Hypertensive crisis during spinal anesthesia due to undiagnosed pheochromocytoma.

Undiagnosed pheochromocytoma poses significant intraoperative challenges to the anesthesiologist. These tumors generally cause profound hypotension after spinal anesthesia. We present an unusual case of a hypertensive crisis occurring in a patient under spinal anesthesia. Due to intraoperative hemodynamic instability, the case was converted to general anesthesia with a volatile anesthetic. Postoperative workup was consistent with a pheochromocytoma. Pheochromocytomas are rare, but given their significant intraoperative morbidity and mortality, they should be considered in the differential diagnosis of unexpected intraoperative hemodynamic changes. Copyright:

INTRODUCTION

Pheochromocytomas are rare catecholamine-producing tumors of adrenal chromaffin cells that account for fewer than 1% of cases of hypertension.[1] Undiagnosed pheochromocytomas represent a formidable challenge to the anesthesiologist because of their extremely high intraoperative mortality rate, which ranges from 30% to 80% in the literature.[234] The sympathectomy from spinal anesthesia can lead to profound hypotension in patients with pheochromocytomas secondary to a chronically contracted intravascular volume.[5] We report an unusual occurrence of hypertensive crisis under spinal anesthesia in a patient undergoing bilateral knee arthroplasties. Informed consent for publication of this case report was obtained from the patient. The EQUATOR CARE guidelines were followed in the writing of this case report.[6]

CASE REPORT

A 68-year-old female with osteoarthritis presented for bilateral knee arthroplasties. Her medical history included chronic hypertension, hypothyroidism, and right-sided breast cancer treated with chemotherapy, radiation, and lumpectomy 10 years ago. Home medications included amlodipine, losartan, and levothyroxine; the patient reported an allergy to iodine. She denied the use of tobacco, alcohol, or drugs. Her preoperative laboratory parameters included a comprehensive metabolic panel, complete blood count, and thyroid function studies which were all within normal ranges. She was 157 cm tall and weighed 72 kg, with a body mass index of 29.2 kg/m2. On the morning of surgery, the patient was reevaluated in the holding area, physical examination was unremarkable, and an anesthetic plan was developed for spinal anesthesia with monitored anesthesia care.

On arrival to the operating room (OR), the patient's blood pressure (BP) was 142/70 mmHg and her heart rate was 85 beats per minute (BPM). With the patient seated upright, a 24-gauge spinal needle was used to inject 1.7 mL of 0.75% hyperbaric bupivacaine and 20 μg of fentanyl into the intrathecal space at the L4–L5 interspace using a midline approach. Bilateral sensory blockade to the T4 level was confirmed. The BP decreased to 97/62 mmHg after the spinal anesthetic, and 10 mg of ephedrine was administered with good response as the BP increased to 115/60 mmHg with the next measurement. A propofol infusion was started at 75 μg/kg/min. Approximately 15 min later, a right lower extremity tourniquet was inflated, and surgical incision was made. After 97 min, the right lower extremity tourniquet was deflated, and the patient immediately became acutely hypertensive with a BP of 235/105 mmHg and a heart rate of 52 BPM. Five milligrams of hydralazine was administered, and the BP decreased to 190/80 mmHg. The patient suddenly developed a supraventricular tachycardia with a heart rate of 140 BPM and her BP remained elevated at 195/103 mmHg. The patient remained hypertensive and tachycardic despite the administration of 20 mg of esmolol, 2.5 mg of metoprolol, and 25 mcg of fentanyl. Due to the continued hemodynamic instability, a decision was made to convert to general anesthesia, and the airway was secured with an endotracheal tube. An arterial blood gas was drawn, which showed a significant metabolic acidosis and hyperglycemia [Table 1]. Anesthesia was maintained with sevoflurane for the rest of the case. The patient remained tachycardic with heart rates in the 110s, but the BP gradually decreased over the next few minutes. The remainder of the case proceeded uneventfully, and the patient was successfully extubated at the end of surgery. The total duration of the surgical procedure was 3 h and 3 min. After extubation in the OR, her BP was 126/70 mmHg and heart rate was 112 BPM.

