Effects of terlipressin infusion during hepatobiliary surgery on systemic and splanchnic haemodynamics, renal function and blood loss: a double-blind, randomized clinical trial

Magdy Mohammed Mahdy, Mostafa Samy Abbas, Emad Zarief Kamel, Mohamed Fathy Mostafa, Ragaa Herdan, Shimaa Abbas Hassan, Ramy Hassan, Ahmed M Taha, Tameem M Ibraheem, Bashir A Fadel, Mohammed Geddawy, Jehan Ahmed Sayed, Osama Ali Ibraheim, Magdy Mohammed Mahdy, Mostafa Samy Abbas, Emad Zarief Kamel, Mohamed Fathy Mostafa, Ragaa Herdan, Shimaa Abbas Hassan, Ramy Hassan, Ahmed M Taha, Tameem M Ibraheem, Bashir A Fadel, Mohammed Geddawy, Jehan Ahmed Sayed, Osama Ali Ibraheim

Abstract

Background: Terlipressin, in general, is a vasopressor which acts via V1 receptors. Its infusion elevates mean blood pressure and can reduce bleeding which has a splanchnic origin. The primary outcome was to assess the impact of intraoperative terlipressin infusion on portal venous pressure during hepatobiliary surgery; the 2ry outcomes included effects upon systemic hemodynamics, estimated blood loss, and postoperative renal functions.

Methods: This prospective randomized study involved 50 patients undergoing hepatobiliary surgery who were randomly and equally allocated into terlipressin group, or a control group. The terlipressin group received an initial bolus dose of (1 mg over 30 min) followed by a continuous infusion of 2 μg/kg/h throughout the procedure and gradually weaned over the first four postoperative hours, whereas the control group received the same volumes of normal saline. The portal venous pressure changes were measured directly through a portal vein angiocatheter.

Results: Portal pressure was significantly reduced over time in the terlipressin group only (from 17.88 ± 7.32 to 15.96 ± 6.55 mmHg, p < .001). Mean arterial blood pressure was significantly higher in the terlipressin group. Estimated blood loss was significantly higher in the control group than the terlipressin group (1065.7 ± 202 versus 842 ± 145.5 ml; p = 0.004), and the units of packed RBCs transfused were significantly higher in the control group ((0-2) versus (0-4) p = 0.003). There was no significant difference between groups as regards the incidence of acute kidney injury.

Conclusion: Intraoperative infusion of terlipressin during hepatobiliary surgery was shown to improve intraoperative portal hemodynamics with subsequent reduction in blood loss.

Trial registration: Clinical trial number and registry URL: Trial registration number: NCT02718599 . Name of registry: ClinicalTrials.gov. URL of registry: https://ichgcp.net/clinical-trials-registry/NCT02718599 . Date of registration: March 2016. Date of enrolment of the first participant to the trial: April 2016.

Keywords: Blood loss; Hemodynamics; Portal pressure; Terlipressin.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
CONSORT flow diagram
Fig. 2
Fig. 2
Intraoperative changes in the portal vein. Caption; (a)portal venous pressure, (b) Portal venous pH, (c) Portal venous partial pressure of CO2, (d) portal venous blood lactate level. Data are presented as mean ± SD. (*) significant change from the baseline value. P-value < 0.05 was considered statistically significant

