Neuroprotective Goal Directed Hemodynamic Optimization in Post-cardiac Arrest Patients

Not Applicable

Completed

Conditions: Cardiac Arrest
Cerebral Ischemia

Interventions: Other: MAP > 65mmHg
Other: Neuroprotective goal directed hemodynamic optimization

Registration Number: NCT02541591

Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

Brief Summary: The primary objective of the Neuroprotect trial is to assess whether or not a new goal directed hemodynamic optimization strategy can reduce cerebral ischemia in post-cardiac arrest (CA) patients.

Detailed Description: Unconscious patients admitted to the intensive care unit after being successfully resuscitated from cardiac arrest (CA) are at high risk for death, and neurological deficits are common among survivors. Nevertheless, the optimal hemodynamic strategy to ensure optimal cerebral perfusion and maximal outcome has not been studied by a randomized controlled trial. In the absence of good evidence, current post-CA guidelines are adapted from sepsis guidelines and recommend targeting a mean arterial pressure (MAP) above 65 mmHg (Peberdy ea, Circulation 2010). Importantly, post-CA patients have a large cerebral penumbra at risk for infarction when resuscitated to suboptimal MAP's. In a large subset of post-CA patients the lower threshold of cerebral autoregulation is shifted rightward and these patients might benefit from resuscitation to higher MAP's (Sundgreen ea, Stroke 2001) in order to ensure adequate cerebral oxygenation. Our research group previously showed that a MAP of 85-100mmHg results in optimal cerebral perfusion in post-CA patients (Ameloot ea, resuscitation 2015). Two retrospective and 2 prospective observational studies suggested an association between higher MAP's and better outcome in post-CA patients (Ameloot ea, resuscitation 2015). However, the value of these trials is limited by their observational design. The question remains as to whether patients with higher MAP's do have a better outcome due to more optimal cerebral perfusion and less cerebral damage or whether a higher MAP is merely a non-causal marker of more limited disease severity in these patients. In other words, the primary research question is whether we can reduce cerebral ischemia and improve prognosis of post-cardiac arrest survivors by targeting higher mean systemic blood pressures thereby optimizing cerebral perfusion during their stay in the intensive care unit. To answer this, we propose a multicenter interventional open label investigator driven randomized controlled trial to compare a goal-directed potentially neuro-protective hemodynamic optimization strategy with the current standard of care. Primary efficacy endpoints of the study will include extent of cerebral damage as assessed with diffusion weighted magnetic resonance imaging (DW-MRI), functional and neurocognitive testing, biomarkers of brain injury and survival rates. The final utilization goal of the Neuroprotect post-CA trial is to show that our adapted hemodynamic protocol reduces cerebral ischemia, and improves survival and functional outcome of post-cardiac arrest patients.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 112

Inclusion Criteria

Out-of-hospital CA of presumed cardiac cause irrespective of the presenting rhythm
Unconsciousness (Glasgow coma scale < 8) at hospital admission
Age ≥ 18 years
Sustained return of spontaneous circulation (ROSC) (=when chest compressions have not been required for 20 consecutive minutes)

Exclusion Criteria

Suspected or confirmed intracranial bleeding or stroke
Known limitations in therapy or Do Not Resuscitate-order
Known disease compromising 180 day survival
Known pre-CA cerebral performance category 3-4
Previous stroke (TIA can be included)
MRI incompatible cardiac or neurosurgical device
Systolic blood pressure < 90 mmHg on norepinephrine > 1 mcg/kg/min).
Open chest
ECMO (extracorporeal membrane oxygenation)
Pregnancy

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	MAP > 65mmHg	MAP\>65mmHg
Neuroprotect	Neuroprotective goal directed hemodynamic optimization	MAP between 85-100mmHg SVO2 between 65-75%

Primary Outcome Measures

Name	Time	Method
% of Ischaemic Voxels With an ADC<0.65 mm2/s on Day 4-5 (Diffusion Weighted MRI)	day 4-5	cerebral ischemia in post-cardiac arrest (CA) patients as quantified by the apparent diffusion coefficient (ADC) on diffusion weighted MRI (DW-MRI) to be performed at day 4- 5 post-CA using ADC scores in 11 pre-specified brain regions (frontal cortex, parietal cortex, temporal cortex, occipital cortex, precentral cortex, postcentral cortex, caudate nucleus, putamen, thalamus, cerebellum, pons).

Secondary Outcome Measures