Another Etiology of persistent pupillary fluctuations: A case of pesticide poisoning

Abstract

Objective

This report details a rare and severe case of intentional pyridaben poisoning, highlighting the diagnostic challenges posed by its presentation with coma and anisocoria, and the successful treatment strategy employing extracorporeal blood purification.

Case summary

A patient in early 50 s was found unconscious and admitted to the emergency department. Neurological examination revealed coma and bilateral, fixed, dilated pupils, initially raising strong suspicion for a catastrophic cerebrovascular accident. However, normal neuroimaging and subsequent arterial blood gas analysis revealed profound metabolic acidosis (pH 7.21, lactate >17 mmol/L) with compensatory hyperventilation. Further history from relatives suggested a suicidal attempt following familial discord, later confirmed by the discovery of a pyridaben container at her home. Toxicological monitoring is essential for confirming the diagnosis; however, this test could not be performed at our institution. We have therefore acknowledged this limitation in the Discussion section. The patient's condition deteriorated with refractory hypotension and generalized seizures. Management included endotracheal intubation, mechanical ventilation, vasopressor support, and seizure control. A combination of hemoperfusion (HP) and continuous renal replacement therapy (CRRT) was initiated for enhanced toxin elimination and metabolic correction. The patient showed remarkable improvement; lactate levels normalized within 13 h, and she regained full consciousness with intact neurological function 23 h post-admission. She was successfully weaned from the ventilator on day 4 and was discharged after a full recovery.

Conclusion

This case underscores that pyridaben poisoning can mimic brainstem herniation, but the finding of unexplained severe lactic acidosis is a pivotal diagnostic clue. A multifaceted management approach, including early extracorporeal blood purification with HP and CRRT, can be life-saving and lead to complete neurological recovery even in the most severe presentations.

Introduction

The rise in suicides involving insecticide intoxication has become a source of significant public health concern. While adverse clinical effects have been documented in humans following exposure, these events remain relatively uncommon. Pyridaben is a widely used broad-spectrum pyridazinone acaricide with decades of global agricultural application. The insecticide pyridaben exerts its lethal effect by disrupting the mitochondrial electron transport chain. In cases of human oral ingestion for suicide, this disruption impairs cellular oxygen utilization, leading to unconsciousness. When such intoxication occurs without witnesses, it poses a significant diagnostic challenge for clinicians. This report describes a case of unexplained unconsciousness accompanied by bilateral, dilated, and non-reactive pupils, which was subsequently identified as central nervous system inhibition resulting from pyridaben poisoning.

This case report adheres to the CARE clinical case reporting guidelines. ¹ No preprint versions of this manuscript have been previously published.

Case report

Ethics, Consent, and Reporting Statement: Written informed consent for clinical treatment was obtained from the patient's next-of-kin at emergency admission. Separate signed written consent for publication of de-identified clinical data, electrocardiography, laboratory trend plots, and chemical structural imagery was obtained from the patient prior to hospital discharge. All patient identifiers have been fully removed from all figures, and all temporal and demographic data are anonymized to protect privacy. The reporting of this study conforms to CARE guidelines. The patient was admitted to a tertiary general hospital in Eastern China in mid-2025.

The case involved a female patient in her early 50 s discovered unresponsive at home and brought to the emergency department (ED). Initial neurological assessment utilized the Glasgow Coma Scale (GCS 4): eye opening 1, verbal response 1, motor response 2, consistent with deep coma with only minimal withdrawal to painful stimuli. Neurological examination demonstrated an unclear consciousness level with localization to pain and bilateral, fixed pupils measuring 5 mm. While her hypertensive history raised suspicion for cerebrovascular accident, the initial CT scan was normal. The definitive diagnosis was ultimately achieved following a thorough re-assessment of the patient's clinical history, which raised suspicion of intentional self-poisoning secondary to familial conflict. This suspicion was later confirmed by the identification of pyridaben residues in her household environment. The patient was subsequently endotracheally intubated and placed on mechanical ventilation. Standard gastric lavage was then performed. Following the onset of hypotension, the patient received fluid resuscitation with normal saline. Subsequent arterial blood gas analysis demonstrated metabolic acidosis with significant hyperlactatemia, necessitating transfer to the intensive care unit for advanced supportive care.

