|Year : 2022 | Volume
| Issue : 1 | Page : 1-6
Management of rodenticide poisoning: Tamil Nadu chapter of Indian Society of gastroenterology guidelines
Chundamannil Eapen Eapen1, Velusamy Balasubramanian2, Ganesan Ramamoorthy3, Venkataraman Jayanthi4, Malathi Sathiyasekaran5, Natarajan Murugan6, Kallipatti Ramasamy Palaniswamy6, Pazhanivel Mohan7, Karunakaran Premkumar8, Balakrishnan S Ramakrishna9, Ramkumar Govindarajan3, Ramasubramanian Ramalingam10, Revathy Marimuthu Shanmugham11, Jeyaraj Ubaldhus6, Venkatkrishnan Leelakrishnan12
1 Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
2 Tamil Nadu Gastroenterologist Trust, Chennai, Tamil Nadu, India
3 Department of Medical Gastroenterology, Thanjavur Medical College, Thanjavur, Tamil Nadu, India
4 Department of Hepatology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
5 Department of Gastro Sciences, Advanced Endoscopy and Liver Diseases, MGM Health Care, Chennai, Tamil Nadu, India
6 Department of Medical Gastroenterology, Apollo Hospitals, Chennai, Tamil Nadu, India
7 Department of Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
8 Department of Medical Gastroenterology, Madras Medical College, Chennai, Tamil Nadu, India
9 Institute of Gastroenterology, Hepatobiliary Science and Transplantation, SRM Institutes for Medical Science, Chennai, Tamil Nadu, India
10 Department of Medical Gastroenterology, Thoothukudi Medical College, Thoothukudi, Tamil Nadu, India
11 Department of Medical Gastroenterology, Stanley Medical College, Chennai, Tamil Nadu, India
12 Department of Gastroenterology and Hepatology, PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, India
|Date of Submission||30-Nov-2021|
|Date of Decision||02-Dec-2021|
|Date of Acceptance||02-Dec-2021|
|Date of Web Publication||01-Jan-2022|
Chundamannil Eapen Eapen
Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Rodenticide ingestion, a common mode of suicide in Tamil Nadu and other states in southern and western parts of India, can lead to hepatotoxicity and death. Most rodenticide agents contain phosphorus, a potent toxin. The only definitive management in a patient who develops rodenticide induced acute liver failure is urgent liver transplantation. A study conducted across Tamil Nadu in 2019 documented that the majority (>99%) of rodenticide hepatotoxicity patients cannot access urgent liver transplantation. The current guidelines proposed by the Tamil Nadu chapter of the Indian Society of Gastroenterology are focused on improving survival in these patients, especially by nontransplant treatments. The indications for the use of plasma exchange, an emerging treatment which improves survival in acute liver failure, are described. In resource-constrained settings, it is preferable to avoid the use of sedative drugs, in rodenticide hepatotoxicity patients, who do not have encephalopathy. These management guidelines are specifically meant for use by doctors in primary health centers and in secondary hospitals who care for patients with rodenticide ingestion and hepatotoxicity. We hope these guidelines may also help inform health care policy in Tamil Nadu state to improve survival in patients with rodenticide hepatotoxicity by cost-effective interventions.
