or varying severity of SARS-CoV-2 infection on a scale of 1-9 (where 1-3 is inappropriate, 4-6 is uncertain and 7-9 is appropriate). A summary of the anonymised results was discussed at an online meeting moderated by an expert in RAND methodology. The modified online survey comprising 76 questions, subdivided into investigations (16), non-invasive respiratory support (18), basic intensive care unit management of ARDS (20), management of refractory hypoxaemia (8), pharmacotherapy (7) and anticoagulation (7), was completed again. RESULTS: Disagreement between experts was significant only when addressing the appropriateness of diagnostic bronchoscopy in patients with confirmed or suspected COVID-19. Adherence to existing published guidelines for the management of ARDS for relevant evidence-based interventions was recommended. Responses of the experts to the final survey suggested that the supportive management of ARDS should be the same, regardless of a COVID-19 diagnosis. For patients with ARDS with COVID-19, the panel recommended routine treatment with corticosteroids and a lower threshold for full anticoagulation based on a high index of suspicion for venous thromboembolic disease. CONCLUSION: The expert panel found no reason to deviate from the evidence-based supportive strategies for managing ARDS outlined in recent guidelines.

Health inequities in out-of-hospital cardiac arrest.

PURPOSE OF REVIEW: Out-of-hospital cardiac arrest (OHCA) is a time-critical emergency in which a rapid response following the chain of survival is crucial to save life. Disparities in care can occur at each link in this pathway and hence produce health inequities. This review summarises the health inequities that exist for OHCA patients and suggests how they may be addressed. RECENT FINDINGS: There is international evidence that the incidence of OHCA is increased with increasing deprivation and in ethnic minorities. These groups have lower rates of bystander CPR and bystander-initiated defibrillation, which may be due to barriers in accessing cardiopulmonary resuscitation training, provision of public access defibrillators, and language barriers with emergency call handlers. There are also disparities in the ambulance response and in-hospital care following resuscitation. These disadvantaged communities have poorer survival following OHCA. SUMMARY: OHCA disproportionately affects deprived communities and ethnic minorities. These groups experience disparities in care throughout the chain of survival and this appears to translate into poorer outcomes. Addressing these inequities will require coordinated action that engages with disadvantaged communities.

Advanced Life Support Update.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2022. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2022 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

Prehospital continuous positive airway pressure (CPAP) for acute respiratory distress: a randomised controlled trial.

OBJECTIVE: To compare the efficacy of continuous positive airway pressure (CPAP) versus usual care for prehospital patients with severe respiratory distress. METHODS: We conducted a parallel group, individual patient, non-blinded randomised controlled trial in Western Australia between March 2016 and December 2018. Eligible patients were aged ≥40 years with acute severe respiratory distress of non-traumatic origin and unresponsive to initial treatments by emergency medical service (EMS) paramedics. Patients were randomised (1:1) to usual care or usual care plus CPAP. The primary outcomes were change in dyspnoea score and change in RR at ED arrival, and hospital length of stay. RESULTS: 708 patients were randomly assigned (opaque sealed envelope) to usual care (n=346) or CPAP (n=362). Compared with usual care, patients randomised to CPAP had a greater reduction in dyspnoea scores (usual care -1.0, IQR -3.0 to 0.0 vs CPAP -3.5, IQR -5.2 to -2.0), median difference -2.0 (95% CI -2.5 to -1.6); and RR (usual care -4.0, IQR -9.0 to 0.0 min-1 vs CPAP -8.0, IQR -14.0 to -4.0 min-1), median difference -4.0 (95% CI -5.0 to -4.0) min-1. There was no difference in hospital length of stay (usual care 4.2, IQR 2.1 to 7.8 days vs CPAP 4.8, IQR 2.5 to 7.9 days) for the n=624 cases admitted to hospital, median difference 0.36 (95% CI -0.17 to 0.90). CONCLUSIONS: The use of prehospital CPAP by EMS paramedics reduced dyspnoea and tachypnoea in patients with acute respiratory distress but did not impact hospital length of stay. TRIAL REGISTRATION NUMBER: ACTRN12615001180505.

Effect of Lower vs Higher Oxygen Saturation Targets on Survival to Hospital Discharge Among Patients Resuscitated After Out-of-Hospital Cardiac Arrest: The EXACT Randomized Clinical Trial.

