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CLINICAL TRIALS MONITOR Neurointensivists in Germany and the U.S. to Study Lower Sedation in Stroke Patients By Robert Kowalski, MD With a trend of reduced sedation levels The MODERNISE trial includes safety measures for potential taking hold in general intensive care units, a adverse events, including osmotherapeutics if needed for ICP neurointensive care center in Germany has management. The study also will employ bispectral index (BIS) designed a study to evaluate the impact of monitoring to assess depth of sedation. Specific sedative or lessening sedation in Neuro ICUs. analgesic agents used during the trial are at the discretion of treating physicians. Based at Heidelberg University, with enrollment at a second center in the U.S. Enrollment began at the University of Heidelberg in December anticipated, the trial proposes to randomize 2015 with three patients recruited thus far. Discussions are ventilated patients treated for severe stroke underway to also enroll patients at the Maine Medical Center in in the ICU to moderate or deep sedation for three full days, and Portland, Maine. assess ICU course and safety. In addition to ICU length of stay, secondary outcome measures The study, MOderate vs DEep Regime in NeuroIntensive care in the study are hospital length of stay, ventilator-free time in the SEdation (MODERNISE), would enroll 100 patients with ischemic ICU, duration of vasopressor dependence, duration of analgesia stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. dependence, sepsis incidence, functional outcome as measured Half would be assigned to deep sedation, defined as a Richmond by the modified Rankin Scale (mRS) at three months, and Agitation Sedation Scale (RASS) score less than -3, and half to complications and mortality. lighter sedation for the study period. The primary outcome measure is Neuro ICU length of stay. Overall, the trial may provide guidance on applicability of sedation measures increasingly used in other ICUs to the Neuro “I think neurocritical care patients have been neglected in ICU setting, Dr. Bösel said. sedation studies so far, probably because it is so hard to measure wakefulness and differentiate effects of sedation from the effects “Daily wake-up tests, now almost customary in the general ICU, of brain injuryin these patients,” said Julian Bösel, MD, director of have not shown advantages in small studies in neurocritical care the Neurocritical Care Unit of the University of Heidelberg, and patients, rather to the contrary. Maybe a continuously moderate principal investigator of the trial. sedation and gradual weaning from that is better, but that has never been investigated in prospective randomized fashion,” “The deleterious effects of sedation shown in other ICU said Dr. Bösel. “MODERNISE is a pilot study to fill that gap, and populations (delirium, cognitive dysfunction, GI paralysis, directed at feasibility and safety, to start with.” immunosuppression and infection, prolonged coma) certainly apply to neurocritical care patients, as well.” Dr. Bösel said. Julian Bösel, MD Patients enrolled in the trial will undergo either moderate or deep sedation by study criteria for 72 hours, a time period corresponding with the acute phase of illness in the stroke subtypes included. “I initially wanted to have a longer time window, but it just seemed too demanding for a two-center study with minimal funding in terms of data load. It is also very hard to keep a lot of influences stable in that environment for longer,” Dr. Bösel said. Part of the hesitance to use lighter sedation levels on neurocritical care patients may stem from concerns about reducing or eliminating benefits that deeper sedation provides patients with severe acute neurologic injuries, Dr. Bösel said. Assessing this is part of the rationale for the MODERNISE trial. “Low sedation is feared in the neurocritical care patient because of possible increases in ICP and also following the rationale that putting the brain in the resting state by deep sedation may be beneficial with regard to the energy balance, suppressing depolarizations, avoiding extremes in ICP/CPP/MAP,” he said. “But that has never been sufficiently proven.” 16


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