Deaths caused by ingestion of rat poison containing yellow phosphorus is a major problem in a few States. A six-month survey carried out in six districts in Tamil Nadu in 2019 by the Tamil Nadu chapter of Indian Society of Gastroenterology (TN-ISG) found 450 people suffered from liver toxicity caused by ingestion of rat poison. Of them, 131 patients died while 28 were discharged in a moribund state. Extrapolating it for the entire State, researchers estimated 1,584 such cases in 2019 in just six months with about 554 deaths. Tamil Nadu has introduced a legislation to curb unrestricted access to rodenticide containing yellow phosphorus.
Until a few years ago, urgent liver transplantation was the only life saving option for such patients who developed acute liver failure. Beginning December 2017, a team of researchers from CMC Vellore has been using plasma exchange through a centrifugal method — a simple and less expensive treatment — to save the lives of such people. Impressed by the success of the plasma exchange treatment by CMC Vellore and following the identification of rat poison (rodenticide) ingestion as the cause of liver failure and deaths, the Tamil Nadu government through the Tamil Nadu Accident and Emergency Care Initiative of the National Health Mission (TAEI-NHM) programme started using plasma exchange in six apex government hospitals to treat these patients in March 2022. Prior to this, Madras Medical College, Stanley Medical College in Chennai and Coimbatore Medical College were using plasma exchange to treat rodenticide hepatotoxicity. Currently, 17 government hospitals across 15 districts in the State undertake plasma exchange to treat rodenticide-induced acute liver injury and acute liver failure cases.
“In 2022-2023, 1,237 acute liver toxicity patients due to rat poisoning in Tamil Nadu were treated with plasma exchange. Of them, 825 survived and were discharged. The survival rate was 63.9%,” says Dr. Maruthu Thurai Sambandam, Tamil Nadu State Programme Manager, TAEI-NHM.
“Liver failure due to rat poison ingestion may be due to overactive immune responses. We have found markers for innate immune responses turned on in patients with acute liver failure following ingestion of rat poison containing yellow phosphorus. Plasma exchange dampens these overactive immune responses, which helps save lives,” says Dr. Uday Zachariah from the Department of Hepatology at CMC Vellore and a member of the team that initiated the plasma exchange programme for liver failure at CMC Vellore.
In a retrospective analysis of 32 children at CMC Vellore with acute liver injury or acute liver failure due to rodenticidal ingestion, eight children were extremely sick and were eligible for plasma exchange. Of the eight, six children survived (75%). In another study at CMC Vellore which included adults, of the 81 patients who were eligible for and underwent plasma exchange, 65 patients survived (80.2%). Of the 81 patients who underwent plasma exchange, 32 had acute liver failure and 22 of the 32 such patients were saved through plasma exchange.
“Initially only those who were severely sick — acute liver failure — were treated with plasma exchange. The focus was on establishing the safety of the treatment rather than measuring the efficacy. We now use plasma exchange even in patients with acute liver injury, which is one stage earlier than acute liver failure,” says Dr. C.E. Eapen, from CMC Vellore and a senior member of the plasma exchange treatment team. Earlier initiation of plasma exchange treatment has saved more patients. Patients with acute liver injury can progress to acute liver failure very quickly, even within a few hours.
According to the TN-ISG study, currently over 99% of hepatotoxicity patients due to rodenticide ingestion in the State cannot access urgent liver transplantation. The major constraint is the lack of a matched deceased donor or a live-related donor. If liver transplantation is very expensive, patients are then required to remain on lifelong immuno-suppressants medications, which further increases the cost. In comparison, the plasma exchange treatment, which involves removal (pheresis) of patient plasma and replacement of healthy plasma from voluntary blood donors, costs only one-tenth to one- twentieth of liver transplantation. Normally, patients would require three plasma exchange sessions spread over three days; a decision to continue plasma exchange is taken on a daily basis.
Worldwide, regular dialysis has not been shown to improve survival in patients with acute liver failure. “This may be because standard dialysis technique removes only small- and medium-sized molecules, while plasma exchange helps remove macro molecules too,” says Dr. Zachariah. “The removal of specific macromolecules may be an important reason why we are seeing increased success in treating patients with rodenticide ingestion-induced liver toxicity.”
“A pilot study was undertaken seven years ago at the Madras Medical College to use plasma exchange to treat patients with yellow phosphorus poisoning,” says Dr. Krishnasamy Narayanasamy, former Head of the Department of Hepatology, Madras Medical College and currently the Vice Chancellor, TN Dr. MGR Medical University. A field visit in and around Thanjavur and interaction with patients, their family members and other stakeholders helped in sensitising the Tamil Nadu government and finally the establishment of a programme for the care of patients with rat killer poison ingestion.
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