General Principles and Second Insults

The prevention and management of systemic complications after neurosurgical procedures follows general principles of “intensive care” medicine. It is, however, important to realize that systemic complications and second insults may initiate or aggravate cerebral damage. Aggressive treatment aimed at preventing and limiting second insults is of paramount importance. The main second insults, their causes, and adverse effects on brain homeostasis and function are summarized in Table 41-2, further illustrating the complex interactions between systemic events and CNS function.

TABLE 41-2 Systemic Second Insults

ADH, antidiuretic hormone; CBF, cerebral blood flow; CBV, cerebral blood volume; CPP, cerebral perfusion pressure; CSF, cerebrospinal fluid; ICP, intracranial pressure; IV intravenous.

Conversely, CNS events may induce systemic derangement. For example, in response to raised intracranial pressure (ICP), mean arterial blood pressure (MABP) may increase as a compensatory mechanism to ensure adequate cerebral perfusion (Cushing response). In such situations, treatment of hypertension is contraindicated, as this may exacerbate cerebral ischemia. In other situations, however, arterial hypertension may aggravate the occurrence of cerebral edema and/or increase the risk of intracranial bleeding. Surgeons may request prevention of any episode of high blood pressure (BP) in situations where adequate hemostasis was difficult, or conversely may wish to maintain BP at relatively high levels when cerebral vasospasm may be a problem, for example after cerebral aneurysm surgery. The clinical dilemma is to balance the necessity of limiting edema formation and the risk of postoperative hemorrhage with the goal of maintaining adequate perfusion. Knowledge of the operative findings and close interaction with the surgeon are of paramount importance.

Many drugs routinely used in neurosurgical patients (e.g., steroids, antiepileptic agents) may cause complications or side effects; awareness of potential side effects is essential. CNS damage, particularly to the hypothalamic region, brainstem, and cervical spinal cord may lead to disturbance in temperature control, causing hypo- or hyperthermia. In patients with spinal cord injury, loss of autonomic sympathetic function may further lead to peripheral vasodilation and low BP. In the absence of beta-blocking agents, hypotension in combination with bradycardia is strongly suggestive of damage to the spinal cord.

Cardiac Dysfunction

Electrocardiographic (ECG) abnormalities, usually diffuse ST-segment changes mimicking cardiac ischemia and cardiac arrhythmias, may be caused by SAH, TBI, or raised ICP. The devastating effects of a sudden catecholamine release following acute intracranial bleeding have recently received further attention. The left ventricle suffers a typical bulging (indicating ischemic changes and functional impairment) which has been awarded the term Takotsubo syndrome, with reference to the shape of a pot used by ancient Japanese fishermen for catching octopus. The extent of left ventricular dysfunction is variable, but it may lead to extreme cardiac failure and pulmonary edema.^11,12

Neurogenic Pulmonary Edema

The development of neurogenic pulmonary edema has been described early in the postoperative period after a variety of neurosurgical procedures, including brain tumors (particularly those resected in the posterior fossa), cysts, hydrocephalus, intracranial hemorrhages, and brainstem lesions.^13–16 Although an infrequent event, this is potentially life threatening and requires rapid evaluation and emergent therapy in the ICU. A 9% mortality rate directly attributable to neurogenic pulmonary edema has been reported in a recent review of this condition. Generally this complication appears in the initial 4 hours after the neurologic event and is more common in women than in men, possibly related to the preponderance of cases in patients with SAH.¹⁶ The mechanisms underlying this condition are unclear; a sudden central sympathetic discharge may trigger pulmonary venoconstriction, systemic arterial hypertension, increased left ventricle afterload, increased capillary permeability in the pulmonary vascular bed, and simultaneously cause cardiac ischemia and ventricular failure.^12,17 Because of these multiple mechanisms, neurogenic pulmonary edema can be interpreted as noncardiogenic or, at least in part, as cardiogenic.¹⁸ Both low and high protein content have been reported in the edema fluid.^16,19 It is commonly associated with raised ICP, so in addition to therapies directed at intracranial hypertension, therapeutic measures are mostly supportive. To attenuate the massive sympathetic discharge, opioids and sedatives are used. Supplemental oxygen is uniformly required, and tracheal intubation with mechanical ventilation and application of positive end-expiratory pressure (PEEP) has been reported in about 75% of patients.¹⁶ Diuretics have been used, provided volume status is adequate, but diuresis causes less effect than in cardiac edema. Most patients require vasoactive drugs.¹⁹

