title: Optimizing sedation in patients with acute brain injury.
abstract: Daily interruption of sedative therapy and limitation of deep sedation have been shown in several randomized trials to reduce the duration of mechanical ventilation and hospital length of stay, and to improve the outcome of critically ill patients. However, patients with severe acute brain injury (ABI; including subjects with coma after traumatic brain injury, ischaemic/haemorrhagic stroke, cardiac arrest, status epilepticus) were excluded from these studies. Therefore, whether the new paradigm of minimal sedation can be translated to the neuro-ICU (NICU) is unclear. In patients with ABI, sedation has 'general' indications (control of anxiety, pain, discomfort, agitation, facilitation of mechanical ventilation) and 'neuro-specific' indications (reduction of cerebral metabolic demand, improved brain tolerance to ischaemia). Sedation also is an essential therapeutic component of intracranial pressure therapy, targeted temperature management and seizure control. Given the lack of large trials which have evaluated clinically relevant endpoints, sedative selection depends on the effect of each agent on cerebral and systemic haemodynamics. Titration and withdrawal of sedation in the NICU setting has to be balanced between the risk that interrupting sedation might exacerbate brain injury (e.g. intracranial pressure elevation) and the potential benefits of enhanced neurological function and reduced complications. In this review, we provide a concise summary of cerebral physiologic effects of sedatives and analgesics, the advantages/disadvantages of each agent, the comparative effects of standard sedatives (propofol and midazolam) and the emerging role of alternative drugs (ketamine). We suggest a pragmatic approach for the use of sedation-analgesia in the NICU, focusing on some practical aspects, including optimal titration and management of sedation withdrawal according to ABI severity.
authors.affiliation: Department of Intensive Care Medicine, CHUV-University Hospital, CH-1011, Lausanne, Switzerland. mauro.oddo@chuv.ch.|Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, CH-1011, Lausanne, Switzerland. mauro.oddo@chuv.ch.
authors.forename: Mauro
authors.initials: M
authors.lastname: Oddo
authors.affiliation: School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.|Neurointensive Care, Department of Emergency and Intensive Care, San Gerardo Hospital, Monza, Italy.|Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.
authors.forename: Ilaria Alice
authors.initials: IA
authors.lastname: Crippa
authors.affiliation: Department of Medicine and Interdepartmental Division of Critical Care Medicine, Mount Sinai Hospital, University of Toronto, 600 University Ave #18-216, Toronto, M5G 1X5, Canada.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Mehta
authors.affiliation: Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK.
authors.forename: David
authors.initials: D
authors.lastname: Menon
authors.affiliation: Department of Anesthesiology and Intensive Care, Hôpital Michallon, Grenoble University Hospital, F-38043, Grenoble, France.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Payen
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.
authors.forename: Fabio Silvio
authors.initials: FS
authors.lastname: Taccone
authors.affiliation: School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.|Neurointensive Care, Department of Emergency and Intensive Care, San Gerardo Hospital, Monza, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Citerio
mesh_terms: D000698:Analgesia / Q000009:adverse effects / Q000379:methods; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D003422:Critical Care / Q000379:methods*; D016638:Critical Illness / Q000451:nursing; D054810:Deep Sedation / Q000009:adverse effects / Q000379:methods* / Q000592:standards*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D007362:Intensive Care Units; D007649:Ketamine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008874:Midazolam / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015742:Propofol / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D012121:Respiration, Artificial / Q000009:adverse effects / Q000451:nursing
chemical_list: D006993:Hypnotics and Sedatives; D007649:Ketamine; D008874:Midazolam; D015742:Propofol