Ann Surg Oncol DOI 10.1245/s10434-015-4519-y

ORIGINAL ARTICLE – ENDOCRINE TUMORS

Hemodynamic Stability During Pheochromocytoma Resection: Lessons Learned Over the Last Two Decades Margaret Livingstone, MD1 , Kaylene Duttchen, MD, FRCPC1, Jenny Thompson, MD1, Zahid Sunderani, MD1, Geoffrey Hawboldt, MD, FRCPC1, M. Sarah Rose, PhD2, and Janice Pasieka, MD, FRCSC, FACS1 1

University of Calgary, Calgary, AB, Canada; 2Alberta Health Services, Calgary, AB, Canada

ABSTRACT Background. Ideal perioperative management of pheochromocytomas/paragangliomas (pheo) is a subject of debate and can be highly variable. The purpose of this study was to identify potential predictive factors of hemodynamic instability during pheo resection. Methods. A retrospective review of pheo resections from 1992 to 2013 was undertaken. Intraoperative hemodynamics, patient demographics, tumor characteristics, and perioperative management were examined. Postoperative intensive-care admission, myocardial infarction, stroke, and 30-day mortality were reviewed. Linear regression was used to analyze factors influencing intraoperative hemodynamics. Results. During the 20-year study period, 100 patients underwent pheo resection. Postoperative morbidity and mortality was significantly reduced (p = 0.003) in the last 10 years of practice, and there was a trend towards greater morbidity and mortality with intraoperative hemodynamic instability (p = 0.06). The preoperative dose of phenoxybenzamine and the number of laparoscopic procedures has increased in the last decade [59 mg (95 % CI 32–108) to 106 mg (95 % CI 91–124), p = 0.008, and 27 vs. 54 %, p = 0.05, respectively]. Increased preoperative phenoxybenzamine dose was a significant predictor of improved intraoperative hemodynamic stability (p = 0.01). Lack of intraoperative magnesium use resulted in greater hemodynamic instability as preoperative systolic blood pressure increased (p = 0.002). Conclusions. Postoperative outcomes following pheo resection have improved over the last two decades. Preoperative a-blockade plays a significant role in improving

intraoperative hemodynamics and post-op outcomes. Increased doses of phenoxybenzamine and utilization of laparoscopic approaches have likely contributed to improved outcomes in the last decade. Intraoperative magnesium use may provide protection against hemodynamic instability and warrants further study.

Pheochromocytoma and paragangliomas (pheo) are rare catecholamine-secreting tumors derived from chromaffin cells. Uncontrolled release of catecholamines into the bloodstream can produce hypertension, tachyarrhythmias, and life-threatening crises characterized by hypertensive encephalopathy, neurological deficits, and severe arterial spasms causing unconsciousness, metabolic acidemia, and death.1 The pathophysiologic effects of pheochromocytomas are of particular concern during surgical resection as nociceptive stimuli or tumor manipulation can produce catecholamine surges and severe hemodynamic disturbances.2 Hemodynamic stability during these resections remains a challenge. Determinants of intraoperative hemodynamic stability remain unclear. Several factors, including tumor characteristics, preoperative a-blockade, surgical technique, and intraoperative management, may have a role in perioperative hemodynamics and outcomes.1 The objectives of this study were to (1) identify predictive factors of intraoperative hemodynamic instability; (2) investigate the relationship between hemodynamic instability and morbidity/mortality with pheochromocytoma resection at our institution; and (3) to examine changes in outcomes, patients, and practice over a 20-year period. METHODS

Ó Society of Surgical Oncology 2015 First Received: 4 December 2014 M. Livingstone, MD e-mail: [email protected]

A retrospective review of pheochromocytoma and paraganglioma resections performed from 1992 to 2013 was undertaken. Overall, 100 consecutive cases performed

M. Livingstone et al. TABLE 1 Patient demographics, tumor characteristics, perioperative management, and overall morbidity and mortality Variable

Median (IQR)

N (%)

Age (years)

50 (36–62)

88

Weight (kg)

74 (61–85)

70

Tumor size (cm)

4.2 (3.0–5.7)

70

Preoperative SBP (mmHg)a

136 (127–150)

88

Anesthesia duration (hours:min)

5:55 (5:01–6:46)

88

Preoperative phenoxybenzamine (mg)b

120 (65–15)

73

Duration of a-blockade therapy (days)

10 (7–19)

81

Male sex

42/88 (47.7)

Pregnant

1/46 (1.1)

Tumor location (adrenal)

