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 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
Disruption of physiological (homeostatic) measures
- Blood-brain barrier disruption, cerebral vasodilation, neuronal depolarization and release of excitatory neurotransmitters → cerebral edema → ↑ ICP
- Mitochondrial dysfunction → impaired cerebral metabolism → neuronal cell death
- Stress-induced hyperglycemia → endothelial dysfunction of the cerebral blood vessels → cerebral vasoconstriction or vasodilation → cerebral hypoxia or cerebral hyperemia
- Loss of brain injury secondary to critical care measures of → increased risk of
- Injury to hypothalamus and/or pituitary → and
- Initiation of reparative responses: activation of the inflammatory cascade → hyperthermia and hyperglycemia
Oxygenation and ventilation
Control of PaO2 (oxygenation)
- Target: Normoxia or mild hyperoxia 
Measures to achieve target oxygenation
- Avoid hypotension: See ''Blood pressure and cerebral perfusion pressure'' below.
- Oxygen therapy
Airway management: if necessary, intubate ( ) according to local hospital protocols 
- Carefully consider : Ketamine usually preferred if no 
- See for further details.
Control of PaCO2 (ventilation)
- Target PaCO2: 35–45 mmHg (normocapnia) 
- Measures to achieve target ventilation 
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 (CPP) between 60–70 mm Hg by maintaining (MAP) between 65–100 mm Hg 
Avoid hypovolemia and hypervolemia when resuscitating a patient with an . Hypovolemia decreases cerebral perfusion, worsens cerebral ischemia, and may potentiate thromboses in the injured tissue. Hypervolemia worsens cerebral edema. 
- Target: SBP > 90 mm Hg or mean arterial pressure (MAP) > 80 mm Hg 
- Treatment 
- See “Blood pressure management” in .
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.
- Target blood sugar: normoglycemia
Avoid dextrose-containing solutions in the resuscitation of nonhypoglycemic patients with an acute CNS insult. 
- Seizure prophylaxis 
- Seizure treatment: Seizures detected clinically or on EEG should be managed with
- Suggested anticonvulsants 
- General considerations
- Hyponatremia 
- Severe elevation (> 160 mEq/L): gradual correction (see “Treatment” section in hypernatremia)
- Mild–moderate elevation (up to 160 mEq/L): consider gradual correction
Neurogenic fever and targeted temperature management
Neurogenic fever (central hyperthermia) 
- Definition: Noninfectious fever after an is likely caused by injury to the hypothalamic thermoregulation centers.
- Epidemiology: seen in up to 37% of patients with TBI; may also occur after stroke or neurosurgical intervention
- Implication: associated with worse neurological outcomes and increased mortality
Targeted temperature management (TTM)
- Definition: controlled maintenance of a target body temperature aimed to prevent secondary brain injury after an
- Target body temperature: differs according to the inciting event
Measures to achieve TTM 
- Physical/surface cooling: may be local (e.g., head cooling with a cooling helmet) or general (e.g., with cooling blankets/pads) 
- Endovascular cooling (e.g., rapid IV infusion with cold normal saline) 
- Pharmacological hypothermia (for therapeutic hypothermia): hypothermia-inducing drugs (e.g., cannabinoids, opioids) 
- acetaminophen )  (e.g.,
Intracranial pressure (ICP)
- Target: Maintain ICP below 20–22 mm Hg 
- Treatment: See .
- Monitoring: ICP is not routinely monitored, but patients should be observed for .
- Patients without features of raised ICP or hypoxia: supine position with no elevation of the head 
- Patients with aspiration or airway obstruction: head end elevation to 30º  or those at risk of
- Red cell transfusion: Transfuse packed red cells if Hb ≤ 7 g/dL (restrictive threshold) 
- Spontaneous intracerebral hemorrhage (ICH): Platelet transfusion is not recommended in patients with ICH who are on antiplatelet therapy 
- TBI: There is currently no clear recommendation for/against platelet transfusion in patients with TBI and concurrent thrombocytopenia, platelet dysfunction, or antiplatelet therapy. 
- Consider platelet transfusion if platelet count is less than 80–100,000/mm3 in patients planned for neurosurgery or invasive procedures. 
- Neurological insult typically leads to a . 
- 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.
- Identify and treat hypoxia.
- Maintain normocapnia (consider short-term hypocapnia in patients with or .
- Blood pressure management
- Consider seizure prophylaxis and/or seizure management (if appropriate)
- Identify and treat electrolyte abnormalities.
- Identify and treat hyperthermia.
- Patient positioning
- Support nutritional needs.