Original Article
Experience in the treatment of chlorfenapyr poisoning
2023 Volume 48 Issue 4 Pages 221-225
Details
2023 Volume 48 Issue 4 Pages 221-225
In China, the extensive use of the pesticide chlorfenapyr has led to an increase in chlorfenapyr poisoning. However, there are limited reports on chlorfenapyr poisoning, and most of them are fatal cases. This study retrospectively analyzed four patients admitted to the emergency room after chlorfenapyr intake and detected different concentrations of chlorfenapyr in their plasma. Among them, one patient died and three patients survived. Case 1 suffered respiratory and circulatory failure with a deep coma shortly after oral administration of 100 mL of a the chlorfenapyr-containing mixture and died 30 min after admission. Case 2 experienced transient nausea and vomiting after oral administration of chlorfenapyr (50 mL). The patient had normal laboratory results and was discharged with no further treatment. Case 3 developed nausea and vomiting and a light coma after taking 30 mL of chlorfenapyr orally. He underwent blood perfusion and plasma exchange in the intensive care unit (ICU) and was discharged with recovery. A two-week follow-up visit, however, revealed hyperhidrosis. Case 4 (advanced age with severe underlying disease) developed a light coma after oral intake of 30 mL of chlorfenapyr. Subsequently, pulmonary infection and gastrointestinal bleeding were developed. The patient experienced blood perfusion and mechanical ventilation in the ICU and finally survived after treatment. The present study provides the basic information, plasma concentration of toxins, onset of poisoning and treatment process of the four patients mentioned above, providing novel insights into the clinical diagnosis and treatment of chlorfenapyr poisoning.
Insecticides are the most commonly used pesticides in agricultural production. The restriction on highly toxic organophosphorus insecticides has led to the development of new types of insecticides. The World Health Organization classifies chlorfenapyr, a new pyrrole compound with excellent and long-lasting insecticidal and acaricidal effects (Albers et al., 2006), as a moderately hazardous pesticide (World Health Organization (WHO), 2020). The increasingly widespread application of chlorfenapyr has increased clinical poisoning fatalities. However, due to the atypical symptoms of acute chlorfenapyr poisoning, clinicians, patients, and their families are not sufficiently aware of its high lethality, resulting in adverse clinical outcomes. Currently, specific antidotes and standardized protocols for the clinical treatment of chlorfenapyr poisoning are unavailable. As a result, symptomatic and supportive treatment is the only option. This study reported the clinical features and treatment process of four patients with chlorfenapyr poisoning, aiming to deepen the comprehension of clinical workers on chlorfenapyr poisoning and improve its diagnosis and treatment.
This study retrospectively analyzed four patients with chlorfenapyr poisoning admitted to the emergency room in Clinical Medical College of Yangzhou University. The general information, clinical symptoms, basic vital signs, blood test, bedside cardiac function and other parameters were recorded. The treatment process and clinical outcome of the four patients were described.
Case 1: A 57-year-old male patient was in good health previously. After oral administration of 100 mL of chlorfenapyr-containing suspension (chlorfenapyr 10%, tolfenpyrad 10%), he went into a deep coma with reduced respiration (Table 1). Upon admission, the patient’s bilateral pupils were 5 mm in diameter with no light reflex. Physical examination indicated temperature of 36°C, blood pressure of 60/30 mmHg, respiration rate of 5 breaths/min, heart rate of 45 beats/min, and an undetectable peripheral capillary oxygen saturation (SpO2). The arterial blood gas analysis (ABG) showed PH of 7.13 and lactate (Lac) > 20 mmol/L (Table 2). Echocardiography revealed a significant attenuation of cardiac activity, a diffuse and considerable weakening of myocardial contractility, and a 35% left ventricular ejection fraction (LVEF). The blood concentrations for chlorfenapyr were 45300 ng/mL and 15000 ng/mL for tolfenpyrad (Fig. 1). After admission to the emergency room (ER), the patient received intubation, mechanical ventilation, fluid infusion and inotropic agents. However, 30 min later, he experienced cardiac arrest and was cleared death after resuscitation failed.
