• Clinical science
  • Clinician

Secondary brain injury and neuroprotective measures


Secondary brain injury is an indirect injury caused by physiological changes that are triggered by an acute CNS insult (e.g., traumatic brain injury, stroke, cerebral hypoxia secondary to cardiac arrest) and/or the management of the primary insult. Unlike primary brain injury, which refers to the direct, immediate, and potentially irreversible neuronal damage from an acute CNS insult, secondary brain injury is preventable or can be minimized with the early administration of neuroprotective measures. Neuroprotective measures involve the early and aggressive control of factors that are implicated in the etiology of secondary brain injury. Such measures include optimization of oxygenation, ventilation, blood pressure, blood sugar, body temperature, intracranial pressure, and electrolyte levels. In addition, seizure prophylaxis and treatment, nutritional support, and patient positioning are important aspects of neuroprotective measures.


  • Secondary brain injury: indirect brain injury that results from physiological changes triggered by acute CNS insults and/or treatment measures for acute CNS insults that affect ICP, oxygenation, blood pressure, etc.
  • Neuroprotective measures: measures to prevent and/or minimize secondary brain injury in the immediate management of patients who have sustained an acute CNS insult


An acute CNS insult can trigger any of the following, resulting in secondary brain injury. [1][2][3]

Secondary brain injury is preventable. Neuroprotective measures to prevent or minimize secondary brain injury should be initiated as early as possible in all patients with acute CNS insults.

Oxygenation and ventilation

Avoid hypoxia, hyperoxia, hypocapnia, and hypercapnia in patients with acute CNS insult. [2]

Control of PaO2 (oxygenation)

Hypoxia and hyperoxia can worsen neurological outcome and should be avoided.

Routine use of supplemental oxygen in nonhypoxic patients is of no clinical benefit in the prevention of secondary brain injury. [7]

Control of PaCO2 (ventilation)

Hypercapnia (including permissive hypercapnia) and long-term hypocapnia worsen neurological outcome in patients with acute CNS insults and should be avoided. [2]

Hypocapnia should only be used as a temporizing measure for patients with signs of cerebral herniation syndromes while simultaneously initiating definitive management for ↑ ICP. [6]

Blood pressure and cerebral perfusion pressure

Blood pressure control after acute CNS insult is complex and the optimal treatment goals are yet to be established. The main aim is to maintain cerebral perfusion pressure (CPP) between 60–70 mm Hg by maintaining mean arterial pressure (MAP) between 65–100 mm Hg [2][9][3]

Avoid hypovolemia and hypervolemia when resuscitating a patient with an acute CNS insult. Hypovolemia decreases cerebral perfusion, worsens cerebral ischemia, and may potentiate thromboses in the injured tissue. Hypervolemia worsens cerebral edema. [4]

Hypotensive patients

Hypotension should be avoided in all patients with depressed consciousness as it decreases CBF, thus worsening neurological outcomes and increasing the mortality risk. [2][10][11]

Hypertensive patients

The SBP threshold at which to administer antihypertensives and target SBP differ according to the etiology of the acute CNS insult. [17][18][19]

Ischemic stroke

Intracranial hemorrhage (including TBI)

  • Target SBP: 140–180 mm Hg [17][20][21]
  • Timing: Initiate treatment as soon as possible in patients with SBP > 180 mm Hg [18][22][11][19]
  • Commonly used antihypertensive agents [18][11]

Blood sugar

Blood glucose should be checked at presentation and serially monitored. Strict blood glucose control is recommended as hypoglycemia or hyperglycemia worsen the neurological outcome after an acute CNS insult.

Avoid dextrose-containing solutions in the resuscitation of nonhypoglycemic patients with an acute CNS insult. [4]

Seizure prophylaxis and treatment

Because seizures may be clinically inapparent in comatose patients or those on neuromuscular blockers, continuous EEG monitoring is recommended in this group of patients.

