Neurocritical Care

18. Early Hypotension and Fever

A 50-year-old man with history of hypertension, heavy smoking, and alcoholism was admitted with poor-grade subarachnoid hemorrhage (WFNS grade IV). Cerebral angiogram showed an anterior communicating artery aneurysm, which was successfully coiled. His condition improved after placement of a ventriculostomy catheter, but shortly thereafter his level and content of consciousness started to fluctuate because of alcohol withdrawal. Despite treatment with benzodiazepines and dexmedetomidine, he had frequent episodes of agitation, diaphoresis, hyperthermia, and tachycardia. He remained intubated and mechanically ventilated. Serial transcranial Doppler measurements showed progressively increasing mean blood flow velocities in the anterior and middle cerebral arteries bilaterally starting on post bleeding day 6. On day 8, a CT angiogram confirmed the presence of mild to moderate diffuse vasospasm, but with normal mean transit time and cerebral blood flow on the CT perfusion. On post bleeding days 10 and 11 he was responding better to commands. However, a day later he suddenly developed a fever of 40 degrees Celsius and became abruptly hypotensive. He is again stuporous.

What do you do now?

Major medical complications can be expected in any mechanically ventilated patient with an acute brain injury, and they may come suddenly. Basically, acute fever and hypotension—manifestations of systemic inflammatory response syndrome (Table 18.1)—should always trigger immediate activation of the sepsis management protocol. Any delays can be problematic, even more so in patients with possible compromise of cerebral perfusion. The general principles of management of septic shock apply to patients with acute brain injury (Table 18.2).

In critically ill neurologic patients certain aspects of care may have to be adjusted. Aggressive fluid resuscitation should be started emergently with 1000–2000 mL of crystalloids over 30 minutes. In patients with cerebral edema we think that normal saline is preferable to lactated Ringer to avoid fluids with lower tonicity. Colloids (albumin) can also be used. The usual set target in the treatment of sepsis is a mean arterial pressure of 65 mmHg, but a higher target may be necessary in patients at risk of cerebral ischemia. Serum lactate should be measured quickly and it is an important indicator of the seriousness of the situation. A serum lactic acid level > 4 mmol/L indicates tissue hypoperfusion and calls for aggressive hemodynamic support. The patient’s urinary output needs to be closely monitored for the development of oliguria (less than 20 ml/hour). Goal-directed therapy within the first 6 hours (aiming for a central venous oxygen saturation ≥ 70%) may reduce mortality. Norepinephrine is the initial vasopressor of choice. It may be supplemented with low dose vasopressin (0.04 units per minute) if the blood pressure target is not achieved. Epinephrine and dopamine are reasonable options. However, the pure alpha adrenergic agonist phenylephrine is not a good choice in septic shock because it can reduce cardiac output (i.e., stroke volume) and patients with sepsis may already have myocardial dysfunction. In fact, these patients should have an urgent echocardiogram. If the left ventricular ejection fraction is reduced and shock persists, dobutamine—an inotropic agent—should be started. After the patient has been successfully resuscitated, fluid administration must be very conservative (i.e., fluid balance even to negative) to prevent complications from fluid overload (principally related to capillary leak leading to pulmonary edema). However, this approach can create a dilemma in certain acute neurological disorders. In patients with brain edema, maintaining a negative fluid balance is actually desirable. Instead, patients with symptomatic vasospasm can become ischemic if they develop intravascular volume contraction.

TABLE 18.1 Systemic Inflammatory Response Syndrome (SIRS)*

Physiological variable


Body temperature

> 38.5–¡C or < 35¡C

Heart rate

> 90 beats per minute

Respiratory rate

> 20 breaths per minute or PaCO2 < 32 mmHg

White blood cell count

> 12,000 cells/mm3, 4,000 cells/mm3, or > 10% bands

* SIRS with proven infection defines sepsis.

TABLE 18.2 Initial Treatment of Septic Shock with Special Considerations in Neurological Patients

Start aggressive fluid resuscitation immediately
1–2 liters of 0.9% NaCl (may add intermittent infusions of 250 cc of albumin 5%)

Define resuscitation goal
A MAP goal higher than the usual 65 mmHg may be necessary in neurocritical patients with compromised cerebral perfusion

Start vasopressor if MAP below target after fluid challenge
Norepinephrine, low dose vasopressin, epinephrine
Phenylephrine is not adequate

Obtain echocardiogram and assess systolic function
Start dobutamine if decreased left ventricular ejection fraction


Conservative fluid strategy after resuscitation goal is achieved
Can use diuretics if MAP stable and evidence of cerebral edema or raised ICP

Diagnosis of infectious source
Panculture (blood cultures, urinalysis with culture and sensitivity, sputum sample)
Culture CSF

Start broad-spectrum antibiotics as soon as possible

Consider hydrocortisone if vasopressor dependence

Avoid activated human recombinant protein C if increased risk of ICH

Blood product administration
Consider red blood cell transfusion to keep hemoglobin > 9–10 g/dL if cerebral perfusion is compromised
Platelet transfusion to keep platelet count > 50,000 if recent ICH or neurosurgery
FFP to correct coagulopathy if recent ICH or neurosurgery