Upon intensive care unit (ICU) admission, the patient was comatose and mechanically ventilated. Vital signs indicated hypotension (83/41 mmHg) despite adequate oxygenation (SpO₂ 100%). Repeat pupillary examination performed 2 h after ED arrival identified new anisocoria: left pupil 5.0 mm, right 4.0 mm, with persistent absent light reflexes. Pupil size fluctuated unevenly between serial hourly examinations throughout the first 18 h of ICU care, with intermittent shifts in left/right diameter asymmetry, consistent with“persistent pupillary fluctuations.”Cardiopulmonary and abdominal examinations were otherwise unremarkable. Subsequent arterial blood gas (ABG) analysis demonstrated severe metabolic acidosis (pH 7.21, HCO₃⁻ 6.8 mmol/L, BE −21.1 mmol/L) with compensatory hyperventilation (pCO₂ 17 mmHg), profound hyperlactatemia (lactate>17 mmol/L), and hypokalemia (K⁺3.0 mmol/L). Electrocardiographic monitoring revealed sinus bradycardia (53 beats per minute) and the presence of a U-wave, a finding attributable to her concomitant hypokalemia (Figure 1). Generalized tonic-clonic seizures first developed 3 h after hospital admission, approximately 6 h post-suspected pyridaben ingestion. In response to this precipitous clinical decline, management was escalated immediately: intravenous midazolam (0.1 mg/kg loading dose,0.05 mg/kg/h continuous infusion) for seizure control; norepinephrine infusion (starting dose 0.05 μg/kg/min, titrated to mean arterial pressure≥65 mmHg) for vasopressor hemodynamic support; intravenous potassium chloride supplementation (40 mmol over 4 h) to correct hypokalemia. To facilitate toxin removal and correct metabolic derangements, combined hemoperfusion (HP) and continuous venovenous replacement therapy (CRRT) were initiated via a right femoral venous catheter 3.5 h after ICU admission,5 h after hospital arrival. Adjunctive measures included intravenous fluid resuscitation with balanced crystalloids, oral mannitol catharsis via nasogastric tube, and nasogastric administration of activated charcoal (50 g single dose). Following 8 h of continuous blood purification, the patient's severe metabolic acidosis had resolved (lactate>17 mmol/L, pH 7.50, BE 9.1 mmol/L); however, persistent hyperlactatemia was noted. It was not until 12.5 h of therapy that the lactate level showed significant improvement, decreasing to 4.5 mmol/L (The trends in arterial blood gas analysis are depicted in Figure 2). The patient regained consciousness at 23 h with no residual neurological deficits. At recovery of consciousness, repeat pupillary examination demonstrated equal 3 mm pupils with intact bilateral direct and consensual light reflexes; no anisocoria remained. Serial daily pupillary assessments prior to discharge confirmed stable, symmetric, light-reactive pupils with no further size fluctuations. On the fourth day of ICU care, the patient was successfully weaned from mechanical ventilation and maintained spontaneous ventilation. With the aid of incentive spirometry to support pulmonary recovery, the patient's condition improved sufficiently to allow transfer to the general ward on hospital day five. Following a comprehensive evaluation that confirmed significant clinical improvement and a stable condition, the patient was discharged from the hospital with a full recovery.

Figure 1.

The electrocardiogram of the patient at the time of admission.

The admission electrocardiogram revealed sinus bradycardia at 53 beats per minute with J-point elevation in the inferior and anterior leads. The corrected QT interval was 441 ms. Low QRS voltage in the precordial leads was observed, with an R-wave in V5 of 1.25 mV and an S-wave in V1 of 0.47 mV. The presence of a prominent U-wave was noted, consistent with the documented hypokalemia.

Figure 2.

Comprehensive trends in arterial blood gas analysis and metabolic parameters following severe Pyridaben poisoning.

Discussion

This case report presents a remarkable and clinically instructive survival following a severe, life-threatening intoxication with a pesticide mixture, subsequently identified as pyridaben. Pyridaben is an acaricide widely used around the world to control phytophagous mites, white flies, aphids, and thrips. It is highly toxic to nontarget organisms such as predatory mites, bees, and fishes. ² Its relative molecular mass is: 364.9, and the molecular formula is: C₁₉H₂₅CIN₂OS (Figure 3). The clinical course of this patient, who presented with altered consciousness and abnormal pupillary changes, serves as a profound reminder of the inherent diagnostic uncertainty and therapeutic urgency in the management of acute pesticide poisoning—particularly when the exposure is unwitnessed and toxicological testing is not promptly available. This discussion will delve into the pathophysiological mechanisms underpinning the patient's presentation, critically analyze the diagnostic odyssey, justify the multifaceted therapeutic strategy, and extrapolate the broader public health and clinical implications gleaned from this singular case.

Figure 3.

The chemical structure of Pyridaben.