| Case | Age (y) |
Dosage (mL) |
Concentration (ng/mL) |
Symptoms | Th (min) |
Tgl (min) |
Tbp (min) |
APACHE-II | GCS | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|
| Case 1 | 57 | 100 | 45300 | coma, weak breathing | 30 | 40 | / | 30 | 5 | died |
| Case 2 | 28 | 50 | 4266 | nausea, vomiting | 60 | 68 | / | 0 | 15 | survived |
| Case 3 | 68 | 30 | 34650 | confusion, nausea, vomiting, abdominal pain | 180 | 192 | 431 | 13 | 13 | survived |
| Case 4 | 76 | 30 | < 1 | confusion | 60 | 69 | 349 | 28 | 6 | survived |
Th: the time from oral administration of chlorfenapyr to hospital; Tgl: the time from oral administration of chlorfenapyr to gastric lavage; Tbp: the time from oral administration of chlorfenapyr to blood purification therapy; APACHE-II: Acute Physiology and Chronic Health Evaluation-II; GCS: Glasgow Coma Scale.
| Case 1 | Case 2 | Case 3 | Case 4 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 1 | Day 1 | Day 1 | Day 2 | Day 3 | Day 1 | Day 2 | Day 3 | ||||
| PH | 7.13 | - | 7.42 | 7.44 | 7.42 | 7.31 | 7.43 | 7.38 | |||
| PaO2 | 86.7 | - | 88.9 | 103 | 122.1 | 74.5 | 78.5 | 132.6 | |||
| Lac | > 20 | - | 2.6 | 1.7 | 1.2 | 11.4 | 3.4 | 2.7 | |||
| WBC | 5.35 | 8.04 | 15.06 | 16.05 | 8.53 | 11.76 | 13.92 | 13.38 | |||
| cTnI | < 0.012 | < 0.012 | < 0.012 | < 0.014 | - | < 0.012 | - | < 0.048 | |||
| CK-MB | 3.45 | - | 0.53 | 0.67 | 1.79 | - | - | 104 | |||
| SCr | 79.1 | 58.3 | 64 | 67.9 | 79.6 | 64.4 | 124.3 | 90.5 | |||
| BUN | 3.8 | 3.53 | 4.55 | 4.6 | 6.96 | 4.89 | 8.84 | 10.57 | |||
| AST | 66 | 30 | 22 | 25 | 28 | 48 | 392 | 152 | |||
| ALT | 16 | 12 | 30 | 28 | 25 | 12 | 58 | 43 | |||
| LVEF | 35% | 65% | 57% | 63% | 66% | 54% | 64% | 66% | |||
PaO2: partial pressure of oxygen in arterial blood (normal range: 83–108 mmHg); Lac: lactic acid (normal range: 0.5–2.2 mmol/L); WBC: white blood cells (normal range: 3.5–9.5 × 109/L); cTnI: cardiac troponin I (normal range: 0–0.034 ng/mL); CK-MB: creatine kinase isoenzyme (normal range: 0–2.03 ng/mL); SCr: Serum creatinine (normal range: 58–110 umol/L); Blood urine nitrogen (normal range: 1.7–8.3 mmol/L); Aspartate aminotransferase (normal range: 17–59 u/L); Alanine transaminase (normal range: 21–72 u/L); LVEF: left ventricular ejection fraction (normal range: 55–70%).
Plasma concentration of toxicants examined by liquid chromatography-mass spectrometry.
Case 2: A 28-year-old female patient was previously in good health. She was admitted to our department after complaining of vomiting for one hour due to the administration of chlorfenapyr (10% chlorfenapyr 50 mL) (Table 1). She was conscious when she was admitted, with a temperature of 36.5°C, blood pressure of 125/75 mmHg, respiration rate of 15 breaths/min, and heart rate of 78 beats/min. The blood test results showed no significant abnormalities (Table 2). Echocardiography indicated that the LVEF was normal. Furthermore, the blood concentration of chlorfenapyr was 4266 ng/mL (Fig. 1). The gastric lavage and fluid infusion were performed to reduce toxin absorption and protect the patient’s organ function. She declined admission to the ICU for continued treatment and left the ER. A 15-days follow-up suggested no toxic sequelae and no significant abnormalities in laboratory tests.
