CASE REPORT |
https://doi.org/10.5005/jp-journals-11006-0136 |
Emerging Indications for Extracorporeal Interventions: Hemoperfusion for Glufosinate Ammonium Poisoning
1–3Department of Critical Care Medicine, Vijaya Medical & Educational Trust, Chennai, Tamil Nadu, India
4Department of Nephrology, Vijaya Medical & Educational Trust, Chennai, Tamil Nadu, India
5Department of General Medicine, Vijaya Medical & Educational Trust, Chennai, Tamil Nadu, India
Corresponding Author: Venkatesh Narendiran, Department of Critical Care Medicine, Vijaya Medical & Educational Trust, Chennai, Tamil Nadu, India, Phone: +91 8660394037, e-mail: drvenkatnaren05@gmail.com
Received: 24 November 2023; Accepted: 02 August 2024; Published on: 27 August 2024
ABSTRACT
Aim and background: Glufosinate-ammonium (GLA), a herbicide, commonly used in Andhra Pradesh, becomes toxic upon accidental consumption in undiluted form, affecting multiple organ systems. There is no specific antidote, only symptomatic treatment available for this type of poisoning. Conventional treatment methods may not always yield satisfactory outcomes due to varied toxicokinetics. This case report highlights the significance of promptly initiating resin hemoperfusion to effectively clear the lipophilic glufosinate compounds in an intensive care setting.
Case description: A 50-year-old male presented to our hospital after ingesting approximately 250 mL of 13.5% GLA compound. He exhibited altered sensorium and seizures, which were attributed to hyperammonemia. After stabilizing airway, breathing, and circulation (ABC), he underwent two cycles of resin-based hemoperfusion lasting 3.6 hours each, resulting in a gradual reduction in ammonium levels and an improvement in sensorium. Eventually, he was weaned off and extubated successfully from mechanical ventilation and discharged without any neurological deficits.
Conclusion: This approach yielded several positive outcomes like reduction of hyperammonemia, improvement of neurological manifestations, shortened intensive care unit (ICU) stay, facilitated early weaning from mechanical ventilation.
Clinical significance: The early recognition of neurological symptoms and the timely implementation of hemoperfusion, were instrumental in achieving positive outcomes.
Keywords: Case report, Extracorporeal interventions, Glufosinate ammonium, Hemoperfusion
How to cite this article: Narendiran V, Challa Venkat S, Venkatachalam B, et al. Emerging Indications for Extracorporeal Interventions: Hemoperfusion for Glufosinate Ammonium Poisoning. Indian J Crit Care Case Rep 2024;3(5):145–146.
Source of support: Nil
Conflict of interest: None
Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.
INTRODUCTION
Glufosinate ammonium (GLA), a synthetic organophosphate/phosphonoglycine compound, is commonly used in agricultural settings. The accidental or deliberate ingestion of glufosinate can lead to severe neurological manifestations and multiple organ dysfunction syndrome (MODS). Conventional treatment methods for glufosinate poisoning may not always yield satisfactory outcomes due to varied toxicokinetics. In recent years, a new approach has emerged, gaining attention from the medical community—hemoperfusion (HP). Hemoperfusion involves the extracorporeal removal of toxins from the bloodstream, effectively clearing harmful substances that conventional therapies will not eliminate. This case report underscores the timely application and efficiency of hemoperfusion as a treatment for glufosinate poisoning and its potential as principal therapy to conventional treatments, scrutinizing its role in reducing the neurological severity to enhance outcomes.
CASE DESCRIPTION
A 50-year-old male with no comorbidities came with an alleged history of herbicide consumption (13.5% GLA—approximately 250 mL). He was initially taken to a nearby hospital, where gastric lavage was done, and shifted to our institute for further management. Besides vomiting, he had no other symptoms initially. The patient was admitted to our emergency department (ED) with altered sensorium and occasionally obeying commands. His systemic examination was unremarkable. Subsequently, the patient had a seizure episode, which was treated with injection lorazepam 4 mg intravenous (IV). After stabilization of airway, breathing, and circulation (ABC), the patient was initiated on IV atropine and pralidoxime regimen and shifted to intensive care unit (ICU) for further management.
Investigations revealed increased ammonia (246), serum glutamic oxaloacetic transaminase (SGOT) (200), serum glutamic pyruvic transaminase (SGPT) (98), and hypokalemia (3.2). Arterial blood gas (ABG) showed respiratory acidosis. He was initially supported with noninvasive ventilation (NIV) and IV atropine, IV pralidoxime, empirical IV antibiotics, laxatives, fluids, and other supportive medications. Within a few hours, his Glasgow Coma Scale (GCS) became <8, he developed respiratory distress and was intubated and put on volume-controlled ventilation. Apart from supportive care, he underwent two sessions of hemoperfusion with resin cartridge (HA230X) lasting 3.5 hours each, leading to a downward trend in serum ammonia levels. On the 5th day, he developed fever and hypotension with urine culture growing Pseudomonas aeruginosa, which was treated with piperacillin–tazobactam as per our hospital antibiogram.