Hypercoagulopathy and Thrombosis Prophylaxis

Release of factors from damaged brain tissue may induce local and systemic hypercoagulopathy.^20–22 Various studies have confirmed a transient hypercoagulopathy syndrome both in the immediate postoperative phase after brain surgery and in patients with TBI.^20,23–25 In patients with a subdural hematoma, consumption of clotting factors may lead to coagulopathy in up to 22% of the patients.²⁶

Deep venous thrombosis (DVT) has been reported to occur in 18% to 50% of neurosurgical cases²⁷ and pulmonary embolism (PE) in 0% to 25%. DVT and PE incidence is particularly high in brain tumor patients. Nevertheless, neurosurgeons tend to underestimate the risk of DVT and PE²⁸ and are sometimes reluctant to routinely prescribe anticoagulant prophylaxis for fear of increasing the risk of postoperative bleeding.²⁹ Options for prevention of thrombosis prophylaxis in neurosurgical patients include both mechanical (graduated compression stockings, intermittent pneumatic compression stockings) and pharmacologic (low dose of classic heparin and low-molecular-weight heparin) therapies. Intuitively, mechanical therapies carry less associated risk, but pharmacologic approaches are more effective in preventing thrombotic complications. Various studies have indeed shown a higher incidence of postoperative hemorrhagic complications,³⁰ but not all are clinically relevant.

Overall, existing evidence, however, shows that the beneficial effects in reducing DVT and in particular PE^31,32 outweigh a slightly increased risk of clinically significant hemorrhagic complications with anticoagulant prophylaxis.

These data support the administration of antithrombotic prophylaxis to patients undergoing neurosurgical procedures,³³ including those with intracranial hemorrhagic lesions,³⁴ closed TBI,^35,36 or high-risk trauma patients.^37,38 It has been recommended to remove catheters or drainage tubes in the postoperative phase when anticoagulant effects are low (e.g., just prior to administration of next dose).³⁹

Uncertainty exists on the preferred choice of medication, optimal dosing regimen, and time of initiation of thrombosis prophylaxis, particularly in patients with higher risk for bleeding. Any decision regarding the use of thrombosis prophylaxis must weigh efficacy against harm from the proposed intervention. In addition, early mobilization in the postoperative phase, whenever possible, is recommended. More consensus exists concerning routine administration of anticoagulant therapy in patients with spinal cord injuries.

Supratentorial Procedures

Infratentorial Procedures

The care for patients in the direct postoperative phase following infratentorial procedures poses specific problems. Postoperative complications in the posterior fossa can lead to rapid deterioration because of the relatively small infratentorial volume reserve and the immediate compression of the brainstem, resulting in respiratory insufficiency and acute herniation. Irritation of the brainstem may induce large swings in arterial BP, enhancing the risk of postoperative hemorrhage during hypertensive episodes. Cranial nerves are more susceptible to damage due to surgical manipulation than peripheral nerves.⁴⁶ Lesions of the lower cranial nerves may lead to a diminished gag reflex, with increased risk of aspiration and pneumonia. After surgery in the cerebellopontine angle, specific attention should be paid to the function of the trigeminal and facial nerves and prophylactic measures to prevent damage of the cornea taken.

After any infratentorial procedure, the risk of acute hydrocephalus due to obstruction at the level of the fourth ventricle is present. Increased pressure in the infratentorial compartment may, in rare cases in which supratentorial CSF drainage is performed, cause upward (inverse) herniation.

These specific aspects warrant routine admission of all patients who have undergone posterior fossa surgery to the ICU for careful observation and monitoring. Particular attention should be paid to the presence of the gag reflex before extubation and in the early stages after extubation, and frequent monitoring of the respiratory status and adequacy of respiration is imperative.