References

    1. Giglio M, Marucci M, Testini M, Brienza N. Goal-directed haemodynamic therapy and gastrointestinal complications in major surgery: a meta-analysis of randomized controlled trials. Br J Anaesth. 2009;103(5):637–646. doi: 10.1093/bja/aep279.
    1. Holland J, Carey M, Hughes N, Sweeney K, Byrne PJ, Healy M, et al. Intraoperative splanchnic hypoperfusion, increased intestinal permeability, down-regulation of monocyte class II major histocompatibility complex expression, exaggerated acute phase response, and sepsis. Am J Surg. 2005;190(3):393–400. doi: 10.1016/j.amjsurg.2005.03.038.
    1. Filsoufi F, Rahmanian PB, Castillo JG, Scurlock C, Legnani PE, Adams DH. Predictors and outcome of gastrointestinal complications in patients undergoing cardiac surgery. Ann Surg. 2007;246(2):323. doi: 10.1097/SLA.0b013e3180603010.
    1. Bennett-Guerrero E, Welsby I, Dunn T, Young L, Wahl T, Diers T, et al. The use of a postoperative morbidity survey to evaluate patients with prolonged hospitalization after routine, moderate-risk, elective surgery. Anesth Analg. 1999;89(2):514–519.
    1. Tassoudis V, Vretzakis G, Petsiti A, Stamatiou G, Bouzia K, Melekos M, et al. Impact of intraoperative hypotension on hospital stay in major abdominal surgery. J Anesth. 2011;25(4):492. doi: 10.1007/s00540-011-1152-1.
    1. Goldmann A, Hoehne C, Fritz GA, Unger J, Ahlers O, Nachtigall I, et al. Combined vs. isoflurane/fentanyl anesthesia for major abdominal surgery: effects on hormones and hemodynamics. Med Sci Monit. 2008;14(9):CR445–CCR52.
    1. Brienza N, Giglio MT, Marucci M, Fiore T. Does perioperative hemodynamic optimization protect renal function in surgical patients? A meta-analytic study. Crit Care Med. 2009;37(6):2079–2090. doi: 10.1097/CCM.0b013e3181a00a43.
    1. Jhanji S, Vivian-Smith A, Lucena-Amaro S, Watson D, Hinds CJ, Pearse RM. Haemodynamic optimisation improves tissue microvascular flow and oxygenation after major surgery: a randomised controlled trial. Crit Care. 2010;14(4):R151. doi: 10.1186/cc9220.
    1. Lobo SM, Lobo FR, Polachini CA, Patini DS, Yamamoto AE, de Oliveira NE, et al. Prospective, randomized trial comparing fluids and dobutamine optimization of oxygen delivery in high-risk surgical patients [ISRCTN42445141] Crit Care. 2006;10(3):R72. doi: 10.1186/cc4913.
    1. Moreau R, Asselah T, Condat B, De Kerguenec C, Pessione F, Bernard B, et al. Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study. Gut. 2002;50(1):90–94. doi: 10.1136/gut.50.1.90.
    1. L-p Z, Li M, Yang L. Effects of different vasopressors on hemodynamics in patients undergoing orthotopic liver transplantation. Chin Med J. 2005;118(23):1952.
    1. Mukhtar A, Salah M, Aboulfetouh F, Obayah G, Samy M, Hassanien A, et al. The use of terlipressin during living donor liver transplantation: effects on systemic and splanchnic hemodynamics and renal function. Crit Care Med. 2011;39(6):1329–1334. doi: 10.1097/CCM.0b013e3182120842.
    1. Lai E, Fan S-T, Lo C-M, Chu K-M, Liu C-L, Wong J. Hepatic resection for hepatocellular carcinoma. An audit of 343 patients. Ann Surg. 1995;221(3):291. doi: 10.1097/00000658-199503000-00012.
    1. Narahara Y, Kanazawa H, Taki Y, Kimura Y, Atsukawa M, Katakura T, et al. Effects of terlipressin on systemic, hepatic and renal hemodynamics in patients with cirrhosis. J Gastroenterol Hepatol. 2009;24(11):1791–1797. doi: 10.1111/j.1440-1746.2009.05873.x.
    1. Uriz J, Ginès P, Cárdenas A, Sort P, Jiménez W, Salmerón JM, et al. Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome. J Hepatol. 2000;33(1):43–48. doi: 10.1016/S0168-8278(00)80158-0.
    1. Fahrner R, Patsenker E, De Gottardi A, Stickel F, Montani M, Stroka D, et al. Elevated liver regeneration in response to pharmacological reduction of elevated portal venous pressure by terlipressin after partial hepatectomy. Transplantation. 2014;97(9):892–900. doi: 10.1097/TP.0000000000000045.
