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Annals of Surgical Oncology

, Volume 22, Supplement 3, pp 646–654 | Cite as

Preoperative Metyrosine Improves Cardiovascular Outcomes for Patients Undergoing Surgery for Pheochromocytoma and Paraganglioma

  • Heather Wachtel
  • Edward H. Kennedy
  • Salman Zaheer
  • Edmund K. Bartlett
  • Lauren Fishbein
  • Robert E. Roses
  • Douglas L. Fraker
  • Debbie L. Cohen
Endocrine Tumors

Abstract

Background

The goal of preoperative pharmacotherapy for pheochromocytoma (PCC) and paraganglioma (PGL) resection is to minimize intraoperative hemodynamic instability and perioperative cardiovascular complications, but no standard preoperative regimen exists. Historically, treatment used metyrosine and phenoxybenzamine (MP). The recent metyrosine shortage required that phenoxybenzamine alone (PA) be used for treatment. The authors examined their experience to determine the impact of preoperative metyrosine treatment on patient outcomes.

Methods

A retrospective cohort study investigated patients who underwent initial PCC/PGL resection (2000–2014). The primary outcome was intraoperative hemodynamics, measured by heart rate (HR) and systolic blood pressure (SBP). The secondary outcomes included perioperative complications and cardiovascular-specific complications (CVC). Univariate analysis was performed, and adjusted risk differences were estimated after confounding was taken into account.

Results

Of 174 patients, 142 (81.6 %) were in the MP group. The MP and PA patients had comparable intraoperative use of antihypertensives (83.9 vs 78.1 %; p = 0.443), vasopressors (74.6 vs 87.5 %; p = 0.120), and fluid resuscitation (mean, 24.4 vs 24.8 ml/min; p = 0.761). Although the perioperative complication rate did not differ significantly between the MP and PA groups (respectively 23.4 vs 34.4 %; p = 0.198), the PA patients had a 15.8 % higher rate of CVC even after controlling for confounders (p = 0.034). Compared with the MP patients, the PA patients had significantly more hemodynamic instability intraoperatively, with a greater range in HR (7.4 bpm; p = 0.034) and SBP (14.8 mmHg; p = 0.020).

Conclusions

In this study, preoperative metyrosine improved intraoperative hemodynamic stability and decreased CVC rates in patients undergoing PCC/PGLresection. These data suggest that the addition of preoperative metyrosine may improve operative outcomes.

Keywords

Propensity Score Paraganglioma Catecholamine Level Phenoxybenzamine Catecholamine Excess 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

The authors thank Andrew Rhodes, DO, and Isadora Cerullo, BA, for contributions to data acquisition.

Conflict of interest

There are no conflicts of interest.

Supplementary material

10434_2015_4862_MOESM1_ESM.docx (24 kb)
Supplementary material 1 (DOCX 25 kb)

