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)

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.

Serial assessments of cardiac output and mixed venous oxygen saturation in comatose patients after out-of-hospital cardiac arrest

“…This study was a prespecified analyses from the BOX-trial, a randomized, controlled, multi-center study comparing two MAP targets (63 mmHg and 77 mmHg) in a double-blind intervention and comparing liberal and restrictive oxygenation targets in an open-label intervention [ 18 , 26 , 27 ]. Furthermore, all patients had device-based temperature control targeting 36 °C for 24 h followed by rewarming to 37 °C with 0.5 °C per hour to 37 °C.…”

“…The inclusion and exclusion criteria for the BOX-trial are outlined in the main papers and in Additional file 1 . Additional exclusion criteria for this substudy are death prior to PAC insertion, complications such as ventricular arrhythmias during the procedure or if PAC measurement such as thermodilution was not done within 2 h after admission [ 27 ]. Pre-hospital data were collected systematically according to Utstein guidelines.…”

“…The PAC was removed either at the time of discharge from the ICU or after 72 h unless it was required for further clinical hemodynamic monitoring. The institutions' post-cardiac arrest care protocols have been previously described [ 18 , 27 ] and detailed in the Additional file 1 .…”

Blood pressure and oxygenation targets after out-of-hospital cardiac arrest-trial (BOX)

“…The aim of the trial was to evaluate the difference in a target MAP of 63 vs. 77 mmHg on CO, SVR, and pulmonary capillary wedge pressure. 7 …”

Lower versus higher blood pressure targets in comatose patients resuscitated from out‐of‐hospital cardiac arrest—Protocol for a secondary Bayesian analysis of the box trial

“…Almost 1 in 2 patients with out‐of‐hospital cardiac arrest (OHCA), who remain comatose after resuscitation, succumb to hypoxic brain injury and withdrawal of life sustaining therapies in the ICU 4–6 . Pilot studies have suggested that higher mean arterial pressure (MAP) post‐OHCA, typically achieved using vasopressors like noradrenaline, may reduce brain injury 7–10 . However, vasopressors carry risks such as cardiac arrhythmias, myocardial ischemia, and increased afterload, and are associated with adverse outcomes 11 …”