    1. Reddy MS, Kaliamoorthy I, Rajakumar A, Malleeshwaran S, Appuswamy E, Lakshmi S, et al. Double-blind randomized controlled trial of the routine perioperative use of terlipressin in adult living donor liver transplantation. Liver Transpl. 2017;23(8):1007–1014. doi: 10.1002/lt.24759.
    1. Wagener G, Gubitosa G, Renz J, Kinkhabwala M, Brentjens T, Guarrera JV, et al. Vasopressin decreases portal vein pressure and flow in the native liver during liver transplantation. Liver Transpl. 2008;14(11):1664–1670. doi: 10.1002/lt.21602.
    1. Fayed N, Refaat E, Yassein T, Alwaraqy M. Effect of perioperative terlipressin infusion on systemic, hepatic, and renal hemodynamics during living donor liver transplantation. Journal of Crit Care. 2013;28(5):775–782. doi: 10.1016/j.jcrc.2013.02.016.
    1. Kalambokis G, Economou M, Paraskevi K, Konstantinos P, Pappas C, Katsaraki A, et al. Effects of somatostatin, terlipressin and somatostatin plus terlipressin on portal and systemic hemodynamics and renal sodium excretion in patients with cirrhosis. J Gastroenterol Hepatol. 2005;20(7):1075–1081. doi: 10.1111/j.1440-1746.2005.03902.x.
    1. Hong S, Lee J, Choi J, Chung H, Park J, Park C. Perioperative assessment of terlipressin infusion during living donor liver transplantation. J Int Med Res. 2012;40(1):225–236. doi: 10.1177/147323001204000123.
    1. Ioannou G, Doust J, Rockey DC. Terlipressin in acute oesophageal variceal haemorrhage. Aliment Pharmacol Ther. 2003;17(1):53–64. doi: 10.1046/j.1365-2036.2003.01356.x.
    1. Møller S, Hansen EF, Becker U, Brinch K, Henriksen JH, Bendtsen F. Central and systemic haemodynamic effects of terlipressin in portal hypertensive patients. Liver. 2000;20(1):51–59. doi: 10.1034/j.1600-0676.2000.020001051.x.
    1. Morelli A, Ertmer C, Lange M, Westphal M. Continuous terlipressin infusion in patients with septic shock: less may be best, and the earlier the better? Intensive Care Med. 2007;33(9):1669. doi: 10.1007/s00134-007-0676-1.
    1. Umgelter A, Reindl W, Schmid RM, Huber W. Continuous terlipressin infusion in patients with persistent septic shock and cirrhosis of the liver. Intensive Care Med. 2008;34(2):390–391. doi: 10.1007/s00134-007-0877-7.
    1. Abbas MS, Mohamed KS, Ibraheim OA, Taha AM, Ibraheem TM, Fadel BA, et al. Effects of terlipressin infusion on blood loss and transfusion needs during liver resection: a randomised trial. Acta Anaesthesiol Scand. 2019;63:34–39. doi: 10.1111/aas.13226.
    1. Raedler C, Voelckel WG, Wenzel V, Krismer AC, Schmittinger CA, Herff H, et al. Treatment of uncontrolled hemorrhagic shock after liver trauma: fatal effects of fluid resuscitation versus improved outcome after vasopressin. LWW; 2004.
    1. Yagi S, Iida T, Taniguchi K, Hori T, Hamada T, Fujii K, et al. Impact of portal venous pressure on regeneration and graft damage after living-donor liver transplantation. Liver Transpl. 2005;11(1):68–75. doi: 10.1002/lt.20317.
    1. Kam P, Williams S, Yoong F. Vasopressin and terlipressin: pharmacology and its clinical relevance. Anaesthesia. 2004;59(10):993–1001. doi: 10.1111/j.1365-2044.2004.03877.x.
    1. Krag A, Møller S, Henriksen JH, Holstein-Rathlou NH, Larsen FS, Bendtsen F. Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome. Hepatology. 2007;46(6):1863–1871. doi: 10.1002/hep.21901.
    1. Mutlu GM, Factor P. Role of vasopressin in the management of septic shock. Intensive Care Med. 2004;30(7):1276–1291. doi: 10.1007/s00134-004-2283-8.
    1. Yim SY, Seo YS, Jung CH, Kim TH, Kim ES, Keum B, et al. Risk factors for developing hyponatremia during Terlipressin treatment. J Clin Gastroenterol. 2015;49(7):607–612. doi: 10.1097/MCG.0000000000000217.

Source: PubMed

3
Předplatit