Mechanical ventilation
Careful titration of PEEP if raised ICP


Sedation and analgesia
Sedation holidays
Minimize use of opiates if possible

Glucose control
Maintain blood sugars between 140–180 mg/dL


MAP, mean arterial pressure; CSF, cerebrospinal fluid; ICH, intracranial hemorrhage; FFP, fresh frozen plasma; PEEP, positive end expiratory pressure; ICP, intracranial pressure

Patients with refractory septic shock may be treated with corticosteroids (hydrocortisone 50 mg intravenously every 6 hours). Corticosteroids may reduce vasopressor dependency but do not appear to improve survival. Their use should not be a problem in critical neurological patients. However, recombinant human activated protein C must not be administered to patients with intracranial hemorrhage or recent neurosurgery, because there is an increased risk of hemorrhage associated with the use of this drug.

Early initiation of broad-spectrum antibiotics is crucially important. Ideally, they should be started within the first hour of the diagnosis of septic shock. Pancultures should be obtained before the first antibiotic dose if at all possible, but cannot delay the start of antibiotics. Nosocomial meningitis may be associated with early sepsis, and thus cultures should include a cerebrospinal fluid sample in any patient with cerebrospinal fluid diversion devices (ventriculostomy, lumbar drainage) or previous neurosurgical procedures.

Septic shock guidelines generally recommend transfusion of red blood cells only when the hemoglobin concentration is below 7 g/dL. While we still do not know the ideal hemoglobin target in patients with severe acute brain insults, such as severe traumatic head injury or poor-grade subarachnoid hemorrhage, improving oxygen carrying capacity may be particularly beneficial in these patients with compromised cerebral perfusion and recent or persistent hypotension. Until more information is available, we aim at a higher target of hemoglobin concentration of 9–10 g/dL in critically ill neurological patients who are septic and hypotensive.

Glucose management should also be more cautious in patients with acute brain injury. Cerebral microdialysis studies have shown that neuroglycopenia and anaerobic metabolism can occur with glycemias between 60–80 mg/dL, which are levels often considered acceptable in other patients. We use insulin infusions in hyperglycemic patients but cautiously. Our target is generally to keep serum glucose between 140–180 mg/dL avoiding too tight control.

High positive end expiratory pressure (PEEP) can improve oxygenation in patients with sepsis complicated by acute respiratory distress syndrome. High PEEP is not contraindicated in patients with raised intracranial pressure, but the effect of gradual increases in PEEP on the intracranial pressure need to be carefully monitored.

Sedation should be guided by a protocol with a clear goal (e.g., a sedation level defined by the Richmond Agitation Sedation Scale, RASS) and scheduled drug interruptions. These sedation holidays allow us to follow the neurological examination and also reduce the incidence of delirium (see chapter 17). We must remember that opiates are excellent analgesic agents but will greatly confound the neurological examination. The confounding effect of opiates may be quite prolonged in elderly patients and those with liver or renal failure.

Our patient was promptly resuscitated with fluids and norepinephrine. Broad-spectrum antibiotics were started within 30 minutes of the onset of hypotension. The source of sepsis was eventually recognized to be ventilator associated pneumonia. Despite rapid control of the hypotension and adequate treatment of the infection, the brief hypotension proved too much for our patient. He remained stuporous and a repeat head CT scan four days later showed multifocal brain infarctions. This case illustrates that the brain is exquisitely sensitive to ischemia, particularly after a major initial insult such as SAH in our case.

Fever is ubiquitous in critically ill patients and central fever is even more common in patients with acute brain injury. Pancultures should be obtained including CSF when appropriate (meningitis may cause severe sepsis) Yet, when fever is accompanied by hypotension, patients should be rapidly treated for early sepsis following a comprehensive protocol. Any delay in reversing the situation may cause additional brain injury.


· Although components of the systemic inflammatory response syndrome (e.g., persistent fever, tachycardia), can be attributed to the brain injury in acute neurological patients, the occurrence of sudden hypotension and high fever should always activate a septic shock protocol.

· The general principles of septic shock management are generally appropriate in patients with acute brain injury, but there are notable differences.

· Obtain samples for pancultures immediately including CSF.

· The brain is at risk for additional injury from systemic complications, and rapid fluid resuscitation, administration of vasopressors and inotropes, broad coverage with antibiotics, blood transfusion, and glucose control are essential first measures.

Further Reading

American College of Chest Physicians. Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20:864–874.

Daniels R. Surviving the first hours in sepsis: getting the basics right (an intensivist’s perspective). J Antimicrob Chemother. 2011;Suppl 2:ii11–ii23.

Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R et al for the International Surviving Sepsis Campaign Guidelines Committee. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Crit Care Med 2008; 36:296–327.

Godoy DA, Di Napoli M, Rabinstein AA. Treating hyperglycemia in neurocritical patients: benefits and perils. Neurocrit Care 2010; 13:425–438.

National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Comparison of two fluid management strategies in acute lung injury. N Engl J Med 2006; 354:2564–2575.

Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368–1377.

Russell JA. Management of sepsis. N Engl J Med 2006; 355:1699–1713.