Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

Invasive mechanical ventilation in cardiogenic shock complicating acute myocardial infarction: A contemporary Danish cohort analysis.

PURPOSE: Invasive mechanical ventilation (IMV) is widely used in patients with cardiogenic shock following acute myocardial infarction (AMICS), but evidence to guide practice remains sparse. We sought to evaluate trends in the rate of IMV utilization, applied settings, and short term-outcome of a contemporary cohort of AMICS patients treated with IMV according to out-of-hospital cardiac arrest (OHCA) at admission. METHODS: Consecutive AMICS patients receiving IMV in an intensive care unit (ICU) at two tertiary centres between 2010 and 2017. Data were analysed in relation to OHCA. RESULTS: A total of 1274 mechanically ventilated AMICS patients were identified, 682 (54%) with OHCA. Frequency of IMV increased during the study period, primarily due to higher occurrence of OHCA admissions. Among 566 patients with complete ventilator data, positive-end-expiratory pressure, inspired oxygen fraction, and minute ventilation during the initial 24 h in ICU were monitored. No differences were observed between 30-day survivors and non-survivors with OHCA. In non-OHCA, these ventilator requirements were significantly higher among 30-day non-survivors (P for all<0.05), accompanied by a lower PaO2/FiO2 ratio (median 143 vs. 230, P < 0.001) and higher arterial lactate levels (median 3.5 vs. 1.5 mmol/L, P < 0.001) than survivors. Physiologically normal PaO2 and pCO2 levels were achieved in all patients irrespective of 30-day survival and OHCA status. CONCLUSION: In the present contemporary cohort of AMICS patients, physiologically normal blood gas values were achieved both in OHCA and non-OHCA in the early phase of admission. However, increased demand of ventilatory support was associated with poorer survival only in non-OHCA patients.

Non-COVID-19 intensive care admissions during the pandemic: a multinational registry-based study.

BACKGROUND: The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, there is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment. METHODS: We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry. FINDINGS: Among 1 642 632 non-COVID-19 admissions, there was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95% CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95% CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes. INTERPRETATION: Increased ICU mortality occurred among non-COVID-19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles.

Neurofilament Light Chain and Glial Fibrillary Acidic Protein as early prognostic biomarkers after out-of-hospital cardiac arrest.

AIMS: Neurofilament Light Chain (NfL) and Glial Fibrillary Acidic Protein (GFAP) are proteins released into the bloodstream upon hypoxic brain injury. We evaluated the biokinetics and examined the prognostic performance of serum NfL and GFAP in comatose out-of-hospital cardiac arrest (OHCA) patients. Furthermore, we compared the prognostic performance to that of serum Neuron Specific Enolase (NSE). METHODS: This is a sub-study of the "Targeted temperature management for 48 vs 24 hours" (NCT01689077) trial. NfL and GFAP serum values from 82 patients were examined in blood samples collected at 24, 48 and 72 hours (h) after reaching target temperature of 33 ± 1 °C. This temperature was reached within a median of 281-320 minutes after intensive care unit admission. GFAP was analysed at 48 and 72 h. The neuroprognostic performance of NfL and GFAP was evaluated after 6 months follow-up. RESULTS: NfL and GFAP values were significantly higher in patients with a poor outcome (Cerebral Performance Category (CPC) score 3-5) vs. good outcome (CPC 1-2). NfL 24 h: 1371.5 (462.0; 2125.1) vs. 24.8 (14.0; 61.6). GFAP 48 h: 1285.3 (843.9; 2236.7) vs. 361.2 (200.4; 665.6) (both p < 0.001). Both biomarkers were promising markers of poor functional outcome at 24 and 48 h respectively: NfL 24 h: AUROC 0.95 (95% CI: 0.91-1.00). GFAP 48 h: AUROC 0.88 (95% CI: 0.81-0.96). NfL and GFAP both predicted outcome better than NSE at 48 h (both p < 0.01). At 72 h NfL but not GFAP outperformed NSE (p = 0.01). CONCLUSION: Serum NfL and GFAP may be strong biomarkers of poor functional outcome after OHCA from an early timepoint.