Keywords: Guidelines, management, phosphorus poison, rat killer
|How to cite this article:|
Eapen CE, Balasubramanian V, Ramamoorthy G, Jayanthi V, Sathiyasekaran M, Murugan N, Palaniswamy KR, Mohan P, Premkumar K, Ramakrishna BS, Govindarajan R, Ramalingam R, Shanmugham RM, Ubaldhus J, Leelakrishnan V. Management of rodenticide poisoning: Tamil Nadu chapter of Indian Society of gastroenterology guidelines. Gastroenterol Hepatol Endosc Pract 2022;2:1-6
|How to cite this URL:|
Eapen CE, Balasubramanian V, Ramamoorthy G, Jayanthi V, Sathiyasekaran M, Murugan N, Palaniswamy KR, Mohan P, Premkumar K, Ramakrishna BS, Govindarajan R, Ramalingam R, Shanmugham RM, Ubaldhus J, Leelakrishnan V. Management of rodenticide poisoning: Tamil Nadu chapter of Indian Society of gastroenterology guidelines. Gastroenterol Hepatol Endosc Pract [serial online] 2022 [cited 2022 Jan 29];2:1-6. Available from: http://www.ghepjournal.com/text.asp?2022/2/1/1/334702
| How Did These Guidelines Come About? Response of Tamil Nadu Chapter of Indian Society of Gastroenterology to a Societal Need|| |
A survey done under the aegis of the Tamil Nadu chapter of Indian Society of Gastroenterology (TN-ISG) from January to June 2019 identified rodenticide ingestion as the commonest cause of acute hepatotoxicity in Tamil Nadu. Of 451 rodenticide hepatotoxicity patients in 6 districts of Tamil Nadu, 75% were 15–34 years old and 159 patients (35%) had poor outcome (131 died, 28 discharged in moribund state). Of these patients, 396 patients had conservative management, 54 patients underwent plasma exchange (PLEX) while only one patient had liver transplantation [Figure 1]. These guidelines are a response by the TN-ISG to address this disease of epidemic proportions affecting the youth of Tamil Nadu.
|Figure 1: The skewed access to specialised treatments in 451 rodenticide hepatotoxicity patients in the Tamil Nadu chapter of Indian Society of Gastroenterology 2019 study. 75% of patients were 15–34 years old, 35% of patients died/were discharged in moribund state|
Click here to view
Patients with rodenticide hepatotoxicity can be treated by urgent liver transplantation and nontransplant options. At present, the majority (>99%) of rodenticide hepatotoxicity patients in Tamil Nadu cannot access urgent liver transplantation. This resource constraint probably applies to most patients with severe acute liver injury or acute liver failure in the rest of India as well. In contrast to developed nations, access to urgent liver transplantation is out of reach for most patients in India at the present time. Hence, the focus in India is to maximize patient survival with nontransplant treatments.
The standard care for managing any poison should be applied immediately to patient who has ingested rodenticide. Subsequently, the patient needs to be monitored in an easily accessible facility within the same locality. Patients who develop hepatotoxicity need close monitoring.
Recent Liver Transplant Society of India guidelines focus on urgent liver transplantation to treat rodenticide hepatotoxicity.
PLEX appears to improve survival in rodenticide hepatotoxicity patients.,,, Protocol for use of low volume PLEX to treat patients with severe liver injury have been published. Specialized treatment like PLEX needs to be provided in each district of Tamil Nadu.
Sensing the need for guidelines for managing patients who ingest rodenticide and those with hepatotoxicity, especially regarding nontransplant treatments, experts from TN-ISG have brought out these guidelines. The focus of these guidelines is to improve survival in patients with acute hepatotoxicity without urgent liver transplantation. In this context, avoiding sedative drugs, if possible, maybe important. Indications and contra-indications for the use of PLEX to treat these patients are also given, for the first time.
The TN-ISG guidelines address management of patient with rodenticide poisoning in three sections:
- Day 1 management of a patient who has consumed rodenticide
- Management of patient with rodenticide hepatotoxicity
- Follow up care after discharge from hospital.
| Day 1 Management of Patient Who Has Consumed Rodenticide|| |
Admitting the patient who has ingested rodenticide for monitoring
Phosphorus, commonly used as a rodenticide, is a potent toxin. It is not clear how this poison damages tissues and vital organs. Of the vital organs, the commonest organ affected is the liver, which in some patients leads to liver failure and death. It is not clear as to how many patients who ingest rodenticide will develop hepatotoxicity. The risk factors for developing hepatotoxicity need to be studied.
The clinical observation that the patient who has ingested rodenticide may look well initially and may develop hepatotoxicity 5 days later suggests that rather than direct toxicity to the liver, hepatotoxicity is a secondary event. It is not known if secondary events like formation of active metabolite of the poison or overactive host response (inflammatory response/innate immune response) to the ingested poison contributes to liver damage.