After posterior fossa surgery, some patients may develop a syndrome of aseptic meningitis.⁴⁷ This is characterized by meningeal symptoms, headaches, and an inflammatory response of the CSF in the absence of evidence for infection. The origin of this syndrome has not been fully clarified, but symptoms may resolve sooner with intermittent CSF drainage.

An infrequent transitory complication observed after resection of large midline posterior fossa tumors is cerebellar mutism.⁴⁷ The exact cause is poorly understood, but a vascular phenomenon has been hypothesized.⁴⁸

Cerebrovascular Procedures

Postoperative care for patients undergoing cerebrovascular surgery poses specific challenges in neurointensive care. In patients operated for arteriovenous malformations, the risk of seizures is particularly high, and focal deficits may occur secondary to changes in cerebral hemodynamics. Following treatment for a cerebral aneurysm, medical and cerebral complications can occur either related to the disease or to treatment (surgical clipping or endovascular coiling). Medical complications specifically linked to SAH are neurogenic pulmonary edema, cardiac arrhythmias, and ventricular failure.¹¹ Electrolyte disturbances, in particular hyponatremia, are also frequently observed.⁴⁹

The main cerebral complications are:

Rebleeding occurs mainly in the first weeks after the aneurysmal rupture, and current approaches are to prevent rebleeding by early surgical clipping or endovascular obliteration of the aneurysmal sack. Delayed cerebral ischemia, often due to vasospasm is—besides rebleeding—the most common cause of death and disability due to SAH. The reported incidence of this complication varies widely, but angiographic vasospasm is seen with angiography in over 67% of untreated patients at the time of maximum spasm around the end of the first week.⁵⁰

Delayed cerebral ischemia (DCI) is considered to be caused by vasospasm. However, not all patients with DCI have vasospasm. Inversely, not all patients with vasospasm develop clinical symptoms and signs of DCI. Recent studies show that DCI cannot always be attributed to vasospasm but more to the occurrence of microthrombosis.^51,52 DCI is associated with an activation of the coagulation cascade within a few days after SAH, preceding the time window during which vasospasm occurs. Furthermore, both impaired fibrinolytic activity and inflammatory and endothelium-related processes may lead to the formation of microthrombi, further promoting the development of DCI.

Clinically evident delayed ischemic deficits (DID) affect approximately one third of patients. Various studies have shown a beneficial effect of the administration of oral calcium antagonists in preventing DID.^53,54 Beneficial effects of intravenous administration of nimodipine remain unproven.

Following evidence that patients with SAH had reduced blood volume, plasma volume, and erythrocyte mass, triple-H therapy (hypervolemia, hypertension, and hemodilution) was proposed for both prophylaxis and treatment of DID after SAH. Various studies have shown a reduction of DID with triple-H prophylaxis,⁵⁵ but some debate remains.^56,57

The usefulness of triple-H treatment is generally accepted, but it has never been unequivocally demonstrated by a randomized controlled trial to be superior to simple moderate fluid loading. The relative importance of the three components of triple-H therapy is uncertain.^58,59 Adequate fluid loading should be considered the most important aspect of early treatment and prophylaxis of DID, but it may be considered reasonable to reserve the more vigorous loading and induced hypertension for situations in which there is clinical evidence of delayed ischemia.^59–61

Progressive signs of DID may require more aggressive approaches including angioplasty.⁶² Transluminal balloon angioplasty is generally recommended, but this requires special equipment and a highly skilled and experienced interventional neuroradiology team. Alternatively, “chemical angioplasty” in which the angiography catheter is used to instill papaverine or nimodipine may be considered.⁶³

Chemical angioplasty often has to be repeated within hours or days and carries complications including pupillary changes, seizures, or respiratory arrest with vertebral artery injection. Alternatively, possibilities of cisternal therapy should be considered, injecting recombinant tissue plasminogen activator (tPA) or urokinase in the basal cisterns to break down the accumulated blood,⁶⁴ or even nitric oxide donors to improve vascular tone.

