Seizures After Surgery: Causes and Risk Factors

Seizures occurring after surgery can be alarming and may result from factors related to the procedure, anesthesia, or a patient’s underlying health. While not extremely common, they require careful evaluation to determine the cause and prevent complications. Identifying potential triggers is crucial for both patients and healthcare providers.

Several physiological and medical factors contribute to seizure risk following surgery. Understanding these causes helps in managing and reducing the likelihood of seizures in vulnerable individuals.

Role Of Anesthetic Agents

Anesthetic agents significantly influence postoperative seizure risk. Certain anesthetics have neuroexcitatory effects, particularly in individuals with predisposing neurological conditions or metabolic vulnerabilities. While most modern anesthetics minimize adverse neurological outcomes, some can lower the seizure threshold, increasing susceptibility to abnormal electrical activity.

Etomidate, a commonly used induction agent, has been documented to provoke myoclonic movements and, in rare cases, generalized seizures, especially in patients with a history of epilepsy or cortical irritability. Sevoflurane, an inhalational anesthetic, has been linked to epileptiform activity on electroencephalography (EEG), particularly at lower doses.

Anesthetic agents influence seizure susceptibility through various mechanisms. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has both pro- and anticonvulsant effects depending on dose and patient-specific factors. At subanesthetic doses, it can induce cortical excitation, potentially triggering seizures in susceptible individuals. At higher doses, it dampens excitatory neurotransmission, offering neuroprotection. Propofol, another widely used anesthetic, is generally anticonvulsant due to its gamma-aminobutyric acid (GABA) activity potentiation, but paradoxical excitatory effects have been observed during induction and emergence, particularly in younger patients and those with preexisting neurological conditions.

Beyond direct pharmacological effects, anesthesia induction and emergence contribute to seizure risk. Rapid fluctuations in cerebral blood flow, oxygenation, and neurotransmitter balance during these phases can create transient cortical instability, particularly in individuals with epilepsy. Withdrawal of anesthetic agents such as barbiturates and benzodiazepines can lead to rebound excitability, increasing seizure likelihood, especially in cases requiring prolonged sedation.

Surgical Stress Response

Surgery induces physiological stress that can affect neurological stability. The body’s response involves neuroendocrine, autonomic, and inflammatory pathways, all of which can alter neuronal excitability.

The hypothalamic-pituitary-adrenal (HPA) axis activates in response to surgical stress, releasing cortisol and other glucocorticoids that modulate metabolic and immune functions. These hormones alter neurotransmitter balance, particularly GABA and glutamate signaling, which can lower the seizure threshold.

Sympathetic nervous system activation compounds this effect by increasing catecholamine release, particularly norepinephrine and epinephrine. These neurotransmitters enhance cardiovascular output but also impact neuronal excitability. Elevated catecholamine levels contribute to cortical hyperactivity, potentially precipitating seizures. Rapid fluctuations in blood pressure and cerebral perfusion can lead to transient ischemic changes, exacerbating electrical instability in the brain. This is especially relevant in neurosurgical procedures or patients with cerebrovascular conditions.

Surgical trauma also triggers systemic inflammation, releasing proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which have been implicated in neuronal hyperexcitability. These cytokines can disrupt blood-brain barrier integrity, allowing peripheral immune mediators to influence central nervous system function. In some cases, this inflammatory response may lead to postoperative neuroinflammation, increasing seizure frequency in individuals with epilepsy.

Medication Interactions And Withdrawal

Pharmacological factors significantly contribute to postoperative seizures, particularly through drug interactions and abrupt discontinuation of certain medications. Many surgical patients take long-term medications, and perioperative adjustments can inadvertently lower the seizure threshold.

Drugs affecting the central nervous system, such as antidepressants, antipsychotics, and certain analgesics, may interact with anesthetics or postoperative medications, increasing neuronal excitability. Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and sertraline have been associated with seizure risk due to their serotonergic effects. Combined with other serotonergic agents like tramadol, a common postoperative analgesic, they can induce serotonin syndrome, characterized by autonomic instability, hyperreflexia, and, in severe cases, seizures.

Withdrawal of medications with anticonvulsant properties can also precipitate seizures. Patients with epilepsy or those on benzodiazepines for anxiety or muscle relaxation may experience withdrawal-induced hyperexcitability if these drugs are suddenly discontinued. Abrupt cessation of barbiturates or gabapentinoids, often prescribed for chronic pain, can trigger withdrawal seizures. This risk is particularly pronounced in patients requiring prolonged fasting before surgery, as missing even a single dose can disrupt neurochemical stability.

