European Journal of Cardiovascular Medicine

Paraquat is a widely employed herbicide known for its effectiveness in agricultural weed management. However, its use poses significant health hazards due to its extreme toxicity when ingested, with fatality rates ranging from 60% to 90% in severe cases^{1, 2}. The chemical acts as a pro-oxidant, triggering oxidative stress that results in damage to cellular structures and functions. This toxicity is most evident in vital organs such as the lungs, kidneys, and liver, often leading to multi-organ dysfunction and failure^{3, 4}.

Unlike many toxic substances, paraquat lacks an effective antidote, creating challenges in its clinical management. Its rapid systemic absorption following ingestion accelerates the onset of severe complications, necessitating urgent and specialized interventions⁵. The pathophysiological effects are primarily mediated by the production of reactive oxygen species (ROS), which disrupt normal cellular processes. The lungs are especially vulnerable, as paraquat accumulates in alveolar cells, causing inflammation and progressive fibrosis, ultimately impairing respiratory function⁶.

The clinical presentation of paraquat poisoning can vary widely depending on the dose and time to treatment. Symptoms often begin with gastrointestinal distress, including nausea and vomiting, and can quickly progress to systemic effects such as acute renal injury, respiratory failure, and circulatory collapse. Without prompt medical intervention, severe cases frequently result in death^{7, 8}.

In response to the high mortality associated with paraquat ingestion, there has been considerable research into therapeutic approaches that can mitigate its toxic effects. Charcoal Hemoperfusion (CHP) has emerged as a potentially effective intervention, particularly when administered early. This treatment works by filtering paraquat from the bloodstream, reducing systemic exposure, and potentially limiting organ damage. Studies, such as those by Xiao et al. (2020), have demonstrated improved survival rates in patients receiving CHP within the first 12 hours of ingestion⁹.

Adjunctive therapies aimed at managing oxidative stress, such as the use of antioxidants, have also shown promise. Antioxidants like vitamins C and E have been studied for their ability to neutralize free radicals and reduce oxidative damage, offering a supportive role in paraquat poisoning management¹⁰. Research by Hong et al. (2003) highlighted the protective effects of these antioxidants in reducing lung injury in experimental models¹¹.

Timely diagnosis and intervention are critical in altering the prognosis of paraquat poisoning. Delays in treatment are strongly correlated with poorer outcomes, underscoring the need for heightened awareness and readiness in clinical settings. The integration of advanced treatment modalities such as CHP and supportive antioxidant therapy into routine care has the potential to improve survival outcomes¹², ¹³.

This case series seeks to evaluate the survival benefits of early CHP and compare its effectiveness to standard treatment protocols. Since there are no antidotes for treating Paraquat poisoning the standard treatment with CHP and Hemodialysis were introduced to treat the patients but the factors affecting this treatment are duration of presentation after consumption and initiation of treatment.

Hence this study has an impact of vision on these above factors for further research and evaluation.

AIM OF THE STUDY

• To assess the benefit of outcome in patients who receive Early Charcoal Hemoperfusion along with standard treatment comparing to only standard treatment.

Objective of the study

Primary Objectives:

To evaluate the effectiveness of early extracorporeal clearance technique with Charcoal Hemoperfusion, compared to standard care alone in improving survival outcomes for patients with paraquat poisoning.

Secondary Objectives:

1. To analyze the impact of the amount of toxin ingested and time to presentation, on treatment outcomes and survival.
2. To assess the complications associated with Paraquat poisonin

This Observational- Cross sectional study was conducted Emergency Medicine department of KLE’s Dr PrabhakarKore Hospital & MRC. Duration of study was 1 year (November 2023 - November 2024)

Sample Size: 12 patients

Sampling technique: Total number of patients registered during study period are being included in the study.

Inclusion Criteria:

1)  Oral Paraquat poisoning

2) Age group of more than 18 years

Exclusion Criteria:

1)     Any patient with comorbid diseases are excluded.

Study protocol:

• Patients presenting with Paraquat poisoning to ED were included in the study taking into consideration the inclusion and exclusion criteria

The following data were collected:

1. Demographical factors (age, sex and past medical/surgical history)
2. Time of ingestion of Paraquat compound and Time of presentation to hospital after Ingestion of Paraquat compound
3. Amount of Paraquat compound ingested
4. The type of Incident - Homicidal/suicidal or accidental
5. Symptoms at the time of presentation
6. Treatment details – Hemoperfusion with Standard treatment and Standard treatment alone; Hemodialysis performed or not.
7. The time of initiation of Charcoal Hemoperfusion and number of sessions undergone
8. Complications recorded
9. Death or survival

Primary Assessment was performed- Airway, Breathing, Circulation, Disability and Exposure

Secondary Assessment –Signs and Symptoms, Allergy, Medications, Past Medical History, Last Meal time and Events were Assessed.