Case 3: A 68-year-old male patient had previously been diagnosed with hypertension and cerebral infarction. He was admitted to a local hospital for “taking chlorfenapyr (10% chlorfenapyr 30 mL) three hours ago” and underwent gastric lavage. The patient experienced severe nausea and vomiting, with discomfort in the upper and middle abdomen (Table 1). He gradually developed unconsciousness. When been transferred to our ER, he was in a light coma with a blunted light reflex in both pupils. The physical exam revealed a body temperature of 37.1°C, blood pressure of 134/88 mmHg, respiration rate of 18 breaths/min and heart rate of 65 beats/min. Laboratory tests showed light elevated Lac in ABG and high level of WBC counts in blood routine exams (Table 2). Echocardiography indicated LVEF was within the normal range. The blood concentration of chlorfenapyr was 34650 ng/mL (Fig. 1). After admission to the ICU, catharsis, blood perfusion and plasma exchange were performed. Anti-infection and high flow oxygen therapy were performed as the patient developed pulmonary infection during the treatment. The patient’s conditions finally improved after the comprehensive treatment, and he was discharged on the 5th day after poisoning. On the 15th day after discharge, the patient was followed up and complained hyperhidrosis. His liver and kidney function and myocardial injury markers showed no significant abnormalities during follow-up.
Case 4: A 76-year-old male patient had a history of hypertension and gastric cancer. He was admitted to our ER due to “unconsciousness for one hour after oral administration of chlorfenapyr (10% chlorfenapyr)”. He was in a light coma when admitted, with urinary and fecal incontinence (Table 1). The light reflexes were blunted in both pupils. His temperature was 36.8°C, blood pressure was 160/100 mmHg, respiration rate was 25 breaths/min, heart rate was 91 beats/min, SpO2 was 85%. ABG showed PH of 7.31 and Lac of 11.4 mmol/L. Blood routine exam defined WBC counts of 11.76 × 109/L (Table 2). As indicated by echocardiography, the LVEF was normal. The plasma concentration of chlorfenapyr was below 1 ng/mL (Fig. 1). Tracheal intubation, fluid infusion, and gastric lavage were immediately performed in the ER. After admission to the ICU, the patient received blood perfusion and mechanical ventilation. During the hospitalization, he developed pulmonary infection and gastrointestinal bleeding. After appropriate symptomatic therapy, the patient was recovered and discharged on the 16th day after poisoning. The follow-up showed no toxic symptoms on 15 days after discharge.
Recently, the extensive usage of chlorfenapyr has resulted in an increase in reported poisonings. Several deaths from chlorfenapyr poisoning have been reported in Korea, Japan, India (Lee et al., 2013; Hoshiko et al., 2007; Tharaknath et al., 2013), and China (Luo et al., 2020; Liao et al., 2022). The Food and Agriculture Organization/WHO established 0.03 mg/kg as the acute reference dose (ARfD) for human exposure to chlorfenapyr. Furthermore, the EU Food Safety Authority’s criterion is 0.015 mg/kg, with no lethal dose reported (European Food Safety Authority (EFSA), 2019). Chlorfenapyr, a pyrrole compound, is metabolized to the active metabolite CL303268 in vivo. Chlorfenapyr poisoning causes the decoupling of oxidative phosphorylation in the mitochondria, preventing the conversion of adenosine diphosphate (ADP) to adenosine triphosphate (ATP), blocking the energy generation (United States Environmental Protection Agency., 2001). Dizziness, weakness, nausea, and whole-body sweating, are common symptoms of poisoning, which can be linked to energy deficit in high-energy-consuming organs such as the brain and skeletal muscles (Fig. 2). Patients may experience a transient relief from their symptoms after treatment; however, after 1–2 weeks, they may develop coma, hyperthermia, rhabdomyolysis, respiratory and circulatory failure, cardiac arrest, and even death (Ku et al., 2015).
Mechanism and syndromes of chlorfenapyr poisoning.