Use of prone position ventilation in patients with COVID-19 induced severe ARDS supported with V-V ECMO: A danish cohort study with focus on adverse events.

INTRODUCTION: Prone position ventilation (PPV) of patients with adult respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO) may improve oxygenation and alveolar recruitment and is recommended when extensive dorsal consolidations are present, but only few data regarding adverse events (AE) related to PPV in this group of patients have been published. METHODS: Nationwide retrospective analysis of 68 COVID-19 patients admitted from March 2020 - December 2021 with severe ARDS and need of V-V ECMO support. The number of patients treated with PPV, number of PPV-events, timing, the time spent in prone position, number and causes of AE are reported. Causes to stop the PPV regimen and risk factors for AE were explored. RESULTS: 44 out of 68 patients were treated with PPV, and 220 PPV events are evaluated. AE were identified in 99 out of 220 (45%) PPV events and occurred among 31 patients (71%). 1 fatal PPV related AE was registered. Acute supination occurred in 19 events (9%). Causes to stop the PPV regimen were almost equally distributed between effect (weaned from ECMO), no effect, death (of other reasons) and AE. Frequent causes of AE were pressures sores and ulcers, hypoxia, airway related and ECMO circuit related. Most AE occurred during patients first or second PPV event. CONCLUSIONS: PPV treatment was found to carry a high incidence of PPV related AE in these patients. Causes and preventive measures to reduce occurrence of PPV related AE during V-V ECMO support need further exploration.

Platform trials.

Platform trials focus on the perpetual testing of many interventions in a disease or a setting. These trials have lasting organizational, administrative, data, analytic, and operational frameworks making them highly efficient. The use of adaptation often increases the probabilities of allocating participants to better interventions and obtaining conclusive results. The COVID-19 pandemic showed the potential of platform trials as a fast and valid way to improved treatments. This review gives an overview of key concepts and elements using the Intensive Care Platform Trial (INCEPT) as an example.

Bleeding patients on extracorporeal membrane oxygenation have reduced platelet aggregation and plasma fibrinogen: a longitudinal observational study.

This study investigated changes in coagulation and associations with occurrence of bleeding and thrombosis during extracorporeal membrane oxygenation (ECMO) therapy. The study included 100 adult ECMO-patients. Standard coagulation parameters, platelet aggregation and thromboelastometry (ROTEM®) were compared with healthy controls. Data on bleeding and thrombosis were collected until recovery or death. Mortality data were collected 30 days after weaning from ECMO. During ECMO therapy, 53 patients experienced at least one moderate or major bleed. Among these, 42 (79%) patients experienced the first bleeding on day 1 or 2. Platelet aggregation and ROTEM® revealed a hypocoagulable state in ECMO patients when compared with healthy controls. Patients bleeding on day 1 or 2, had lower platelet count (p = 0.04), poorer platelet aggregation and lower levels of fibrinogen (p < 0.01) than patients not bleeding on day 1 or 2. Further, ROTEM® clot propagation was reduced in bleeding patients (p < 0.001). Mortality was higher among bleeding patients than patients not bleeding on day 1 or 2 (67% versus 34%, p < 0.01). Congruity existed between ROTEM® measurements and standard coagulation assays, but plasma fibrinogen had a stronger association with bleeding than ROTEM® measurements. The present study does not support ROTEM® analysis as a routine part of coagulation monitoring during ECMO therapy.

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.

Beneficial Effects of Ketone Ester in Patients With Cardiogenic Shock: A Randomized, Controlled, Double-Blind Trial.

