Traumatic Brain Injury
Monitoring
Intracranial Pressure Monitoring
Brain Tissue Oxygen Monitoring
Non-Pharmacological Therapy
Red Cell Transfusion
Decompressive Craniectomy
- Hutchinson. Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension (RESCUEicp). N Engl J Med 2016;375:1119-1130
- Cooper. Decompressive craniectomy in diffuse traumatic brain injury (DECRA). N Engl J Med 2011;364:1493-502
- Jiang. Efficacy of standard trauma craniectomy for refractory intracranial hypertension with severe traumatic brain injury: a multicenter, prospective, randomized controlled study. J Neurotrauma 2005;22(6):623-628
- Taylor. A randomized trial of very early decompressive craniectomy in children with traumatic brain injury and sustained intracranial hypertension. Childs Nerv Syst. 2001;17(3):154-62
Induced Hypothermia
- Cooper. Effect of Early Sustained Prophylactic Hypothermia on Neurologic Outcomes Among Patients With Severe Traumatic Brain InjuryThe POLAR Randomized Clinical Trial. JAMA 2018;320(21):2211-2220
- Andrews. Hypothermia for Intracranial Hypertension after Traumatic Brain Injury (Eurotherm3235 Trial). N Engl J Med 2015;epublished October 7th
- Clifton. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol 2011;10:131-39
- Clifton. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med 2001;344:556-63
Hyperventilation
Pharmacotherapy
Progesterone
Tranexamic Acid
- Rowell. Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury. JAMA 2020;324(10):961-974
- The CRASH-3 Trial Collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomized, placebo-controlled trial. Lancet. 2019;394(10210):1713–23
Cerebral Infarction
Thrombolysis
Thrombolysis - tPA
- Ma. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. N Engl J Med 2019;380:1795–1803
- Hacke. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke (ECASS 3). N Engl J Med 2008;359(13):1317-29
- Clark. Recombinant Tissue-Type Plasminogen Activator (Alteplase) for Ischemic Stroke 3 to 5 Hours After Symptom Onset. The ATLANTIS Study. JAMA 1999;282(21):2019-2026
- Hacke. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet 1998; 352(9136):1245-51
- NINDS study group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333(24):1581-7
- Hacke. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995; 274(13):1017-25
Thrombolysis - Tenecteplase
- Kvistad. Tenecteplase Versus Alteplase for the Management of Acute Ischaemic Stroke in Norway (NOR-TEST 2, Part A): A Phase 3, Randomised, Open-Label, Blinded Endpoint, Non-Inferiority Trial. Lancet Neurol 2022 21(6) 511-19
- Campbell. Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke. (EXTEND-IA TNK Part 2). JAMA 2020;323(13):1257-1265
- Campbell. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. (EXTEND-IA TNK). N Engl J Med 2018;378:1573-1582
Thrombectomy
Thrombectomy - Anterior Circulation
- Berkhemer. A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke (MR CLEAN). N Engl J Med 2015;372:11-20
- Campbell. Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection (EXTEND-IA). N Engl J Med 2015;372:1009-1018
- Saver. Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke (SWIFT-PRIME). N Engl J Med 2015;372:11-20
- Jovin. Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke (REVASCAT). N Engl J Med 2015; 372:2296-2306
- Goyal. Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke (ESCAPE). N Engl J Med 2015; 372:1019-1030
Thrombectomy - Posterior Circulation
Thrombectomy - Extended Window
- Jovin. Trial of Thrombectomy 6 to 24 Hours after Stroke Due to Basilar-Artery Occlusion. N Engl J Med 2022; 387:1373-1384
- Nogueira. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct (DAWN). N Engl J Med 2018; 378:11-21
- Albers. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging (DEFUSE-3). N Engl J Med 2018; 378:708-718
Medical Management
Dual Antiplatelet Therapy
Other Management
Red Cell Transfusion
Decompressive Craniectomy
- Jüttler. Hemicraniectomy in Older Patients with Extensive Middle-Cerebral-Artery Stroke (Destiny II). N Engl J Med 2014;370:1091-1100
- Hofmeijer. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial (HAMLET). Lancet Neurol 2009;8:326–33
- Jüttler. Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY). A Randomized, Controlled Trial. Stroke 2007;38:2518
- Vahedi. Sequential-Design, Multicenter, Randomized, Controlled Trial of Early Decompressive Craniectomy in Malignant Middle Cerebral Artery Infarction (DECIMAL Trial). Stroke. 2007;38:2506
Tracheostomy
- Bösel. Effect of Early vs Standard Approach to Tracheostomy on Functional Outcome at 6 Months Among Patients With Severe Stroke Receiving Mechanical Ventilation (SETPOINT2). JAMA. 2022;327(19):1899-1909
- Bösel. Stroke-Related Early Tracheostomy Versus Prolonged Orotracheal Intubation in Neurocritical Care Trial (SETPOINT). Stroke 2013;44:21–28
Cerebral Venous Sinus Thrombosis
Cerebral Haemorrhage
Blood Pressure
Surgery
- Hanley. Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet 2019; 393(10175):1021-1032
- Mendelow. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet 2013;382: 397–408
- Medelow. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 2005;365:387-397
Anticoagulation Reversal
- Connolly. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. N Engl J Med 2019;380:1326-1335
- Sarode. Efficacy and Safety of a 4-Factor Prothrombin Complex Concentrate in Patients on Vitamin K Antagonists Presenting With Major Bleeding. Circulation 2013;128:1234–1243
Aneurysmal Subarachnoid Haemorrhage
Red Cell Transfusion
Nimodipine
- Pickard. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ 1989;298(6674):636–642
- Allen. Cerebral Arterial Spasm – A Controlled Trial of Nimodipine in Patients with Subarachnoid Hemorrhage. N Engl J Med 1983; 308:619-624
Clazosentan
- Macdonald. Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol 2011;10:618–25
