Lung Transplant Success in Severe Diquat Poisoning: A Case Report

Introduction

Diquat (1,1′-ethylene-2,2′-bipyridinium ion; DQ) is a nonselective and highly effective herbicide classified within the bipyridine compound family, specifically related to paraquat. It is widely used in China due to its low cost and high efficiency, especially with paraquat being off the market. Recently, there has been an increase in reported cases of diquat poisoning [1–3]. Diquat is extremely lethal to humans, with the minimum lethal dose for adults being 15 mL of a 20% concentrated formulation [4]. Currently, there is no specific antidote available. Existing clinical treatment options are relatively limited, primarily including corticosteroids, immunomodulation, antioxidant therapies, and blood purification methods [5], and these therapeutic interventions do not guarantee long-term survival for individuals diagnosed with pulmonary fibrosis. Lung transplantation (LT) is recognized as the only therapeutic option for patients who develop irreversible pulmonary fibrosis following herbicide intoxication [6,7]. In this case report, we present the clinical progression of recovery in a young woman who underwent sequential double-lung transplantation after diquat poisoning.

Case Report

We admitted a 26-year-old woman who experienced nausea, vomiting, coughing, and general fatigue after ingesting 80 mL of 20% diquat (Nuo’er Diquat) after a family argument. She was immediately transferred to a local hospital, where she received gastric lavage, diarrhea management, and hemoperfusion. Subsequently, she was referred to the First Hospital of Jilin University for specialized treatment of multi-organ dysfunction. Thoracic computed tomography (CT) performed on the first day is shown in Figure 1A. On the 13th day, she suddenly had difficulty breathing, and a thoracic CT scan revealed bilateral pneumonia, primarily characterized by interstitial changes (Figure 1B). Non-invasive ventilatory support was provided for this condition. One day later, an arterial blood gas analysis conducted with an inspired oxygen concentration of 100% revealed an oxygen tension of 40 mmHg and a carbon dioxide tension of 39 mmHg. The patient subsequently underwent tracheal intubation and invasive ventilatory support. Despite varying levels of respiratory assistance, her dyspnea gradually worsened. A thoracic CT scan conducted on November 20, 2024 (Figure 1C) indicated progression of pulmonary fibrosis throughout the clinical evaluation. A multidisciplinary team of specialists assessed the patient’s condition and reached a consensus that lung transplantation (LT) was the only viable option for survival. On the 24th day after the poisoning incident, the patient was placed on veno-venous extracorporeal membrane oxygenation (V-V ECMO) as supportive treatment, with arterial blood gas analysis showing a pO2 of 44 mmHg and a pCO2 of 39 mmHg. On the 28th day, she underwent sequential bilateral lung transplantation through bilateral anterior lateral incisions. Preoperative liver and kidney function improved significantly (Figure 2). The durations of cold ischemia for the right and left lungs were recorded as 7.5 h and 9 h, respectively, and the ECMO mode was adjusted to veno-arterial (V-A) during the operation. Postoperatively, the patient was admitted to the Intensive Care Unit (ICU).

On the 6th day after surgery, the patient experienced sudden dyspnea. Based on the CT results, a pulmonary embolism was suspected (Figure 1D). Subsequently, right upper-lobe resection surgery was performed, after which she was returned to ICU. The postoperative pathological report indicated right upper-lobe pulmonary infarction.

Postoperatively, the immunosuppressive drugs administered included tacrolimus (FK506) and cyclosporine (CsA). The patient exhibited compromised pulmonary ventilation capabilities, multiple muscular dysfunctions, and symptoms of anxiety and depression. Due to her suicidal ideation involving diquat, the psychotherapy team intervened early for treatment. Additionally, rehabilitation training commenced promptly following the patient’s removal from mechanical ventilation and ECMO, paralleling the initiation of psychotherapy. The patient received prophylactic antimicrobial agents to mitigate the risk of bacterial, fungal, and viral infections. Following the surgical procedure, routine institutional protocols were adhered to, which included conducting blood tests, chest radiography, and bronchoscopy. The patient was discharged on the 132nd day after surgery.

About 6 months after her lung transplantation, she patient returned due to bronchial stenosis and a bronchopleural fistula (Figure 1E). Airway-covered stent implantation was done to address the bronchopleural fistula. More than 1 month after the treatment, she had made a good recovery and has been able to resume a normal life (Figure 1F). An illustration of the clinical course and perioperative events can be found in Figure 3.

Discussions

Diquat (DQ) is a substitute herbicide for paraquat and is structurally similar to it. Diquat can be absorbed through the gastrointestinal tract, skin, and respiratory system [8]. It is then rapidly distributed to various organs and tissues via the bloodstream due to its strong oxidizing properties [9], which can damage multiple organs throughout the body [10]. Some reports indicate that the highest concentration of diquat is found in the kidneys, lungs, liver, brain, and heart [1].