BACKGROUND: Cardiogenic shock (CS) is a life-threatening condition with sparse treatment options. The ketone body 3-hydroxybutyrate has favorable hemodynamic effects in patients with stable chronic heart failure. Yet, the hemodynamic effects of exogenous ketone ester (KE) in patients with CS remain unknown. OBJECTIVES: The authors aimed to assess the hemodynamic effects of single-dose enteral treatment with KE in patients with CS. METHODS: In a double-blind, crossover study, 12 patients with CS were randomized to an enteral bolus of KE and isocaloric, isovolumic placebo containing maltodextrin. Patients were assessed with pulmonary artery catheterization, arterial blood samples, echocardiography, and near-infrared spectroscopy for 3 hours following each intervention separated by a 3-hour washout period. RESULTS: KE increased circulating 3-hydroxybutyrate (2.9 ± 0.3 mmol/L vs 0.2 ± 0.3 mmol/L, P < 0.001) and was associated with augmented cardiac output (area under the curve of relative change: 61 ± 22 L vs 1 ± 18 L, P = 0.044). Also, KE increased cardiac power output (0.07 W [95% CI: 0.01-0.14]; P = 0.037), mixed venous saturation (3 percentage points [95% CI: 1-5 percentage points]; P = 0.010), and forearm perfusion (3 percentage points [95% CI: 0-6 percentage points]; P = 0.026). Right (P = 0.048) and left (P = 0.017) ventricular filling pressures were reduced whereas heart rate and mean arterial and pulmonary arterial pressures remained similar. Left ventricular ejection fraction improved by 4 percentage points (95% CI: 2-6 percentage points; P = 0.005). Glucose levels decreased by 2.6 mmol/L (95% CI: -5.2 to 0.0; P = 0.047) whereas insulin levels remained unaltered. CONCLUSIONS: Treatment with KE improved cardiac output, biventricular function, tissue oxygenation, and glycemic control in patients with CS (Treatment With the Ketone Body 3-hydroxybutyrate in Patients With Cardiogenic Shock [KETO-SHOCK1]; NCT04642768).

Long-term outcomes in COVID-19 patients admitted to intensive care in Denmark: A nationwide observational study.

BACKGROUND: Among ICU patients with COVID-19, it is largely unknown how the overall outcome and resource use have changed with time, different genetic variants, and vaccination status. METHODS: For all Danish ICU patients with COVID-19 from March 10, 2020 to March 31, 2022, we manually retrieved data on demographics, comorbidities, vaccination status, use of life support, length of stay, and vital status from medical records. We compared patients based on the period of admittance and vaccination status and described changes in epidemiology related to the Omicron variant. RESULTS: Among all 2167 ICU patients with COVID-19, 327 were admitted during the first (March 10-19, 2020), 1053 during the second (May 20, 2020 to June 30, 2021) and 787 during the third wave (July 1, 2021 to March 31, 2022). We observed changes over the three waves in age (median 72 vs. 68 vs. 65 years), use of invasive mechanical ventilation (81% vs. 58% vs. 51%), renal replacement therapy (26% vs. 13% vs. 12%), extracorporeal membrane oxygenation (7% vs. 3% vs. 2%), duration of invasive mechanical ventilation (median 13 vs. 13 vs. 9 days) and ICU length of stay (median 13 vs. 10 vs. 7 days). Despite these changes, 90-day mortality remained constant (36% vs. 35% vs. 33%). Vaccination rates among ICU patients were 42% as compared to 80% in society. Unvaccinated versus vaccinated patients were younger (median 57 vs. 73 years), had less comorbidity (50% vs. 78%), and had lower 90-day mortality (29% vs. 51%). Patient characteristics changed significantly after the Omicron variant became dominant including a decrease in the use of COVID-specific pharmacological agents from 95% to 69%. CONCLUSIONS: In Danish ICUs, the use of life support declined, while mortality seemed unchanged throughout the three waves of COVID-19. Vaccination rates were lower among ICU patients than in society, but the selected group of vaccinated patients admitted to the ICU still had very severe disease courses. When the Omicron variant became dominant a lower fraction of SARS-CoV-2 positive patients received COVID treatment indicating other causes for ICU admission.

Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

Long-term survival, functional capacity and quality of life after refractory out-of-hospital cardiac arrest treated with mechanical circulatory support.

