Successful management with hemoperfusion and antidotal therapy of severe combined dichlorvos and rodenticide poisoning: a case report

Abstract

Background

This case report presents a rare instance of combined dichlorvos (organophosphate) and brodifacoum (rodenticide) poisoning. By analyzing the clinical presentation and therapeutic course, we aim to provide insights into the challenges and management strategies associated with multi-agent toxic exposures.

Case presentation

A 73-year-old male with a history of hypertension and depression was admitted after ingesting approximately 150 mL of dichlorvos and 10 mL of brodifacoum. He underwent 18 days of comprehensive treatment, including gastric decontamination with induced emesis and activated charcoal, administration of specific antidotes (a total of 1189 mg atropine, 21.8 g pralidoxime iodide, and 660 mg vitamin K1), and extracorporeal detoxification via hemoperfusion and hemofiltration. Supportive care involved infection control, nutritional supplementation, and monitoring of coagulation and electrolyte status. The patient developed early complications, including hematemesis, epistaxis, and persistent coagulopathy, as well as transient alterations in consciousness and cholinesterase levels below 200 U/L. With prompt and aggressive intervention, his clinical condition gradually stabilized, and he was discharged in good condition. Follow-up revealed coagulopathy, with deep vein thrombosis requiring oral anticoagulation.

Conclusion

Combined organophosphate and rodenticide poisoning presents a complex toxicological scenario, characterized by overlapping and synergistic effects on the nervous and coagulation systems. Cholinesterase levels below 200 U/L may serve as a critical marker of severity in patients without pre-existing liver disease. Hemoperfusion effectively facilitates toxin clearance, though adjustments to pralidoxime iodide dosing may be warranted during extracorporeal therapy. Following blood purification therapy, no toxin was detected in the patient’s plasma, and long-term coagulation abnormalities associated with super warfarin exposure were not observed in this case. Additionally, electrolyte disturbances and myocardial biomarkers such as myoglobin and troponin require close observation, as they may reflect ongoing systemic injury. While this case highlights several clinical considerations, further studies are needed to establish standardized protocols for managing multi-toxin exposures of this nature.

Background

Dichlorvos (DDVP) is a potent organophosphate pesticide that irreversibly inhibits cholinesterase activity, leading to excessive accumulation of acetylcholine at synaptic junctions and resulting in overstimulation of cholinergic receptors and the manifestation of cholinergic toxicity [1]. In contrast, brodifacoum is a second-generation coumarin-derived anticoagulant rodenticide that disrupts the coagulation cascade by inhibiting the hepatic synthesis of vitamin K–dependent clotting factors, including factors II, VII, IX, and X [2]. When ingested concurrently, these two toxic agents may exert compounded effects through distinct but potentially interacting mechanisms. The combination poses significant diagnostic and therapeutic challenges, particularly due to the potential for synergistic toxicity, impaired metabolism, and overlapping clinical features [3]. Despite the severity of such poisonings, literature on the concurrent management of organophosphate and rodenticide co-ingestion remains scarce. In this report, we describe a rare case of combined DDVP and brodifacoum poisoning and provide a comprehensive account of the clinical course, treatment strategies, and key insights from the successful management of this life-threatening intoxication.

Case presentation

A 73-year-old male with a history of hypertension and poorly controlled depression was found by his family vomiting at approximately 5:00 AM in mid-February. Upon inquiry, he admitted to having ingested about 150 mL of DDVP and 10 mL of rodenticide one hour prior. He arrived at the emergency department at 5:57 AM, ambulatory but supported by family members. On initial evaluation, his vital signs were as follows: blood pressure 137/116 mmHg, temperature 36.2 °C, heart rate 78 bpm, and respiratory rate 21 breaths per minute. He was alert and oriented, with equal and reactive pupils measuring 2.5 mm bilaterally. Physical examination revealed intermittent muscle tremors and a strong irritant odor on his clothing. His skin was dry, the oral mucosa was intact, and no significant wet rales were noted on lung auscultation. Electrocardiography showed sinus rhythm with widened P waves, high left ventricular voltage, and nonspecific ST-T segment changes.