All data was entered and analyzed.

Data collection procedure:

1. All Paraquat patients presenting to the clinic or admitted to the hospital during the study period was screened for eligibility based on inclusion and exclusion criteria.
2. Informed consent was obtained from all participants before enrollment.

3. The following data were collected:
4. Demographical factors (age, sex and past medical/surgical history)
5. Time of ingestion of Paraquat compound and Time of presentation to hospital after Ingestion of Paraquat compound
6. Amount of Paraquat compound ingested
7. The type of Incident - Homicidal/suicidal or accidental
8. Symptoms at the time of presentation
9. Treatment details – Hemoperfusion with Standard treatment and Standard treatment alone; Hemodialysis performed or not.
10. The time of initiation of Charcoal Hemoperfusion and number of sessions undergone
11. Complications recorded
12. Death or survival

4. Primary Assessment was performed- Airway, Breathing, Circulation, Disability and Exposure
5. Secondary Assessment –Signs and Symptoms, Allergy, Medications, Past Medical History, Last Meal time and Events were Assessed
6. Collected data was stored securely in an encrypted electronic database accessible only to authorized study personnel.

DEMOGRAPHIC RESULTS

The study included 5 female (42%) and                                        The study included 2 patients between

 7 male (58%).Statistically and clinically                                     18-25 years of age (16.66%), 7 patients between  

not significant                                                                             25-35 year age (58.3%), 2 patients between 35-35                                         

(16.66%), and 1 patient above 45 years of age group

                                                                                                       (8.3%). Statistically and clinically not significant.

No patients had any significant past medical or surgical history or any comorbidities.

2 patients presented within 6 hours in which one survived.4 patients presented Within 12 hours (2 survived and 2 died).2 patients presented between 12-24 hours In which both of them died.4 patients presented after 24 hours 3 died and 1 survived Patients who arrived within 12 hours survival is 50 % and it is statistically and Clinically significant. Those who have come after 12 hours survival rate is less than 25% Which is also statistically and clinically significant.

1 Patient presented with consumption of less than 5 ml and survived. More than 5-15 ml 80 % mortality,16-30 ml 50 % mortality, more than 30 ml  75% mortality. It is statistically and clinically significant.

THE TYPE OF INCIDENT

All 12 patients the type of incident was suicidal in nature. Clinically and statistically Not significant.

In our Case series 10 out of 12 patients presented with vomiting (83.3%),8 out of 12 patients  Presented with throat pain (66.7%),abdominal pain 4/12 cases (33.3%),4 out of 12 cases(33.3%) Presented with respiratory symptoms.

Out of 12 patients who presented 6 patients underwent Hemoperfusion and 3 patients Underwent Hemodialysis and 1 patient underwent both Hemoperfusion and Hemodialysis.

If CHP was initiated within 6 hours of presentation ¾ th of the patients survived (75%)

If CHP was initiated  within 6 - 12 hours 25 % survived.Ifinittated after 12 hours 50 % survived

2 patients died who underwent only 1 session of CHP.2 died who underwent 2 session of CHP  1 patient survived who underwent 1 session of CHP and 2 patients who underwent 4 sessions Survived.

Most common complications seen were ARDS 5/12 cases (41.7%),Acute kidney injury 5 out of 12 cases (41.7%),Multiorgan Dysfunction syndrome 2/12 cases (16.7%),oral ulcers 3 out of 12 cases (25%)

Lung fibrosis 3 out of 12 cases (25 %)

8 out of 12 patients underwent CHP and only 3 survived (37.7)

4 patients underwent Hemodilaysis in which 1 survived (25%)

Out of 12 patients 4 survived and 8 patients died.

Out of 12 patients 8 patients underwent CHP and 3 survived. (37.5%) 4 patients only received only standard treatment in which only 1 survived (25%)

The present study aimed to evaluate the survival benefits of early Charcoal Hemoperfusion (CHP) compared to standard treatments in patients with Paraquat poisoning.

