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ORIGINAL ARTICLE  
Ahead of print publication
Role of therapeutic plasma exchange in rat killer (yellow phosphorous) poisoning


 Department of Transfusion Medicine, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India

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Date of Submission10-Feb-2021
Date of Decision23-Mar-2022
Date of Acceptance05-Jun-2022
Date of Web Publication26-Sep-2022
 

   Abstract 

Context: Yellow phosphorus (YP) 3% is one of the rodenticides available, which is a potent hepatotoxin and it is fatal. Management of YP poisoning is difficult since there is no antidote available; only definitive management is liver transplantation. Therapeutic plasma exchange (TPE) helps the YP poisoning patients by removing the poison or its metabolite or the inflammatory mediators released in the body in response to toxin.
AIMS: To determine the role of TPE in rat killer (YP) poisoning.
SETTINGS AND DESIGN: This was a descriptive period study conducted from November 2018 to September 2020.
SUBJECTS AND METHODS: Sixteen consecutive YP poisoning patients were included in the study (n = 16). A total of 48 sessions of TPE were carried out. Liver function tests such as serum glutamic-oxaloacetic transaminase, SGPT, total bilirubin, and direct bilirubin as well as coagulation profile such as prothrombin time, activated partial thromboplastin time, and international normalized ratio were analyzed at the time of admission, after each TPE session, and at the time of discharge.
STATISTICAL ANALYSIS USED: The results were recorded, and it was analyzed statistically by SPSS version 17.
RESULTS: Liver function tests improved significantly from the time of admission and after each TPE and at the time of discharge (P < 0.05). Coagulation profile improved statistically (P < 0.05). Thirteen patients were improved in their clinical status, and three patients left the hospital citing personal reasons.
CONCLUSIONS: TPE could potentially bridge the gap between medical management and liver transplantation in cases of YP poisoning.

Keywords: Rat killer poisoning, therapeutic plasma exchange, yellow phosphorous


How to cite this URL:
Radhakrishnan K, Thokala RP, Anandan A, Rengan CS. Role of therapeutic plasma exchange in rat killer (yellow phosphorous) poisoning. Asian J Transfus Sci [Epub ahead of print] [cited 2022 Dec 4]. Available from: https://www.ajts.org/preprintarticle.asp?id=356878



   Introduction Top


Yellow phosphorous (YP) is one of the rodenticides known to cause significant end-organ damage and death. Fatal dose of YP ingestion is 1 mg/kg body weight. Liver failure in rat killer poisoning (YP) patients requires liver transplantation as the treatment option if found unresponsive to medical management. Therapeutic plasma exchange (TPE) in this setting has the benefit to save a patient from a potential liver transplantation by removing the inflammatory mediators induced by the toxin/poison. The aim of the study was to determine the role of TPE in rat killer (YP) poisoning.


   Subjects and Methods Top


This was a descriptive study carried out at the Department of Transfusion Medicine, Sri Ramachandra Medical College and Research Institute. This was a period study conducted between November 2018 and September 2020. A total of sixteen patients were included in this study period.

Inclusion criteria

All the patients who had orally ingested rat killer poison as a paste (contains YP, a hepatotoxin).

Exclusion criteria

  • Patients who had orally ingested rat killer poison in cake form (contains bromadiolone, a hemotoxin)
  • Patients who had exposure to yellow phosphorus other than orally ingested form, i.e., skin contact and gas exposure
  • All the patients who had consumed other poisons
  • Patients who were <18 years of age.


Methodology

The initial evaluation of the patient was done by the treating physician and the request for carrying out TPE was received in the transfusion medicine department. All of the TPE sessions in this study were carried out in the intensive care unit with continuous monitoring of patient blood pressure, heart rate, oxygen saturation, temperature, and general condition. All of the TPE sessions were performed by placing central venous double-lumen catheter in internal jugular vein in this study.

Acid citrate dextrose (ACD-A) was the choice of anticoagulant used during the TPE procedure in all of the patients. ACD-A is used in apheresis procedure to prevent blood from clotting inside the apheresis kit and its tubings. ACD-A does not cause systemic anticoagulation unlike heparin.