Initial management included induced emesis with warm water (he refused gastric lavage), during which approximately 6000 mL of gastric contents were expelled until the fluid appeared clear. This was followed by administration of 50 g of activated charcoal in divided oral doses. Intravenous atropine (2 mg every 10 min initially) and pralidoxime iodide (0.8 g) were initiated, resulting in heart rate stabilization around 100 bpm. At 7:00 AM, laboratory tests revealed a plasma cholinesterase level of < 200 U/L (normal range 5900–12220 U/L). The patient’s mental status subsequently deteriorated, with somnolence and decreased oxygen saturation (SpO₂ 90%), prompting initiation of high-flow oxygen and escalation of atropine dosing. At 8:30 AM, a central venous catheter was placed in the right internal jugular vein, along with a left femoral venous catheter for hemodialysis access. Blood toxicology at 9:00 AM confirmed DDVP at 2.16 mmol/L and brodifacoum at 0.13 µmol/L, with trace amounts of diazepam; cholinesterase activity was 17%. At 10:00 AM, the patient developed hematemesis characterized by black gastric fluid and had concurrent epistaxis. A nasogastric tube was placed, and vitamin K₁ and hem coagulase were administered. He was transferred to the intensive care unit (ICU) at 11:00 AM.

In the ICU, respiratory support was maintained with high-flow oxygen, and chest radiography suggested aspiration pneumonia. Piperacillin-tazobactam was initiated accordingly. Antidotal therapy was continued with atropine (10 mg every 10 min initially, later tapered due to signs of atropine toxicity), pralidoxime iodide (2 g every 6 h), and vitamin K₁ (1 mg twice daily). Extracorporeal blood purification included two hemoperfusion sessions and nine hours of continuous Veno venous hemofiltration (Fig. 1). The patient exhibited extensive ecchymoses in the inguinal regions and forearms (Fig. 2). Coagulation studies revealed thrombocytopenia (platelets 50 × 10⁹/L, normal range 125–350), markedly prolonged activated partial thromboplastin time (APTT 141.4 s, normal range 24–40 s), and unmeasurable thrombin time (TT, 16–26 s), prompting transfusion of 400 mL fresh frozen plasma (FFP).

Fig. 1.

Clinical implementation of continuous hemofiltration during intensive care. The image shows the patient undergoing continuous venovenous hemofiltration (CVVH) in the intensive care unit. The dialysis machine is visible on the right, with vascular access established via dual-lumen catheterization. Multiple antidotes, including vitamin K₁ and hemoperfusion cartridges, are prepared at the bedside. The patient was receiving high-flow oxygen support, extracorporeal blood purification, and close hemodynamic monitoring during the critical phase of organophosphate and rodenticide poisoning management

Fig. 2.

Resolution of extensive ecchymoses in the inguinal regions and forearms. The left image shows extensive ecchymosis in the inguinal region, while the right image displays subcutaneous ecchymosis over the right forearm. Black marker outlines indicate the maximal extent of subcutaneous hemorrhage during the peak of coagulopathy. Compared to earlier documentation, both images demonstrate reduced ecchymotic areas with fading discoloration, indicating the absence of active bleeding and significant improvement in coagulation status

Follow-up toxicology testing at 11:00 PM on Day 1 showed a decline in serum DDVP to 0.51 mmol/L, while brodifacoum was undetectable. Cholinesterase activity had improved to 24% (365 U/L). On Day 2, both toxins were undetectable, and cholinesterase activity further increased to 32% (734 U/L). Despite toxin clearance, laboratory findings revealed persistent coagulopathy (platelets 40 × 10⁹/L, hemoglobin 92 g/L) and elevated D-dimer levels. Continued oral bleeding contraindicated the use of anticoagulants. On Day 3, the patient developed fever with a maximum temperature of 40.5 °C and tachycardia (heart rate 110 bpm). Atropine was tapered to 2 mg every 2 h, and the dose of pralidoxime iodide was reduced. Cholinesterase activity had risen to 36% (556 U/L) by this time, and further increased to 48% (1380 U/L) by Day 8. The patient was discharged in stable condition on Day 18 (Fig. 3).

