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Background: In the management of patients resuscitated from out-of-hospital cardiac arrest, a primary goal is to restore sufficient oxygen delivery (DO 2 ) to meet demands in oxygen consumption (VO 2 )., Methods and Results: This post hoc analysis of the BOX (Blood Pressure and Oxygen Targets) study included adult patients who were comatose and experienced out-of-hospital cardiac arrest from a presumed cardiac cause, who were randomized to a mean arterial blood pressure (MAP) target of 63 mm Hg (MAP63) or 77 mm Hg (MAP77) and a Restrictive PaO 2 target of 9 to 10 kPa versus a Liberal target of 13 to 14 kPa in a 2×2 factorial design. A pulmonary artery catheter was inserted following randomization. DO 2 and VO 2 were calculated as: DO 2 =cardiac output × arterial oxygen content, and VO 2 = cardiac output × arteriovenous oxygen difference. Of 789 patients, 730 (92.5%) were included in this substudy. A total of 362 patients were randomized to MAP77, and 368 to MAP63, 368 to a liberal Pao 2 target, and 362 to a restrictive target. At all prespecified time points, DO 2 in MAP77 was higher compared with MAP63, with a cumulative treatment effect of 203 L (95% CI, 132-274) O 2 after 36 hours. VO 2 was higher in MAP77 after 36 hours, with a cumulative treatment effect of 21.9 L (95% CI, 5.8-38) O 2 , compared with the MAP63 group., Conclusions: Targeting a MAP of 77 mm Hg resulted in an overall increase in DO 2 and a smaller increase in VO 2 compared with a MAP target of 63 mm Hg. A higher Pao 2 target did not result in any difference in DO 2 or VO 2 .

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., Competing Interests: Declaration of Competing Interest Dr Christian Hassager received research grants from the Lundbeck Foundation(R186-2015-2132), the Novo Nordisk Foundation (NNF20OC0064043), and the Danish Heart Foundation (21-R151-A10091-22200). Dr Jacob Eifer Møller received an institutional research grant from Abiomed and Novo Nordic Foundation. Speakers' fees were received from Abbott, Abiomed, and Boehringer Ingelheim. The remaining authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aim: Bystander defibrillation is associated with increased survival with good neurological outcome after out-of-hospital cardiac arrest (OHCA). Dispatch of lay responders could increase defibrillation rates, however, survival with good neurological outcome in these remain unknown. The aim was to compare long-term survival with good neurological outcome in bystander versus lay responder defibrillated OHCAs., Methods: This is a sub-study of the BOX trial, which included OHCA patients from two Danish tertiary cardiac intensive care units from March 2017 to December 2021. The main outcome was defined as 3-month survival with good neurological performance (Cerebral Performance Category of 1or 2, on a scale from 1 (good cerebral performance) to 5 (death or brain death)). For this study EMS witnessed OHCAs were excluded., Results: Of the 715 patients, a lay responder arrived before EMS in 125 cases (16%). In total, 81 patients were defibrillated by a lay responder (11%), 69 patients by a bystander (10%) and 565 patients by the EMS staff (79%). The 3-month survival with good neurological outcome was 65% and 81% in the lay responder and bystander defibrillated groups, respectively (P = 0.03)., Conclusion: In patients with OHCA, 3-month survival with good neurological outcome was higher in bystander defibrillated patients compared with lay responder defibrillated patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘The BOX Trial has been supported by a Novo Nordisk grant (NNF17OC0028706) from the Novo Nordisk Foundation. Prof. Hassager’s work is funded by a grant from the Lundbeck Foundation (R186-2015-2132), and Dr. Beske’s work is funded by a grant from the Novo Nordisk Foundation (NNF20OC0064043). The authors have no other conflicts of interest to declare.’., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: The aim was to investigate the advanced hemodynamic effects of the two MAP-targets during intensive care on systemic hemodynamics in comatose patients after cardiac arrest., Design: Secondary analysis of a randomized controlled trial., Setting: Primary vasopressor used was per protocol norepinephrine. Hemodynamic monitoring was done with pulmonary artery catheters (PAC) and measurements were made on predefined time points. The primary endpoint of this substudy was the difference in cardiac index within 48 h from a repeated measurements-mixed model. Secondary endpoints included systemic vascular resistance index (SVRI), heart rate, and stroke volume index., Patients: Comatose survivors after out-of-hospital cardiac arrest., Interventions: The "Blood pressure and oxygenations targets after out-of-hospital cardiac arrest (BOX)"-trial was a randomized, controlled, double-blinded, multicenter-study comparing targeted mean arterial pressure (MAP) of 63 mmHg (MAP63) vs 77 mmHg (MAP77)., Measurements and Main Results: Among 789 randomized patients, 730 (93%) patients were included in the hemodynamic substudy. From PAC-insertion (median 1 hours after ICU-admission) and the next 48 hours, the MAP77-group received significantly higher doses of norepinephrine (mean difference 0.09 µg/kg/min, 95% confidence interval (CI) 0.07-0.11, p group  < 0.0001). Cardiac index was significantly increased (0.20 L/min/m 2 (CI 0.12-0.28), p group  < 0.0001) as was SVRI with an overall difference of (43 dynes m 2 /s/cm 5 (CI 7-79); p group  = 0.02). Heart rate was increased in the MAP77-group (4 beats/minute; CI 2-6, p group  < 0.003), but stroke volume index was not (p group  = 0.10)., Conclusions: Targeted MAP at 77 mmHg compared to 63 mmHg resulted in a higher dose of norepinephrine, increased cardiac index and SVRI. Heart rate was also increased, but stroke volume index was not affected by a higher blood pressure target., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Out-of-hospital cardiac arrest (OHCA) survivors remaining comatose are often circulatory unstable with high mortality in the first days following resuscitation. Elevated lactate will reflect the severity and duration of hypoperfusion in cardiac arrest. Further, the severity of hypoperfusion could modify the effect on survival of different mean arterial blood pressure (MAP) targets., Methods: In this sub-study of the BOX trial, adult successfully resuscitated comatose OHCA patients (n = 789) with a presumed cardiac cause were randomized to a MAP target of 63 mmHg vs. 77 mmHg. Patients were arbitrarily grouped in low-lactate: <25% of sample, medium-lactate: 25%-75%, and high >75 percentile according to blood lactate levels at hospital arrival as a surrogate of the severity of hypoperfusion. Invasive hemodynamic evaluations were performed using an arterial catheter and pulmonary artery catheter (PAC), and data from admission to 48 hours (h) were recorded. Logistic regression analysis evaluated whether lactate levels (as continuous and categorical) modify the effect of MAP targets on mortality at 365 days., Results: The three lactate groups had initial lactate levels of low-lactate: <2.9 mmol/L, medium-lactate: 2.9-7.9 mmol/L, and high-lactate > 7.9 mmol/L. All patients were randomized to a 63 mmHg or 77 mmHg MAP target. The proportion of patients in the high-MAP target group was 100/201 (50%), 178/388 (46%), and 114/197 (58%) for low, medium, and high-lactate groups respectively. At admission, the high-lactate groups had a lower MAP compared to the medium-lactate (2.6 mmHg (95% CI: 0.1-5.0 mmHg, p = 0.02), and the low-lactate group, (3.6 mmHg (95% CI: 0.8-6.5 mmHg, p < 0.01). Accordingly, the vasoactive inotropic score was 79% (95%CI: 42%-124%%) higher with increasing initial lactate level (High-lactate vs. low-lactate) with the largest difference at 6 hours (110.6% (95%CI: 54.4%-187.2%) higher in high-lactate patients). No difference in the cardiac index or systemic vascular resistance was observed between lactate groups. The initial lactate level (continuous) modified the effect of the two MAP targets (p = 0.04). In the highest lactate group, the mortality was 100/197 (51%), and with an odds ratio (OR): 1.7 (95%CI: 0.9-3.0) if randomized to MAP 77 mmHg compared to MAP 63 mmHg. In the lowest lactate group, the mortality was 35/201(17%) and similar if randomized to a MAP target of 77 mmHg (OR: 1.1 (95% CI: 0.5-2.3))., Conclusion: Comatose OHCA patients with high initial lactate levels required more vasoactive drugs on the first two days of ICU admission to meet the blood pressure target and had a poorer prognosis. No indication that aiming for a higher MAP target is beneficial in patients with an initial high lactate level was found, however, given the post-hoc nature of this study, these results should be considered hypothesis-generating., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)