A.1. The patient who has ingested rodenticide should be admitted in hospital for 5 days to look for any complications. The patient needs daily clinical and laboratory (hemogram, liver function tests [LFT], prothrombin time/international normalized ratio (PT/INR), sodium, potassium, creatinine) assessment (Level of evidence: Low; Grade of recommendation: Strong).
Identifying the poison(s) consumed by the patient
For prompt institution of appropriate treatment, it is important to ascertain the type and dose of poison ingested. The treatment to be given and complications to be looked for will depend on the type of poison ingested. Rodenticides include phosphorus and anti-coagulants. A patient may consume other poisons and alcohol in addition to rodenticide.
It is useful to identify a list of locally available types and brands of agrarian poisons which are commonly consumed with suicidal intent in that locality (for example: rodenticides, poisonous plants such as oleander and oduvanthalai, insecticides [like organophosphorus]). A preprepared pictorial chart of these poisons can help to rapidly ascertain the poison consumed.
Paracetamol overdose is the commonest cause of acute hepatotoxicity in the West. Paracetamol is a stable substance and paracetamol levels in blood can be measured. In contrast, phosphorus is unstable, and hence, more challenging to identify in body fluids. At present, we do not have a reliable test to identify phosphorus or its metabolites in patients who ingest rodenticide.
A.2. Details of poison ingested can be ascertained by interviewing the patient or family member; by obtaining the package/covering of the poison and its pamphlet and by asking them to identify the poison from a display board with images of different rodenticides available for purchase in the locality (Level of evidence: Low; Grade of recommendation: Weak).
Gastric lavage to treat patient who presents early after rodenticide ingestion
As with any ingested poison, gastric lavage may help, especially in a patient who presents within few hours of ingestion of rodenticide. Phosphorus is an inflammable substance and the rare occurrence of spontaneous combustion and explosion when a patient who had presumably consumed rodenticide underwent nasogastric aspiration prior to gastric lavage has been described.
A.3. The patient presenting within 4 h of ingestion of rodenticide should have gastric lavage, if feasible (Level of evidence: Low; Grade of recommendation: Strong).
Oral activated charcoal to help remove the ingested poison
Oral activated charcoal may adsorb and thus help remove ingested poison.
A.4. The patient should be given oral activated charcoal (25–100 g, mixed with water) (Level of evidence: Low; Grade of recommendation: Strong).
N-acetyl cysteine to prevent rodenticidal hepatotoxcity
Phosphorus poisoning does not have an antidote.
N-acetyl cysteine used to treat acute hepatotoxicity due to paracetamol overdose has anti-oxidant action (it provides cysteine for glutathione synthesis). Raised plasma levels of von Willebrand factor (VWF) – a clotting protein – predict in-hospital death in rodenticide hepatotoxicity patients. N-acetyl cysteine has VWF lowering effect. Thus, N-acetyl cysteine, with its anti-oxidant and VWF lowering effects, may benefit these patients.
N-acetyl cysteine (oral and intravenous) administration is efficacious in preventing and treating hepatotoxicity in patients with paracetamol overdose. Earlier administration of N–acetyl cysteine (within 8 h of acute overdose) has better efficacy in this regard.
It is not known if N–acetyl cysteine administration in a patient who has consumed rodenticide will prevent hepatotoxicity or retard progression of hepatotoxicity.
A.5. The patient needs to be given oral N–acetyl cysteine 600 mg 2 times a day for 1 week (Level of evidence: Low; Grade of recommendation: Weak).
Ameliorating gastric inflammation in patient who has consumed rodenticide
Rodenticide ingestion can uncommonly cause necrosis and even perforation of upper gastrointestinal tract.
A.6. The patient needs to be given a proton pump inhibitor for 1 week (Level of evidence: Low; Grade of recommendation: Weak).