Introduction: Studies on long-term outcomes after refractory out-of-hospital cardiac arrest (OHCA) treated with mechanical circulatory support (MCS) are limited. This study aimed to evaluate long-term neurologically intact survival, functional capacity and quality of life after refractory OHCA treated with MCS. Methods: This was a follow-up study of survivors after refractory OHCA treated with MCS. Follow-up examinations comprised clinical assessment with transthoracic echocardiography and cardiopulmonary exercise test (CPX). Neurological and cognitive screening was evaluated with the Cerebral Performance Category (CPC) and Montreal Cognitive Assessment (MoCA test). A good neurological outcome was defined as CPC 1 or CPC 2. Health-related quality of life was measured by questionnaires (Short Form-36 (SF-36)). Results: A total of 101 patients with refractory OHCA were treated with MCS at Aarhus University Hospital between 2015 and 2019. The total low-flow time was median 105 min [IQR, 94-123] minutes. The hospital discharge rate was 27%. At a mean follow-up time of 4.8 years ± 1.6 (range 2.8-6.1 years), 21 patients remained alive of whom 15 consented to participate in the present study. Good neurological outcome with CPC 1-2 was found in 93% (14/15) patients. No severe cognitive function was discovered; mean MoCA score of 26.4 ± 3.1. Functional capacity examined by CPX showed acceptable VO2 max values (23.9 ± 6.3 mL/kg/min). Mean SF-36 scores revealed an overall high level of quality of life in long-term survivors. Conclusions: Long-term survival with a good neurological outcome with functional recovery was high in patients with refractory OHCA treated with MCS. These patients may expect a reasonable quality of life after discharge despite prolonged resuscitation.

The Nordic perioperative and intensive care registries-Collaboration and research possibilities.

BACKGROUND: The Nordic perioperative and intensive care registries have been built up during the last 25 years to improve quality in intensive and perioperative care. We aimed to describe the Nordic perioperative and intensive care registries and to highlight possibilities and challenges in future research collaboration between these registries. MATERIAL AND METHOD: We present an overview of the following Nordic registries: Swedish Perioperative Registry (SPOR), the Danish Anesthesia Database (DAD), the Finnish Perioperative Database (FIN-AN), the Icelandic Anesthesia Database (IS-AN), the Danish Intensive Care Database (DID), the Swedish Intensive Care Registry (SIR), the Finnish Intensive Care Consortium, the Norwegian Intensive Care and Pandemic Registry (NIPaR), and the Icelandic Intensive Care Registry (IS-ICU). RESULTS: Health care systems and patient populations are similar in the Nordic countries. Despite certain differences in data structure and clinical variables, the perioperative and intensive care registries have enough in common to enable research collaboration. In the future, even a common Nordic registry could be possible. CONCLUSION: Collaboration between the Nordic perioperative and intensive care registries is both possible and likely to produce research of high quality. Research collaboration between registries may have several add-on effects and stimulate international standardization regarding definitions, scoring systems, and benchmarks, thereby improving overall quality of care.

Selection of patients for mechanical circulatory support for refractory out-of-hospital cardiac arrest.

OBJECTIVE: To describe characteristics of patients admitted with refractory cardiac arrest for possible extracorporeal cardiopulmonary resuscitation (ECPR) and gain insight into the reasons for refraining from treatment in some. METHODS: Nationwide retrospective cohort study involving all tertiary centres providing ECPR in Denmark. Consecutive patients admitted with ongoing chest compression for evaluation for ECPR treatment were enrolled. Presenting characteristics, duration of no-flow and low-flow time, end-tidal carbon dioxide (ETCO2), lactate and pH, and recording of reasons for refraining from ECPR documented by the treating team were recorded. Outcomes were survival to intensive care unit admission and survival to hospital discharge. RESULTS: Of 579 patients admitted with refractory cardiac arrest for possible ECPR, 221 patients (38%) proceeded to ECPR and 358 patients (62%) were not considered candidates. Median prehospital low-flow time was 70 min (IQR 56 to 85) in ECPR patients and 62 min (48 to 81) in no-ECPR patients, p<0.001. Intra-arrest transport was more than 50 km in 92 (42%) ECPR patients and 135 in no-ECPR patients (38%), p=0.25. The leading causes for not initiating ECPR stated by the treating team were duration of low-flow time in 39%, severe metabolic derangement in 35%, and in 31% low ETCO2. The prevailing combination of contributing factors were non-shockable rhythm, low ETCO2, and metabolic derangement or prehospital low-flow time combined with low ETCO2. Survival to discharge was only achieved in six patients (1.7%) in the no-ECPR group. CONCLUSIONS: In this large nationwide study of patients admitted for possible ECPR, two-thirds of patients were not treated with ECPR. The most frequent reasons to abstain from ECPR were long duration of prehospital low-flow time, metabolic derangement and low ETCO2.