68/85 (79.8)

Metastases present

8/88 (8.4)

Familial

23/88 (25.6)

Paraganglioma

19/88 (20.9)

Surgical technique Open

39/88 (44.3)

Laparoscopic

43/88 (48.9)

Converted

6/88 (6.8)

Hormone

c

Norepinephrine

61/76 (81.1)

Dopamine

5/76 (5.4)

Epinephrine Magnesium used

10/76 (13.5) 20/88 (22.7)

Vasopressin used

14/88 (15.9)

Mortality

0/88 (0)

MI, stroke, or ICU

11/88 (12.5)

ICU intensive care unit, IQR interquartile range, MI myocardial infarction, SBP systolic blood pressure a Preoperative SBP defined as the first non-invasive blood pressure recorded by the anesthesiologist on arrival to the operating room b

Total phenoxybenzamine dose per 24 h prior to surgery

c

Predominant hormone secreted by the tumor

by the same surgeon were reviewed. Patients with missing anesthetic records or no preoperative diagnosis of a pheochromocytoma were excluded, resulting in a total of 88 cases for final analysis. Preoperative data included patient age, sex, weight, height, comorbidities, pregnancy, familial association [including Von Hippel Lindau, multiple endocrine neoplasia type 2 (MEN2), and neurofibromatosis], tumor location and size, and the presence of metastases. The predominant hormone secreted (epinephrine, norepinephrine, or dopamine) was noted based on the highest plasma concentration (ng/L). Preoperative duration of a-blockade therapy (days) and dose (mg/24 h) was reviewed, and all patients included

in our study received phenoxybenzamine during their preoperative preparation. Preoperative systolic blood pressure (SBP), defined as the first non-invasive reading recorded in the operating room on the day of surgery, was noted. Intraoperative data, including surgical technique (laparoscopic vs. open), anesthetic duration, and administration of magnesium sulfate and vasopressin by the anesthesiologist, were recorded. Intraoperative fluid administration was not consistently recorded on the anesthetic records and was thus excluded from this study. The primary outcomes examined included intraoperative hemodynamic instability and perioperative morbidity/mortality. Intraoperative hemodynamic instability was defined as [10 hypo/hypertensive episodes where the anesthesiologist had to respond with a vasoactive substance. Perioperative morbidity/mortality was defined as intensive care unit (ICU) admission, myocardial infarction (MI), stroke, and mortality in a 30-day postoperative period. At our institution it is not routine for patients undergoing pheochromocytoma resections to be admitted to the ICU postoperatively. Patients were started on phenoxybenzamine 2–7 days before admission to hospital. Following admission, they received a further 5–10 days of a-blockade with phenoxybenzamine in hospital. All patients received a high salt diet and saline intravenous infusion. Management was titrated to achieve a blood pressure below 140/90 mmHg with orthostatic hypotension and a clinical assessment of euvolemia. A b-blocker was added in cases of persistent tachycardia (heart rate [ 120 beats/min), an epinephrine secreting tumor, tachyarrhythmias, and persistent hypertension despite adequate a-blockade. The sample was described using the median and interquartile range (IQR) for continuous variables, and percentage for categorical variables. Relationships between each potential predictor variables (Table 1) and hemodynamic instability were investigated using simple linear regression with the (log) number of hypo/hypertensive episodes as the outcome. A multivariable linear regression model was then developed in which all potential predictor variables significant at p \ 0.2 in the individual analysis were entered into the full model. Using a manual backwards approach, variables were retained in the model if p \ 0.05 or if there was evidence of confounding to arrive at the final model. Comparison of morbidity/mortality and hemodynamic instability were examined using Fisher’s exact test. Changes in practice between the first and most recent decade were examined using a two-sample t test for anesthetic duration and Fisher’s exact test for surgical technique (laparoscopic vs. open), and administration of magnesium sulfate and vasopressin by the anesthesiologist during surgery.