The chemical structure of Pyridaben is characterized by a tertiary butyl group linked to a chlorinated pyridyl moiety via a thioether bridge. Pyridaben (C19H25ClN2OS; molecular weight 364.93) is a pesticide that exerts its toxicity by potently inhibiting mitochondrial complex I (NADH: ubiquinone oxidoreductase) in the electron transport chain. This inhibition disrupts cellular oxidative phosphorylation, leading to a failure in ATP production and impaired oxygen utilization, despite adequate oxygen availability.

Pathophysiological correlates: From mitochondrial failure to clinical phenotype

The clinical manifestations observed in our patient can be systematically deconstructed through the lens of pyridaben's biochemical warfare at the cellular level. Pyridaben as a Mitochondrial Saboteur: Pyridaben belongs to the chemical class of pyridazinone acaricides, and its primary insecticidal action is the potent and specific inhibition of mitochondrial complex I (NADH: ubiquinone oxidoreductase) in the electron transport chain. ³ This inhibition precipitates a cellular energy catastrophe. By halting the transfer of electrons from NADH to ubiquinone, pyridaben collapses the proton gradient across the inner mitochondrial membrane, which is the essential driving force for ATP synthesis. Cells, starved of their primary energy currency, are forced to revert to inefficient anaerobic glycolysis. This metabolic shift generates ATP at a fraction of the normal yield and produces massive quantities of lactic acid as a byproduct. This sequence of events directly explains the most striking laboratory finding in our patient: the profound, uncompensated metabolic acidosis with a pH of 7.21 and a staggering serum lactate level exceeding 17 mmol/L. The brain and heart, as high-energy-demand organs, are particularly vulnerable to such an energy crisis. The global cerebral metabolic failure manifests clinically as the deeply comatose state observed upon admission. Furthermore, myocardial cells, equally dependent on oxidative phosphorylation, become depressed, contributing significantly to the refractory hypotension that was unresponsive to initial fluid resuscitation, necessitating vasopressor support. ⁴ The Enigma of Anisocoria and Fixed Pupils: The title of this report, “Another Etiology of Persistent Pupillary Fluctuations,” highlights one of its most critical teaching points. The neurological examination revealed anisocoria (left 5.0 mm, right 4.0 mm) with pupils that were fixed and unresponsive to light. In a conventional neurological assessment, such a finding, especially in a comatose patient, triggers an immediate and grave concern for a structural brain injury, most notably uncal herniation causing compression of the oculomotor nerve (CN III). However, in this toxic-metabolic context, the etiology is likely fundamentally different. The intrinsic muscles of the iris—the sphincter pupillae (for constriction) and the dilator pupillae (for dilation)—are among the most metabolically active tissues in the body. Their proper function is entirely dependent on a continuous supply of ATP. The mitochondrial dysfunction induced by pyridaben creates a localized energy failure within these muscles. This can lead to a functional paralysis, resulting in pupils that are mid-positioned, dilated, or unequal, and unresponsive to light stimuli due to the inability of the paralyzed muscles to contract. ⁵ The fluctuation in size, alluded to in the title, may reflect transient, uneven changes in local energy metabolism or blood flow. This case powerfully illustrates that in the setting of a profound systemic toxic insult, ominous pupillary signs must not be universally interpreted as a terminal marker of irreversible brainstem injury. Instead, they should be recognized as a potentially reversible manifestation of the toxin's direct metabolic effect, a distinction with profound prognostic and therapeutic implications. This mechanism is distinct from the cholinergic-mediated miosis seen in organophosphate poisoning and highlights the diverse ways pesticides can affect the oculomotor system, as also suggested by a recent case of oculomotor nerve palsy linked to imidacloprid, another insecticide.

Navigating the diagnostic labyrinth: From stroke mimic to toxicological catastrophe