Platelet Function in Acute Kidney Injury: A Systematic Review and a Cohort Study.

Acute kidney injury (AKI) patients have increased bleeding risk, which could be partially due to acquired platelet dysfunction. We conducted a systematic review and a cohort study to investigate platelet function and count in AKI and their association with AKI-related bleeding and mortality. Through a systematic literature search in PubMed and Embase, we identified 9 studies reporting platelet function and 56 studies reporting platelet count or platelet indices in AKI patients. Overall, platelet aggregation was reduced in AKI patients in nonintensive care unit (ICU) settings but not in ICU settings, except that reduced aggregation was associated with renal replacement therapy. Thrombocytopenia in AKI was frequent and often predictive of mortality. In our cohort study, we prospectively included 54 adult ICU patients who developed AKI within 24 hours of ICU admission and 33 non-AKI ICU controls. Platelet function was measured with light transmission aggregometry and flow cytometry. AKI patients bled more frequently than non-AKI patients (p = 0.04), and bleeding was associated with increased 30-day mortality in AKI (p = 0.02). However, platelet function was not different between AKI and non-AKI patients (aggregation: all p > 0.52; flow cytometry: all p > 0.07) and platelet function was not associated with bleeding in AKI. In conclusion, a reduced platelet count is frequent in AKI, but the literature on platelet function in AKI is sparse. In a cohort study, we demonstrated that patients with AKI within 24 hours of ICU admission exhibited increased bleeding tendency but this was not associated with reduced platelet function.

Prolonged Cardiogenic Shock Due to Hydrogen Sulfide Intoxication Requiring Long-Term Venoarterial Extracorporeal Membrane Support.

We describe a case of severe biventricular failure and cardiovascular collapse following exposure to the manure gas hydrogen sulfide. Initial tests indicated uncoupling of cellular bioenergetics in addition to myocardial damage. Cardiopulmonary support with venoarterial extracorporeal membrane oxygenation was initiated, and the patient could be successfully weaned from support after 28 days. (Level of Difficulty: Advanced.).

Extracorporeal cardiopulmonary resuscitation: a national study on the association between favourable neurological status and biomarkers of hypoperfusion, inflammation, and organ injury.

AIMS: In refractory out-of-hospital cardiac arrest (OHCA) with prolonged whole-body ischaemia, global tissue injury proceeds even after establishment of circulation with extracorporeal cardiopulmonary resuscitation (ECPR). We aimed to investigate the role of biomarkers reflecting hypoperfusion, inflammation, and organ injury in prognostication of patients with refractory OHCA managed with ECPR. METHODS AND RESULTS: This nationwide retrospective study included 226 adults with refractory OHCA managed with ECPR in Denmark (2011-2020). Biomarkers the first days after ECPR-initiation were assessed. Odds ratio of favourable neurological status (Cerebral Performance Category 1-2) at hospital discharge was estimated by logistic regression analyses. Cut-off values were calculated using the Youden's index. Fifty-six patients (25%) survived to hospital discharge, 51 (91%) with a favourable neurological status. Factors independently associated with favourable neurological status were low flow time <81 min, admission leukocytes ≥12.8 × 109/L, admission lactate <13.2 mmol/L, alkaline phosphatase (ALP) < 56 (day1) or <55 U/L (day2), and day 1 creatine kinase MB (CK-MB) < 500 ng/mL. Selected biomarkers (leukocytes, C-reactive protein, and lactate) were significantly better predictors of favourable neurological status than classic OHCA-variables (sex, age, low-flow time, witnessed arrest, shockable rhythm) alone (P = 0.001) after hospital admission. CONCLUSION: Biomarkers of hypoperfusion (lactate), inflammation (leucocytes), and organ injury (ALP and CK-MB) were independently associated with neurological status at hospital discharge. Biomarkers of hypoperfusion and inflammation (at hospital admission) and organ injury (days 1 and 2 after ECPR) may aid in the clinical decision of when to prolong or terminate ECPR in cases of refractory OHCA.