Hemodynamic Stability During Pheochromocytoma Resection TABLE 2 Individual predictors of hemodynamic instability (significant at p \ 0.20) N

Estimated coefficient

SE (estimated coefficient)

p value

Preoperative phenoxybenzamine dose

73

-0.0031

0.0015

0.041

Intraoperative use of vasopressin

88

0.63

0.26

0.019

Metastases present

88

-0.50

0.34

0.152

Paraganglioma

88

0.46

0.24

0.057

Hormone (norepinephrine)

76

-0.45

0.27

0.096

Hormone (dopamine)

76

0.82

0.43

0.061

Tumor size (log cm)

70

0.27

0.20

0.192

Preoperative SBP

88

0.011

0.0052

0.035

Intraoperative use of magnesium

88

0.44

0.23

0.063

SBP systolic blood pressure, SE standard error of the estimated coefficient

RESULTS A total of 100 patients were identified as having a pheochromocytoma resection from 1992 to 2013. Of these cases, 88 had a preoperative diagnosis of pheo and complete anesthetic records for analysis. Overall, 27.3 % (95 % CI 18.3–37.8) experienced hemodynamic instability. The median age was 50 years (IQR 32–62) and 47.7 % of the sample were male. Twenty percent of cases were paragangliomas and the majority of tumors were adrenal (80 %). Familial association (including von Hippel–Lindau, MEN2, and neurofibromatosis) was observed in 26 % of patients. Tumors were predominantly norepinephrinesecreting (81 %), and median tumor size was 4.2 cm (IQR 3.0–5.7). An equivalent number of laparoscopic and open procedures were performed (48.9 and 44.3 %, respectively), and median preoperative SBP was 136 mmHg (IQR 127–150) after a-blockade. Median preoperative daily phenoxybenzamine was 119 mg (IRQ 70–150), and preoperative phenoxybenzamine dose was not specified in 15 cases. Other methods of preoperative a-blockade were not used in the immediate preoperative period and were therefore excluded from the analysis. On average, total anesthetic and operative time was approximately 6 h (Table 1). Risk Factors Several individual predictors of intraoperative hemodynamic instability were identified for inclusion in the multivariable linear regression model (Table 2). Variables not individually significant predictors of hemodynamic instability were age (p = 0.274), weight (p = 0.228), duration of anesthesia (p = 0.811), sex (p = 0.230), location of tumor (p = 0.846), familial association (p = 0.638), surgical technique (open vs. laparoscopic; p = 0.490),

epinephrine (p = 0.558), and duration of a-blockade (p = 0.592). In the multivariable regression model (Table 3), there was a significant interaction observed between intraoperative magnesium use and preoperative SBP in predicting hemodynamic instability (p = 0.016). In cases where the anesthesiologist administered magnesium, there was a slight decrease in hemodynamic instability as preoperative SBP increased (p = 0.552). However, in cases where magnesium was not given, the number of unstable episodes increased significantly and non-linearly as preoperative SBP increased (p = 0.002) (Fig. 1). Preoperative phenoxybenzamine dose was associated with less intraoperative hemodynamic instability [b^ ¼ 0:36 (95 % CI -0.6 to -0.09), p = 0.010] per 100 mg increase in preoperative phenoxybenzamine. Increased doses of preoperative phenoxybenzamine did not predict lower preoperative SBP (p = 0.955). Cases with intraoperative vasopressin use had more hemodynamic instability [b^ ¼ 0:58 (95 % CI 0.05 to 1.11), p = 0.032]. After controlling for these variables, none of the other variables were significant, nor was there any evidence of confounding.

Perioperative Outcomes In these 88 patients, there was no perioperative mortality and no strokes, and there was one post-operative MI and 10 ICU admissions, for a total number of 11 negative outcomes (12.5 %). In those cases where hemodynamic instability was present, five patients had an ICU admission and one had a perioperative MI, for a total of 26.3 % (95 % CI 9.1–51.2 %), compared with only six ICU admissions (8.7 %, 95 % CI 3.3–18.0 %) in patients who were hemodynamically stable (p = 0.055). Length of ICU stay was not recorded.

M. Livingstone et al. TABLE 3 Multivariable regression model: predictors of intraoperative hemodynamic instability Variable

Estimated coefficient

SE (estimated coefficient)

95 % CI (estimated coefficient)

p value

Preoperative phenoxybenzamine dose (mg)a

-0.0036

0.0013

-0.006 to -0.0009

0.010

-0.0057

0.0095

-0.025 to 0.013

0.552

Preoperative SBP Milligrams used No milligrams used Intraoperative vasopressin use Magnesium used Constant

0.022

0.006

0.010–0.034

0.001

0.58

0.27

0.05–1.11

0.032

4.23

1.58

1.08–7.39

0.009

-0.98

0.88

-2.73 to 0.77

0.266

Hemodynamic instability = log (number of hypo/hypertensive episodes) SBP systolic blood pressure, SE standard error of the estimated coefficient a

N = 73; 15 patients excluded from the multivariable model due to missing values for preoperative phenoxybenzamine dose

Interaction between Magnesium and preoperative SBP

20 10

Hypo and Hyper episodes

30

significant (p = 0.504), and the use of vasopressin increased from 0 to 19.2 % (p = 0.115). There was no difference in location of the tumor (p = 0.285), hormone secreted (p = 0.227 for dopamine, p = 0.457 for norepinephrine, and p = 1.00 for epinephrine), paraganglioma (p = 0.508), familial association (p = 0.336), metastases (p = 0.620), and preoperative SBP (p = 0.955).

