Volume: 10 Issue: 1
Year: 2022, Page: 11-19, Doi: https://doi.org/10.47799/pimr.1001.03
Received: Dec. 23, 2021 Accepted: Feb. 2, 2022 Published: Feb. 2, 2022
Background: Protamine neutralises heparin after separation from cardiopulmonary bypass. This study aimed to evaluate the effects of lidocaine on protamine induced pulmonary vascular constriction in paediatric cardiothoracic surgery.
Methods: This was a single-centre, prospective, double-blind and randomised study conducted among eighty pediatric patients with acyanotic congenital cardiac disease, scheduled for elective on-pump cardiac surgery under general anaesthesia. In the study, the participants were divided into four groups: Group NPHL- nonpulmonary hypertension with lidocaine preconditioning, group NPHS- nonpulmonary hypertension with normal saline (as placebo), group PHL- pulmonary hypertension with lidocaine preconditioning, and group PHS- pulmonary hypertension with normal saline (as placebo).
Results: Pulmonary vasoconstriction occurred in 11.25% of cases after protamine administration. Both the NPHS and PHS groups exhibited an increase in mean airway pressure (Paw), Respiratory index (RI), alveolar-arterial oxygen difference (A-aDO2), pulmonary artery pressure (PAP) and decreased dynamic pulmonary compliance (Cydn) and oxygen index (OI) after protamine administration. However, these changes were not observed in the NPHL and PHL groups with lidocaine preconditioning. Plasma levels of TXB2 in the NPHS and PHS groups were higher than the NPHL and PHL groups, but 6-keto-PGF1 alpha levels were lower in the NPHS and PHS groups than in the NPHL and PHL groups.
Conclusion: In congenital heart disease, repair without cardiopulmonary bypass is not possible in most cases. Prior to reversing heparin with protamine, preconditioning lidocaine reverses protamine-induced pulmonary vasoconstriction and improves lung function.
Keywords: Cardiopulmonary bypass, lidocaine, protamine, pulmonary hypertension
Holzmacher, J L & Sarani, B . 2017. Indications and Methods of Anticoagulation Reversal. Surg Clin North Am 97(6):1291–1305.
Boer, C, Meesters, M I, Veerhoek, D & Vonk, Aba . 2018. Anticoagulant and side-effects of protamine in cardiac surgery: a narrative review. Br J Anaesth 120(5):914–927.
Sokolowska, E, Kalaska, B, Miklosz, J & Mogielnicki, A . 2016. The toxicology of heparin reversal with protamine: past, present and future. Expert Opin Drug Metab Toxicol 12(8):897–909.
Zaidan, J R, Johnson, S, Brynes, R, Monroe, S & Guffin, A V . 1986. Rate of protamine administration: its effect on heparin reversal and anti-thrombin recovery after coronary artery surgery. Anesth Analg 65:377–80.
Shanberge, J N & Quattrociocchi-Longe, T M . 1989. Influence of platelet factor 4 on the neutralisation of heparin by protamine. Ann N Y Acad Sci 556:354–65.
Meesters, M I, Veerhoek, D & De Lange, F . 2016. Effect of high or low protamine dosing on postoperative bleeding following heparin anticoagulation in cardiac surgery. A randomised clinical trial. Thromb Haemost 116:251–61.
Bruck, S, Skrabal, C, Tr€ager, K & Reinelt, H . 2014. Risk factors for adverse reactions after protamine administration in adult patients undergoing cardiac surgeryda case report and literature review. Anasthesiol Intensivmed Notfallmed Schmerzther 49:360–366.
Kimmel, S E, Sekeres, M, Berlin, J A & Ellison, N . 2002. Mortality and adverse events after protamine administration in patients undergoing cardiopulmonary bypass. Anesth Analg 94(6):1402–1410.
Guan, Z, Shen, X, Zhang, Y J, Li, X G, Gao, Y F & Tan, J . 2018. use of epoprostenol to treat severe pulmonary vasoconstriction induced by protamine in cardiacsurgery. Medicine (Baltimore) 97:10908.
Kruzliak, P, Maruyama, J & Maruyama, K . 2014. Role of nitric oxide in pathophysiology and treatment of pulmonary hypertension. Vitam Horm 96:407–431.
Whitman, G J, Martel, D & Weiss, M . 1990. Reversal of protamine-induced catastrophic pulmonary vasoconstriction by prostaglandin E1. Ann Thorac Surg 50:303–308.
Singh, S, Laing, E F, Owiredu, Wkba, Singh, A & Annamalai, A . 2013. A Study of the Efficacy of Cardiac Antidysrhythmic Drugs in Attenuating Haemodynamic Responses to Laryngoscopy and Endotracheal Intubation in the Black Population. Journal of Anesthesia and Clinical research 4(6):1–6.
Horiguchi, T, Enzan, K, Mitsuhata, H, Murata, M & Suzuki, M . 1995. Heparin-protamine complexes cause pulmonary hypertension in goats. Anesthesiology 83(4):786–91.
Morel, D R, Zapol, W M, Thomas, S J, Kitain, E M, Robinson, D R & Moss, J . 1987. C5a and thromboxane generation associated with pulmonary vaso-and broncho-constriction during protamine reversal of heparin. Anesthesiol 66:597–604.
Petidis, K, Douma, S, Doumas, M, Basagiannis, I, Vogiatzis, K & Zamboulis, C . 2008. The interaction of vasoactive substances during exercise modulates platelet aggregation in hypertension and coronary artery disease. BMC Cardiovascular Disorders 8:11.
Woods, B D & Sladen, R N . 2009. Perioperative considerations for the patient with asthma and bronchospasm. British Journal of Anaesthesia 103(1):57–65.
Cassuto, J, Sinclair, R & Bonderovic, M . 2006. Anti-inflammatory properties of local anesthetics and their present and potential clinical implications. Acta Anaesthesiol Scand 50:265–282.
Feng, G, Liu, S, Wang, G L & Liu, G J . 2008. Lidocaine attenuates lipop- olysaccharide induced acute lung injury through inhibiting NF- kappaB activation. Pharmacology 81:32–40.
Hamp, T, Krammel, M, Weber, U, Schmid, R, Graf, A & Plöchl, W . 2013. The effect of a bolus dose of intravenous lidocaine on the minimum alveolar concentration of sevoflurane: a prospective, randomised, double-blinded, placebo-controlled trial. Anesth Analg 117:323–331.
Weinberg, L, Jang, J & Rachbuch, C . 2017. The effects of intravenous lignocaine on depth of anaesthesia and intraoperative haemodynamics during open radical prostatectomy. BMC Res Notes 10:248.
Bindslev, L, Cannon, D, Sykes, M K & Chir, B . 1986. Effect of lignocaine and nitrous oxide on hypoxic pulmonary vasoconstriction in the dog constant-flow perfused left lower lobe preparation. BJA 58:315–320.
Kulsum, S S, Singh, S H, Annamalai, A A & Mahrous, D E . 2013. Can sodium channel blocker lidocaine attenuate haemodynamic responses to endotracheal intubation in patients with coronary artery disease effectively? J Anesthesiol 1(3):27–35.
Singh S, Okyere I, Annamalai A, Singh A. A Study of the Effectiveness of Lidocaine to Treat Severe Pulmonary Vascular Constriction induced by Protamine . Perspectives in Medical Research. 2022;10(1):11-19 DOI: 10.47799/pimr.1001.03