Fig. 3.

Recovery status of the patient following ICU discharge. The patient is shown sitting upright in a general ward bed after being transferred from the intensive care unit. Clinical signs of stabilization included improved consciousness, resolution of bleeding manifestations, and restoration of cholinesterase activity. No supplemental oxygen or extracorporeal support was required at this stage. The image reflects significant functional recovery following 18 days of intensive antidotal therapy, extracorporeal detoxification, and supportive care for combined organophosphate and rodenticide poisoning

At outpatient follow-up eight days post-discharge, laboratory results indicated ongoing coagulopathy, and Doppler ultrasound confirmed deep vein thrombosis. Rivaroxaban was initiated for anticoagulation. Serial laboratory data, including toxin levels, cholinesterase activity, and coagulation indices, are summarized in Figs. 4, 5, 6 and 7.

Fig. 4.

Temporal trends in platelet count and hemoglobin levels during hospitalization. Line graph illustrating the changes in platelet (PLT, ×10⁹/L) and hemoglobin (HGB, g/L) levels from Day 1 to Day 26 of hospitalization. Both parameters declined rapidly during the early phase, with platelets reaching a nadir below 50 × 10⁹/L and hemoglobin falling from 256 g/L to approximately 140 g/L within the first 48 h, reflecting acute gastrointestinal and mucosal bleeding. Subsequent gradual recovery was observed following administration of vitamin K₁, transfusion of FFP, and cessation of active bleeding. A notable spike in platelet count near Day 18 may reflect rebound thrombopoiesis or inflammatory response

Fig. 5.

Serial changes in plasma cholinesterase concentration and enzymatic activity during treatment. This figure illustrates the dynamic recovery of plasma cholinesterase levels (U/L, left Y-axis) and corresponding enzymatic activity (% of normal, right Y-axis) following organophosphate poisoning. At admission (day 1), cholinesterase activity was profoundly suppressed (< 200 U/L; <20%), indicating severe intoxication. A steady upward trend was observed following administration of pralidoxime iodide and atropine, along with extracorporeal blood purification. By day 10, both enzyme quantity and activity showed substantial recovery, corresponding with marked clinical improvement

Fig. 6.

Dynamic trends in serum potassium and D-dimer levels throughout the clinical course. This figure presents the temporal relationship between serum potassium concentration (mmol/L, right Y-axis) and D-dimer levels (mg/L, left Y-axis) from admission to day 26

Fig. 7.

Dynamic trends in PT, APTT and INR levels throughout the clinical course. As demonstrated in this figure, the patient exhibited severely prolonged APTT (sec, left Y-axis) and coagulopathy during the first night of admission. PT (sec, left Y-axis) remained largely unchanged, while INR (right Y-axis) exhibited mild elevation within normal range during the initial days of admission, subsequently stabilizing around 1.0. Following therapeutic interventions on the same day—including hemoperfusion, vitamin K supplementation, and transfusion of 400 mL FFP—the coagulation profile normalized by the next day and remained stable throughout hospitalization. The patient received continuous vitamin K therapy during the inpatient period but declined further supplementation after discharge. Notably, no significant coagulation abnormalities were detected on day 26 post-poisoning. This clinical course markedly differs from the typical prolonged coagulopathy observed in conventional brodifacoum poisoning cases, potentially offering new insights for therapeutic strategies in future management of such intoxications

