Sedation Depth in Neurocritical Care (MODERNISE)

Heidelberg University

Status and phase: Unknown; Phase 2

Conditions: Sedation of Cerebrovascular Ventilated Critical Care Patients

Treatments: Drug: Vasopressors to maintain normal blood pressure values, if needed; Drug: Osmotherapeutics to lowr intracranial pressure, if needed; Other: Intensive Care Sedation (depth, level); Procedure: Decompressive neurosurgery, if needed; Procedure: Endovascular stroke care to treat brain vessel occlusions, if needed

Study type: Interventional

Funder types: Other

Identifiers

NCT02317497

MODERNISE_Prot_HD

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. age 18 years or older, either sex,

2. one of the following confirmed admission diagnoses:

   • non-traumatic acute ischemic infarction (AIS)
   • non-traumatic intracerebral hemorrhage (ICH)
   • non-traumatic subarachnoid hemorrhage (SAH),

3. ventilated with expected need of further artificial ventilation for more than 72h,

4. expected ICU-LOS of more than 5 days,

5. informed consent by a legal representative.

Exclusion criteria

1. pregnancy
2. intubation and artificial ventilation for less than 3 days
3. severe adult respiratory distress Syndrome (ARDS)
4. severe sepsis
5. other systemic disorders that demand deep sedation
6. extreme agitation
7. need of pharmacological paralysis
8. epileptic state
9. refractory intracranial hypertension
10. participation in any other interventional trial
11. life expectancy < 3 weeks, very poor prognosis

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Moderate sedation (M)

Experimental group

Description:

1. Moderate sedation defined by target RASS of \>= -3. The intervention (M) is sedation by use of any sedative and/or analgesic medication(s) left at the discretion of the treating physicians targeted at a RASS of \>= -3 (patient responds to verbal stimulus) from randomization for the next 72h. RASS will be assessed once every 8 h (at he beginning of each shift) and measures undertaken to achieve the target level. If safety-limits are violated, sedation may have to be deepened below the target level for 8h and re-assessed at the beginning of the next shift with the aim to approach the target level of the intervention group again.

Treatment:

Drug: Osmotherapeutics to lowr intracranial pressure, if needed

Procedure: Decompressive neurosurgery, if needed

Procedure: Endovascular stroke care to treat brain vessel occlusions, if needed

Other: Intensive Care Sedation (depth, level)

Drug: Vasopressors to maintain normal blood pressure values, if needed

Deep sedation (D)

Active Comparator group

Description:

2. Deep sedation defined by target RASS of \< -3. The control (D) is sedation by use of any sedative and/or analgesic medication(s) left at the discretion of the treating physicians targeted at a RASS of \< -3 (patient does not respond to verbal stimulus) from randomization for the next 72h. RASS will be assessed once every 8 h (at he beginning of each shift) and measures undertaken to achieve the target level. If safety-limits are violated, sedation may have to be reduced above the target level for 8h and re-assessed at the beginning of the next shift with the aim to approach the target level of the control group again.

Treatment:

Drug: Osmotherapeutics to lowr intracranial pressure, if needed

Procedure: Decompressive neurosurgery, if needed

Procedure: Endovascular stroke care to treat brain vessel occlusions, if needed

Other: Intensive Care Sedation (depth, level)

Drug: Vasopressors to maintain normal blood pressure values, if needed