Electrolyte abnormalities

Sodium disorders and hypokalemia are the most common electrolyte abnormalities seen after an acute CNS insult. [30][31]

Disorders of sodium balance [32]

  • General considerations
    • Identify and treat the underlying cause.
    • Sodium disturbances are often self-limiting in patients with brain injury.
  • Hyponatremia [32]
    • Acutely symptomatic patients: prompt treatment with gradual correction (see “Treatment” in hyponatremia and SIADH)
    • Asymptomatic patients: Supportive treatment strategy is usually appropriate.
  • Hypernatremia [33]
    • Severe elevation (> 160 mEq/L): gradual correction (see “Treatment” section in hypernatremia)
    • Mild–moderate elevation (up to 160 mEq/L): consider gradual correction

Symptomatic hypernatremia should be corrected gradually to minimize the risk of cerebral and pulmonary edema. Symptomatic hyponatremia should be corrected gradually to minimize the risk of central pontine myelinolysis. [32]

Disorders of potassium balance

Neurogenic fever and targeted temperature management

Neurogenic fever (central hyperthermia) [34][35]

In patients with acute CNS insults, fever should be aggressively treated as it is associated with a poor neurological outcome and increased risk of mortality.

Targeted temperature management (TTM)

  • Definition: controlled maintenance of a target body temperature aimed to prevent secondary brain injury after an acute CNS insult
  • Target body temperature: differs according to the inciting event
  • Measures to achieve TTM [42]


Intracranial pressure (ICP)

  • Target: Maintain ICP below 20–22 mm Hg [2][12][3]
  • Treatment: See ICP management.

Patient positioning


Nutrition [50][51]

  • Neurological insult typically leads to a hypermetabolic state. [52]
  • Early (ideally within 24 hours) nutritional support (enteral and parenteral) improves neurological outcomes compared to delayed nutritional support.
  • Enteral nutrition is preferred if possible; patients with low GCS or dysphagia may require a nasogastric or nasojejunal tube.