References

  1. 1.
    Walther MM, Keiser HR, Linehan WM. Pheochromocytoma: evaluation, diagnosis, and treatment. World J Urol. 1999;17:35–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Lenders JW, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. Lancet. 2005;366:665–75.PubMedCrossRefGoogle Scholar
  3. 3.
    Tauzin-Fin P, Sesay M, Gosse P, Ballanger P. Effects of perioperative alpha1 block on haemodynamic control during laparoscopic surgery for phaeochromocytoma. Br J Anaesth. 2004;92:512–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Flavio Rocha M, Faramarzi-Roques R, Tauzin-Fin P, Vallee V, Leitao de Vasconcelos PR, Ballanger P. Laparoscopic surgery for pheochromocytoma. Eur Urol. 2004;45:226–32.Google Scholar
  5. 5.
    Prys-Roberts C. Phaeochromocytoma—recent progress in its management. Br J Anaesth. 2000;85:44–57.PubMedCrossRefGoogle Scholar
  6. 6.
    Duh QY. Evolving surgical management for patients with pheochromocytoma. J Clin Endocrinol Metab. 2001;86:1477–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Hull CJ. Phaeochromocytoma: diagnosis, preoperative preparation, and anaesthetic management. Br J Anaesth. 1986;58:1453–68.PubMedCrossRefGoogle Scholar
  8. 8.
    Apgar V, Papper EM. Pheochromocytoma: anesthetic management during surgical treatment. AMA Arch Surg. 1951;62:634–48.PubMedCrossRefGoogle Scholar
  9. 9.
    Kvale WF, Manger WM, Priestley JT, Roth GM. Pheochromocytoma. Circulation. 1956;14(4 Part 1):622–30.Google Scholar
  10. 10.
    Plouin PF, Duclos JM, Soppelsa F, Boublil G, Chatellier G. Factors associated with perioperative morbidity and mortality in patients with pheochromocytoma: analysis of 165 operations at a single center. J Clin Endocrinol Metab. 2001;86:1480–6.PubMedGoogle Scholar
  11. 11.
    Pacak K. Preoperative management of the pheochromocytoma patient. J Clin Endocrinol Metab. 2007;92:4069–79.PubMedCrossRefGoogle Scholar
  12. 12.
    Mannelli M, Dralle H, Lenders JW. Perioperative management of pheochromocytoma/paraganglioma: is there a state of the art? Horm Metab Res. 2012;44:373–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Lenders JW, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metabol. 2014;99:1915–42.CrossRefGoogle Scholar
  14. 14.
    Brogden RN, Heel RC, Speight TM, Avery GS. Alpha-methyl-p-tyrosine: a review of its pharmacology and clinical use. Drugs. 1981;21:81–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Fishbein L, Orlowski R, Cohen D. Pheochromocytoma/paraganglioma: review of perioperative management of blood pressure and update on genetic mutations associated with pheochromocytoma. J Clin Hypertens Greenwich Conn. 2013;15:428–34.CrossRefGoogle Scholar
  16. 16.
    Gupta PK, Gupta H, Sundaram A, et al. Development and validation of a risk calculator for prediction of cardiac risk after surgery. Circulation. 2011;124:381–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Strasberg SM, Linehan DC, Hawkins WG. The accordion severity grading system of surgical complications. Ann Surg. 2009;250:177–86.PubMedCrossRefGoogle Scholar
  18. 18.
    Bang H, Robins JM. Doubly robust estimation in missing data and causal inference models. Biometrics. 2005;61:962–73.PubMedCrossRefGoogle Scholar
  19. 19.
    van der Laan MJ, Polley EC, Hubbard AE. Super learner. Stat Appl Genet Mol Biol. 2007;6:article 25.Google Scholar
  20. 20.
    Sjoerdsma A, Engelman K, Spector S, Udenfriend S. Inhibition of catecholamine synthesis in man with alpha-methyl-tyrosine, an inhibitor of tyrosine hydroxylase. Lancet. 1965;2:1092–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Engelman K, Horwitz D, Jequier E, Sjoerdsma A. Biochemical and pharmacologic effects of alpha-methyltyrosine in man. J Clin Invest. 1968;47:577–94.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Steinsapir J, Carr AA, Prisant LM, Bransome ED Jr. Metyrosine and pheochromocytoma. Arch Intern Med. 1997;157:901–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Perry RR, Keiser HR, Norton JA, et al. Surgical management of pheochromocytoma with the use of metyrosine. Ann Surg. 1990;212:621–8.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Ulchaker JC, Goldfarb DA, Bravo EL, Novick AC. Successful outcomes in pheochromocytoma surgery in the modern era. J Urol. 1999;161:764–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Orchard T, Grant CS, van Heerden JA, Weaver A. Pheochromocytoma: continuing evolution of surgical therapy. Surgery. 1993;114:1153–8; discussion 1158–9.Google Scholar
  26. 26.
    Russell WJ, Metcalfe IR, Tonkin AL, Frewin DB. The preoperative management of phaeochromocytoma. Anaesth Intensive Care. 1998;26:196–200.PubMedGoogle Scholar
  27. 27.
    Bruynzeel H, Feelders RA, Groenland TH, et al. Risk factors for hemodynamic instability during surgery for pheochromocytoma. J Clin Endocrinol Metab. 2010;95:678–85.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Heather Wachtel
    • 1
  • Edward H. Kennedy
    • 2
  • Salman Zaheer
    • 1
  • Edmund K. Bartlett
    • 1
  • Lauren Fishbein
    • 3
  • Robert E. Roses
    • 1
  • Douglas L. Fraker
    • 1
  • Debbie L. Cohen
    • 4
  1. 1.Department of SurgeryHospital of the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Center for Clinical Epidemiology and BiostatisticsUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Division of Endocrinology, Diabetes and Metabolism, Department of MedicineHospital of the University of PennsylvaniaPhiladelphiaUSA
  4. 4.Division of Renal, Electrolytes, and Hypertension, Department of MedicineHospital of the University of PennsylvaniaPhiladelphiaUSA

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