0

DISCUSSION 100

120

140

160

180

200

Preop SBP

FIG. 1 Illustration of the interaction between magnesium use and preoperative SBP in predicting the total number of hypo/hypertensive episodes. Blue circles indicate the use of magnesium and red circles indicate no use of magnesium. For patients in whom the anesthesiologist used magnesium, there was a slight but non-significant (estimated coefficient = -0.003; 95 % CI -0.021 to 0.015; p = 0.743) decrease in the number of hypo/hypertensive episodes as preoperative SBP increased. For patients in whom the anesthesiologist did not use magnesium, the number of hypo/hypertensive episodes increased significantly and non-linearly as preoperative SBP increased (estimated coefficient = 0.019; 95 % CI 0.007–0.031; p = 0.002). preop preoperative, SBP systolic blood pressure

Comparison of Practice Over Two Decades Examination of the last 10 years of practice (N = 73) compared with the first decade (N = 15) demonstrated a large decrease in perioperative morbidity/mortality (7 vs. 40 %, respectively; p = 0.003) and intraoperative hemodynamic instability [23.3 % (95 % CI 14.2–34.6 %) vs. 46.7 % (95 % CI 21.3–73.4 %); p = 0.11]. Recent practice included more laparoscopic procedures (54 vs. 27 %; p = 0.05). Average preoperative phenoxybenzamine dose increased from 59 mg (95 % CI 32–108) to 106 mg (95 % CI 91–124) in the last decade (p = 0.008). The use of magnesium increased from 13.3 to 24.7 % but this was not

This study examined perioperative morbidity/mortality and risk factors for intraoperative hemodynamic instability during pheochromocytoma resection. Overall mortality was low and perioperative outcomes have improved in the last two decades of resections. Lower preoperative dose of phenoxybenzamine, intraoperative use of vasopressin, and lack of magnesium sulfate were predictive factors of hemodynamic instability. Perioperative morbidity and mortality with pheo resection has drastically improved in recent years. Early reports indicated mortality rates as high as 20 %3; however, this figure has declined to 0–4 % in more recent studies.2,4,5 This is comparable to our study, with a mortality rate of 0 %. Postoperative complications were present in 12.5 % of cases in our study, and previous case series have demonstrated complication and ICU admission rates of up to 47 %.2 Our study observed a nearly sixfold decline in perioperative mortality/morbidity over two decades. Improvements in perioperative outcomes have previously been attributed to advances in diagnosis, localization, pharmacologic agents, surgical technique, and hemodynamic monitoring.6,7 Increased preoperative dose of phenoxybenzamine and utilization of laparoscopic technique over the last 10 years were observed in our study. These changes in practice have likely contributed to the improvements in perioperative outcomes.