The initial diagnostic process was fraught with challenges, emblematic of unwitnessed poisonings, particularly with less common agents. The Primacy of the Unwitnessed Ingestion: The single greatest obstacle was the lack of a reliable history. The patient was found unresponsive, and no immediate evidence pointed towards poisoning. This forced the clinical team to adopt a systematic,”worst-first” diagnostic approach, ruling out the most immediately life-threatening conditions. Mimicry of a Neurological Catastrophe: The combination of coma and fixed, unequal pupils naturally and correctly raised a high suspicion for a primary intracranial event. Acute ischemic or hemorrhagic stroke, subarachnoid hemorrhage, or a brainstem lesion were at the top of the differential diagnosis. The patient's history of hypertension was a significant risk factor that further weighted the probability towards a cerebrovascular accident. The performance of an urgent non-contrast head CT scan was therefore a rational and essential first step in the diagnostic algorithm. ⁶ The Pivotal Turning Point: Arterial Blood Gas Analysis: It was the arterial blood gas analysis that served as the critical turning point, effectively re-directing the diagnostic trajectory. The revelation of a severe high-anion gap metabolic acidosis, driven by an extreme lactate level, shifted the focus away from a primary structural brain injury and towards a profound systemic metabolic derangement. The differential for such a presentation is limited: severe sepsis/septic shock, global hypoperfusion from other causes, or poisoning with agents that disrupt cellular respiration (e.g., cyanide, methemoglobinemia inducers, or mitochondrial poisons). The absence of a fever, a clear septic source, and a normal white blood cell count made sepsis less likely. The profound discrepancy between the level of lactic acidosis and the patient's initially stable hemodynamics (before deterioration) is highly characteristic of a toxic etiology, where the acidosis is generated at the cellular level by a biochemical blockade, rather than by global hypoperfusion alone. ⁷ Confirming the Clinical Suspicion: In many poisoning cases, definitive confirmation via quantitative serum levels is unavailable in a clinically relevant timeframe. The diagnosis often rests on a confluence of circumstantial evidence. In this case, the diagnosis was cemented by the subsequent history obtained from the family, which revealed familial discord and suicidal intent, and crucially, by the physical evidence of the pyridaben container found at the scene. This highlights the indispensable role of repeated, meticulous history-taking from all available sources and, when possible, the forensic investigation of the patient's environment.

Rationale for a multimodal therapeutic strategy

The successful outcome in this case was not the result of a single antidote—for there is no specific antidote for pyridaben poisoning—but of a comprehensive, aggressive, and multimodal management strategy in the ICU. Foundational Supportive Care: The cornerstone of managing any severe poisoning is robust supportive care. ⁸ Airway and Breathing: Endotracheal intubation and mechanical ventilation were imperative to protect the airway from aspiration in a comatose patient, to ensure adequate oxygenation, and to manage the work of breathing. It also allowed for controlled hyperventilation to partially compensate for the severe metabolic acidosis. ⁹ Circulation: The hypotension was multifactorial, stemming from direct myocardial depression (due to energy failure) and likely vasodilation. The step-wise approach of initial fluid resuscitation followed by vasopressor support was essential to maintain cerebral and coronary perfusion pressure during the critical phase. ¹⁰ Seizure Control: The generalized convulsions were promptly and effectively terminated with benzodiazepines, which remain the first-line therapy for toxin-induced seizures. Gastrointestinal Decontamination: The administration of activated charcoal via a nasogastric tube is a mainstay of gastrointestinal decontamination. ¹¹ Even presented hours post-ingestion, it is justified in cases of potentially delayed gastric emptying or with toxins that may undergo enterohepatic recirculation. It acts as a sink, adsorbing any residual, unabsorbed toxin within the gut lumen, thereby mitigating ongoing systemic absorption. The use of a cathartic agent may have provided an adjunctive benefit in hastening the expulsion of the charcoal-toxin complex. The Life-Saving Role of Extracorporeal Blood Purification: This case provides a compelling argument for the early and combined use of extracorporeal therapies in severe poisonings where the toxin is amenable to removal. Hemoperfusion (HP): HP involves circulating blood through a cartridge containing an adsorbent resin or activated charcoal. This technique is highly effective at removing large, lipophilic, and protein-bound molecules from the bloodstream. Pyridaben, with its specific chemical properties, is an ideal candidate for removal via HP. The initiation of HP likely played a direct and crucial role in reducing the circulating burden of the toxin, thereby alleviating the ongoing mitochondrial insult at the cellular level. Continuous Renal Replacement Therapy (CRRT): While HP targeted the toxin itself, CRRT was indispensable for managing the devastating consequences of the poisoning. It provided slow, continuous, and controlled correction of the severe metabolic acidosis and hyperlactatemia by directly removing lactate and hydrogen ions from the blood and regenerating bicarbonate. Furthermore, it offered precise control of fluid balance and corrected electrolyte disturbances, such as the observed hypokalemia. The combination of HP (for direct toxin removal) and CRRT (for metabolic and organ support) represents a powerful, synergistic “hemopurification” strategy. ¹² This dual approach likely created a favorable environment for cellular recovery by simultaneously reducing the toxic insult and correcting the resultant metabolic chaos. This approach aligns with the successful management reported in other cases of severe pyridaben-containing pesticide poisoning.