Effect of calcium vs. placebo on long-term outcomes in patients with out-of-hospital cardiac arrest.

OBJECTIVE: The Calcium for Out-of-hospital Cardiac Arrest (COCA) trial was a randomized, placebo-controlled, double-blind trial of calcium for out-of-hospital cardiac arrest. The primary and secondary outcomes have been reported previously. This article describes the long-term outcomes of the trial. METHODS: Patients aged ≥18 years were included if they had a non-traumatic out-of-hospital cardiac arrest during which they received adrenaline. The trial drug consisted of calcium chloride (5 mmol) or saline placebo given after the first dose of adrenaline and again after the second dose of adrenaline for a maximum of two doses. This article presents pre-specified analyses of 6-month and 1-year outcomes for survival, survival with a favorable neurological outcome (modified Rankin Scale of 3 or less), and health-related quality of life. RESULTS: A total of 391 patients were analyzed. At 1 year, 9 patients (4.7%) were alive in the calcium group while 18 (9.1%) were alive in the placebo group (risk ratio 0.51; 95% confidence interval 0.24, 1.09). At 1 year, 7 patients (3.6%) were alive with a favorable neurological outcome in the calcium group while 17 (8.6%) were alive with a favorable neurological outcome in the placebo group (risk ratio 0.42; 95% confidence interval 0.18, 0.97). Outcomes for health-related quality of life likewise suggested harm of calcium but results were imprecise with wide confidence intervals. CONCLUSIONS: Effect estimates remained constant over time suggesting harm of calcium but with wide confidence intervals. The results do not support calcium administration during out-of-hospital cardiac arrest. TRIAL REGISTRATION: ClinicalTrials.gov-number, NCT04153435.

Changes over time in characteristics, resource use and outcomes among ICU patients with COVID-19-A nationwide, observational study in Denmark.

BACKGROUND: Characteristics and care of intensive care unit (ICU) patients with COVID-19 may have changed during the pandemic, but longitudinal data assessing this are limited. We compared patients with COVID-19 admitted to Danish ICUs in the first wave with those admitted later. METHODS: Among all Danish ICU patients with COVID-19, we compared demographics, chronic comorbidities, use of organ support, length of stay and vital status of those admitted 10 March to 19 May 2020 (first wave) versus 20 May 2020 to 30 June 2021. We analysed risk factors for death by adjusted logistic regression analysis. RESULTS: Among all hospitalised patients with COVID-19, a lower proportion was admitted to ICU after the first wave (13% vs. 8%). Among all 1374 ICU patients with COVID-19, 326 were admitted during the first wave. There were no major differences in patient's characteristics or mortality between the two periods, but use of invasive mechanical ventilation (81% vs. 58% of patients), renal replacement therapy (26% vs. 13%) and ECMO (8% vs. 3%) and median length of stay in ICU (13 vs. 10 days) and in hospital (20 vs. 17 days) were all significantly lower after the first wave. Risk factors for death were higher age, larger burden of comorbidities (heart failure, pulmonary disease and kidney disease) and active cancer, but not admission during or after the first wave. CONCLUSIONS: After the first wave of COVID-19 in Denmark, a lower proportion of hospitalised patients with COVID-19 were admitted to ICU. Among ICU patients, use of organ support was lower and length of stay was reduced, but mortality rates remained at a relatively high level.