Anesthesiology 2003; 98:1338 – 44 © 2003 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Terlipressin Versus Norepinephrine to Correct Refractory Arterial Hypotension after General Anesthesia in Patients Chronically Treated with Renin-Angiotensin System Inhibitors Gilles Boccara, M.D., Ph.D.,* Alexandre Ouattara, M.D., M.Sc.,* Gilles Godet, M.D.,* Eric Dufresne, M.D.,* Michèle Bertrand, M.D.,* Bruno Riou, M.D., Ph.D.,† Pierre Coriat, M.D.‡ Background: Terlipressin, a precursor that is metabolized to lysine-vasopressin, has been proposed as a drug for treatment of intraoperative arterial hypotension refractory to ephedrine in patients who have received long-term treatment with renin- angiotensin system inhibitors. The authors compared the effec- tiveness of terlipressin and norepinephrine to correct hypoten- sion in these patients. Methods: Among 42 patients scheduled for elective carotid endarterectomy, 20 had arterial hypotension following general anesthesia that was refractory to ephedrine. These patients were the basis of the study. After randomization, they received either 1 mg intravenous terlipressin (n  10) or norepineph- rine infusion (n  10). Beat-by-beat recordings of systolic arte- rial blood pressure and heart rate were stored on a computer. The intraoperative maximum and minimum values of blood pressure and heart rate, and the time spent with systolic arterial blood pressure below 90 mmHg and above 160 mmHg, were used as indices of hemodynamic stability. Data are expressed as median (95% confidence interval). Results: Terlipressin and norepinephrine corrected arterial hypotension in all cases. However, time spent with systolic arterial blood pressure below 90 mmHg was less in the terlip- ressin group (0 s [0 –120 s] vs. 510 s [120 –1011 s]; P < 0.001). Nonresponse to treatment (defined as three boluses of terlip- ressin or three changes in norepinephrine infusion) occurred in zero and eight cases (P < 0.05), respectively. Conclusions: In patients who received long-term treatment with renin-angiotensin system inhibitors, intraoperative refrac- tory arterial hypotension was corrected with both terlipressin and norepinephrine. However, terlipressin was more rapidly effective for maintaining normal systolic arterial blood pres- sure during general anesthesia. ARTERIAL hypotension following general anesthesia in- duction that is refractory to ephedrine has been reported in patients undergoing long-term therapy with angioten- sin-converting enzyme inhibitors (ACEIs) or angioten- sin-II receptor antagonists (AIIRAs). 1,2 Use of terlipressin (a drug precursor metabolized to lysine-vasopressin by plasmatic esterases) has been proposed for the treat- ment of refractory intraoperative hypotension in pa- tients undergoing long-term treatment with renin-angio- tensin system inhibitors. 1,3 Terlipressin, which has been used for hemorrhage from rupture of esophageal varices, acts via the vasopressin system, which may be consid- ered as the third physiologic system for the modulation of arterial blood pressure. 4 The vasopressin system consists essentially of arginine- vasopressin, a postpituitary nine amino-acid peptide, which stimulates vasopressin receptors, especially vas- cular V1a receptors, inducing marked arterial constric- tion. Use of vasopressin has been previously suggested for the treatment of circulatory arrest and hemorrhagic and septic shock. 5–7 Significant vasoconstriction has been noted in healthy and endotoxemic sheep (a 40% and 120% increase, respectively, in systemic vascular resistance) when terlipressin was infused 30 min before norepinephrine. 8 Recently, when terlipressin was given with ephedrine, it was shown to be effective in reversing intraoperative systemic hypotension refractory to ephedrine alone. 9 However, the administration of terlipressin on its own to treat intraoperative arterial hypotension has not been compared with use of vasopressors, such as sympathetic adrenoceptor agonists. Therefore, we conducted a pro- spective randomized study to compare terlipressin to the standard vasopressor agent (norepinephrine) for treat- ment of refractory artery hypotension following general anesthesia in patients undergoing carotid surgery and chronically treated with ACEIs or AIIRAs. Methods Study Population This prospective study was approved by the ethical committee for human research of our hospital, and writ- ten informed consent was obtained in all patients. Pa- tients scheduled for elective carotid endarterectomy un- der general anesthesia and undergoing long-term treatment with ACEIs or AIIRAs for arterial hypertension were selected for this prospective study. Exclusion cri- teria included emergency surgery, administration of ACEIs for chronic cardiac failure, untreated or uncon- trolled coronary artery disease, chronic renal disease (estimated creatinine clearance less than 70 ml/min with * Staff Anesthesiologist, ‡ Professor and Chairman, Department of Anesthesi- ology and Intensive Care, † Professor of Anesthesiology and Chairman, Depart- ment of Emergency Medicine and Surgery, Centre Hospitalo-Universitaire Pitié-Salpétrière. Received from the Department of Anesthesiology and Intensive Care and Department of Emergency Medicine and Surgery, Centre Hospitalo-Universitaire Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France. Submitted for publication August 5, 2002. Accepted for publication January 14, 2003. Support was provided solely from departmental and institutional sources. Terlipressin was a gift from the hospital pharmacy department. Address reprint requests to Dr. Boccara: Département d’ Anesthésie-Réanima- tion, Groupe Hospitalier de la Pitié-Salpétrière, 47-83 Boulevard de l’ Hôpital, 75651 Paris Cedex 13, France. Address electronic mail to: g.boccara@noos.fr. Individual article reprints may be purchased through the Journal Web site, www.anesthesiology.org. Anesthesiology, V 98, No 6, Jun 2003 1338 Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/98/6/1338/653557/0000542-200306000-00007.pdf by guest on 05 October 2022