Importance: The administration of a high fraction of oxygen following return of spontaneous circulation in out-of-hospital cardiac arrest may increase reperfusion brain injury. Objective: To determine whether targeting a lower oxygen saturation in the early phase of postresuscitation care for out-of-hospital cardiac arrest improves survival at hospital discharge. Design, Setting, and Participants: This multicenter, parallel-group, randomized clinical trial included unconscious adults with return of spontaneous circulation and a peripheral oxygen saturation (Spo2) of at least 95% while receiving 100% oxygen. The trial was conducted in 2 emergency medical services and 15 hospitals in Victoria and South Australia, Australia, between December 11, 2017, and August 11, 2020, with data collection from ambulance and hospital medical records (final follow-up date, August 25, 2021). The trial enrolled 428 of a planned 1416 patients. Interventions: Patients were randomized by paramedics to receive oxygen titration to achieve an oxygen saturation of either 90% to 94% (intervention; n = 216) or 98% to 100% (standard care; n = 212) until arrival in the intensive care unit. Main Outcomes and Measures: The primary outcome was survival to hospital discharge. There were 9 secondary outcomes collected, including hypoxic episodes (Spo2 <90%) and prespecified serious adverse events, which included hypoxia with rearrest. Results: The trial was stopped early due to the COVID-19 pandemic. Of the 428 patients who were randomized, 425 were included in the primary analysis (median age, 65.5 years; 100 [23.5%] women) and all completed the trial. Overall, 82 of 214 patients (38.3%) in the intervention group survived to hospital discharge compared with 101 of 211 (47.9%) in the standard care group (difference, -9.6% [95% CI, -18.9% to -0.2%]; unadjusted odds ratio, 0.68 [95% CI, 0.46-1.00]; P = .05). Of the 9 prespecified secondary outcomes collected during hospital stay, 8 showed no significant difference. A hypoxic episode prior to intensive care was observed in 31.3% (n = 67) of participants in the intervention group and 16.1% (n = 34) in the standard care group (difference, 15.2% [95% CI, 7.2%-23.1%]; OR, 2.37 [95% CI, 1.49-3.79]; P < .001). Conclusions and Relevance: Among patients achieving return of spontaneous circulation after out-of-hospital cardiac arrest, targeting an oxygen saturation of 90% to 94%, compared with 98% to 100%, until admission to the intensive care unit did not significantly improve survival to hospital discharge. Although the trial is limited by early termination due to the COVID-19 pandemic, the findings do not support use of an oxygen saturation target of 90% to 94% in the out-of-hospital setting after resuscitation from cardiac arrest. Trial Registration: ClinicalTrials.gov Identifier: NCT03138005.

Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.

Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. Design, Setting, and Participants: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. Interventions: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Main Outcomes and Measures: The primary outcome was a composite of tracheal intubation or mortality within 30 days. Results: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. Trial Registration: isrctn.org Identifier: ISRCTN16912075.

Adult Basic Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care Science With Treatment Recommendations on basic life support summarizes evidence evaluations performed for 22 topics that were prioritized by the Basic Life Support Task Force of the International Liaison Committee on Resuscitation. The evidence reviews include 16 systematic reviews, 5 scoping reviews, and 1 evidence update. Per agreement within the International Liaison Committee on Resuscitation, new or revised treatment recommendations were only made after a systematic review. Systematic reviews were performed for the following topics: dispatch diagnosis of cardiac arrest, use of a firm surface for CPR, sequence for starting CPR (compressions-airway-breaths versus airway-breaths-compressions), CPR before calling for help, duration of CPR cycles, hand position during compressions, rhythm check timing, feedback for CPR quality, alternative techniques, public access automated external defibrillator programs, analysis of rhythm during chest compressions, CPR before defibrillation, removal of foreign-body airway obstruction, resuscitation care for suspected opioid-associated emergencies, drowning, and harm from CPR to victims not in cardiac arrest. The topics that resulted in the most extensive task force discussions included CPR during transport, CPR before calling for help, resuscitation care for suspected opioid-associated emergencies, feedback for CPR quality, and analysis of rhythm during chest compressions. After discussion of the scoping reviews and the evidence update, the task force prioritized several topics for new systematic reviews.

A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.

BACKGROUND: Concern about the use of epinephrine as a treatment for out-of-hospital cardiac arrest led the International Liaison Committee on Resuscitation to call for a placebo-controlled trial to determine whether the use of epinephrine is safe and effective in such patients. METHODS: In a randomized, double-blind trial involving 8014 patients with out-of-hospital cardiac arrest in the United Kingdom, paramedics at five National Health Service ambulance services administered either parenteral epinephrine (4015 patients) or saline placebo (3999 patients), along with standard care. The primary outcome was the rate of survival at 30 days. Secondary outcomes included the rate of survival until hospital discharge with a favorable neurologic outcome, as indicated by a score of 3 or less on the modified Rankin scale (which ranges from 0 [no symptoms] to 6 [death]). RESULTS: At 30 days, 130 patients (3.2%) in the epinephrine group and 94 (2.4%) in the placebo group were alive (unadjusted odds ratio for survival, 1.39; 95% confidence interval [CI], 1.06 to 1.82; P=0.02). There was no evidence of a significant difference in the proportion of patients who survived until hospital discharge with a favorable neurologic outcome (87 of 4007 patients [2.2%] vs. 74 of 3994 patients [1.9%]; unadjusted odds ratio, 1.18; 95% CI, 0.86 to 1.61). At the time of hospital discharge, severe neurologic impairment (a score of 4 or 5 on the modified Rankin scale) had occurred in more of the survivors in the epinephrine group than in the placebo group (39 of 126 patients [31.0%] vs. 16 of 90 patients [17.8%]). CONCLUSIONS: In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group. (Funded by the U.K. National Institute for Health Research and others; Current Controlled Trials number, ISRCTN73485024 .).