Hemodynamic Stability During Pheochromocytoma Resection

Changes in preoperative pharmacological management have impacted morbidity/mortality in pheochromocytoma surgery. Therapy is aimed at controlling hypertension and preventing perioperative complications. Current guidelines state all patients should receive appropriate preoperative medical management to block the effects of circulating catecholamines7; this is accomplished primarily through ablockade with an a-adrenergic antagonist. Decreased perioperative mortality and morbidity in pheochromocytoma resection has been largely attributed to preoperative preparation with a-adrenergic antagonists.8 However, some have challenged the role of preoperative a-blockade. Boutros et al. reviewed 63 cases of pheochromocytoma surgery, of which 29 did not receive any preoperative a-blocker therapy. All patients were discharged from hospital without clinical evidence of stroke or MI, leading the authors to conclude that pheochromocytoma can be successfully performed without preoperative a-adrenergic blockade.9 This conclusion was contrasted by Steinsapir et al. who reviewed 33 cases and found that those without preoperative medical management had higher intraoperative peak systolic pressure and increased mortality rates.10 Our study suggests preoperative a-blockade plays a role in both intraoperative hemodynamic stability and perioperative outcomes. All patients included in our study were prescribed phenoxybenzamine as the primary preoperative a-blocking agent. b-Adrenergic blocking agents were highly variable. The last 10 years of our study demonstrated a significant decline in perioperative morbidity/mortality and a twofold increase in preoperative phenoxybenzamine dose. Although one cannot conclude direct causation, it does raise the question as to whether increased phenoxybenzamine dose has contributed to decreased morbidity/mortality. Increased preoperative phenoxybenzamine dose was, in fact, a significant predictor of improved intraoperative hemodynamic stability in this study. Previous studies have noted doses of phenoxybenzamine ranging from 10 to 240 mg,2,11 with reported daily dose averages ranging from 29 to 44 mg.12 The average daily dose of phenoxybenzamine was substantially higher in our series and increased from 68 to 120 mg/day over two decades of practice. Phenoxybenzamine is a non-competitive a-blocker; therefore, surges in intraoperative catecholamines during surgery will not result in drug displacement. This may result in improved intraoperative hemodynamic stability with non-competitive a-adrenergic blockade. There is theoretical concern of prolonged hypotension and reflex tachycardia with the use of phenoxybenzamine13; however, our study suggests that high doses of phenoxybenzamine are safe. There was overall low morbidity/mortality that declined further in the last 10 years when higher doses of phenoxybenzamine were utilized.

Minimally invasive adrenalectomy has also been shown to lower perioperative morbidity. Laparoscopic approaches are associated with less pain, lower morbidity rates, shorter hospital stays, more rapid recovery, and better cosmetic results.14 Laparoscopic adrenalectomy for pheochromocytoma has been shown to be both safe and effective15; thus, it is reasonable to conclude that, in this study, the increased use of laparoscopy for pheochromocytoma resection has contributed to improved outcomes over the last decade. Intravenous magnesium sulfate has gained recent interest in the management of intraoperative hemodynamics during pheochromocytoma surgery. The value of magnesium in pheochromocytoma excision is based on its unique mechanisms of action. Magnesium exerts a direct vasodilatory effect on blood vessel walls and, in addition, it has been shown to inhibit catecholamine release from the adrenal medulla and adrenergic nerve terminals and block peripheral catecholamine receptors directly.16,17 This makes magnesium particularly valuable during maneuvers that cause indirect catecholamine release, such as intubation and surgical stimulation. This, coupled with the peripheral anti-adrenergic effects of magnesium, is the basis for its use in the perioperative management of these tumors.18 Case studies have reported success in providing hemodynamic stability using magnesium as a single agent, an adjunct to other therapies, and as a rescue drug. In a study of 17 cases of pheochromocytoma resection, James observed that magnesium sulfate as the sole vasoactive agent provided good cardiovascular control for 11 cases.17 Several other case reports have utilized magnesium sulfate in combination with other vasoactive agents to achieve hemodynamic goals.16,19 This review demonstrates the safe use of magnesium sulfate in 20 pheochromocytoma resections. In addition, lack of intraoperative magnesium sulfate administration was associated with intraoperative hemodynamic instability. This effect was amplified as preoperative SBP increased. This suggests that the hemodynamic benefits of magnesium may be of particular value in patients presenting to the operating room for resection with persistent hypertension despite preoperative medical management. Intraoperative vasopressin use was also identified as a predictive factor for hemodynamic instability. Vasopressin is a naturally occurring hormone produced by the hypothalamus that acts to increase water reabsorption in the kidneys and cause systemic vasoconstriction. In clinical practice, vasopressin has been utilized in cases of refractory hypotension following tumor resection.20 Therefore, it is follows that, in our study, vasopressin use was seen more frequently in cases with increased hemodynamic instability.

M. Livingstone et al.

Limitations of this study include the accuracy of anesthetic charting and its retrospective design. Manual charting of blood pressures has decreased variation compared with automatic blood pressure records.21 It is difficult to make statistical comparisons between the first and second decade due to the small number of surgeries in the first decade. Improved morbidity over time may be due to system changes not reflected in this study. It is likely that increased experience of the perioperative team, including surgery, critical care, and nursing, has impacted morbidity over the last two decades. This effect is not easily quantified and should be considered when interpreting the results of this study. Finally, the retrospective nature of this study prevents us from drawing conclusions about causality. Only significant correlations may be noted.

3. 4.

5.

6.

7.

8. 9.