Management of patient who has ingested anti-coagulant containing rodenticide
Prolonged PT/INR is an adverse prognostic factor in acute liver failure. PT/INR is included in scores to predict outcomes in patients with acute liver failure. However, correction of the prolonged PT/INR by transfusions of fresh frozen plasma to treat patients with acute liver failure is not recommended in the absence of active bleeding. Some rodenticides contain anticoagulants such as warfarin and related compounds, coumarins, and indandiones – consumption of these compounds can prolong PT/INR by vitamin K antagonism; hence, in these patients, if PT/INR is prolonged, vitamin K supplementation needs to be given. Rarely, vitamin K1 intravenous injections can cause anaphylactoid reactions.
A.7. If the ingested poison contains anti-coagulant, PT/INR needs to be tested and if prolonged, the patient needs to be given Vitamin K (Level of evidence: Low; Grade of recommendation: Strong).
| Managing Patient with Rodenticidal Hepatotoxicity (i.e., With Any Liver Function Test Abnormality/Prolonged International Normalized Ratio)|| |
Admitting the patient with rodenticidal hepatotoxicity for monitoring
The patient with hepatotoxicity needs close monitoring for the development of complications like coagulopathy and encephalopathy. In patients with acute liver injury (has coagulopathy, no encephalopathy) and acute liver failure (has encephalopathy), standard management of a critically ill patient needs to be applied.
B.1. The patient needs to be managed in a closely monitored environment like high dependency unit / intensive care unit with frequent clinical and daily laboratory (hemogram, LFTs, PT/INR, sodium, potassium, and creatinine) assessment (Level of evidence: Low; Grade of recommendation: Strong).
Identifying poison(s) consumed by the patient
Please see discussion preceding Consensus statement A2.
B.2. Details of poison ingested can be ascertained by interviewing the patient or family member; by obtaining the package or covering of the poison and its pamphlet and by asking them to identify the poison from a display board with image of different rodenticides available for purchase in the locality (Level of evidence: Low; Grade of recommendation: Weak).
N-acetyl cysteine to treat rodenticidal hepatotoxcity
Please see discussion preceding Consensus statement A5.
B.3. The patient needs to be given intravenous N-acetyl cysteine (150 mg/kg body weight in 250 ml 5% dextrose over 1 h, followed by 50 mg/kg in 500 ml 5% dextrose over 4 h, then 100 mg/kg dose in 1000 ml 5% dextrose over 16 h) (Level of evidence: Low; Grade of recommendation: Strong).
Ameliorating gastric inflammation in patient with rodenticidal hepatotoxicity
Please see discussion preceding Consensus statement A6.
B.4. The patient needs to be given proton pump inhibitor for 1 week (Level of evidence: Low; Grade of recommendation: Weak).
Management of patient who has ingested anti-coagulant containing rodenticide
Please see discussion preceding Consensus statement A7.
B.5. If the ingested poison contains anti-coagulant, PT/INR needs to be tested and if prolonged, the patient needs to be given vitamin K for 3 days (Level of evidence: Low; Grade of recommendation: Strong).
Treatment of cerebal edema in patients with rodenticide induced acute liver failure
Cerebral edema is a serious complication of rodenticide hepatotoxicity. Anticerebral edema measures are needed to treat this.
B.6. Patient with encephalopathy needs anti-cerebral edema measures (nurse in semi-reclined posture with head end up by 20°–30°. Intravenous mannitol (0.5–1 g/kg body weight) bolus, as required (Level of evidence: Moderate; Grade of recommendation: Strong).
Caution on use of sedative drugs in patients with rodenticidal hepatotoxicity
The use of sedation in patients with acute hepatotoxicity and cerebral edema is aimed primarily at reducing surges in intracranial pressure. In patients with hepatic dysfunction, the metabolism of sedative drugs is likely to be impaired (most of the sedative drugs are metabolized in the liver). This can lead to prolonged half-life of the sedative in circulation and precipitate drowsiness/respiratory depression. Thus, in patients with hepatotoxicity, without encephalopathy, it is preferable to avoid sedative drugs. Cerebral edema is an event in the later stages of liver failure, and judicious use of sedatives in patients already in encephalopathy needs to be made.
