Management of Complications From Brain Metastasis Treatment

A Narrative Review

Kevin Diao; Alan J. Sosa; Gabriel Zada; Seema Nagpal; Eric L. Chang


Chin Clin Oncol. 2022;11(2):11 

In This Article

Complications After Neurosurgical Resection

The morbidity and mortality of neurosurgical interventions for brain metastases have improved considerably in the last few decades.[116,117] An analysis of over 13,500 admissions for metastatic brain tumor resections across the US demonstrated that the mortality rate had decreased by 49% from 1988 to 2000.[118] The mortality risk is now estimated to be approximately 0.7–1.9% based on modern series.[119,120] Nevertheless, caring for the neurosurgical patient requires close observation in the immediate postoperative period. A multidisciplinary approach is favored, and care should be delivered by a team comprised of a neurosurgeon, neuro-intensivists, anesthesiologists, and specialized nursing staff.[121] Timely detection of neurologic changes is crucial for early diagnosis and quick intervention of any post-surgical complications (Table 2).

Neurologic Deficit

As many as 20–40% of patients with metastatic brain tumors will present with focal neurologic deficits.[122] Surgery aims to remove the tumor and reverse or improve neurologic symptoms, but injury to normal brain structures is possible, which may result in permanent neurologic deficits. Numerous modalities are used to preserve neurological function when possible, including advanced neuro-imaging with diffusion tractography imaging, minimally invasive approaches, awake craniotomy for speech monitoring, and use of cortical and subcortical motor mapping during tumor resection. The overall neurologic morbidity is estimated to be 3.9–6%.[120] Patients with new neurologic deficits after surgery should be rapidly assessed to identify potentially reversible causes, including ICH, hematoma, cerebral edema, and seizures. In many cases, however, the probable cause is not discovered, though most deficits improve over time.[123] In one study of neurologic deficits after surgery for primary brain tumors, two-thirds of patients were able to make a complete recovery, and another ~15% had a near-complete recovery with no impairment of function.[124] Neurological and/or neurocognitive rehabilitation have been associated with improved motor and cognitive function and QOL and should be tailored to each patient's specific impairments and goals.[125]

Intracranial Hemorrhage

Hypertension and coagulopathy are the main predisposing risk factors for ICH after neurosurgical resection, and efforts should be focused on prevention and early correction to reduce this risk. Hypertension can be precipitated by pain or may be part of the Cushing reflex. Strict blood pressure control is encouraged during surgery and postoperatively. A retrospective study of over 11,000 patients undergoing craniotomy found that patients who experienced hypertension of ≥160/90 during surgery or in the early postoperative period were more likely to have an ICH event.[126]

Patients with ICH should be managed in an intensive care unit with close management of blood pressure with a goal of <140 mmHg systolic and ICP lowering measures including elevation of the head of bed to 30 degrees, optimizing pain control, and mild sedation for comfort. More aggressive measures such as invasive ICP monitoring, osmotic therapy, hyperventilation, complete sedation, ventricular drainage, and surgical evacuation are options for refractory patients or severe cases.[127]

Cerebral Edema

Cerebral edema is commonly seen after craniotomy and may be exacerbated by prolonged brain retraction and hypertension. The symptoms are generally insidious and non-specific (nausea, diffuse headache). Severe cases may be associated with neurologic deficits depending on the location of the edema. Corticosteroids are usually administered at the time of surgery and then transitioned to a short oral taper to reduce the risk of cerebral edema. Typical dosing is 10 mg IV dexamethasone followed by 4 mg every 6 hours, but the dosing is individualized based on the patient's symptoms before and after surgery. Hyperglycemia is a common side-effect of corticosteroids and blood glucose is closely monitored and corrected postoperatively when levels are >180 mg/dL.[128,129]

Post-operative Seizure

The incidence of postoperative seizure following craniotomy is approximately 5–15%.[130] Precipitating medical factors may include hypoglycemia, electrolyte disturbances, hypoxemia, and/or hypercarbia. Prophylactic antiepileptic drugs (AEDs) are not indicated for patients with brain metastases as they have not shown a benefit in seizure reduction, even in the peri-operative setting.[130,131] Most acute seizures spontaneously resolve within two minutes, but more protracted seizures may require infusion of intravenous benzodiazepines. An urgent CT scan is recommended if a reversible surgical cause is suspected such as cerebral edema, hemorrhage, hematoma, and/or elevated ICP. In addition to treating the underlying condition, AEDs such as levetiracetam or phenytoin should be added for maintenance in the recovery period. Postoperative seizures have a low risk of progression to epilepsy overall but decisions on length of time to continue AEDs should be individualized.


Infections following a craniotomy can include surgical site infections and, rarely, meningitis. Postoperative meningitis is a severe disease with high morbidity and mortality rates, making early diagnosis and treatment crucial. The use of indwelling catheters or other CSF draining devices can increase the risk for meningitis. Antibiotic prophylaxis can be used intraoperatively and most guidelines recommend cefazolin as the antibiotic of choice for prophylaxis in craniotomies, but there is no evidence to support continuation after surgery.[132]

Symptoms of postoperative meningitis compared to community-acquired meningitis are non-specific and should be suspected with fever and/or an altered level of consciousness.[133] The diagnosis is made primarily through CSF gram stain, cell counts, and culture. A positive gram stain should prompt empiric treatment but with a negative gram stain, classic CSF findings of leukocytosis and neutrophilia have low specificity in the postoperative setting. As a result, other lab values may be used to guide clinical decision making. An elevated cell index of ≥5 (a ratio of white blood cells to erythrocytes), high CSF lactate (>4 mmol/L), and elevated procalcitonin have all been associated with bacterial meningitis.[133] The treatment is empiric parenteral antibiotics with vancomycin plus either an anti-pseudomonal cephalosporin or carbapenem per the 2017 Infectious Diseases Society of America (IDSA) guidelines.[134]