Sedation of Cerebrovascular Ventilated Critical Care Patients Clinical Trial
— MODERNISEOfficial 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.
| Status | Not yet recruiting |
| Enrollment | 100 |
| Est. completion date | November 2018 |
| Est. primary completion date | January 2018 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care
| Country | Name | City | State |
|---|---|---|---|
| Germany | NeuroIntensive Care Unit, Department of Neurology, University Hospital Heidelberg | Heidelberg |
| Lead Sponsor | Collaborator |
|---|---|
| Heidelberg University |
Germany,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Intensive Care Unit Length of Stay (ICU-LOS) | • Intensive care unit length of stay (ICU-LOS) [days from admission until discharge from the intensive care unit] | Admission to Discharge, ca. 3 weeks from onset | No |
| Secondary | In-hospital stay | [days from admission until discharge from hospital] | within hospital stay, ca. 3 weeks from onset | No |
| Secondary | Ventilation-free ICU-LOS | [days from ventilator-independence for 24 h until discharge from the intensive care unit] | within hospital stay, ca. 3 weeks from onset | No |
| Secondary | Accumulated Duration of Ventilation | [Sum of half-days on the ventilator until the patient is ventilator-independent for 24 h] | within hospital stay, ca. 3 weeks from onset | No |
| Secondary | Sedation duration | [Sum of half-days on any sedative medication (irrespective of analgesic drugs)] | within hospital stay, ca. 3 weeks from onset | No |
| Secondary | Opioid Analgesia duration | [Sum of half-days on any opioid medication (irrespective of sedative drugs)] | within hospital stay, ca. 3 weeks from onset | No |
| Secondary | Time within sedation goal | [Sum of 8h-shifts fulfilling the randomized sedation target during the 72h after randomization or above that target afterwards within the first NICU week] | within hospital stay, ca. 3 weeks from onset | No |
| Secondary | Accumulated Duration of Ventilator Weaning | [Sum of half-days spent under the application of a ventilator weaning protocol | within hospital stay, ca. 3 weeks from onset | No |
| Secondary | Accumulated Duration of Analgesia and Sedation Dependence | [ Sum of half-days requiring the application of sedatives and analgesics] | within hospital stay, ca. 3 weeks from onset | No |
| Secondary | Accumulated Duration of Vasopressor Dependence | [Sum of half-days spent under any vasopressors] | within hospital stay, ca. 3 weeks from onset | No |
| Secondary | Average ICP during sedation target period (if available) | [Median and interquartile range of 3 x 3 maximum ICP measurements per shift during the 72h after randomization] | within hospital stay, ca. 3 weeks from onset | Yes |
| Secondary | Average BIS during sedation target period | [Median and interquartile range of 3 x 3 x average BIS measurements per shift during the 72h from randomization] | within hospital stay, ca. 3 weeks from onset | No |
| Secondary | Average BIS after sedation target period | [Median and interquartile range of 3 x 3 x average BIS measurements per shift from 72h after randomization to discharge] | within hospital stay, ca. 3 weeks from onset | No |
| Secondary | Occurrence and Duration of Sepsis | [number of episodes and duration of sepsis as defined by international criteria] | within hospital stay, ca. 3 weeks from onset | Yes |
| Secondary | Complications [number and type of pre-defined complications ] | [number and type of pre-defined complications ] | within hospital stay, ca. 3 weeks from onset | Yes |
| Secondary | Functional Outcome [modified Rankin Scale (mRS) | [modified Rankin Scale (mRS) at 3 months from insult] | 3 months from insult | No |
| Secondary | Mortality | [death of any cause and type of death during the ICU-stay or in-hospital stay or within 3 months after admission] | during the ICU-stay or in-hospital stay or within 3 months after admission | Yes |
| Secondary | Cost of Treatment | [total ICU-cost estimated by length of stay and severity-based disease-related Groups] multiplicator of each individual patient] [total ICU-cost estimated by length of stay and severity-based DRG multiplicator of each individual patient] | within hospital stay, ca. 3 weeks from onset | No |