Gradually, his general condition and sensorium improved. We conducted a spontaneous breathing trial, which was successful, and subsequently extubated him. On day 7, he was transferred to the ward in a stable condition. Follow-up in the outpatient department (OPD) after 2 weeks showed intact neurological status.
DISCUSSION
Glufosinate ammonium, an irreversible inhibitor of glutamine synthetase, leads to the accumulation of ammonia in neuronal cells and disrupts their metabolism. Glufosinate ammonium presents with various neurological manifestations: confusion, seizures, nerve palsies (abducent nerve palsy), anterograde and retrograde amnesia, as well as long-term cognitive dysfunction.1 The formulation of GLA consists of glutamate-containing phosphoaminoacid, glufosinate, surfactant molecules, antifoaming agents, and coloring agents. Surfactant molecules exhibit greater cytotoxicity and synergistic activity with glufosinate. Proposed pathophysiological mechanisms include: (1) the structural similarity of GLA to excitatory neurotransmitters, resulting in the activation of glutamate receptors and causing seizures; (2) alterations in the N-methyl-d-aspartate (NMDA) receptor signaling pathway, with accumulated glufosinate compounds hyperstimulating hippocampal areas of the brain, leading to amnesia and cognitive dysfunction; and (3) stimulation of the nitric acid pathway, leading to the development of seizures. Additionally, it exerts toxic effects on other organ systems, such as respiratory abnormalities, cardiac arrhythmias, acute kidney injury (AKI), and hematological changes. Studies have also demonstrated that ingestion of this chemical during pregnancy can adversely affect the fetal brain.2,4
THE EMERGING ROLE OF HEMOPERFUSION IN GLA POISONING
Extracorporeal blood purification procedures show promise as adjunctive treatments for eliminating toxins, drugs, excessive fluid, endotoxins, and inflammatory mediators through diffusion, convection, or adsorption. Hemoperfusion, first studied in animals in 1940 to remove uremic toxins, involves attaching circulating toxic substances to a highly adsorptive membrane through hydrophobic, ionic, and van der Waals interactions, effectively eliminating them from circulation. The adsorbent system consists of a biocompatible cartridge containing activated charcoal or polystyrene/hydrocarbon resins. Charcoal exhibits high affinity for water-soluble molecules, while resins have high affinity for lipid-soluble molecules. In the context of acute severe organophosphorus poisoning, a meta-analysis by Zhang et al. demonstrated that the combination of hemoperfusion with hemofiltration resulted in significant reduction in mortality and decreased atropine dosage requirements. Studies have also indicated that early introduction of hemoperfusion in paraquat poisoning is associated with reduced mortality. Considering hemoperfusion may find expanding indication in toxicology settings in the coming years due to its versatile properties, such as ability to remove larger molecules in an enhanced way and better hemodynamic stability with fewer complications. A decade ago, patients who ingested GLA were treated solely with supportive measures. However, recent case reports have explored extracorporeal elimination as a modality for effective removal of GLA compounds. Park et al. employed intravenous lipid emulsion and hemoperfusion in a GLA poisoning patient with seizures and abducent nerve palsy, resulting in complete recovery without neurological deficits.5,7
In our case, on top of the available evidence, we made the decision to utilize hemoperfusion as the preferred treatment modality. This approach yielded several positive outcomes:
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Reduction of hyperammonemia
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Improvement of neurological manifestations
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Shortened ICU stay
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Facilitated early weaning from mechanical ventilation
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Prevention of mortality
CONCLUSION
In summary, this case demonstrates successful management of a patient with GLA poisoning with multisystemic manifestations. The early recognition of neurological symptoms and the timely implementation of hemoperfusion were instrumental in achieving positive outcomes. Continued awareness of the toxic effects of GLA and proactive integrated management strategies are essential in optimizing outcomes.
ORCID
Venkatesh Narendiran https://orcid.org/0009-0004-4285-9494
Sasi Mayukha Challa Venkat https://orcid.org/0000-0002-4586-9848
Balaji Venkatachalam https://orcid.org/0000-0002-4879-9849
Radha Venkatramanan https://orcid.org/0009-0006-4523-0063
Rangaprasad G https://orcid.org/0009-0007-0489-8101
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5. Tanaka J, Yamashita M, Yamashita M, et al. Two cases of glufosinate poisoning with late onset convulsions. Vet Hum Toxicol 1998;40(4):219–222. PMID: 9682408.
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7. Zhang M, Zhang W, Zhao S, et al. Hemoperfusion in combination with hemofiltration for acute severe organophosphorus pesticide poisoning: a systematic review and meta-analysis. J Res Med Sci 2022;27:33. DOI: 10.4103/jrms.JRMS_822_20
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