Replacement fluids are necessary in all of the TPE cycles; replacement fluids used during the procedure were 5% human albumin (Baxter), fresh frozen plasma, and normal saline 0.9%. Different proportion of replacement fluids was used in this study based on patients coagulation status, albumin level and hematocrit.

To minimize the adverse events related to ACD-A anticoagulant, 10 ml of 10% calcium gluconate in 100 ml normal saline was administered as a continuous drip over 1 h for all the patients during the TPE procedure.

The TPE procedure was carried out using Com.Tec cell separator by Fresenius Kabi. A specialized kit PL1 was used to perform TPE procedure.

Plasma volume (in ml) of the patient was calculated using the following formula:

Plasma volume (ml) = 70 × (1-hematocrit) × body weight (kg).

One plasma volume exchange was planned in all cases, but depending on the patient's clinical condition and laboratory values, the number of plasma volume exchanged varied from 1 to >1.4 in this study.

Statistical analysis

Statistical analysis was carried out using SPSS Inc. Released 2008. SPSS Statistics for windows, Version 17.0. Chicago:SPSS Inc. P < 0.05 was considered statistically significant in this study. Paired t-test was used to compare the values pre- and post-TPE. Wilcoxon signed-rank test was used to analyze the P value.


   Results Top


A total of sixteen patients who were admitted during the study period November 2018 to September 2020 were included in this study. Age and sex details of the patients are described in [Table 1]. Total no of TPE sessions are described in [Table 2]. Total Plasma volume exchanged during each session are described in [Table 3]. Total no of adverse events encountered are described in [Table 4].
Table 1: Age and sex distribution of the patients in this study

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Table 2: Number of therapeutic plasma exchange sessions distribution among the yellow phosphorous poisoning patients in this study

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Table 3: Plasma volume exchanged during the therapeutic plasma exchange procedure in this study

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Table 4: Adverse events encountered during therapeutic plasma exchange procedure in this study

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   Discussion Top


The present study was conducted to evaluate the efficacy of TPE in cases of YP rodenticide poisoning. YP is a readily available rodenticide in the market, which does not have any restrictions to purchase. Management of YP poisoning patients is difficult as there is no antidote available.[1] Frank A. Simon and Larry K. Pickering were one of the very first authors in the literature to report the cases of YP poisoning. They reported three cases with acute toxicity symptoms. Patients initially presented with oral burns, nausea, vomiting, and intense abdominal pain. In our study, eleven patients presented with nausea and vomiting, eight patients presented with abdominal pain, four patients presented with icterus, and three patients presented with altered sensorium.[1]

A study was conducted by McCarron et al., upon acute YP poisoning cases. The authors reported that 53% of patients reported with initial symptoms of vomiting or abdominal pain; 28% of patients had irritability, stupor, and coma; and in 19% of patients, there were mixture of gastrointestinal and neurological manifestations at the time of presentation. When comparing with our study, the most common symptom was nausea and vomiting, which was noted in eleven patients and there were only three patients presented with neurological manifestation at the time of admission at our center.[2]

A study was conducted on the patients who have consumed firecracker which contains YP in Philippines. The authors observed the symptoms and the progress of the acute hepatotoxicity; they noted that at least nine patients in their study had jaundice within 48 h after consumption, and in our study, all of the sixteen patients presented with elevated total and direct bilirubin at the time of admission to hospital. The lag time in patients presenting to our hospital could have worsened the liver function.[3] Smitha Bhat and Kumar P. Kenchetty studied the role of N-acetylcysteine in the cases of YP poisoning; in their case study, out of 100 rodenticide patients, 27 patients were treated with NAC. Among the patients, 19 (73.1%) recovered, 2 (7.7%) died, and 5 (19.2%) were discharged against medical advice. In comparison with our study, all the sixteen patients who received TPE also received NAC soon after the admission into the hospital.[4] In our study, the mean hospital stay was 11.4 days, the mean total bilirubin value at the time of admission was 14.7 g/dl, and the mean total bilirubin value at the time of discharge was 3.5 g/dl after TPE sessions [Table 5]. When comparing the mean total bilirubin value at the time of admission with a mean value at the time of discharge, the value was shown to be statistically significant (P < 0.001). The mean direct bilirubin value at the time of admission was found to be 9.66 g/dl, and the mean direct bilirubin value at the time of discharge was found to be 2.04 g/dl after TPE sessions [Table 6]. When comparing the mean values between admission and discharge, there was a statistical significance (P < 0.001).
Table 5: Comparison of total bilirubin values