B.7. It is preferable to avoid sedation in patients with hepatotoxicity and absence of encephalopathy (Level of evidence: Low; Grade of recommendation: Weak).
Urgent liver transplantation to treat rodenticidal hepatotoxicity
Urgent liver transplantation needs to be considered in patients who worsen and meet listing criteria for the same. Patients who meet listing criteria for urgent liver transplantation are best managed by urgent liver transplantation. It is important to discuss the option of urgent liver transplantation with patient/family members.
B.8. The patient and his/her family members need to be counselled regarding urgent liver transplantation in patient with encephalopathy or with worsening INR. If transplantation is feasible, liaison with a hospital where urgent liver transplantation is performed is needed and decide on patient transfer for the same (Level of evidence: Low; Grade of recommendation: Strong).
PLEX to treat rodenticidal hepatotoxicity
The American Society for Apheresis has now recommended that high-volume PLEX be considered a Category I indication (i.e., as a stand alone first line treatment or along with other treatments) to treat acute liver failure. Based on the volume of plasma exchanged during each session, PLEX for acute liver failure can be classified into high volume, standard volume, and low volume. Recent reports suggest improved survival with PLEX in rodenticide hepatotoxicity patients.,, PLEX is used both as a stand-alone treatment and as a bridge to liver transplantation in patients with rodenticide hepatotoxicity.,,
B.9. PLEX may be initiated as stand-alone treatment or as a bridge to liver transplantation (Level of evidence: Low; Grade of recommendation: Weak).
Indications for plasma exchange
Currently, there are no guidelines as to when PLEX is to be initiated in patients with acute liver injury/acute liver failure. Early institution of PLEX in patients meeting indications for the same (as mentioned in these guidelines) may favourably alter the course of rodenticide hepatotoxicity.
B.10. The indications for PLEX in patient with rodenticide hepatotoxicity are presence of deranged LFT AND any of the following three criteria: INR ≥4, worsening INR on serial tests OR depressed consciousness/altered behaviour (Level of evidence: Low; Grade of recommendation: Weak).
Contra-indications for plasma exchange
Few contraindications to the use of PLEX in severe liver injury patients have been described.
B.11. The contra-indications for PLEX in patient with rodenticide hepatotoxicity are presence of either of the following two criteria: Hemodynamic instability OR active sepsis (Level of evidence: Low; Grade of recommendation: Strong).
Monitoring for complications other than hepatotoxicity
Uncommonly, other vital organs such as kidney, pancreas and heart are also affected.
B.12. The patient needs to be monitored for cardiac toxicity/other complications (Level of evidence: Low; Grade of recommendation: Strong).
Transfer of patient to another hospital
Patients with rodenticide hepatotoxicity may need to be transferred to another hospital for close monitoring and for specialized treatments like PLEX and urgent liver transplantation.
B.13. Patients with hepatotoxicity need to be transferred to hospital with intensive care facilities and option of PLEX. In patients with worsening hepatotoxicity for whom urgent liver transplant is a feasible option, transfer to a hospital with facility for the same needs to be done. The patient transfer is best done in liaison with the medical team at the higher centre (Level of evidence: Low; Grade of recommendation: Strong).
The decision to discharge the patient recovering from rodenticide hepatotoxicity is largely a clinical decision.
B.14. In patients who are stable, with improving clinical and laboratory parameters, the decision to discharge from hospital is made after assessment by the treating clinical team (Level of evidence: Low; Grade of recommendation: Weak).
| Follow-up Care|| |
In TN-ISG 2019 study across Tamil Nadu, 438 of 450 patients (97%) consumed rodenticide with suicidal intent. Marital discord and exam-related stress in children were the commonest stressors identified which triggered this suicide attempt. In most patients, the suicide attempt was an impulsive attempt carried out for the first time on encountering the stressor (only 12% of patients gave a history of prior suicide attempt-all these patients had an underlying psychiatric illness). Both the patient who survives this suicidal attempt and the family need psychosocial support to cope with this illness as well to address the underlying stressors.
