Prodromal complaints and 30-day survival after emergency medical services-witnessed out-of-hospital cardiac arrest.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a frequent and lethal condition with a yearly incidence of approximately 5000 in Denmark. Thirty-day survival is associated with the patient's prodromal complaints prior to cardiac arrest. This paper examines the odds of 30-day survival dependent on the reported prodromal complaints among OHCAs witnessed by the emergency medical services (EMS). METHODS: EMS-witnessed OHCAs in the Capital Region of Denmark from 2016-2018 were included. Calls to the emergency number 1-1-2 and the medical helpline for out-of-hours were analyzed according to the Danish Index; data regarding the OHCA was collected from the Danish Cardiac Arrest Registry. We performed multiple logistic regression to calculate the odds ratio (OR) of 30-day survival with adjustment for sex and age. RESULTS: We identified 311 eligible OHCAs of which 79 (25.4%) survived. The most commonly reported complaints were dyspnea (n = 209, OR 0.79 [95% CI 0.46: 1.36]) and 'feeling generally unwell' (n = 185, OR 1.07 [95% CI 0.63: 1.81]). Chest pain (OR 9.16 [95% CI 5.09:16.9]) and heart palpitations (OR 3.15 [95% CI 1.07:9.46]) had the highest ORs, indicating favorable odds for 30-day survival, while unresponsiveness (OR 0.22 [95% CI 0.11:0.43]) and blue skin or lips (OR 0.30, 95% CI 0.09, 0.81) had the lowest, indicating lesser odds of 30-day survival. CONCLUSION: Experiencing chest pain or heart palpitations prior to EMS-witnessed OHCA was associated with higher 30-day survival. Conversely, complaints of unresponsiveness or having blue skin or lips implied reduced odds of 30-day survival.

Intravenous vs. intraosseous vascular access during out-of-hospital cardiac arrest - protocol for a randomised clinical trial.

Objective: During cardiac arrest, current guidelines recommend attempting intravenous access first and to consider intraosseous access if intravenous access is unsuccessful or impossible. However, these recommendations are only based on very low-certainty evidence. Therefore, the "Intravenous vs Intraosseous Vascular Access During Out-of-Hospital Cardiac Arrest" (IVIO) trial aims to determine whether there is a difference in patient outcomes depending on the type of vascular access attempted during out-of-hospital cardiac arrest. This current article describes the clinical IVIO trial. Methods: The IVIO trial is an investigator-initiated, randomised trial of intravenous vs. intraosseous vascular access during adult non-traumatic out-of-hospital cardiac arrest in Denmark. The intervention will consist of minimum two attempts (if unsuccessful on the first attempt) to successfully establish intravenous or intraosseous vascular access during cardiac arrest. The intraosseous group will be further randomised to the humeral or tibial site. The primary outcome is sustained return of spontaneous circulation and key secondary outcomes include survival and survival with a favourable neurological outcome at 30 days. A total of 1,470 patients will be included. Results: The trial started in March 2022 and the last patient is anticipated to be included in the spring of 2024. The primary results will be reported after 90-day follow-up and are anticipated in mid-2024. Conclusion: The current article describes the design of the Danish IVIO trial. The findings of this trial will help inform future guidelines for selecting the optimal vascular access route during out-of-hospital cardiac arrest.

Lower versus higher oxygenation targets in hypoxaemic ICU patients after cardiac arrest.

AIM: To investigate the effects of lower versus higher oxygenation targets in adult intensive care unit (ICU) patients with hypoxaemic respiratory failure after cardiac arrest. METHODS: Subgroup analysis of the international Handling Oxygenation Targets in the ICU (HOT-ICU) trial which randomised 2928 adults with acute hypoxaemia to targets of arterial oxygenation of 8 kPa or 12 kPa in the ICU for up to 90 days. Here, we report all outcomes up to one year in the subgroup of patients enrolled after cardiac arrest. RESULTS: The HOT-ICU trial included 335 patients after cardiac arrest: 149 in the lower-oxygenation group and 186 in the higher-oxygenation group. At 90 days, 96/147 patients (65.3%) in the lower-oxygenation group and 111/185 patients (60.0%) in the higher-oxygenation group had died (adjusted relative risk (RR) 1.09, 95% confidence interval (CI) 0.92-1.28, p = 0.32); similar results were found at one year (adjusted RR 1.05, 95% CI 0.90-1.21, p = 0.53). Serious adverse events (SAEs) in the ICU occurred in 23% of patients in the lower-oxygenation group and 38% in the higher-oxygenation group (adjusted RR 0.61, 95% CI 0.43-0.86, p = 0.005); the difference was mainly due to more new episodes of shock in the higher-oxygenation group. No statistically significant differences were observed in other secondary outcomes. CONCLUSION: A lower oxygenation target in adult ICU patients with hypoxaemic respiratory failure after cardiac arrest did not result in lower mortality, but fewer SAEs occurred in this group compared to the higher-oxygenation group. All analyses are exploratory only, large-scale trials are needed for confirmation. CLINICAL TRIAL REGISTRY: Clinicaltrials.gov number NCT03174002 (registered May 30, 2017); EudraCT 2017-000632-34 (registered February 14, 2017).