Paraquat poisoning remains a significant clinical challenge due to its high mortality or morbidity rate and lack of an effective antidote. Xiao et al. (2020) demonstrated the importance of early CHP in mitigating pulmonary fibrosis and improving survival in mild to moderate Paraquat poisoning cases. Their findings align with the current study, which observed that early CHP initiation led to improved outcomes. Xiao et al. emphasized the need for intervention within 12 hours post-ingestion, a critical factor also supported by our findings.⁶

Similarly, Wang et al. (2017) reinforced the importance of timing in CHP application, demonstrating that earlier intervention significantly reduces paraquat plasma levels and oxidative damage. Our study corroborates these findings, particularly in cases where CHP was initiated promptly, leading to fewer complications and better survival rates. However, unlike Wang et al., our study included detailed patient-specific factors such as time of presentation and toxin dosage, providing a more comprehensive understanding of outcome determinants.⁵

The protective role of antioxidants in paraquat toxicity, as highlighted by Hong et al. (2003) and Talas et al. (2012), was partially reflected in our observations. Both studies showed that vitamins C and E mitigate oxidative damage in experimental models. Although antioxidant therapy was not a primary focus of our study, the integration of supportive treatments, including antioxidants, may have contributed to improved patient outcomes in conjunction with CHP.^7,8

Dinis-Oliveira et al. (2006) reported a rare survival case of paraquat poisoning following aggressive multidisciplinary treatment. Their findings underscore the necessity of prompt diagnosis and comprehensive care. Our study builds on this by systematically analyzing the impact of early CHP alongside standard treatment protocols, offering additional evidence on survival benefits.³

Merits of the Study

1. Focus on Timing and Dosage: Unlike many previous studies, our research emphasized the critical influence of time to presentation and amount of toxin ingested. This nuanced approach allowed us to identify key factors that significantly impact survival.
2. Comprehensive Data Collection: The inclusion of demographic details, clinical presentation, and treatment specifics adds depth to the analysis, enabling a thorough understanding of paraquat poisoning outcomes.
3. Integration of CHP and Standard Treatments: This study uniquely evaluates the combined efficacy of early CHP with standard treatments, providing novel insights into optimizing clinical management.
4. Case Series Approach: The case series design allowed for detailed documentation of individual patient trajectories, highlighting variations in response to treatment.

Demerits of the Study

1. Small Sample Size: The study was limited to 12 patients, reducing the generalizability of findings. Larger cohorts are necessary to validate the observed trends.
2. Observational Design: As a non-randomized, observational study, it is subject to biases, including selection bias and variability in treatment practices.
3. Limited Follow-Up: The study focused on immediate outcomes, with limited exploration of long-term complications such as chronic pulmonary fibrosis or renal dysfunction.
4. Lack of Comparative Antioxidant Analysis: Although antioxidants were part of the treatment protocol, their specific contribution was not isolated or systematically studied, unlike in studies by Hong et al. and Talas et al.
5. Variability in Timing: Differences in the time of presentation and treatment initiation among patients introduced variability, complicating direct comparisons of outcomes.

Implications for Clinical Practice and Future Research

The findings of this study have important implications for managing paraquat poisoning:

1. Emphasis on Early Intervention: The results reinforce the critical need for early recognition and initiation of CHP, ideally within 12 hours of ingestion, to improve survival outcomes.
2. Multidisciplinary Approach: The integration of CHP with supportive treatments, including gastrointestinal decontamination and antioxidant therapy, highlights the value of a comprehensive care strategy.
3. Protocol Development: The study underscores the importance of developing standardized protocols for paraquat poisoning management, emphasizing timing and patient-specific factors.
4. Need for Larger Studies: Future research should involve larger, randomized controlled trials to validate the survival benefits of early CHP and explore its efficacy across different severity levels of poisoning.
5. Focus on Antioxidants: Given the promising findings of Hong et al. (2003) and Talas et al. (2012), future studies should systematically evaluate the role of antioxidants alongside CHP, including their impact on long-term outcomes.
6. Addressing Limitations: Research addressing the limitations of this study, such as small sample sizes and observational biases, will be crucial for advancing clinical knowledge.
7. Exploration of Alternatives: Investigating newer treatment modalities, such as targeted antioxidant therapies or novel extracorporeal techniques, may provide additional avenues for improving outcomes in Paraquat poisoning.

This study contributes valuable insights to the management of Paraquat poisoning, particularly emphasizing the role of early presentation to Emergency Department and early CHP treatment in improving survival outcomes. While the findings align with existing literature, the inclusion of patient-specific factors and the integration of CHP with standard treatments offer a unique perspectivefor survival benefit.

Despite of limitations, this study lays the groundwork for future research in aiming to refine treatment protocols and enhance patient care in Paraquat poisoning cases.

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