Discussion

This case illustrates the complex toxicodynamic and toxicokinetic interactions involved in the co-ingestion of DDVP and brodifacoum, two agents with distinct mechanisms of toxicity. Brodifacoum exerts its anticoagulant effect by inhibiting the hepatic synthesis of vitamin K–dependent clotting factors, including factors II, VII, IX, and X, predisposing to spontaneous bleeding [2]. DDVP, in contrast, is a cholinesterase inhibitor that induces cholinergic crisis by leading to excessive accumulation of acetylcholine at synaptic junctions [1]. When ingested simultaneously, these agents can produce synergistic toxicity, particularly affecting the coagulation system and central nervous system. In this case, the patient developed hematemesis and epistaxis within hours of ingestion, accompanied by a hemoglobin drop from 141 g/L to 79 g/L by Day 3, consistent with acute gastrointestinal blood loss [2, 3]. Notably, central nervous system depression—manifesting as somnolence and altered consciousness—occurred early, vigilant monitoring of respiratory function and level of consciousness is paramount. One must be highly cautious of the emergence of central respiratory failure, as it is associated with an unfavorable prognosis [4, 5]. The grading criteria for organophosphate poisoning and corresponding antidote dosing recommendations are summarized in Table 1 [5].

Table 1.

Grading criteria and antidote dosing recommendations for organophosphate poisoning

	Grading Criteria	Recommended Initial Dose of Pralidoxime Iodide	Recommended Initial Dose of Atropine	Maintenance Dose of Atropine
Mild Poisoning	Primarily characterized by muscarinic symptoms, with whole blood cholinesterase activity ranging from 50% to 70% of normal.	0.4 g	2-4 mg	0.5 mg (q4-6 h)
Moderate Poisoning	Worsening of the above symptoms with additional nicotinic manifestations, accompanied by whole blood cholinesterase activity between 30% and 50% of normal.	0.8–1.2 g	4-10 mg	0.5-1 mg (q2-4 h)
Severe Poisoning:	Features both muscarinic and nicotinic symptoms, along with clinical signs of major organ failure such as pulmonary edema, respiratory failure, coma, or cerebral edema. Whole blood cholinesterase activity falls below 30% of normal.	1.0–1.6 g	10-20 mg	0.5-1 mg (q1-2 h)

Although pralidoxime chloride is the preferred reactivator, our institution only stocks pralidoxime iodide. Therefore, the dosing recommendations provided herein are for pralidoxime iodide. Patients with acute organophosphate poisoning (AOPP) should receive rapid and adequate atropine administration to achieve “atropinization,” primarily assessed through clinical manifestations including: dry mouth, dry skin and mucous membranes, facial flushing, significant reduction or disappearance of pulmonary rales, pupillary dilation compared to baseline, and heart rate of 90–100 beats/min. Typically, if no symptomatic improvement is observed within 10 min of the initial dose, repeat dosing is indicated. In severe cases, dosing may be repeated every 5 min. Repeat doses generally correspond to moderate or mild dosing levels, with maintenance doses administered once atropinization is achieved

At the pharmacokinetic level, DDVP is known to inhibit cytochrome P450 enzymes [6], however, this does not affect the metabolism of brodifacoum, as it is not hepatically metabolized but primarily redistributes to and deposits in adipose tissue, with subsequent biliary excretion into the intestines and extensive enterohepatic circulation. This redistribution and recirculation process constitutes one of the key mechanisms underlying its prolonged coagulopathy [7]. Despite these interactions, treatment principles aligned with standard monoi toxication protocols, including prompt gastric decontamination, administration of specific antidotes, and the use of extracorporeal detoxification therapies [3].

Management of severe bleeding in super warfarin poisoning requires rapid correction of coagulopathy. Transfusion of FFP at 10–15 mL/kg or the administration of clotting factor concentrates should be considered early in the course [2]. Due to its high lipid solubility and tissue accumulation, brodifacoum has a prolonged half-life, and vitamin K₁ therapy must be continued for 3–6 months to prevent delayed-onset bleeding [8]. Discontinuation of vitamin K₁ prematurely may result in life-threatening hemorrhagic events, including gastrointestinal or intracranial bleeding [8]. Importantly, vitamin K₃ (menadione) is not only ineffective but may also induce hemolysis and is therefore strictly contraindicated.