A burning sensation in the oropharynx, along with nausea, vomiting, and coughing, occur immediately after ingestion of diquat. Subsequently, liver and kidney function gradually worsen as the disease progresses. The pulmonary lesions caused by diquat are often not apparent in the early stages. Diquat results in relatively minimal damage to pulmonary tissues and does not induce significant fibrotic scarring in the lung tissues during the initial stages following exposure. However, increasing reports indicate that the pulmonary lesions caused by diquat resemble to those observed in cases of paraquat poisoning [11,12].

The primary therapeutic approach for DQ involves the removal of toxins and the provision of active organ support therapies, including gastric lavage, hemodialysis, hemoperfusion, and administration of immunosuppressive agents such as methylprednisolone and cyclophosphamide, as well as antioxidant agents. In our patient, despite implementation of these treatments, the progression of bilateral pulmonary fibrosis continued, and no improvement in her condition was observed, even with the support of ECMO. Irreversible pulmonary fibrosis is one of the leading causes of death. In this situation, lung transplantation is considered the only viable option to improve the patient’s chances of survival.

The positive outcome of this case suggests that lung transplantation can be a viable therapeutic option for certain patients experiencing end-stage pulmonary fibrosis accompanied by severe respiratory failure following diquat poisoning. Some reports indicate that lung transplantation for patients with herbicide intoxication is considered viable once there is evidence of recovery in hepatorenal function, and it is not necessary to await full recovery prior to proceeding with the transplantation [13]. Our patient underwent surgery on the 28th day after poisoning, by which point her liver and kidney functions had recovered. Additionally, ECMO is a bridge to lung transplantation for patients following severe herbicide poisoning [6]. Our patient had a successful chance of lung transplantation with ECMO treatment. An insufficient waiting period for lung transplantation (LT) may lead to the recurrence of fibrosis in the transplanted lung. Conversely, an excessively prolonged waiting time increases the risk of airway complications, including preoperative infections and bacterial colonization. Future research should explore the optimal timing for lung transplantation in patients with herbicide poisoning.

Postoperative infections were observed in nearly all patients who survived lung transplantation following herbicide poisoning. Due to multiple factors, including prolonged waiting times and low immune resistance, postoperative pulmonary infection seems inevitable. In this case, our patient was infected with Stenotrophomonas maltophilia and Klebsiella pneumoniae, with a leukocyte count exceeding 15×109/L for a period. She received antibiotics via intravenous injection in conjunction with aerosolized inhalation. For these patients, the prompt administration of high-grade antibiotics is essential to mitigate the risk of infection.

Pulmonary embolism (PE) is often underestimated as a complication that can lead to early postoperative respiratory failure following lung transplantation. A recent report indicates that cardiopulmonary bypass (CPB) and the interruption of venous thromboembolism (VTE) prophylaxis are significant predictors of developing early VTE (defined as VTE occurring within 30 days of transplantation) in this patient population [14]. The most frequent symptom observed was dyspnea. Our patient was suspected to have PE on the 6th postoperative day while she suddenly developed dyspnea. After the pneumoresection and a series of treatments, she recovered from the acute dyspnea. Currently, despite widespread concern regarding VTE, there is no clear data supporting a specific and effective prophylactic strategy.

Airway complications are significant challenges that can affect outcomes following lung transplantation, including issues such as airway rupture, narrowing, and softening [15]. Among these, bronchial stenosis is the most common airway complication after transplantation [16]. Therapeutic interventions for lung transplant recipients experiencing such complications often include bronchoscopic procedures like balloon dilation, forceps manipulation, and cryotherapy for the removal of proliferative necrotic tissue [13]. There are some therapies available for bronchial stenosis, including cryosurgery, local polymyxin E spray, and periodic forceps removal under bronchoscopy. Although the effect of stent implantation is the most direct, it can lead to a variety of complications, and is typically reserved for refractory cases. About 6 months after lung transplantation, our patient developed bronchial stenosis. Despite bronchoscopic treatments, the condition persisted. She then underwent tracheal covered stent implantation and successfully recovered from the bronchial stenosis.

Conclusions

This report details the case of a 26-year-old woman who ingested diquat, underwent bilateral lung transplantation, and was eventually discharged. Although pulmonary fibrosis induced by diquat is rare, it is often fatal. The treatment process for this patient underscores the critical importance of multidisciplinary collaboration. Diquat-induced pulmonary fibrosis progresses rapidly and is irreversible, making early toxin clearance treatments particularly crucial. The optimal timing for lung transplantation may be at around the 28th day, when liver and kidney functions have largely recovered. After surgery, prompt administration of high-grade antibiotics is essential. Clinicians must also be vigilant for the occurrence of venous thromboembolism (VTE) and pulmonary embolism (PE). The complex perioperative complications associated with herbicide poisoning can be effectively managed through a multidisciplinary approach.