The long-term effects of lower versus higher oxygenation levels in adult ICU patients - protocol for a systematic review.

BACKGROUND: Many organs can remain impaired after discharge from the intensive care unit (ICU) leading to temporal or permanent dysfunctions. Long-term impairments may be affected by supplemental oxygen, a common treatment in ICU, having both potential beneficial and harmful long-lasting effects. This systematic review aims to assess the long-term outcomes of lower versus higher oxygen supplementation and/or oxygenation levels in adults admitted to ICU. METHODS: We will include trials differentiating between a lower and a higher oxygen supplementation or a lower and a higher oxygenation strategy in adults admitted to the ICU. We will search major electronic databases and trial registers for randomised clinical trials. Two authors will independently screen and select references for inclusion using Covidence and predefined data will be extracted. The methodological quality and risk of bias of included trials will be evaluated using the Cochrane Risk of Bias tool 2. Meta-analysis will be performed if two or more trials with comparable outcome measures will be included. Otherwise, a narrative description of the trials' results will be presented instead. To assess the certainty of evidence, we will create a 'Summary of findings' table containing all prespecified outcomes using the GRADE system. The protocol is submitted on the PROSPERO database (ID 223630). CONCLUSION: No systematic reviews on the impact of oxygen treatment in the ICU on long-term outcomes, other than mortality and quality of life, have been reported yet. This systematic review will provide an overview of the current evidence and will help future research in the field.

Higher versus lower oxygenation targets in COVID-19 patients with severe hypoxaemia (HOT-COVID) trial: Protocol for a secondary Bayesian analysis.

BACKGROUND: Respiratory failure is the main cause of mortality and morbidity among ICU patients with coronavirus disease 2019 (COVID-19). In these patients, supplemental oxygen therapy is essential, but there is limited evidence the optimal target. To address this, the ongoing handling oxygenation targets in COVID-19 (HOT-COVID) trial was initiated to investigate the effect of a lower oxygenation target (partial pressure of arterial oxygen (PaO2 ) of 8 kPa) versus a higher oxygenation target (PaO2 of 12 kPa) in the ICU on clinical outcome in patients with COVID-19 and hypoxaemia. METHODS: The HOT-COVID is planned to enrol 780 patients. This paper presents the protocol and statistical analysis plan for the conduct of a secondary Bayesian analysis of the primary outcome of HOT-COVID being days alive without life-support at 90 days and the secondary outcome 90-day all-cause mortality. Furthermore, both outcomes will be investigated for the presence heterogeneity of treatment effects based on four baseline parameters being sequential organ failure assessment score, PaO2 /fraction of inspired oxygen ratio, highest dose of norepinephrine during the 24 h before randomisation, and plasma concentration of lactate at randomisation. CONCLUSION: The results of this pre-planned secondary Bayesian analysis will complement the primary frequentist analysis of the HOT-COVID trial and may facilitate a more nuanced interpretation of the trial results.

Handling oxygenation targets in ICU patients with COVID-19-Protocol and statistical analysis plan in the HOT-COVID trial.

BACKGROUND: Coronavirus disease (COVID-19) primarily affects the lungs and lower airways and may present as hypoxaemic respiratory failure requiring admission to an intensive care unit (ICU) for supportive treatment. Here, supplemental oxygen remains essential for COVID-19 patient management, but the optimal dosage is not defined. We hypothesize that targeting an arterial partial pressure of oxygen of 8 kPa throughout ICU admission is superior to targeting 12 kPa. METHODS: The Handling Oxygenation Targets in ICU patients with COVID-19 (HOT-COVID) trial, is an investigator-initiated, pragmatic, multicentre, randomized, parallel-group trial comparing a lower oxygenation target versus a higher oxygenation target in adult ICU patients with COVID-19. The primary outcome is days alive without life-support (use of mechanical ventilation, renal replacement therapy or vasoactive therapy) at day 90. Secondary outcomes are 90-day and 1-year mortality, serious adverse events in the ICU and days alive and out of hospital in the 90-day period, health-related quality-of-life at 1 year, and health economic analyses. One-year follow-up of cognitive and pulmonary function is planned in a subgroup of Danish patients. We will include 780 patients to detect or reject an absolute increase in days alive without life-support of 7 days with an α of 5% and a ß of 20%. An interim analysis is planned after 90-day follow-up of 390 patients. CONCLUSIONS: The HOT-COVID trial will provide patient-important data on the effect of two oxygenation targets in ICU patients with COVID-19 and hypoxia. This protocol paper describes the background, design and statistical analysis plan for the trial.