PERIOPERATIVE management of pheochromocytoma remains an anesthetic challenge.1,2
Acute variations in serum catecholamine levels may present as hypertensive or hypotensive crises, depending on tumor type and stage of the procedure. Major advances in perioperative management included preoperative catecholamine blockade and adequate preoperative volume resuscitation.2
We present a case of massive pheochromocytoma that required urgent surgical resection. The urgency of the case and tumor mass precluded complete preoperative catecholamine blockade. The major perioperative challenge was profound vasoplegic shock after tumor resection.
The unusual feature in this case was that vasopressin therapy was required to reverse the catecholamine-resistant vasoplegic shock that persisted after tumor resection. Although this application of vasopressin has recently been reported, it was in a case of pheochromocytoma that was complicated by massive blood loss.3
Our case is unique because it illustrates the successful application of vasopressin in pheochromocytoma resection, complicated not by hypovolemia but by severe acute catecholamine deficiency resulting from the resection of a giant tumor.
A 47-yr-old man presented to the emergency room in respiratory distress. His vital signs included heart rate of 166 beats/min, blood pressure of 212/153 mmHg, respiratory rate of 45 breaths/min, and a systemic oxygen saturation of 75% on room air. Chest auscultation revealed bilateral rales. The electrocardiogram was remarkable for sinus tachycardia and widespread ST-segment depression. His chest radiograph revealed pulmonary edema.
The patient was placed on mechanical ventilation, and vasodilator therapy with nitroprusside was instituted. He was transferred to cardiac catheterization laboratory for emergent angiography that revealed normal coronary and renal arterial anatomy. Transthoracic echocardiography revealed an ejection fraction of 20%, global left ventricular hypokinesis, and no significant valvular disease.
The patient was admitted to the intensive care unit. His hemoglobin was 19 g/dl, and his creatinine was 3.7 mg/dl. His blood pressure was gradually controlled with both nitroprusside and labetalol. Plasma free normetanephrine was 88.1 nm (range, 0–0.89 nm) and plasma free metanephrine was 35.3 nm (range, 0–0.49 nm). A computed tomographic scan of the abdomen revealed a 10 cm left adrenal mass. He was referred to our institution with a diagnosis of left adrenal pheochromocytoma.
In the intensive care unit there was complete resolution of his cardiomyopathy and acute renal failure. Mechanical ventilation was successfully withdrawn. Repeat transthoracic echocardiography revealed normal left ventricular size and function with no regional wall abnormalities.
The patient was volume resuscitated and commenced on oral phenoxybenzamine. Oral labetalol and nifedipine were then added to achieve a blood pressure of 100/60–120/80 mmHg, complicated by breakthrough hypertensive spells. The hemoglobin was 11.5 g/dl, and serum creatinine was 1.2 mg/dl. Despite breakthrough hypertension, surgery was scheduled because complete preoperative catecholamine blockade was unlikely given the tumor mass and the extreme catecholamine production.
After placement of routine monitors (as recommended by the American Society of Anesthesiologists) and adequate intravenous sedation, a thoracic epidural (T10-T11) was placed without hemodynamic consequence. General anesthesia was induced with propofol 2 mg/kg and fentanyl 10 μg/kg. Vecuronium 0.1 mg/kg was added for neuromuscular blockade (goal train-of-four ratio was less than 25%). The hemodynamic response to tracheal intubation was attenuated with esmolol 1 mg/kg (maximum blood pressure, 128/75 mmHg; maximum heart rate, 100 beats/min). Anesthesia was maintained with isoflurane in oxygen and titrated fentanyl. There was no epidural drug administration.
Invasive hemodynamic monitoring consisted of a left radial arterial line and a pulmonary arterial catheter (via the right internal jugular vein). The baseline hemodynamic profile was as follows: blood pressure 95/65 mmHg, heart rate 70 beats/min (sinus rhythm), central venous pressure 15 mmHg, pulmonary arterial pressure 25/16 mmHg, cardiac index 2.2 l/min/m2, systemic vascular resistance 900–1000 dynes·s·cm−5, and mixed venous saturation 70% (Fio2, 1.0).
Incision, dissection, and tumor manipulation were continuously associated with baseline mean arterial pressure and systemic vascular resistance. Close communication with the surgical team was maintained during the entire procedure. Intravascular volume expansion with crystalloid was titrated to the following goals: central venous pressure of 12–15 mmHg and urine output of at least 1 ml·kg−1·h−1. Blood loss was 0.2 l and crystalloid replacement was 6.0 l in total.
Systemic vascular resistance was maintained at 900–1200 dynes·s· cm−5 with the following agents: isoflurane (1.5 –2.5%, end-tidal concentration), fentanyl (intraoperative total of 40 μg/kg), nicardipine infusion (2–4 mg/h), and labetalol (total 400 mg).
After tumor mobilization, all vasodilators were terminated in anticipation of tumor venous ligation. The patient was mechanically ventilated with pure oxygen, and scopolamine (0.4 mg) was administered for amnesia. Immediately after tumor venous ligation, profound vasoplegic shock developed. The blood pressure was 55/30 mmHg, and the systemic vascular resistance was 300–400 dynes·s·cm−5.
