Secondary brain injury and neuroprotective measures

Last updated: August 17, 2023

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Summarytoggle arrow icon

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.

Definitiontoggle arrow icon

Pathophysiologytoggle arrow icon

An acute CNS insult can trigger any of the following, resulting in secondary brain injury. [2][3][4]

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 ventilationtoggle arrow icon

Avoid hypoxia, hyperoxia, hypocapnia, and hypercapnia in patients with acute CNS insult. [3]

Control of PaO2 (oxygenation) [3]

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. [9]

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. [3]

Hypocapnia should only be used as a temporizing measure for patients with signs of cerebral herniation syndromes while simultaneously initiating definitive management for ↑ ICP. [8][13]


Blood pressure and cerebral perfusion pressuretoggle arrow icon


  • 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 [3][4][14]
  • In patients with ↑ ICP, maintain blood pressure so that CPP remains between 60–80 mm Hg. [15][16]
  • Avoid MAP < 65 mm Hg to minimize the risk of underperfusion and secondary ischemic injury to the brain. [3][17]

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. [6]

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. [3][18][19]

Hypertensive patients

The SBP threshold at which to administer antihypertensives and target SBP differ according to the etiology of the acute CNS insult. [16][25][26]

Ischemic stroke

Intracranial hemorrhage (including TBI)

  • Target SBP: 140–180 mm Hg [16][27][28]
  • Timing: Initiate treatment as soon as possible in patients with SBP > 180 mm Hg [15][19][25][26]
  • Commonly used antihypertensive agents [19][25]


Blood sugartoggle arrow icon

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. [6]

Seizure prophylaxis and treatmenttoggle arrow icon

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 abnormalitiestoggle arrow icon

Sodium disorders and hypokalemia are the most common electrolyte abnormalities seen after an acute CNS insult. Provide electrolyte repletion as needed for electrolyte deficiencies. [37][38]

Disorders of sodium balance [39]

  • General considerations
  • Hyponatremia [39]
    • Acutely symptomatic patients: prompt treatment with gradual correction (see “Treatment” in hyponatremia and SIADH)
    • Asymptomatic patients: Supportive treatment strategy is usually appropriate.
  • Hypernatremia [40]
    • 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. [39]

Disorders of potassium balance

Neurogenic fever and targeted temperature managementtoggle arrow icon

Neurogenic fever (central hyperthermia) [41][42]

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)

Othertoggle arrow icon

Intracranial pressure (ICP)

Patient positioning


Nutrition [57][58]

Acute management checklisttoggle arrow icon

Referencestoggle arrow icon

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  59. $Contributor Disclosures - Secondary brain injury and neuroprotective measures. None of the individuals in control of the content for this article reported relevant financial relationships with ineligible companies. For details, please review our full conflict of interest (COI) policy:.

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