Previous studies indicate that chlorfenapyr poisoning has a high mortality, with a majority of deaths occurring within 7–20 days after poisoning (Davy et al., 2019; Chomin et al., 2018). However, in our report, three of the four patients survived, indicating that the mortality rate may not be as high as that described in the literature. Therefore, clinicians should not assign a “death sentence” to patients who have been exposed to chlorfenapyr but rather treat them positively. The only deceased case in our report was found being poisoned by mixed pesticides including chlorfenapyr and tolfenpyrad. Both substances have acute toxic effect on patients through interfering mitochondrial energy metabolism. The chlorfenapyr concentration in plasma of this patient was as high as 45300 ng/mL. The tolfenpyrad concentration in plasma was 1.5 µg/mL, which was much lower than that reported in the previous deceased case (Hikiji et al., 2013). We consider that high level of chlorfenapyr contributed to the quick death after poisoning, while tolfenpyrad had a synergistic impact.
In all four patients, the blood lactate levels were elevated to varying degrees. Lactic acidosis is clinically associated with blood or cellular hypoxia. But the arterial partial pressure of oxygen (PaO2) didn’t decrease in patients with chlorfenapyr poisoning, suggesting that the shock and acidosis caused by such poisoning is associated with impaired cellular energy metabolism. Furthermore, the liver enzymes and creatinine in serum of the patients stayed in normal or slightly elevate, indicating that livers and kidneys are tolerant to hypoxia in the early stages of chlorfenapyr exposure. The results were in accordance with other studies (Pu et al., 2021). On contrary, the damage to high-energy-consuming vital organs (e.g., brain, heart, skeletal muscle) is much more severe (Gong et al., 2021). After being exposed to chlorfenapyr, Case 1 had cardiogenic shock and significantly decreased LVEF, with unelevated troponin level. We assume that troponin level may be less sensitive than echocardiography in detecting cardiac damage in the early stages of exposure. Moreover, there was no significant decrease in LVEF among the survivors’ early stages, indicating that cardiac function may be a reliable indicator of prognosis in patients with chlorfenapyr poisoning.
Cases 3 and 4 exhibited a considerable reduction in lactate levels within 72 hr of admission, indicating that organ hypoxia and general conditions improved gradually following toxicant clearance. Case 2 survived despite receiving only simple gastric lavage and fluid infusion without blood purification. This may be related to the younger age of the patient. The age of the patient was associated with the risk of death from acute pesticide poisoning, with a 1.14-fold increase in mortality for every 5-year increase in age among females (Noghrehchi et al., 2022). Furthermore, her low toxicant levels in plasma and prompt gastric lavage contributed to her survival.
There are no specific antidotes for chlorfenapyr poisoning. Individuals who have had skin exposure should immediately wash their skin thoroughly under running water. Those who have taken it orally should also eliminate the toxicants from their gastrointestinal tract as soon as possible. Pharmacological treatment includes ATP supplementation, myocardial nutrition, and cerebral edema reduction. Chlorfenapyr is a lipophilic toxicant (Periasamy et al., 2017), which could be absorbed by blood perfusion. Meanwhile chlorfenapyr has a small relative molecular mass and can readily cross cell membranes. It could be removed by continuous renal replacement therapy (CRRT) in the early stages (Han et al., 2019). However, once uncoupling begins, blood purification therapy fails to achieve satisfactory outcomes (Chomin et al., 2018). Furthermore, early administration of extracorporeal membrane oxygenation (ECMO) may reduce morbidity in patients with multiple organ failure accompanied by severe myocardial function suppression. Still more clinical trials are needed to support blood purification therapy and ECMO techniques in treating chlorfenapyr poisoning.
Although the literature reported a high mortality rate of chlorfenapyr poisoning, three out of four patients in the present report survived. As a result, physicians should not give up on such patients quickly. Toxicant concentration measurement is crucial in diagnosis, treatment, and prognosis. In addition, timely toxicant elimination and early organ function support treatment can improve prognosis. Given the rarity and lethality of such poisonings, more relevant poisoning cases need to be collected. Overall, this report improves doctors’ understanding of chlorfenapyr poisoning and provide treatment options in clinic, as well as enhance public awareness of this pesticide poisoning.
Conflict of interestThe authors declare that there is no conflict of interest.