Despite aggressive intravascular volume expansion, norepinephrine (bolus of 50–100 μg; infusion of 10–30 μg/min) and epinephrine (bolus of 50–100 μg; infusion of 10–20 μg/min), the blood pressure only rose to 65/45 mmHg. The profound vasoplegia responded to bolus vasopressin in doses of 10–20 units. The blood pressure steadily increased to 90/60 mmHg, and the systemic vascular resistance increased to the low normal range of 800–900 dynes·s·cm−5. A vasopressin infusion at 0.1 units/min was added to maintain systemic vascular resistance.
After skin closure, the patient followed simple commands and had no focal neurologic deficit. His extremities were warm and his urine output greater than 1 ml·kg−1·h−1. The following infusions maintained his blood pressure of 90/55 mmHg and a systemic vascular resistance of 800–900 dynes·s·cm−5: norepinephrine 13 μg/min, epinephrine 4 μg/min, and vasopressin 0.1 units/min. The central venous pressure was 12 mmHg, and his cardiac index was 2.0–2.5 l/min/m2.
The patient was admitted to the intensive care unit. Tracheal extubation was performed 16 h later. The vasopressor infusions were gradually withdrawn over 24 h: epinephrine first, norepinephrine second, and vasopressin last. Patient-controlled epidural analgesia was begun thereafter. The patient was discharged from the intensive care unit within 48 h. The rest of the hospital stay was uneventful.
This case of massive pheochromocytoma illustrates a clinical approach to catecholamine blockade and catecholamine replacement at the appropriate stages of the procedure. An unusual feature of this case is the application of vasopressin to complete the pharmacologic support of vasomotor tone after tumor resection. Tan et al.
recently described vasopressin in the treatment of catecholamine-resistant hypotension after resection of a pheochromocytoma that was complicated by significant intraoperative blood loss.3
The unique feature of our case is that vasopressin restored vascular tone after pheochromocytoma resection that was uncomplicated by hypovolemia. There was no significant blood loss in this case. Euvolemia was always maintained, as evidenced by a high normal central venous pressure and brisk urine output.
The main etiology of the catecholamine-resistant vasoplegia was the severe abrupt catecholamine deficiency induced on tumor removal. This was exaggerated because of the massive tumor catecholamine secretion. Aggressive exogenous catecholamine replacement did not restore vascular tone. Vasopressin provides an alternative pharmacologic route to reverse catecholamine-resistant vasoplegia. Vasopressin should be readily available as an adjunctive agent for vascular rescue, given that there is almost always a degree of catecholamine-tolerance after resection of a pheochromocytoma.
The ability of vasopressin to reverse catecholamine-resistant vasoplegia has also been described in vasodilatory shock associated with sepsis,4,5
insertion of ventricular-assist devices,6
and organ donation.9
Vasopressin levels in these types of vasodilatory shock are low. The mechanism of this deficiency is unclear, although several hypotheses have been proposed.10,11
The proposals include central depletion of neurohypophyseal stores, decreased stimulation of vasopressin release, and inhibition of vasopressin release.10
A possible explanation for vasopressin deficiency in our case may be the excessive circulating norepinephrine levels that are known to inhibit vasopressin release.12
Chronic increase of circulating norepinephrine would thus chronically inhibit vasopressin release and ultimately down-regulate neurohypophyseal vasopressin synthesis. Thus, after tumor removal, the neurohypophysis is unable to acutely release high levels of vasopressin to restore adequate vasopressin levels and restore vascular tone. This hypothesis requires further investigation, including serum vasopressin assays during the perioperative management of pheochromocytoma.
A limiting factor in this case was the persistent α-blockade because of phenoxybenzamine.1
Although phenoxybenzamine is the standard for preoperative α-blockade, its effects persist for 48 h postoperatively. Doxazosin may be a superior alternative to phenoxybenzamine because it is a specific alpha1-blocker with a shorter half-life: its effects disappear within 12 h postoperatively.13
Prys-Roberts and Farndon concluded that doxazosin was a safe and effective alternative to perioperative phenoxybenzamine.13
As experience with doxazosin increases, nonspecific long-acting α-blockade with phenoxybenzamine may no longer be the standard for preoperative preparation of pheochromocytoma.
A second limiting factor in this case was the lack of preoperative blockade of catecholamine synthesis with methyl-para-tyrosine, the competitive inhibitor of tyrosine hydroxylase.14
Tyrosine hydroxylase is the rate-limiting enzymatic step in endogenous catecholamine production. Synergistic preoperative therapy with methyl-para-tyrosine and α-blockade results in superior perioperative hemodynamic management.15
Although our preoperative protocol for pheochromocytoma typically includes this synergistic combination, this patient was better served with prompt tumor removal. The symptomatic profile of this giant tumor mandated urgent resection, allowing insufficient time to achieve perfect preoperative catecholamine blockade.
A third limiting factor in this case was the choice of labetalol for catecholamine blockade because its half-life of 4–6 h complicates the vasoplegia after tumor removal. Labetalol was chosen because it was part of the preoperative regimen that had achieved near adequate catecholamine blockade. The advantage of this choice was that intraoperative catecholamine excess was asymptomatic. Given that the postoperative vasoplegia lasted 24 h (four times the half-life of labetalol), labetalol was not a major factor in the profound vasoplegia after tumor removal.
In summary, this case highlights vasopressin for hemodynamic rescue in the management of vasoplegic shock after complicated resection of symptomatic pheochromocytoma. The anesthesiologist should have a low threshold to initiating therapy with vasopressin in this setting, especially when the vasoplegia is catecholamine-resistant and hypovolemia has been corrected.
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© 2004 American Society of Anesthesiologists, Inc.