C.1. On follow up, in addition to physical health assessment including LFTs, patients and their families need support from Psychiatrists/trained social workers to help address the underlying trigger which precipitated the suicide attempt (Level of evidence: Low; Grade of recommendation: Strong).
| How to Implement These Guidelines|| |
It is hoped that these guidelines will help in the management of patients soon after ingestion of rodenticide and those who are in the early stages of rodenticide hepatotoxicity. Interventions at these stages are likely to need fewer resources and may help treat more number of patients. Thus, these guidelines are aimed to help doctors in primary health centers and in secondary levels hospitals, who are often the first point of contact by the patient who has consumed rodenticide.
We also hope that these guidelines may help guide health-care policy for Tamil Nadu state to provide cost-effective interventions to tackle this epidemic. The double whammy of much greater patient numbers and less access to specialized treatments, especially in public sector hospitals, need to be addressed. Providing facilities for PLEX at each district hospital in Tamil Nadu is likely to be a cost–effective strategy and needs to be instituted urgently.
These guidelines are currently the first in the world to guide the use of PLEX for acute liver injury or acute liver failure by providing indications and contraindications for the same. While these guidelines are specifically for the management of patients who ingest rodenticide, it is likely that these same guidelines can be applied to patients who consume paracetamol overdose, the commonest cause of acute liver failure in developed countries.
In an attempt to improve survival in the resource-constrained setting, we also highlight the need to avoid the use of sedative drugs, if possible, in rodenticide hepatotoxicity patients.
| Future Work|| |
Most of the guideline statements here are based on clinical experience and opinions of experienced clinicians. Multiple research questions have emerged in this area which calls for further studies. Focussed research is needed on each of the recommendations to prove/improve or disprove these guidelines and thus improve survival in patients who ingest rodenticide.
| Prevention|| |
As with any other ailment affecting man, prevention is better than cure. Multi-pronged steps to prevent rodenticide ingestion and to prevent onset and retard progression of liver injury are likely to be cost-effective. Involvement of general public as well as the governmental agencies is needed to implement these strategies to curtail the high cost to our society in terms of loss of young lives to rodenticide hepatotoxicity.
Dr. Eapen gratefully acknowledges the discussions held and inputs received from Dr. Uday Zachariah and Dr. Ashish Goel toward framing of this document.
Abbreviations: PLEX: Plasma exchange, PT/INR: Prothrombin time/international normalized ratio, TN-ISG: Tamil Nadu chapter of Indian Society of Gastroenterology, VWF: Von Willebrand factor
Committee members: V Balasubramanian, CE Eapen, Ganesan Ramamoorthy, Jayanthi V, Malathi Sathiyasekaran, Murugan N, Palaniswamy KR, Pazhanivel Mohan, Premkumar K, Ramakrishna BS, Ramkumar Govindarajan, Ramasubramanian R, Revathy Shanmugham, Ubaldhus J, Venkatkrishnan L.
Methodology adopted to frame this consensus document
This consensus document was prepared by a 15 member committee nominated by the Tamil Nadu chapter of Indian Society of Gastroenterology. The committee met by online mode on 3 occasions – August 27 2021, October 13 2021 and November 8 2021. The need for these guidelines and the focus areas were discussed at the initial meeting on August 27 2021.
The published literature on rodenticide poisoning was analysed and recommendations made incorporating both the published evidence and clinical judgement. The evidence were categorised as high, moderate and low and recommendations were graded as strong or weak as per the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. same. At present, there is insufficient published data specifically for rodenticide poisoning and hepatotoxicity to guide these recommendations. Hence, the general principles of management of acute poisoning as well of management of acute liver failure were applied.
Twenty two statements were framed based on these discussions and deliberated upon at the October 13 meeting. These statements were then sent by E-mail for voting by the committee members. But for three statements, the remaining 19 statements were approved by ≥80% of the committee members. The three statements without majority consensus were modified and presented again at the meeting on November 08, 2021 and re-voted upon; these three statements were also approved by ≥80% of the committee members.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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