Acute management checklist

  • Identify and treat hypoxia.
  • Maintain normocapnia (consider short-term hypocapnia in patients with signs of ↑ICP or cerebral herniation syndromes).
  • Blood pressure management
  • Normoglycemia
  • Consider seizure prophylaxis and/or seizure management (if appropriate)
  • Identify and treat electrolyte abnormalities.
  • Identify and treat hyperthermia.
  • ICP management.
  • Patient positioning
  • Support nutritional needs.
  • 1. Kinoshita K. Traumatic brain injury: pathophysiology for neurocritical care. Journal of Intensive Care. 2016; 4(1). doi: 10.1186/s40560-016-0138-3.
  • 2. Walls R, Hockberger R, Gausche-Hill M. Rosen's Emergency Medicine. Philadelphia, PA: Elsevier Health Sciences; 2018.
  • 3. Abdelmalik PA, Draghic N, Ling GSF. Management of moderate and severe traumatic brain injury. Transfusion (Paris). 2019; 59(S2): pp. 1529–1538. doi: 10.1111/trf.15171.
  • 4. EC J, JL S, Jr AH, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 2013; 44(3): pp. 870–947. doi: 10.1161/STR.0b013e318284056a.
  • 5. Madan A. Correlation between the levels of SpO2 and PaO2. Lung India. 2017; 34(3): pp. 307–308. doi: 10.4103/lungindia.lungindia_106_17.
  • 6. Vella MA, Crandall ML, Patel MB. Acute Management of Traumatic Brain Injury. Surg Clin North Am. 2017; 97(5): pp. 1015–1030. doi: 10.1016/j.suc.2017.06.003.
  • 7. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019; 50(12). doi: 10.1161/str.0000000000000211.
  • 8. Hatchimonji JS, Dumas RP, Kaufman EJ, Scantling D, Stoecker JB, Holena DN. Questioning dogma: does a GCS of 8 require intubation?. European Journal of Trauma and Emergency Surgery. 2020. doi: 10.1007/s00068-020-01383-4.
  • 9. Moore AJ, Newell DW. Tumor Neurosurgery. Springer Science & Business Media; 2010.
  • 10. Besmertis, L; Bonovich, DC; and Hemphill, JC. The Role of Hypotension in Secondary Brain Injury after Intracerebral Hemorrhage. Stroke. 2001; Vol 32, Issue suppl_1: p. 358. url: https://www.ahajournals.org/doi/10.1161/str.32.suppl_1.358-d.
  • 11. Appleton JP, Sprigg N, Bath PM. Blood pressure management in acute stroke. BMJ. 2016; 1(2): pp. 72–82. doi: 10.1136/svn-2016-000020.
  • 12. Carney N, Totten AM, O’Reilly C, et al. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2016; 80(1): pp. 6–15. doi: 10.1227/neu.0000000000001432.
  • 13. Thompson M, McIntyre L, Hutton B, et al. Comparison of crystalloid resuscitation fluids for treatment of acute brain injury: a clinical and pre-clinical systematic review and network meta-analysis protocol. Systematic Reviews. 2018; 7(1). doi: 10.1186/s13643-018-0790-x.
  • 14. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018; 49(3). doi: 10.1161/str.0000000000000158.
  • 15. Mistri AK, Robinson TG, Potter JF. Pressor Therapy in Acute Ischemic Stroke. Stroke. 2006; 37(6): pp. 1565–1571. doi: 10.1161/01.str.0000222002.57530.05.
  • 16. Sookplung P, Siriussawakul A, Malakouti A, et al. Vasopressor Use and Effect on Blood Pressure After Severe Adult Traumatic Brain Injury. Neurocrit Care. 2010; 15(1): pp. 46–54. doi: 10.1007/s12028-010-9448-9.
  • 17. Chu S, Sansing L. Evolution of blood pressure management in acute intracerebral hemorrhage. F1000Research. 2017; 6: p. 2035. doi: 10.12688/f1000research.11687.1.
  • 18. Hemphill JC, Greenberg SM, Anderson CS et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 2015; 46(7). doi: 10.1161/STR.0000000000000069.
  • 19. Krishnamoorthy V, Chaikittisilpa N, Kiatchai T, Vavilala M. Hypertension After Severe Traumatic Brain Injury. J Neurosurg Anesthesiol. 2017; 29(4): pp. 382–387. doi: 10.1097/ana.0000000000000370.
  • 20. Qureshi AI, Palesch YY, Barsan WG, et al. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med. 2016; 375(11): pp. 1033–1043. doi: 10.1056/nejmoa1603460.
