Infants with gastrointestinal bleeding

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Infants with gastrointestinal bleeding: There are only case reports of argipressin being used for gastrointestinal bleeding.^9,10,11 Argipressin use was reported in 15 children with severe oesophageal variceal bleeding and 2 with peptic ulcer bleeding with control from use of argipressin alone in 9 of 17 episodes. Argipressin was commenced at 0.1 to 0.2 units/minute with titration over 2 hours to control bleeding. The maximum delivered dosage ranged from 0.004 to 0.04 units/kg/min (0.24 to 2.4 units/kg/hour). Control of bleeding did not improve with high dose argipressin and there was a significantly greater incidence of complications in those patients receiving ≥ 0.01 units/kg/min (0.6 units/kg/hour). Complications included electrolyte abnormalities (Na, K, CI or Ca) in 10 infants, fluid overload (4 infants), hypertension (4 infants) and cardiac dysrhythmias (2 infants).¹⁰

Meta-analysis of studies in adults with acute variceal bleeds found that although vasopressor agents reduced mortality and achieved haemostasis, trials of argipressin were not conclusive and argipressin was less effective for haemostasis compared to octreotide or somatostatin. ^{12, 13} Argipressin may be used in combination with nitroglycerin so as to balance its vasoconstrictive effect. Major side effects associated with the use of argipressin include myocardial ischaemia, life threatening arrythmias, mesenteric ischaemia and limb vasoconstriction or ischaemia. Other minor complications include water retention with sodium depletion, benign arrhythmia and acrocyanosis. Monitor cardiac rate

and rhythm, and watch for peripheral ischaemia. Terlipressin may be preferred over argipressin as it has the convenience of bolus administration, decreased cardiotoxicity and its ability to control up to 79% of variceal hemorrhage.^14,15(GOR D)

Pharmacokinetics:

The pharmacology of argipressin in newborns and children has not been sufficiently investigated and data on potential short and long-term adverse effects are still lacking.^14,16Half-life approximately 30 minutes, clinical duration of action 2–3 hours.

Safety:

Safety data of argipressin in paediatric patients is limited.^14,16 Potent vasoconstrictor action may cause ischaemia. Complications are more common when argipressin is co-administered with moderate to high doses of noradrenaline (norepinephrine). Hyponatraemia occurs frequently during argipressin infusion requiring close monitoring of serum sodium and water intake.^1,2 For control of gastrointestinal haemorrhage, argipressin was associated with electrolyte abnormalities (Na, K, CI or Ca) in 10 infants, fluid overload (4 infants), hypertension (4 infants) and cardiac dysrhythmias (2 infants), particularly at doses ≥ 0.01 units/kg/minute.¹⁰

References

1. Baldasso E, Garcia PC, Piva JP, Branco RG, Tasker RC. Pilot safety study of low-dose vasopressin in non-septic critically ill children. Intensive care medicine. 2009;35:355-9.

2. Davalos MC, Barrett R, Seshadri S, Walters HL, 3rd, Delius RE, Zidan M, Mastropietro CW. Hyponatremia during arginine vasopressin therapy in children following cardiac surgery. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2013;14:290-7.

3. Rios DR, Kaiser JR. Vasopressin versus dopamine for treatment of hypotension in extremely low birth weight infants: a randomized, blinded pilot study. The Journal of pediatrics. 2015;166:850-5.

4. Meyer S, McGuire W, Gottschling S, Mohammed Shamdeen G, Gortner L. The role of vasopressin and terlipressin in catecholamine-resistant shock and cardio-circulatory arrest in children: review of the literature. Wiener medizinische Wochenschrift. 2011;161:192-203.

5. Davis AL, Carcillo JA, Aneja RK, Deymann AJ, Lin JC, Nguyen TC, Okhuysen-Cawley RS, Relvas MS, Rozenfeld RA, Skippen PW, Stojadinovic BJ, Williams EA, Yeh TS, Balamuth F, Brierley J, de Caen AR, Cheifetz IM, Choong K, Conway E, Jr., Cornell T, Doctor A, Dugas MA, Feldman JD, Fitzgerald JC, Flori HR, Fortenberry JD, Graciano AL, Greenwald BM, Hall MW, Han YY, Hernan LJ, Irazuzta JE, Iselin E, van der Jagt EW, Jeffries HE, Kache S, Katyal C, Kissoon NT, Kon AA, Kutko MC, MacLaren G, Maul T, Mehta R, Odetola F, Parbuoni K, Paul R, Peters MJ, Ranjit S, Reuter-Rice KE, Schnitzler EJ, Scott HF, Torres A, Jr., Weingarten-Abrams J, Weiss SL, Zimmerman JJ, Zuckerberg AL. American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock. Critical care medicine. 2017;45:1061-93.

6. Mohamed A, Nasef N, Shah V, McNamara PJ. Vasopressin as a rescue therapy for refractory pulmonary hypertension in neonates: case series. Pediatric Critical Care Medicine. 2014;15:148-54.

7. Acker SN, Kinsella JP, Abman SH, Gien J. Vasopressin improves hemodynamic status in infants with congenital diaphragmatic hernia. Journal of Pediatrics. 2014;165:53-8.e1.

8. Lugo N, Silver P, Nimkoff L, Caronia C, Sagy M. Diagnosis and management algorithm of acute onset of central diabetes insipidus in critically ill children. J Pediatr Endocrinol. 1997;10:633-9.

9. Goyal A, Treem WR, Hyams JS. Severe upper gastrointestinal bleeding in healthy full-term neonates. Am J Gastroenterol. 1994;89:613-6.

10. Tuggle DW, Bennett KG, Scott J, Tunell WP. Intravenous vasopressin and gastrointestinal hemorrhage in children. J Pediatr Surg. 1988;23:627-9.

11. Liebman WM. Diagnosis and management of upper gastrointestinal hemorrhage in children. Pediatr Ann. 1976;5:690-9.

12. D'Amico G, Pagliaro L, Pietrosi G, Tarantino I. Emergency sclerotherapy versus vasoactive drugs for bleeding oesophageal varices in cirrhotic patients. The Cochrane database of systematic reviews. 2010:CD002233.

13. Wells M, Chande N, Adams P, Beaton M, Levstik M, Boyce E, Mrkobrada M. Meta-analysis: vasoactive medications for the management of acute variceal bleeds. Aliment Pharmacol Ther. 2012;35:1267-78.

14. Agrawal A, Singh VK, Varma A, Sharma R. Therapeutic applications of vasopressin in pediatric patients. Indian pediatrics. 2012;49:297-305.

15. Arora NK, Ganguly S, Mathur P, Ahuja A, Patwari A. Upper gastrointestinal bleeding: Etiology and management. Indian Journal of Pediatrics. 2002;69:155-68.

16. Biban P, Gaffuri M. Vasopressin and terlipressin in neonates and children with refractory septic shock. Current drug metabolism. 2013;14:186-92.

Original version Date: 28/11/2017	Author: NMF Consensus Group
Current Version number: 1.0	Current Version Date: April 2020
Risk Rating: Medium	Due for Review: April 2023
Approval by: DTC	Approval Date: April 2020

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