- Macdonald. Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke 2012;43:1463–9
- Macdonald. Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial. Stroke 2008;39:3015–21
Tranexamic Acid
Sedation
Dose
No Sedation
Sedation Breaks
- Mehta. Daily Sedation Interruption in Mechanically Ventilated Critically Ill Patients Cared for With a Sedation Protocol. A Randomized Controlled Trial (SLEAP study). JAMA 2012; epublished ahead of print
- Girard.Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial). Lancet 2008;371(9607):126-134
- Kress. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000;342:1471-7
Individual Sedatives
Dexmedetomidine
- Shehabi. Early Sedation with Dexmedetomidine in Critically Ill Patients (SPICE III trial). N Engl J Med 2019;epublished May 19th
- Reade. Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated DeliriumA Randomized Clinical Trial (DahLIA Trial). JAMA 2016;epublished March 15th
- Jakob. Dexmedetomidine vs Midazolam or Propofol for Sedation During Prolonged Mechanical Ventilation: Two Randomized Controlled Trials. JAMA 2012;307(11):1151-1160
- Pandharipande. Effect of sedation with dexmedetomidine versus lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 2007;298:2644-53
Inhaled Sedation
- Miatello. Inhaled isoflurane for sedation of mechanically ventilated children in intensive care (IsoCOMFORT): a multicentre, randomised, active-control, assessor-masked, non-inferiority phase 3 trial. Lancet Respir Med 2025;epublished July 15th
- Jabaudon. Inhaled Sedation in Acute Respiratory Distress SyndromeThe SESAR Randomized Clinical Trial. JAMA 2025;epublished March 18th
Delirium
Monitoring
Pharmacotherapy
Antipsychotics
- Andersen-Ranberg. Haloperidol for the Treatment of Delirium in ICU Patients. N Engl J Med 2022;epublished October 26th
- Girard. Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness. N Engl J Med 2018;379:2506-2516
- Page. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. Lancet Respiratory Medicine 2013;epublished August 21st
Dexmedetomidine
- Reade. Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated DeliriumA Randomized Clinical Trial (DahLIA Trial). JAMA 2016;epublished March 15th
- Shehabi. Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology 2009;111(5):1075-1084
Seizures
Status Epilepticus
Drug Therapy
- Kapur. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. (ESETT). N Engl J Med 2019;381:2103-2113
- Silbergleit. Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus. N Engl J Med 2012;366:591-600
- Alldredge. A Comparison of Lorazepam, Diazepam, and Placebo for the Treatment of Out-of-Hospital Status Epilepticus. N Engl J Med 2001;345:631-637
- Treiman. A Comparison of Four Treatments for Generalized Convulsive Status Epilepticus. N Engl J Med 1998; 339:792-798
Therapeutic Hypothermia
Paediatric Status Epilepticus
- Lyttle. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019;393(10186):2125-2134
- Dalziel. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet 2019;393(10186):2135-2145
- Chamberlain. Lorazepam vs Diazepam for Pediatric Status Epilepticus. JAMA 2014;311(16):1652-1660
EEG
Post Cardiac Arrest EEG
Meningitis
Corticosteroids
Therapeutic Hypothermia
Spinal Cord Injury
Corticosteroids
- Bracken. Efficacy of methylprednisolone in acute spinal cord injury (NASCIS I). JAMA 1984;251:45–52
- Bracken. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study (NASCIS II). N Engl J Med. 1990;322:1405–1411
- Bracken. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study (NASCIS III). JAMA 1997;277(20):1597-604
Guillain-Barré Syndrome
Immunoglobulin
- Walgaard. Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS). Lancet 2021;20(4) 275-283
- Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group. Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome. Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group. Lancet 1997; 349(9047):225-230
- van der Meché. A Randomized Trial Comparing Intravenous Immune Globulin and Plasma Exchange in Guillain–Barré Syndrome. N Engl J Med 1992;326:1123-1129
Plasma Exchange
- Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group. Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome. Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group. Lancet 1997; 349(9047):225-230
- van der Meché. A Randomized Trial Comparing Intravenous Immune Globulin and Plasma Exchange in Guillain–Barré Syndrome. N Engl J Med 1992;326:1123-1129
Mobilisation & Rehabilitation
Mobilisation / Rehabilitation in ICU
- The TEAM Study Investigators and the ANZICS Clinical Trials Group. Early Active Mobilization during Mechanical Ventilation in the ICU. N Engl J Med 2022;epublished October 26th
- Schaller. Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial. Lancet 2016;388(10052):1377–1388
- Schweickert. Early physical and occupational therapy in mechanically ventilated, critically ill patients: A randomised controlled trial. Lancet 2009; 373:1874–1882
Mobilisation / Rehabilitation in the Ward
- Morris. Standardized Rehabilitation and Hospital Length of Stay Among Patients With Acute Respiratory Failure. A Randomized Clinical Trial. JAMA 2016;315(24):2694-2702
- Kayambu. Early physical rehabilitation in intensive care patients with sepsis syndromes: a pilot randomised controlled trial. Intensive Care Med 2015;epublished April 8th
- Gruther. Can Early Rehabilitation on the General Ward After an Intensive Care Unit Stay Reduce Hospital Length of Stay in Survivors of Critical Illness?: A Randomized Controlled Trial. Am J Phys Med Rehabil 2017;96(9):607-615
- Jensen. A recovery program to improve quality of life, sense of coherence and psychological health in ICU survivors: a multicenter randomized controlled trial, the RAPIT study. Intensive Care Med 2016;epublished September 30th
Last updated March 27th, 2025