Hemodynamic evaluation by serial right heart catheterizations after cardiac arrest; protocol of a sub-study from the Blood Pressure and Oxygenation Targets after Out-of-Hospital Cardiac Arrest-trial (BOX)

Johannes Grand, Christian Hassager, Henrik Schmidt, Jacob E Møller, Simon Mølstrøm, Benjamin Nyholm, Jesper Kjaergaard, Johannes Grand, Christian Hassager, Henrik Schmidt, Jacob E Møller, Simon Mølstrøm, Benjamin Nyholm, Jesper Kjaergaard

Abstract

Background: Neurological injury and mortality remain high in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). Hypotension and hypoxia during post-resuscitation care have been associated with poor outcome, but the optimal oxygenation- and blood pressure-targets are unknown. The impact of different doses of norepinephrine on advanced hemodynamic after OHCA and the impact of different oxygenation-targets on pulmonary circulation and resistance (PVR), are unknown. The aims of this substudy of the "Blood pressure and oxygenations targets after out-of-hospital cardiac arrest (BOX)"-trial are to investigate the effect of two different MAP- and oxygenation-targets on advanced systemic and pulmonary hemodynamics measured by pulmonary artery catheters (PAC).

Methods: The BOX-trial is an investigator-initiated, randomized, controlled study comparing targeted MAP of 63 mmHg vs 77 mmHg (double-blinded intervention) and 9-10 kPa versus PaO2 of 13-14 kPa oxygenation-targets (open-label). Per protocol, all patients will be monitored systematically with PACs. The primary endpoint of the hemodynamic-substudy is cardiac output for the MAP-intervention, and PVR for the oxygenation-intervention. For both endpoints, the difference within 48 h between groups are assessed. Secondary endpoints are pulmonary capillary wedge pressure and pulmonary arterial pressure and association between advanced hemodynamic variables and mortality and biomarkers of inflammation and brain injury.

Discussion: In the BOX-trial, patients will be randomly allocated to two levels of MAP and oxygenation, which are central parts of post-resuscitation care and where evidence is sparse. The advanced-hemodynamic substudy will give valuable knowledge of the hemodynamic consequences of changing blood pressure and oxygen-levels of the critical cardiac patient. It will be one of the largest clinical, prospective trials of advanced hemodynamics measured by serial PACs in consecutive comatose patients, resuscitated after OHCA. The randomized and placebo-controlled trialdesign of the MAP-intervention minimizes risk of selection bias and confounders. Furthermore, hemodynamic characteristics and associations with outcome will be investigated.

Trial registration: ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT03141099). Registered March 30, 2017.

Keywords: Blood pressure; Cardiac output; Hemodynamics; Neuroprotection; Out-of-hospital cardiac arrest; Pulmonary artery catheter.

Conflict of interest statement

CH: Lecture honorarium from Abiomed. Research grands: Lundbeck Foundation (R186-2015-2132) and Novo Nordisk Foundation (NNF20OC0064043).

© 2021 The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart summarizing patient enrollment and main study procedures. OHCA: out-of-hospital cardiac arrest; ROSC: return of spontaneous circulation; IHCA: In-hospital cardiac arrest; CPC: cerebral performance category; PAC: Pulmonary artery catheter; T0: time at ICU-admission; ICU: intensive care unit.
Fig. 2
Fig. 2
Detailed overview of study-related procedures. RASS: Richmond Agitation-Sedation Scale; T0: time at ICU-admission; 3 M−FU: 3 months follow-up; Vital: vital signs; A-gas: Arterial blood gas; V-gas: central venous blood gas; ECG12: electrocardiogram; PAC: measurements from pulmonary artery catheter; Crea: creatinine-clearence.

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