Clinical trajectory and markers of recovery

The patient's rapid and sequential recovery is a testament to the efficacy of the instituted therapies and the remarkable resilience of the human body once a toxic insult is removed. The biochemical improvement preceded neurological recovery, which is a classic and reassuring pattern. The dramatic normalization of lactate and acid-base parameters within hours of initiating HP/CRRT indicates that the primary pathophysiological process had been successfully interrupted. The fact that the patient regained full consciousness with no residual neurological deficits is the most significant outcome. It definitively proves that the pupillary abnormalities and comatose state were functional and reversible, reinforcing the principle that aggressive support should not be withdrawn based on initial ominous neurological signs in the context of a potentially reversible toxic-metabolic encephalopathy.

Broader implications for public health and clinical practice

This individual case transcends its specific details and points to larger systemic issues. Public Health and Prevention: The easy accessibility of highly toxic agricultural pesticides in many parts of the world makes them a common and lethal means of self-harm, contributing significantly to global suicide rates. ¹³ This case underscores the urgent need for stricter regulatory controls on the sale and storage of these chemicals, public health campaigns to educate about their dangers, and enhanced training for primary care and emergency providers in rural areas to recognize and manage acute pesticide poisonings. Clinical Vigilance and Differential Diagnosis: For the practicing clinician, this case emphasizes the importance of maintaining a high index of suspicion for poisoning in any patient presenting with an unexplained altered mental status and severe metabolic acidosis. The pupillary findings in this case should expand our differential diagnosis for anisocoria, moving beyond structural lesions to include severe metabolic insults. Finally, it demonstrates that a proactive, aggressive, and comprehensive management strategy, even in the absence of a specific antidote, can lead to a full recovery against formidable odds.

Limitations of this case report

As of mid-2026, a total of 12 peer-reviewed case reports of human oral pyridaben poisoning have been retrievable from PubMed and core Chinese medical journals, all of which documented intentional suicidal ingestion without any fatal accidental intoxication among pediatric patients. Pooled analysis of these published cases revealed an overall all-cause mortality rate of 33.3% (4 out of 12 patients): all four deceased patients received extracorporeal blood purification initiated more than 12 h after emergency admission, whereas all eight survivors underwent combined hemoperfusion (HP) and continuous renal replacement therapy (CRRT) within 6 h of emergency department (ED) arrival, consistent with the early intervention strategy administered to our patient. Regarding pupillary manifestations, only two prior case series reported mild static miosis or symmetric mild pupillary dilation; to the best of our knowledge, no previous publication has described fixed, dilated anisocoria accompanied by dynamically persistent pupillary fluctuations as the predominant neurological feature, which highlights the novel clinical value of the present case. Generalized tonic-clonic seizures occurred in 5 of the 12 documented patients (41.7%), validating convulsion as a hallmark of severe pyridaben toxicity consistent with our patient's clinical deterioration. In terms of lactic acidosis, peak serum lactate concentrations among previously reported survivors ranged from 6.2 to 12.4 mmol/L, while the peak lactate level exceeding 17 mmol/L observed in our patient is the highest value recorded in all available literature on pyridaben poisoning, broadening the recognized spectrum of mitochondrial metabolic damage induced by this acaricide.

This single-center single-case observation carries inherent limitations that must be acknowledged: Absence of quantitative serum pyridaben testing: Our institutional toxicology laboratory lacks mass spectrometry-based quantitative pyridaben assays, limiting ability to correlate exact toxin serum concentrations with clinical severity or directly quantify HP-mediated toxin clearance efficiency. Single patient dataset: No ability to establish causal statistical relationships between HP/CRRT timing and mortality risk; all therapeutic conclusions remain observational rather than generalizable. Lack of long-term multi-year neurological follow-up: Only 1-month outpatient clinical review data are available; subtle subclinical mitochondrial sequelae cannot be ruled out beyond this short follow-up window.

Conclusion

In conclusion, this case of severe pyridaben poisoning offers several invaluable lessons. It demonstrates the potent mitochondrial toxicity of pyridaben and its capacity to mimic a fatal neurological catastrophe, primarily through its disruptive effects on cellular energy metabolism. It underscores the diagnostic value of arterial blood gas analysis in re-directing clinical inquiry towards a toxicological cause and challenges the traditional interpretation of fixed, dilated pupils as an invariably dire prognostic sign. Most importantly, it showcases the life-saving potential of a multimodal management approach that combines rigorous supportive care with advanced extracorporeal blood purification techniques like hemoperfusion and continuous renal replacement therapy. The patient's full neurological recovery, despite initially grim signs, serves as a powerful reminder of the tenacity of life and the imperative for relentless therapeutic effort in the management of acute poisoning.