Table 1

Arterial blood gas at induction of anesthesia

Analyte with normal value range	Patient Results
Glucose (65-99 mg/dL)	350
pH (7.35-7.45)	7.20
pCO2 (35-45 mmHg)	42.2
pO2 (65-100 mmHg room air)	176
BE (−3-+3)	−10
HCO3 (22-26 mmol/L)	17.1
Hct (36%-48%)	38
O2Hb (>90%)	99
Potassium (3.5-5.0 mmol/L)	3.2
Sodium (136-145 mmol/L)	140

pH: Potential hydrogen, pCO2: Partial pressure of carbon dioxide, pO2: Partial pressure of oxygen, BE: Base excess, HCO3: Bicarbonate ion, Hct: Hematocrit, O2Hb: Oxygen saturation of hemoglobin

The patient arrived in the recovery unit with a BP of 105/54 mmHg and heart rate of 109 BPM. In the recovery unit, the patient and her husband were informed about the intraoperative hypertension and further history was elicited. When prompted, they recalled that the patient intermittently experienced episodes of headaches, palpitations, and hypertension at home that resolved within a few minutes. Based on intraoperative events and the additional clinical history, a pheochromocytoma was strongly suspected. Laboratory tests for plasma-free metanephrines and 24-h urine metanephrines were sent. The results [Table 2] showed markedly elevated plasma and urine metanephrines, consistent with a catecholamine-secreting tumor. The patient was referred to an endocrine surgeon for further workup. Subsequent imaging showed thickening of the adrenal glands without evidence of nodules. These findings were highly consistent with the diagnosis of a pheochromocytoma. However, the patient refused further workup and treatment.

Table 2

Results of screening laboratory tests for pheochromocytoma

Analyte with normal value range	Patient Results
24 h urine metanephrines
Metanephrine (90-315 mcg/24 h)	5182
Normetanephrine (122-676 mcg/24 h)	1050
Total metanephrines (224-832 mcg/24 h)	6232
Plasma-free metanephrines
Metanephrine (0-62 pg/mL)	576
Normetanephrine (0-145 pg/mL)	62

DISCUSSION

Undiagnosed pheochromocytomas are of great concern to the anesthesiologist because of their high intraoperative mortality, reported to be between 30% and 80%.[12] Using diagnosis codes from the International Classification of Diseases-9 (ICD-9) (194.0 and 237.3) and ICD-10 (C74.10 and D44.7) to query the electronic medical record database, we identified 169 unique patients with a diagnosis of pheochromocytoma or paraganglioma between June 2007 and May 2019 at our institution. Among them, 67 patients received anesthesia for a surgical procedure. Although these are rarely encountered by anesthesiologists, their serious clinical implications warrant a high index of suspicion and vigilance. The stress of surgery and anesthesia can trigger hypertensive crises and other catecholamine-induced adverse events, leading to intraoperative mortality.[7] In our case, the differential diagnosis for the sudden intraoperative hypertensive crisis after tourniquet release included inadequate anesthesia, iatrogenic causes (e.g., accidental administration of vasopressors), severe hypercarbia, increased intracranial pressure (ICP), myocardial ischemia, bladder distension, thyroid storm, and pheochromocytoma. The patient did not report and discomfort or pain from the surgery making inadequate anesthesia or analgesia unlikely. Administered medications were double-checked to rule out iatrogenic causes. The last vasopressor administration (10 mg of ephedrine) occurred more than an hour before the hypertensive episode. The patient had a normal respiratory rate, and an arterial blood gas showed a normal pCO2 of 42.2 mmHg. The patient had normal mental status, tachycardia, and normal respiratory effort making a Cushing reflex (hypertension, bradycardia, and irregular breathing) from increased ICP an unlikely etiology of the hypertension. Myocardial ischemia can rarely present with severe hypertension due to a sympathetic reflex initiated in the left ventricle.[8] However, our patient did not have electrocardiogram changes suggestive of ischemia. In this patient with hypothyroidism on levothyroxine and normal preoperative thyroid function studies, a thyroid storm was very unlikely. Because the patient remained persistently hypertensive and tachycardic despite initial treatment, we considered pheochromocytoma and converted to general anesthesia for better hemodynamic control.

Usually, the sympathectomy from spinal anesthesia can lead to profound hypotension in patients with pheochromocytomas because of a highly contracted intravascular volume secondary to the chronic catecholamine release.[8] We encountered several case reports of hypertensive crises under general anesthesia in the literature.[91011] However, to our knowledge, there is only one other case report of a hypertensive crisis under spinal anesthesia related to pheochromocytoma, where the patient became acutely hypertensive during bladder tumor manipulation.[12] In our case, we posit that the acidosis and metabolic byproducts from the lower extremity tourniquet release were a trigger for sudden catecholamine release from the pheochromocytoma. The sympathectomy from a spinal anesthetic occurs secondary to local anesthetic inhibition of spinal sympathetic outflow.[13] However, the anesthetic would not be expected to directly inhibit catecholamine-secreting chromaffin cells from a tumor. Therefore, a hypertensive crisis despite a spinal sympathectomy is physiologically viable with a pheochromocytoma. In our case, the intraoperative tachycardia accompanying the hypertension is suggestive of excess epinephrine release. Indeed, the patient's plasma-free metanephrines lab test revealed elevated metanephrine levels but normal normetanephrine levels consistent with a tumor that was primarily secreting epinephrine.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Applicable reporting guideline for case reports (CARE) was followed by the authors.

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Conflicts of interest

There are no conflicts of interest.