REstrictive Versus LIberal Oxygen Strategy and Its Effect on Pulmonary Hypertension After Out-of-hospital Cardiac Arrest (RELIEPH-study)

University of Southern Denmark300 enrolled

Overview

Background: For patients with out-of-hospital cardiac arrest (OHCA) at the intensive care unit (ICU), oxygen therapy plays an important role in post resuscitation care. During hospitalisation, a lot of these patients occur with pulmonary arterial hypertension (PAH). Currently a wide oxygen target is recommended but no evidence regarding optimal treatment targets to minimise the prevalence of PAH exists. Methods: The RELIEPH trial is a substudy within the BOX (Blood pressure and OXygenation targets in post resuscitation care) trial. It is a single-center, parallel-group randomised controlled clinical trial. 300 patients with OHCA hospitalised at the ICU are allocated to one of the two oxygenation interventions, either a restrictive- (9-10 kPa) or liberal (13-14 kPa) oxygen target both within the recommended range. The primary outcome is the fraction of time with pulmonary hypertension (mPAP \>25 mmHg) out of total time with mechanical ventilation. Secondary outcomes are: length of ICU stay among survivors, lactate clearance, right ventricular failure, 30 days mortality and plasma brain natriuretic peptide (BNP) level 48 hours from randomisation. Discussion: This study hypothesises that a liberal target of oxygen reduces the time with PAH during mechanical ventilation compared to a restrictive oxygen target in patients with OHCA at the ICU. When completed, this study hopes to provide new knowledge regarding which oxygen target is beneficial for this group of patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

300

Conditions

Hypertension, Pulmonary Arterial

Interventions

Restrictive PaO2OTHER

Patients are randomized to a PaO2 target of 9-10 kPa (open-label).

Low normal MAPOTHER

The patients are randomized to receive a Phillips M1006B blood pressure measuring module, offset by +10 %. All patients will target a MAP of 70, but due to the offset module, the patients will target an actual blood pressure of 63 mmHg.

Liberal PaO2OTHER

Patients are randomized to a PaO2 target of 13-14 kPa (open-label).

High normal MAPOTHER

The patients are randomized to receive a Phillips M1006B blood pressure measuring module, offset by -10 %. All patients will target a MAP of 70, but due to the offset module, the patients will target an actual blood pressure of 77mmHg.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥18 years * OHCA of presumed cardiac cause * Sustained ROSC * Unconsciousness (Glasgow coma scale \<8) after sustained ROSC Exclusion Criteria: * Conscious patients (obeying verbal commands) * Females of childbearing potential (unless a negative HCG test can rule out pregnancy within the inclusion window) * In-hospital cardiac arrest * OHCA of presumed non-cardiac cause e.g. after trauma or dissection/rupture of major artery or cardiac arrest caused by initial hypoxia (i.e. drowning, suffocation, hanging). * Known bleeding diathesis (medically induced coagulopathy (e.g. warfarin, NOAC, clopidogrel) does not exclude the patient) * Suspected or confirmed acute intracranial bleeding * Suspected or confirmed acute stroke * Unwitnessed asystole * Known limitations in therapy and Do Not Resuscitate-order * Known disease making 180 days survival unlikely * Known pre-arrest cerebral performance category 3 or 4 * \>4 hours (240 minutes) from ROSC to screening * Systolic blood pressure \<80 mmHg in spite of fluid loading/vasopressor and/or inotropic medication/intra-aortic balloon pump/axial flow device * Temperature on admission \<30°C

Outcomes

Primary Outcomes

Pulmonary hypertension

Fraction of time with pulmonary hypertension (mPAP \>25 mmHg) out of total time with mechanical ventilation.

Time frame: Up to 30 days.

Secondary Outcomes

Length of ICU stay.

Length of ICU stay among survivors.

Time frame: Up to 8 weeks.

Lactate clearance.

\>30% reduction in lactate level.

Time frame: 24 hours.

Right ventricular failure.

Cardiac index \<2 and central venous pressure \>18 mmHg.

Time frame: Up to 8 weeks.

Mortality.

Dead or alive.

Time frame: 30 days after ROSC.

Plasma brain natriuretic peptide.

Plasma brain natriuretic peptide level.

Time frame: 48 hours from randomisation.