In this case, primary intervention involved warm water-induced emesis due to patient refusal of gastric lavage tube intubation, which was conducted under continuous medical supervision with vital sign monitoring. However, gastric lavage with airway protection remains our preferred approach for potentially more complete decontamination and aligns with recommended clinical guidelines [5, 9].

Activated charcoal plays a key role in early decontamination. Multiple-dose activated charcoal (MDAC) can adsorb unabsorbed toxins, disrupt enterohepatic recirculation, and enhance systemic toxin elimination through gastrointestinal dialysis [9, 10]. Additionally, osmotic cathartics such as polyethylene glycol electrolyte solution (PEG-ELS) can be employed to accelerate intestinal transit, particularly in cases of ingestion of highly toxic or slow-absorbing substances [9].

Quantitative and functional assays of cholinesterase activity are central to the diagnosis and monitoring of organophosphate poisoning. In this case, the patient had plasma cholinesterase < 200 U/L and activity of 17% on admission—consistent with moderate-to-severe poisoning [1, 5]. As shown in Fig. 5, cholinesterase activity gradually recovered alongside clinical improvement, with the trends of cholinesterase levels and enzymatic activity being largely consistent. The cholinesterase quantity reflects the body’s enzyme-producing capacity (e.g., liver function), whereas its catalytic activity is more closely correlated with the severity of acute poisoning. In clinical practice, cholinesterase activity assay results are often delayed (e.g., toxicology analysis took ~ 2.5 h post-admission in this case), whereas cholinesterase level results are typically available within 1 h. Since antidote dosing relies on cholinesterase activity, this delay may postpone critical treatment. Thus, we propose evaluating whether the grading criteria could complement cholinesterase results to assess poisoning severity and guide antidote dosing—a potential strategy to mitigate treatment delays.

Hemoperfusion and hemofiltration served as essential adjuncts in toxin elimination [5, 11]. Hemoperfusion, which relies on physical adsorption, is especially effective for removing lipid-soluble and protein-bound toxins such as brodifacoum [11]. Hemofiltration, which facilitates convection-based solute removal, can assist in eliminating water-soluble DDVP metabolites [12]. Notably, this patient presented with concomitant rodenticide poisoning carrying hemorrhagic risk. However, brodifacoum specifically inhibits vitamin K-dependent coagulation factor synthesis (not thrombin directly), meaning clinical manifestations emerge only after pre-existing factors are depleted—typically after several days [13]. This mechanistic understanding prompted urgent hemoperfusion intervention. Quantitative toxicology analysis demonstrated rapid toxin clearance, contrasting sharply with brodifacoum’s inherent half-life of 243-1,656 h without extracorporeal elimination [13]. The absence of life-threatening hemorrhage during clinical evolution was directly attributable to timely hemoperfusion, demonstrating definitive therapeutic significance. Atropine and vitamin K₁ are not significantly removed by either modality due to their pharmacokinetic properties—namely, a high volume of distribution and strong protein binding, respectively—thus routine dose adjustments are not required [11, 14]. However, pralidoxime iodide, which is less protein-bound and has a smaller volume of distribution, may be partially removed by these techniques [15]. In summary, we suggest increasing the dose or shortening the dosing interval (e.g., every 4–6 h) during extracorporeal therapy to maintain therapeutic levels. As summarized in Table 2, drug dosing was adjusted according to toxin clearance and biomarker trends.

Table 2.

Pharmacological characteristics of specific antidotes and their pharmacokinetic changes during hemoperfusion and hemofiltration

Parameter	Atropine	Pralidoxime iodide	Vitamin K₁
Molecular Weight	289.4 Da (small, easily cleared)	264.1 Da (small, easily cleared)	450.7 Da (large, less filterable)
Protein Binding	14–22% (low, high free fraction)	Low (limited data, presumed high free fraction)	High (> 90%, mainly lipoprotein-bound)
Volume of Distribution (Vd)	2–4 L/kg (wide tissue distribution)	0.6–1.2 L/kg (blood/ECF predominant)	Small (blood/liver predominant)
Primary Clearance Route	Hepatic (minor renal)	Renal (minor hepatic)	Hepatic (minor biliary/renal)
Effect of HP	Partial removal possible	Partial removal possible	Minimal impact
Effect of HF	Negligible	Partial removal possible	Minimal impact
Clinical Adjustment	No dose adjustment needed	Consider ↑ dose or ↓ dosing interval	No dose adjustment needed