Various studies have shown clinical benefit of this approach, with the added benefit of reducing the incidence of hydrocephalus. Acute hydrocephalus after SAH is not uncommon. The reported frequency depends on the criteria used for the diagnosis and ranges from 9%⁶⁵ up to 67%.⁶⁶ Spontaneous improvement of hydrocephalus has been reported in approximately half of patients with acute hydrocephalus and impaired consciousness on admission, but it may be difficult to predict spontaneous improvement, because treatment is generally instituted. Evidence exists that in the absence of a hematoma with mass effect or an obstructive element, serial lumbar punctures may be the initial optimal method of treatment, reserving continuous CSF drainage procedures for patients in whom the hydrocephalus does not resolve over time.

Clinical Surveillance

Even in this era of sophisticated monitoring procedures, routine clinical examinations are essential. The clinical assessment has the purpose of disclosing major life-threatening complications early after surgery and of assessing and tracking neurologic deficits in the hours to days that follow.

Early Evaluation

A simple check of consciousness, pupils, and the development of focal (mostly motor) deficits remains the most important method for assessing patients in the neurosurgical ICU. Neurologic assessment should be repeated at regular intervals throughout the ICU course; change in examination findings is the most sensitive method for detecting neurologic deterioration.

The level of consciousness should be assessed by the Glasgow Coma Scale (GCS).⁶⁷ In this scale, standardized assessment of three aspects of responsiveness is performed: the eye, motor and verbal reaction (Table 41-5).

TABLE 41-5 Glasgow Coma Scale

NOTES: The best score for each response should be documented and communicated in the format described above. Assessment of the best motor score is based on the best response of the arms. For use in individual patients, separate description of the three components of the Glasgow Coma Scale (GCS) is strongly recommended. For purposes of classification, the total GCS can be calculated by adding the best score obtained in each category. The GCS should be annotated to indicate confounding factors: T signifies an intubated patient; S, sedation; P, neuromuscular blockade.

When administration of painful stimuli is necessary to assess the level of responsiveness, standardized administration is required: pressure on the nail bed and supraorbital pressure to test the localizing response of the motor scale (Figure 41-1).

Figure 41-1 Supraorbital and nailbed pressure for assessment according to the Glasgow Coma Scale.

Accurate determination of the full GCS is not always possible because of sedation and paralysis, but when possible, at least the best motor score should be recorded. Approaches to daily interruption of sedation that allow intermittent wake up in ventilated patients not only help care providers to monitor neurologic status but also have been shown to result in better outcome.⁶⁸ Some authors advocate imputing the eye and verbal scores from the motor score in sedated and/or ventilated patients.⁶⁹

We would prefer an approach in which only the motor score is assessed at times when the level of sedation permits, as this is an important parameter of neurologic function and the main predictor of outcome in unconscious patients. The development of pupillary abnormalities is a sensitive indicator for pressure on the midbrain (tentorial herniation). Pupillary reaction to light is mediated through parasympathetic fibers of the third cranial nerve (oculomotor nerve). Afferent light perception, conducted through the second cranial nerve (optic nerve) connects at the level of the internal eye muscle nuclei to the oculomotor nerve supplying parasympathetic fibers to the sphincter pupillae muscle via the ciliary ganglia.

Pressure on the oculomotor nerve leads to a loss of function of the parasympathetic fibers, causing a diminished pupillary response or absent pupillary reactivity, generally initially on the side of a lesion (Figure 41-2). With progressive increase in pressure, both pupils become dilated and unresponsive to light. In patients with a lesion of the optic nerve, the consensual light reflex—contraction of the pupil when a light is shone into the opposite eye—remains intact.

Figure 41-2 Pupillary reactivity and size.

Further Evaluation

When major complications have been ruled out, it remains necessary to evaluate the persistence of previous deficits, their improvement after surgery, or the appearance of new signs attributable to surgery. It is expected, for example, that following the surgical removal of an eighth nerve neurinoma, some degree of damage of cranial nerve VII can occur. After surgical intervention on structures located in or close to the brainstem, deficits of the lower cranial nerves can occur as well. A careful, complete neurologic examination is required at this stage, since the simple check proposed in the previous section is not meant to fully evaluate cranial nerve function. This evaluation is important, since cranial nerve deficits can require immediate treatment—for example, protection of the ocular bulb to prevent keratitis, or avoidance of oral feeding if swallowing is impaired.