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Table 6: Comparison of direct bilirubin values

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The mean value of aspartate transaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) at the time of admission was 1023.6 IU/ml, and the mean value at the time of discharge was 51.8 IU/L [Table 7]. There was a significant decrease in AST values after TPE sessions, which showed a statistical significance (P < 0.003). The mean alanine transaminase ALT/SGPT value at the time of admission was 346.38 IU/L, and the mean value at the time of discharge was 44 IU/L [Table 8]. There was a significant decrease in ALT values after TPE sessions, which showed a statistical significance (P < 0.003).
Table 7: Comparison of SGOT/AST values

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Table 8: Comparison of SGPT/ALT values

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The mean value of partial thromboplastin time (PTT) at the time of admission was 40.35, and at the time of discharge, the mean value was 24.7 [Table 9]a. There was a statistical significance when comparing the PTT values between the time of admission and at discharge (P < 0.006) [Table 9]b. The mean value of prothrombin time at the time of admission was 42.15, and at the time of discharge, the mean value was 12.06 [Table 10]. There was a statistical significance (P < 0.003) after TPE sessions. The mean value of INR at the time of admission was 2.62, and at the time of discharge, it was 0.93 [Table 11]. There was a statistical significance post-TPE sessions (P < 0.003).
Table 9:

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Table 10: Comparison of PT values, at the time of admission, post every cycle and at the time of discharge

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Table 11: Comparison of INR values

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In our study, a total of 48 sessions of TPE were performed in sixteen patients. The volume of distribution varied from each patient. Between 1.0 and 1.2 volume, 23 sessions were performed; between 1.3 and 1.4 volume, 12 sessions were performed; and >1.4 volume was exchanged in 13 sessions. One patient received six sessions of TPE and one patient received only one session of TPE with most number of patients receiving three sessions of TPE (number of patients 7).

A study was conducted to evaluate the efficacy of TPE in rodenticide poisoning. The total plasma volume exchanged was between 1 and 1.5 volume for 5 consecutive days, with each patient receiving 5 cycles. The authors noted that there was a statistically significant improvement in liver function tests and coagulation profile of the patients (P < 0.05); this was comparable with our study. There was a statistically significant improvement in coagulation profile as well as liver function tests.[5]


   Conclusion Top


In this study, we observed that TPE could potentially alleviate the symptoms caused by YP toxicity and bridge the gap between medical management and liver transplant.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Simon FA, Pickering LK. Acute yellow phosphorus poisoning. “Smoking stool syndrome”. JAMA 1976;235:1343-4.  Back to cited text no. 1
    
2.
McCarron MM, Gaddis GP, Trotter AT. Acute yellow phosphorus poisoning from pesticide pastes. Clin Toxicol 1981;18:693-711.  Back to cited text no. 2
    
3.
Fernandez OU, Canizares LL. Acute hepatotoxicity from ingestion of yellow phosphorus-containing fireworks. J Clin Gastroenterol 1995;21:139-42.  Back to cited text no. 3
    
4.
Bhat S, Kenchetty KP. N-acetyl cysteine in the management of rodenticide consumption – Life saving? J Clin Diagn Res 2015;9:C10-3.  Back to cited text no. 4
    
5.
Banjan DS, Sane K, Wattamvar S, More M. Predictable factors for intervention with heparin free plasmapheresis in impending liver cell failure due to consumption of phosphorus rodenticide. Int J Res Med Sci 2019;7:3026.  Back to cited text no. 5
    

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Correspondence Address:
Chandran Srinivasan Rengan,
Department of Transfusion Medicine, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajts.ajts_20_21




 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11]



 

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