Opioid analgesics introduce additional complexity. While opioids like morphine and fentanyl are generally not proconvulsant, their metabolites can accumulate in patients with renal impairment, leading to neurotoxic effects, including myoclonus and seizures. Meperidine’s metabolite, normeperidine, is particularly notorious for seizure activity, even at therapeutic doses. Additionally, opioid-induced respiratory depression and subsequent hypoxia can create secondary conditions facilitating seizure onset in neurologically vulnerable patients.

Metabolic And Electrolyte Imbalances

Surgical procedures can disrupt metabolic equilibrium, significantly influencing neuronal excitability. Extended fasting, fluid shifts, and physiological stress can lead to metabolic derangements that lower the seizure threshold.

Hypoglycemia deprives neurons of their primary energy source, impairing ATP-dependent ion pumps that maintain membrane stability. This can lead to neuronal depolarization and increased susceptibility to spontaneous electrical discharges. Hyperglycemia, often seen in diabetic surgical patients, contributes to oxidative stress and excitotoxicity, both linked to increased seizure risk.

Electrolyte disturbances, particularly imbalances in sodium, calcium, and magnesium, further compound seizure risk. Hyponatremia, a common postoperative complication due to excessive fluid administration or syndrome of inappropriate antidiuretic hormone (SIADH), can cause cerebral edema and neuronal swelling, creating a hyperexcitable state. Severe hyponatremia has been directly associated with seizure activity, particularly when sodium levels drop below 120 mmol/L. Hypernatremia, from dehydration or excessive sodium correction, can lead to neuronal shrinkage and altered ion gradients, also predisposing patients to seizures. Hypocalcemia interferes with calcium-dependent neurotransmitter release and membrane stability, while hypomagnesemia disrupts NMDA receptor regulation, both contributing to heightened neuronal excitability.

Postoperative Infections And Inflammation

Surgical procedures increase infection and inflammatory response risks, which may contribute to postoperative seizures. Pathogens or exaggerated immune reactions can disrupt brain function.

Patients undergoing major surgeries, particularly involving the central nervous system or prolonged hospital stays, are more likely to develop infections such as bacterial meningitis, encephalitis, or sepsis. These conditions can trigger neuroinflammation, leading to increased intracranial pressure and altered neurotransmitter signaling that promote seizure activity. Even without direct central nervous system infection, systemic inflammation can affect brain excitability by altering blood-brain barrier permeability, allowing inflammatory mediators to disrupt electrical stability.

The inflammatory cascade associated with postoperative complications further exacerbates seizure susceptibility through the release of cytokines such as interleukin-1β (IL-1β) and TNF-α. These molecules enhance excitatory synaptic transmission while reducing inhibitory signaling, fostering conditions conducive to seizures. Common postoperative infections like pneumonia or urinary tract infections can contribute to systemic inflammation that indirectly affects brain excitability. Fever, a hallmark of many infections, lowers the seizure threshold, particularly in individuals with predisposing neurological conditions. Prompt management of postoperative infections with appropriate antimicrobial and anti-inflammatory interventions is necessary to minimize seizure risk and improve recovery outcomes.

Undiagnosed Neurological Conditions

Preexisting but undiagnosed neurological disorders can contribute to postoperative seizures. Many individuals have underlying conditions such as epilepsy, cerebrovascular disease, or structural brain abnormalities that remain asymptomatic until exposed to perioperative stressors.

Physiological changes from surgery, including fluctuations in blood pressure, oxygenation, and metabolic balance, can unmask latent conditions, leading to seizure activity. Previously unrecognized epileptogenic lesions or genetic predispositions to seizure disorders may only become apparent under surgical stress. This makes preoperative neurological screening crucial for patients with a history of unexplained fainting, transient confusion, or subtle motor disturbances that could indicate an undiagnosed seizure disorder.

Other conditions, such as prior strokes, traumatic brain injuries, or neurodegenerative diseases, also contribute to postoperative seizure risk. Patients with silent cerebral infarcts or small vessel disease may have cortical vulnerabilities that become more susceptible to abnormal electrical activity following cerebral perfusion fluctuations. Even in individuals without overt neurological disease, genetic factors affecting ion channel function or neurotransmitter regulation can predispose them to perioperative seizures. Identifying these risks through detailed medical history and, when necessary, preoperative neuroimaging or electrophysiological studies can help guide anesthetic and surgical decisions to reduce seizure occurrence.