The patient also exhibited persistent abnormalities in D-dimer, potassium, myoglobin, and troponin levels. D-dimer elevation likely reflected combined effects of brodifacoum-induced hemorrhage and dichlorvos-mediated endothelial injury [2, 16]. The risk of disseminated intravascular coagulation (DIC) must be considered in the setting of elevated D-dimer, prolonged coagulation times, and thrombocytopenia [8]. Hypokalemia in organophosphate poisoning is multifactorial, resulting from cholinergic-induced fluid loss, muscle depolarization, renal wasting, and atropine-induced hyperthermia [1]. In this case, the hypokalemia was corrected with supplementation, and its fluctuations are shown in Fig. 6. Furthermore, the patient’s admission myoglobin was markedly elevated, and although it initially declined, a rebound occurred on Day 3, accompanied by a rise in troponin levels—suggesting toxin-induced rhabdomyolysis and myocardial injury. These findings were not accompanied by significant ECG changes and may reflect inflammatory cardiotoxicity from the organophosphate or atropine toxicity [17, 18]. To date, there is no evidence linking brodifacoum directly to myoglobin or troponin elevation, although its potential extra-hematologic effects warrant further study.

Of particular interest, despite brodifacoum poisoning, the patient’s coagulation parameters remained largely within normal range except for significant fluctuations observed on the first day of admission (Fig. 7). This stabilization is likely attributable to the rapid reduction in plasma toxicant concentration achieved through hemoperfusion. Following discharge, the patient declined continued vitamin K supplementation. During the follow-up examination 8 days after discharge, the patient showed no abnormalities in PT or APTT but was found to have deep vein thrombosis and was prescribed oral anticoagulant therapy. At the 3-week post-discharge follow-up, the patient’s PT and APTT remained within normal limits, and the deep vein thrombosis showed improvement compared to the previous evaluation. While paradoxical co-occurrence of bleeding and thrombosis has been documented in some rodenticide poisoning cases [2], the absence of ecchymoses or other hemorrhagic manifestations in this patient suggests no direct association between the thrombotic event and prior intoxication. We therefore consider the poisoning episode resolved, but strongly recommend monthly coagulation monitoring during follow-up assessments.

Conclusion

In summary, combined poisoning with DDVP and brodifacoum presents a complex clinical scenario with overlapping toxicological profiles and unique pathophysiological interactions. The co-ingestion of an organophosphate and a long-acting anticoagulant not only results in compounded systemic toxicity but also complicates diagnostic interpretation and therapeutic decision-making. While each toxin alone is well characterized, their simultaneous effects can obscure typical clinical features and exacerbate complications such as coagulopathy, hypokalemia, and organ dysfunction. This case underscores the importance of early recognition, prompt decontamination, targeted antidotal therapy, and the judicious use of extracorporeal blood purification techniques. Continuous monitoring of cholinesterase activity, coagulation parameters, and cardiac biomarkers is essential to guide treatment and assess recovery. Although this is a single case, it provides valuable insights that may inform clinical management strategies in similar complex poisonings. Further clinical studies are warranted to establish standardized protocols for multi-toxin exposures.

Authors’ contributions

H.L and X.L contributed to manuscript preparation. The corresponding author, L.M, W.Y, and H.C conceptualized the presented idea and is responsible for this manuscript. B.D, H.Y, S.F, Y.G, H.S were the attending physicians involved in data collection. L.M and X.L supervised the manuscript. All authors read and approved the final version of the manuscript.

Funding

This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patient’s relative for the publication of this case report and accompanying images.

Competing interests

The authors declare no competing interests.