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INTRODUCTIONGastroesophageal varices are present in approximately 50% of patientswith liver cirrhosis, with the yearly incidence of variceal hemorrhagebeing 5% to 15%. Acute variceal bleeding is an emergency requiringprompt treatment and close observation because it is associated with amortality rate of approximately 20% at 6 weeks. Therefore,pharmacological therapy is recommended when variceal hemorrhageoccurs. Terlipressin, a splanchnic vasoconstrictor analogue, is effectivein controlling acute variceal hemorrhage and is associated withdecreased mortality; it also demonstrated an efficacy of 52% inreversing hepatorenal syndrome (HRS). Terlipressin causes selectivevasoconstriction by stimulating vasopressin 1 (V1) receptors that arelocated in the smooth muscle of the splanchnic vasculature. Itsimultaneously induces aquaporin 2-mediated antidiuresis, causing adecrease in plasma sodium (Na) level because of vasopressin 2 (V2)receptor-mediated water reabsorption in the collecting duct. IncreasedV2 receptor-mediated water reabsorption of electrolyte-free water intothe blood circulation may lead to severe hyponatremia.Terlipressin induced hyponatremia can have catastrophic consequencesand requires close observation, as plasma sodium levels can drop tovery low levels resulting in generalized seizures, as reported in severalstudies. The patients in these studies recovered from altered mentalstate and seizures when their plasma Na levels returned to the normalrange after discontinuing terlipressin treatment, indicating thatterlipressin had caused the development of hyponatremia. Somestudies also showed that hyponatremia frequently occurs duringterlipressin treatment. However, the clinical significance and risk factorsfor terlipressin-induced hyponatremia are not fully elucidated.[1,2]OBJETIVETo describe 3 cases of terlipressin induced hyponatremia, itscharacteristics and review the predisposing clinical risk factors reportedin the recent bibliography.METHODSThe clinical cases were registered in one assistance center in theAutonomous City of Buenos Aires (Argentina). For the literature review,standard search strategies were used in Medline throughhttps://www.ncbi.nlm.nih.gov/pubmed/ site. The strategies were basedon the use of MESH terms ("Terlipressin"[Mesh] AND"Hyponatremia"[Mesh]).CASE- RESULTSCase 1: a 60-year-old man with a history of esophageal varices, benignprostatic hyperplasia and alcoholism, admitted due hematemesis.Terlipressin was started and after 5 days of treatment the patientdeveloped asymptomatic hyponatremia (120 mEq / L) with positive dechallenge.Case 2: a 40-year-old woman with history of portal hypertension ofunknown etiology, esophageal varices hemorrhage and normal renalfunction is admitted for new esophageal varices's hemorrhage andreceives terlipressin. She presented seizures on the third day withserum sodium of 109 mEq/L and normal brain CTS can. The clinicalpicture improved upon suspending terlipressin.Case 3: 59-year-old male with history of alcoholism, was admitted foresophageal varices hemorrhage and receives terlipressin, developingan hyponatremia induced confusional syndrome on the second day. Theadverse reaction was attributed to terlipressin and presented a positiveDISCUSSIONTerlipressin is routinely used to treat patients who experience varicealbleeding. The prevalence of hyponatremia was found to be substantiallyhigh when terlipressin was used as a splanchnic vasoconstrictorindicating that this complication should not be neglected. Theadministration of terlipressin activates not only V1 receptors that causesplanchnic vasoconstriction but also V2 receptors, consequentlydecreasing solute-free water clearance owing to an increase in urinaryexcretion of aquaporin-2. The prevalence of hyponatremia in differentstudies were around 35 to 67%.[3,4]In patients with advanced liver disease with low baseline serum Nalevels, the renal V2 receptors are likely to be already occupied byendogenous vasopressin. Therefore, terlipressin-induced antidiureticactivity due to V2 receptor stimulation is low in patients with high Child-Pugh scores. Young age was also found to be an important risk factorbecause their renal V2 receptors are not occupied by ligand. Themedian time for recovery of serum Na level was reported to be 4 daysafter discontinuation of terlipressin. Although the serum Na levelplummeted with the use of terlipressin, Na levels returned to baselinelevels a few days after terlipressin withdrawal, indicating that hypertonicsaline should not be used. Hyponatremia developed very frequently inpatients treated with terlipressin, especially in younger patients withbetter liver function and high serum Na level. Although the side effectseems to be mild in most cases, serum Na level can decrease rapidly,leading to severe rapid hyponatremia, seen in 19% of patients.Close observation of the changes in serum Na level during terlipressintreatment is necessary, especially in young patients with low BMI.References:1. ?íma M, Pokorný M, Paďour F, Slanař O. Terlipressin Induced SevereHyponatremia. Prague Med Rep. 2016;117(1):68-72.2. Poulsen A, Krag A. Severe hyponatraemia to terlipressin treatment. UgeskrLaeger. 2013;175(39):2250-1. Danish.3. Yim SY, Seo YS, Jung CH et al. Risk Factors for Developing HyponatremiaDuring Terlipressin Treatment: A Retrospective Analyses in Variceal Bleeding. JClin Gastroenterol. 2015;49(7):607-12.4. Solà E, Lens S, Guevara M et al. Hyponatremia in patients treated withterlipressin for severe gastrointest