Anesthetic Implications of Hyperhomocysteinemia in Neurosurgical Practice: A Case-Based Narrative

Hyperhomocysteinemia (HHC) is related to a metabolic disorder homocystinuria, which is associated with cystathionine β‐synthase deficiency. Homocysteine accumulation is associated with disorders of various systems and is a risk factor for stroke, thromboembolism, and coronary artery disease.[1] We describe the anesthetic management of HHC patient for neurosurgery, which is not previously described. Written informed consent was obtained.

A 25-year-old lady weighing 81 kg (body mass index: 31.24 kg/m²) with HHC presented with weight gain, menstrual irregularities, headache, and blurring of vision (since 6 months). She had features of Cushing's disease like short neck, cervicodorsal pad of fat, moon-like facies, truncal obesity with Mallampatti grade 3, upper lip bite test-2, thyromental distance > 6.5 cm, controlled diabetes mellitus, hypertension, and hypothyroidism. Her serum cortisol level was 24.20 µg/dl (normal 2.3–11.9 µg/dL), adrenocorticotropic hormone 67.54 pg/mL (normal 7–63 pg/mL), and 1.2 × 1.5 × 1.3 cm pituitary tumor on magnetic resonance imaging ([Fig. 1]). Six years ago she was diagnosed with cerebral venous and left upper limb venous thrombosis with elevated serum homocysteine of 33.5 µmol/L (normal < 13.9 µmol/L and presently 26 µmol/L) with normal protein C and S values. Current imaging revealed a posterior superior sagittal sinus residual thrombus with normal echocardiogram and deep vein thrombosis scan. She was scheduled for endoscopic transnasal transsphenoidal (TNTS) excision of the tumor. Her medications included tablets metformin, telmisartan, insulin injection (all omitted on the day of surgery), levetiracetam, folic acid, vitamin B12, thyroxine, and acenocoumarin (stopped 2 days prior to surgery), which was bridged with subcutaneous unfractionated heparin (UFH) 5000 IU injection 6th hourly until procedural morning with prothrombin time of 11.6 seconds, activated partial thromboplastin time of 21.3seconds, and international normalized ratio (INR) of 1.2 (1.82 two days prior).

Fig. 1 Magnetic resonance imaging (MRI) brain showing lesion in the pituitary area.

In the operating room, after attaching the standard monitors and preoxygenation, anesthesia was induced with intravenous fentanyl, propofol, atracurium, and intubated with C-MAC video-laryngoscope and mechanically ventilated. Anesthesia was maintained with sevoflurane (0.8–1 minimum alveolar concentration) in oxygen and air (1:1) and fentanyl atracurium infusion. Invasive arterial monitoring and mechanical thromboprophylaxis with intermittent pneumatic compression devices were done. Intraoperative period was uneventful with minimal blood loss and balanced electrolytes. At the end of surgery, upon awakening and reversal of neuromuscular blockade, the trachea was extubated. Mechanical thromboprophylaxis was continued in the intensive care unit and she was mobilized at the earliest after maintaining adequate hydration. UFH was started (following normal computed tomographic scan) on postoperative day 3 with acenocoumarin the day after. Her further hospital stay was uneventful.

Homocysteine being an intermediate product of methionine metabolism is usually converted to cysteine or recycled back to methionine with the help of vitamins B6, B12, and folate and this process essentially maintains deoxyribonucleic acid production and repair. Congenital HHC presents with mental retardation, skeletal abnormalities, thromboembolism, ectopia lentis, and young age atherosclerosis, with 20% mortality. Chronic renal failure, hypothyroidism, anemia, and cofactor deficiency contribute to secondary HHC.[2] The aggregate of oxidized homocysteine and low-density lipoprotein cause endothelial damage, vascular smooth muscle proliferation, and atherothrombosis, which results in cerebrovascular and cardiovascular thromboembolism.[2]

Our patient with a combination of HHC, overweight, and Cushing's disease (a hypercoagulable state by itself) was at increasingly high risk for perioperative thromboembolism.[3] Balancing between potential thrombosis and postoperative hematoma in neurosurgery was the unique challenge here for which acenocoumarin was discontinued 48 hours prior to surgery (in place of usual 3–5 days) and bridged with UFH in accordance with a consensus advisory on perioperative anticoagulant management in high-risk patients for thromboembolism with INR below 2 to 2.5.[4] [5] Considering the duration for effective hemostasis in a narrow corridor surgery such as TNTS especially for a large pituitary tumor (as our case) with a possible potential breach in the extensive microvascular networks around the pituitary gland, postoperative anticoagulants were started after 48 hours of surgery.[3] [6]

HHC can cause hypoglycemia secondary to insulin release by methionine while Cushing's is associated with hyperglycemia necessitating vigilant monitoring for hypoglycemia and hyperglycemia here.[1] Also, tranexamic acid known to better operating conditions in endoscopic TNTS could not be used due to the risk of potentiating thrombosis.[7] The features of difficult airway require the use of video-laryngoscope and titration of anesthetics. In HHC patients, homocysteine levels > 22 μmol/L were associated with venous thrombosis and < 25 μmol/L reduced annual stroke recurrence.[2] Homocysteine reduction therapies in mitigating cardiovascular complications and stroke is debatable.[2] [8] Hence, folic acid and vitamin supplementation, regular screening for any thromboembolic event, and management would become important. As neurosurgeries are mostly urgent surgeries, there seems to be no cutoff values for homocysteine levels for these procedures.

To conclude, prothrombotic propensity of HHC pose great challenge during neurosurgery as decision for perioperative timing of anticoagulants should balance between stroke and intracranial hematoma. Hence, neurosurgical patients with HHC, metabolic, and endocrine disorders would require a tailored approach to address airway, risk of thrombosis, hemodynamics, and perioperative glucose levels for safe outcome.

Conflict of Interest

None declared.

• References

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Artikel online veröffentlicht:
06. Januar 2026