Sedation of Cerebrovascular Ventilated Critical Care Patients Clinical Trial
Official title:
MOderate vs DEep Regimen in NeuroIntensive Care SEdation
Background: Sedation of the intensive care unit (ICU) patient is necessary to relieve the
patient from pain, anxiety and agitation and to enable mechanical ventilation, diagnostic
investigations and invasive procedures. While sedation policy has shifted from deep sedation
to moderate, minimal, or even no sedation in the general ICU, optimal sedation of the
cerebrovascular ICU patient is unclear and controversial.
Method: MOderate vs DEep Regime in NeuroIntensive care SEdation (MODERNISE) is a
prospective, randomized, open, two-center trial. Patients with acute ischemic stroke,
intracerebral hemorrhage or subarachnoid hemorrhage who need to be ventilated are eligible
for enrollment. It is intended to enroll 50 patients per group (n=100). Patients are
randomized within 72h from admission to either moderate sedation as defined by Richmond
Agitation Sedation Scale (RASS) >= -3 or to deep sedation as defined by RASS < -3 for the
next 72h, after which weaning from sedation is aimed for in a stepwise fashion in both
groups. If reduction of sedation is not feasible, patients remain at their respective
sedation level for another 12 hours, and sedation reduction is then tried again. Patients
are multimodally monitored for systemic and cerebral parameters (the latter including
bispectral index (BIS) monitoring). The primary endpoint is ICU length of stay (ICU-LOS);
secondary endpoints are several pre-defined variables of the ICU course, feasibility of
sedation levels without violation of pre-defined safety criteria, pre-defined complications,
and short- and long-term functional outcome and mortality.
Conclusion: The feasibility, safety and benefits of moderate as opposed to deep sedation
even in the acute phase of severe cerebrovascular disease needs to be clarified in a
prospective randomized study. Results from this study might change sedation regimes and help
prevent unwanted effects of deep sedation in the brain-injured patient.
Executive Summary Rationale While sedation policy has shifted from deep sedation to
moderate, minimal, or even no sedation in the general ICU, optimal sedation of the
cerebrovascular neuro-ICU (NICU) patient is unclear and controversial. The rationale of this
study is to analyze potential benefits, feasibility and safety of moderate as opposed to
deep sedation.
Aim and hypothesis MODERNISE is a pilot trial aiming to investigate the safety, feasibility
and potential benefits of moderate vs. deep sedation in patients with severe ischemic
stroke, intracerebral hemorrhage or subarachnoid hemorrhage. The primary objective is to
compare moderate sedation and deep sedation with respect to ICU-LOS.
Design MODERNISE is a prospective, randomized, controlled, outcome observer-blinded,
two-center trial. Patients are randomized to either moderate sedation as defined by RASS) >=
-3 or to deep sedation as defined by RASS < -3.
Study Outcomes The primary endpoint is ICU-LOS. Secondary endpoints are the ventilation-free
ICU-LOS, ventilation duration, sedation duration, complications (including episodes of
treatment-demanding increases of intracranial pressure (ICP), episodes of hypotension,
episodes of cerebral hypoperfusion, pneumonia, sepsis, ileus, episodes of paroxysmal
sympathetic hyperactivity (PSH)), time within sedation goal, demand of sedatives, demand of
analgesics, demand of vasopressors, scores (RASS, nociception coma scale (NCS), Glasgow Coma
Scale (GCS), intensive care delirium screening checklist (ICDSC), confusion assessment
method - ICU (CAM-ICU), ICU mortality, in-hospital mortality, modified Rankin Scale (mRS) at
90 days, PTSD at 90 days.
Discussion To clarify the benefits of moderate sedation in critical care ventilated stroke
patients, a randomized multicentre trial is clearly needed. If this two-center pilot trial
shows differences in relevant parameters of the ICU course and gives promising safety and
feasibility results, a multi-centre trial may be planned on this basis.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care