von Hippel-Lindau Disease (VHL)

Airway is unremarkable - There is no VHL airway. No dysmorphology, no fixed obstruction — intubate as you would anyone else. What changes is everything around the tube, because laryngoscopy and induction of anesthesia are recognized triggers of a hypertensive crisis in a patient carrying an unrecognized pheochromocytoma.

Pheochromocytoma is the emergency - Pheochromocytoma is reported in up to 60% of VHL patients and is frequently asymptomatic, since many are found on surveillance rather than by symptoms. VHL tumors tend to secrete norepinephrine, so normetanephrine is the elevated metabolite and levels run higher than in MEN2. Patients are screened with annual blood or urinary fractionated metanephrines from age 5 — find that result before any elective case, whatever the surgery is for. Unrecognized, the tumor announces itself as unexplained severe hypertension, tachycardia, and arrhythmias after induction.

Alpha before beta blockade - Start an alpha-adrenergic blocker 10 to 14 days before resection to control blood pressure and re-expand a contracted intravascular volume. Phenoxybenzamine (irreversible, non-selective, half-life around 24 hours) is the usual agent; prazosin, terazosin, and doxazosin are selective alpha-1 alternatives that cause less reflex tachycardia because alpha-2 inhibitory activity stays intact. Add a beta blocker only once alpha blockade is established — beta first leaves alpha stimulation unopposed and precipitates hypertensive crisis. Adequacy is judged against the Roizen criteria, and successful blockade shows up as a normalized blood pressure with mild orthostasis.

Drugs to avoid - Ketamine is out for its sympathomimetic effect, as are ephedrine and the histamine releasers atracurium and morphine. Metoclopramide is contraindicated — it can trigger hypertensive crisis and adrenergic myocarditis with cardiogenic shock. Glucagon likewise releases catecholamines. Desflurane can drive tachycardia and hypertension when the concentration is increased rapidly; sevoflurane is preferred for its lack of arrhythmogenic potential. Labetalol is a poor choice here: its IV alpha-to-beta antagonism ratio is about 1:7, so it behaves as a beta blocker and can worsen hypertension, then leave persistent hypotension and bradycardia once the tumor is out.

Induction and access - Place the arterial line before induction; the lability starts at laryngoscopy. Premedicate with an anxiolytic such as midazolam. Propofol for induction if left ventricular function is good; a cardio-stable slow induction with divided-dose propofol, etomidate, or a narcotic-based technique if there is catecholamine cardiomyopathy. Two peripheral IVs minimum, central access if you expect vasopressors, and TEE or a PA catheter if the ventricle is poor.

Intraoperative hypertensive crisis - Peritoneal insufflation and tumor handling release catecholamines abruptly and can produce myocardial ischemia or stroke. Have short-acting vasodilators running or drawn up — nitroprusside, nitroglycerin, or a calcium channel blocker such as nifedipine or clevidipine, which also address the coronary vasospasm catecholamine excess can cause. Phentolamine works fast with a 10 to 15 minute duration. For rate control, esmolol 500 to 1,000 mcg/kg over one minute followed by 50 mcg/kg/min titrated to a maximum of 200 mcg/kg/min — but only on top of established alpha blockade.

Collapse after tumor ligation - Once the tumor's venous drainage is ligated, blood pressure can fall precipitously as endogenous catecholamines disappear against chronically downregulated alpha receptors. Volume plus phenylephrine or norepinephrine first. For refractory hypotension, vasopressin 0.01 to 0.03 units/min is particularly effective because it works independently of peripheral adrenergic receptors; methylene blue is the fallback for true vasoplegia.

Postoperative glucose and pressure - Check blood sugar every 4 to 6 hours after resection. Catecholamines suppress insulin secretion, so their sudden withdrawal produces rebound insulin release and hypoglycemia. Up to half of patients remain hypertensive for a few days and norepinephrine levels take days to normalize, so persistent hypertension is not automatically a failed resection — though it can signify residual tumor. Anyone still requiring vasopressors goes to ICU, not PACU.

Raised intracranial pressure - CNS hemangioblastomas occur in 13% to 72% of patients and present with headache, vomiting, ataxia, and sensory or motor deficits. On MRI they appear as a cystic lesion with an enhancing mural nodule; surveillance imaging of brain and entire spine is done every 2 years from age 16, so ask for it. Where intracranial pressure is raised, the usual constraints apply — avoid hypercarbia and hypoxia, keep the head up with venous drainage unobstructed, and blunt the pressor response to laryngoscopy.

Neuraxial technique - About 20% of CNS hemangioblastomas are spinal, and these are highly vascular tumors. A cord lesion and raised intracranial pressure each argue against a neuraxial block, and you cannot tell which you are dealing with without the MRI of brain and entire spine that VHL surveillance already provides. Get the imaging before offering a spinal or epidural.

Hypervascular tumors bleed - Unrestrained HIF signaling drives VEGF and PDGF, so these lesions are vascular by design. Extensive hemangioblastomas are embolized preoperatively specifically to reduce bleeding at resection. Type and cross early and have the product in the room rather than ordered.

Renal function - Renal cysts occur in 59% to 63% of patients and renal cell carcinoma in 25% to 45%, generally bilateral and multifocal, and many patients have already had a nephrectomy or an ablation. Check the creatinine and the operative history before dosing renally cleared drugs or reaching for an NSAID.

Vision and hearing - Retinal hemangioblastomas affect 45% to 59% of patients and can leak, producing fibroglial bands, retinal detachment, vitreous hemorrhage, and glaucoma. Endolymphatic sac tumors occur in 2% to 11%, are often bilateral, and cause tinnitus, vertigo, hearing loss, and facial weakness. Protect the eyes deliberately and establish how the patient hears you before relying on verbal instruction at emergence.

Baseline neurological exam - Document motor, sensory, and cerebellar findings before induction. With spinal cord lesions in play and often a long prone or sitting case ahead, a new postoperative deficit needs a recorded starting point to be interpreted at all.

von Hippel-Lindau disease is an autosomal dominant multisystem tumor syndrome caused by mutation of the VHL tumor suppressor gene on chromosome 3, with a prevalence of roughly 1 in 30,000 to 1 in 50,000 and an average age of onset of 26 years. The VHL protein normally targets hypoxia-inducible factor for degradation; when it fails, HIF and its downstream growth factors — VEGF, PDGF-B, and erythropoietin — are upregulated without restraint, producing a lifetime of hypervascular tumors and cysts. Perioperatively this creates three distinct problems: pheochromocytoma, reported in 0% to 60% of patients; central nervous system and retinal hemangioblastomas, with CNS lesions in 13% to 72% (about 80% intracranial, 20% spinal); and renal cell carcinoma in 25% to 45% on a background of bilateral renal cysts. Any of the three can be present and undiagnosed when the patient arrives for unrelated surgery.