  • 21. Hill MD, Muir KW. INTERACT-2. Stroke. 2013; 44(10): pp. 2951–2952. doi: 10.1161/strokeaha.113.002790.
  • 22. Chang JJ, Sanossian N. Pre-Hospital Glyceryl Trinitrate: Potential for Use in Intracerebral Hemorrhage. Journal of neurological disorders. 2013; 2(1). doi: 10.4172/2329-6895.1000141.
  • 23. American College of Surgeons and the Committee on Trauma. ATLS Advanced Trauma Life Support. Chicago: American College of Surgeons; 2018.
  • 24. Yerram S, Katyal N, Premkumar K, Nattanmai P, Newey CR. Seizure prophylaxis in the neuroscience intensive care unit. Journal of Intensive Care. 2018; 6(1): p. 17. doi: 10.1186/s40560-018-0288-6.
  • 25. Gilmore EJ, Maciel CB, Hirsch LJ, Sheth KN. Review of the Utility of Prophylactic Anticonvulsant Use in Critically Ill Patients With Intracerebral Hemorrhage. Stroke. 2016; 47(10): pp. 2666–2672. doi: 10.1161/strokeaha.116.012410.
  • 26. Beleza P. Acute Symptomatic Seizures. Neurologist. 2012; 18(3): pp. 109–119. doi: 10.1097/nrl.0b013e318251e6c3.
  • 27. Xu JC, Shen J, Shao WZ, et al. The safety and efficacy of levetiracetam versus phenytoin for seizure prophylaxis after traumatic brain injury: A systematic review and meta-analysis. Brain injury. 2016; 30(9): pp. 1054–61. doi: 10.3109/02699052.2016.1170882.
  • 28. Bakr A, Belli A. A systematic review of levetiracetam versus phenytoin in the prevention of late post-traumatic seizures and survey of UK neurosurgical prescribing practice of antiepileptic medication in acute traumatic brain injury. Br J Neurosurg. 2018; 32(3): pp. 237–244. doi: 10.1080/02688697.2018.1464118.
  • 29. Yang Y, Zheng F, Xu X, Wang X. Levetiracetam Versus Phenytoin for Seizure Prophylaxis Following Traumatic Brain Injury: A Systematic Review and Meta-Analysis. CNS Drugs. 2016; 30(8): pp. 677–88. doi: 10.1007/s40263-016-0365-0.
  • 30. Pin-on P, Saringkarinkul A, Punjasawadwong Y, Kacha S, Wilairat D. Serum electrolyte imbalance and prognostic factors of postoperative death in adult traumatic brain injury patients. Medicine. 2018; 97(45): p. e13081. doi: 10.1097/md.0000000000013081.
  • 31. El-Fawal BM, Badry R, Abbas WA, Ibrahim AK. Stress hyperglycemia and electrolytes disturbance in patients with acute cerebrovascular stroke. Egypt J Neurol Psychiatry Neurosurg. 2019; 55(1). doi: 10.1186/s41983-019-0137-0.
  • 32. Bradshaw K, Smith M. Disorders of sodium balance after brain injury. Continuing Education in Anaesthesia Critical Care & Pain. 2008; 8(4): pp. 129–133. doi: 10.1093/bjaceaccp/mkn019.
  • 33. Haddad SH, Arabi YM. Critical care management of severe traumatic brain injury in adults. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2012; 20(1): p. 12. doi: 10.1186/1757-7241-20-12.
  • 34. Mazer L, Tapper EB, Piatkowski G, Lai M. The need for antibiotic stewardship and treatment standardization in the care of cirrhotic patients with spontaneous bacterial peritonitis - a retrospective cohort study examining the effect of ceftriaxone dosing. F1000Research. 2014; 3: p. 57. doi: 10.12688/f1000research.3-57.v2.
  • 35. Pandey S, Pandey AK. Intra-articular & Allied Injections. JP Medical Ltd; 2017.
  • 36. Lewis SR, Evans DJ, Butler AR, Schofield-Robinson OJ, Alderson P. Hypothermia for traumatic brain injury. Cochrane Database Syst Rev. 2017. doi: 10.1002/14651858.cd001048.pub5.
  • 37. Kuczynski AM, Demchuk AM, Almekhlafi MA. Therapeutic hypothermia: Applications in adults with acute ischemic stroke. Brain circulation. 2019; 5(2): pp. 43–54. doi: 10.4103/bc.bc_5_19.
  • 38. Tahir R, Pabaney A. Therapeutic hypothermia and ischemic stroke: A literature review. Surg Neurol Int. 2016; 7(15): p. 381. doi: 10.4103/2152-7806.183492.