CONCLUSIONS This study demonstrates an improvement in perioperative morbidity and mortality following pheochromocytoma surgery over the last two decades of practice. In addition, there has been a trend towards increased hemodynamic stability during resection. Significant predictors of intraoperative hemodynamic instability identified include lower preoperative phenoxybenzamine dose, intraoperative use of vasopressin, and lack of magnesium sulfate administration. The role of intraoperative magnesium administration for hemodynamic management during pheochromocytoma resection warrants further study in a randomized controlled trial. It is difficult to determine the cause of improved perioperative outcomes in recent practice, and this may be accounted for by increased preoperative use of a-blocking agents and utilization of a laparoscopic approach. One cannot quantify how the evolving experience of the multidisciplinary team was factored into the improved outcomes seen in the last decade. CONFLICT OF INTEREST Margaret Livingstone, Kaylene Duttchen, Jenny Thompson, Zahid Sunderani, Geoffrey Hawboldt, M. Sarah Rose, and Janice Pasieka have no financial or commercial interests to disclose.

10. 11.

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18. 19.

20.

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pheochromocytoma and paraganglioma resection. Anesth Analg. 2000;91:1118–23. Apgar V, Papper EM. Pheochromocytoma: anesthetic management during surgical treatment. Arch Surg. 1951;62:634–48. Desmonts JM, le Houelleur J, Remond P, Duvaldestin P. Anaesthetic management of patients with pheochromocytoma: a review of 102 cases. Br J Anaesth. 1977;49:991–7. Van Heerden HA, Roland CF, Carney JA, et al. Long-term evaluation following resection of apparently benign pheochromocytoma(s)/paraganglioma(s). World J Surg. 1990;14:325–9. Warner MA, vanHeerden JA. Anesthetic and surgical management at the May Clinic. In: Manager WM, Gifford RW (eds). Clinical and experimental pheochromocytoma. 2nd ed. Cambridge: Blackwell Science;1996; 388–407. Pacak K, Eisenhofer G, Ahlman H et al. Pheochromocytoma: recommendations for clinical practice from the first international symposium. Nat Clin Pract Endocrinol Metab. 2007; 3:92–102. Wellbourn RB. Early surgical history of phaeochromocytoma. Br J Surg. 1987;74:594–6. Boutros A, Bravo E, Zenettin G, et al. Perioperative management of 63 patients with pheochromocytoma. Cleve Clin J Med. 1990;57:613–617. Steinsapir J, Carr A, Prisant M, et al. Metyrosin and pheochromocytoma. Arch Intern Med. 1997;157:901–6. Horst-Schrivers A, Kerstens M, Wolffenbuttel B. Preoperative pharmacological management of phaeochromocytoma. Neth J Med. 2006;64(8):290–5. Agrawal R, Mishra S, Bhatia E, et al. Prospective study to compare the perioperative hemodynamic alterations following preparation for pheochromocytoma surgery by phenoxybenzamine or prazosin. World J Surg. 2014;38:716–23. Bruynzeel H, Feelders A, Groenland T, et al. Risk factors for hemodynamic instability during surgery for pheochromocytoma. J Clin Endorcinol Metab. 2010;95:678–85. Gagner M, Pomp A, Neniford B, et al. Laparoscopic adrenalectomy: lessons learned from 100 consecutive procedures. Ann Surg. 1997;226:238–46. Kim H, Kim G, Sung G. Laparoscopic adrenalectomy for pheochromoctyoma: comparison with conventional open adrenalectomy. J Endourol. 2004;18:251–5. Jankovic R, Konstantinovic S, Milic D, et al. Can a patient be successfully prepared for pheochromocytoma surgery in three days? A case report. Minerva Anestesiol. 2007;73:245–8. James M. Use of magnesium sulphate in the anaesthetic management of pheochromocytoma: a review of 17 anaesthetics. Br J Anaesth. 1989;62:616–23. James M. Clinical use of magnesium infusions in anesthesia. Anesth Analg. 1992;74:129–36. Evan G. Magnesium sulfate and epidural anesthesia in pheochromocytoma and severe coronary artery disease. Anesth Analg. 1995;81:414–6. Lord M, Augoustides J. Perioperative management of pheochromocytoma: focus on magnesium, clevidipine, and vasopressin. J Cardiothor Vasc Anesth. 2012;26(3):526–31. Cook R, McDonald J, Nunziata E. Differences between handwritten and automatic blood pressure records. Anesthesiology 1989;71:385–90.

Hemodynamic Stability During Pheochromocytoma Resection: Lessons Learned Over the Last Two Decades.

Ideal perioperative management of pheochromocytomas/paragangliomas (pheo) is a subject of debate and can be highly variable. The purpose of this study...
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