  • 39. Kurisu K, Yenari MA. Therapeutic hypothermia for ischemic stroke; pathophysiology and future promise. Neuropharmacology. 2018; 134: pp. 302–309. doi: 10.1016/j.neuropharm.2017.08.025.
  • 40. Lascarrou J-B, Merdji H, Le Gouge A, et al. Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm. N Engl J Med. 2019; 381(24): pp. 2327–2337. doi: 10.1056/nejmoa1906661.
  • 41. Polderman KH, Varon J. Confusion Around Therapeutic Temperature Management Hypothermia After In-Hospital Cardiac Arrest?. Circulation. 2018; 137(3): pp. 219–221. doi: 10.1161/circulationaha.117.029656.
  • 42. Yu S, Lee J, Zhang J. Neuroprotective mechanisms and translational potential of therapeutic hypothermia in the treatment of ischemic stroke. Neural Regeneration Research. 2017; 12(3): p. 341. doi: 10.4103/1673-5374.202915.
  • 43. Sun YJ, Zhang ZY, Fan B, Li GY. Neuroprotection by Therapeutic Hypothermia. Frontiers in neuroscience. 2019; 13: p. 586. doi: 10.3389/fnins.2019.00586.
  • 44. Zhang M, Wang H, Zhao J, et al. Drug-induced hypothermia in stroke models: does it always protect?. CNS Neurol Disord Drug Targets. 2013; 12(3): pp. 371–80. doi: 10.2174/1871527311312030010.
  • 45. Saxena MK, Taylor C, Billot L, et al. The Effect of Paracetamol on Core Body Temperature in Acute Traumatic Brain Injury: A Randomised, Controlled Clinical Trial. PLoS ONE. 2015; 10(12): p. e0144740. doi: 10.1371/journal.pone.0144740.
  • 46. Lelubre C, Bouzat P, Crippa IA, Taccone FS. Anemia management after acute brain injury. Critical Care. 2016; 20(1). doi: 10.1186/s13054-016-1321-6.
  • 47. Stolla M, Zhang F, Meyer MR, Zhang J, Dong J. Current state of transfusion in traumatic brain injury and associated coagulopathy. Transfusion (Paris). 2019; 59(S2): pp. 1522–1528. doi: 10.1111/trf.15169.
  • 48. Baharoglu MI, Cordonnier C, Salman RA-S, et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. The Lancet. 2016; 387(10038): pp. 2605–2613. doi: 10.1016/s0140-6736(16)30392-0.
  • 49. Kaufman RM, Djulbegovic B, Gernsheimer T. Platelet Transfusion: A Clinical Practice Guideline From the AABB. Ann Intern Med. 2015; 162(3): pp. 205–213. doi: 10.7326/M14-1589.
  • 50. Wirth R, Smoliner C, et al. Guideline clinical nutrition in patients with stroke. Exp Transl Stroke Med. 2013; 5(1). doi: 10.1186/2040-7378-5-14.
  • 51. Perel P, Yanagawa T, Bunn F, Roberts IG, Wentz R. Nutritional support for head-injured patients. Cochrane Database Syst Rev. 2006. doi: 10.1002/14651858.cd001530.pub2.
  • 52. Frankenfield DC, Ashcraft CM. Description and prediction of resting metabolic rate after stroke and traumatic brain injury. Nutrition. 2012; 28(9): pp. 906–911. doi: 10.1016/j.nut.2011.12.008.
  • Rabinstein AA. Optimal Blood Pressure After Intracerebral Hemorrhage. Stroke. 2018; 49(2): pp. 275–276. doi: 10.1161/strokeaha.117.020058.
  • Elisha S, Nagelhout JJ, Heiner JS. Current Anesthesia Practice - E-Book. Elsevier Health Sciences; 2019.
  • Nentwich LM, Jr BGM, Kahn JH. Acute Ischemic Stroke, An Issue of Emergency Medicine Clinics - E-Book. Elsevier Health Sciences; 2012.
  • Spencer MP. Ultrasonic Diagnosis of Cerebrovascular Disease. Springer Science & Business Media; 2012.
  • Le Roux P, Menon DK, Citerio G, et al. Consensus Summary Statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care. Neurocrit Care. 2014; 21(S2): pp. 1–26. doi: 10.1007/s12028-014-0041-5.
  • Fomchenko EI, Gilmore EJ, Matouk CC, Gerrard JL, Sheth KN. Management of Subdural Hematomas: Part I. Medical Management of Subdural Hematomas. Curr Treat Options Neurol. 2018; 20(8). doi: 10.1007/s11940-018-0517-2.
last updated 09/22/2020
{{uncollapseSections(['Lp1wJ30', 'Fp1gr30', 'Kp1Uq30', 'pp1Lq30', 'rp1fI30', 'qp1Cq30', 'Hp1KI30', '7p14I30', 'Ip1YI30', 'op10q30', 'Gp1BI30'])}}