“Evaluation of ECG changes and POP (Peradeniya Organophosphorus Poisoning) score as a prognostic marker in organophosphorus compound poisoning subject in a tertiary care center of Central India.”

Organophosphorus compounds (OPCs) are a category of chemicals frequently employed as pesticides, insecticides, and herbicides in agricultural, horticultural, industrial, and home contexts globally.1 OPCs are utilized in warfare as nerve agents and, regrettably, as a means for self-inflicted poisoning. Organophosphorus poisoning, whether deliberate or inadvertent, constitutes a substantial health issue in rural areas of developing nations, resulting in considerable mortality and morbidity, with approximately 200,000 fatalities annually. Research indicates that 80% of hospital admissions for pesticide poisoning result from organophosphate compound (OPC) poisoning, with around 90% of cases classified as suicidal and 8-10% attributed to accidental exposure.2

The prevalence of organophosphate poisoning in India remains ambiguous, with fatalities occurring more frequently in the southern and central regions. OPC poisoning is frequently employed for self-harm owing to its accessibility and availability.3 Suicidal poisoning rates range from 10.3% to 43.8%, with the situation increasing post-COVID-19 owing to mental stress, anxiety, and sadness.4 OPCs are generally esters, amides, or thiol derivatives of phosphoric or phosphonic acids. They function as inhibitors of the acetylcholinesterase enzyme, leading to the buildup of acetylcholine at cholinergic transmission sites, which is responsible for the physiologic symptoms of OPC poisoning. The clinical symptoms of OPC poisoning are separated into muscarinic, nicotinic, and central nervous system effects.5,6

Intoxication with OP substances is often complicated by respiratory failure, aspiration pneumonia, convulsions, CNS depression, and ventricular tachyarrhythmias. OPC poisoning frequently results in cardiac problems that can be severe and sometimes lethal. Timely recognition and assertive treatment of OPC poisoning are frequently critical for survival; therefore, predictive prognostic indicators would assist doctors in categorizing patients according on their risk of decline. A variety of clinical and laboratory markers have been employed to evaluate the degree of poisoning and forecast clinical outcomes in patients admitted with organophosphate compound poisoning.

The Peradeniya Organophosphorus Poisoning Score (POPS) is used for measuring the severity of poisoning based on five cardinal manifestations i.e., pulse rate, respiration rate, pupil size, fasciculations, degree of awareness, and seizure activity. The POP score at the time of presentation to the hospital is beneficial in determining the severity of poisoning and forecasting the length of hospital stay.7

Due to the lack of publications regarding cardiac effects of OPC poisoning, further study is needed to characterize the clinical profile of OPC poisoning, including ECG alterations and electrolyte derangements, and to establish a correlation with morbidity and mortality. This information will help to enhance the management and prognosis of patients with OPC poisoning.

Aims and Objectives

1.            To determine the clinical profile of Organophosphorus Compound poisoning, specifically ECG alterations, to correlate with morbidity and mortality.

2.            To determine the correlation of ECG abnormalities with patient prognosis.

3.            To assess OP poisoning severity using the Peradeniya Organophosphorus Poisoning (POP) score.

4.            To evaluate the subject’s outcome based on ECG alterations and POP score in OP poisoning.

This was a prospective, cross-sectional study conducted over 18 months (10th August 2022 to 10th February 2024) at the Department of Medicine, Netaji Subhash Chandra Bose Medical College & Hospital, Jabalpur, Madhya Pradesh, India. Study participants were patients aged 10 years and above with a history of organophosphorus chemical (OPC) exposure in last 24 hrs and typical clinical signs during the study, who presented at emergency department of study site. Patients with other poisonings, dubious diagnosis, prior treatment with atropine, prior OPC poisoning history, pre-existing cardiac illness, long QT syndrome, or recent drug use lengthening the QT interval were excluded. The estimated sample size was 135 participants and calculation was based on the following parameters: Z = 1.96 at a 95% Confidence Interval, S = Standard Deviation, D = Margin of Error, Relative Error of Mean (d) = 3% = 0.238, S = 1.09. Prior records from the study site were reviewed and patients were randomly selected. Informed consent was obtained from all patients. Data was collected by history-taking via personal interviews with clinical examination by trained medical personnel and investigations documented using a structured schedule (case report form). ECG recordings were made using the Mindray BeneHeart R3 equipment and treatment details were noted. Data was entered in Microsoft Excel sheet. Data analysis was performed using SPSS 26.0 software. Descriptive analyses were employed for variables in groups. Chi-square test, student-t test, and ANOVA test were used to determine relationship among variables. Pearson and Spearman correlation tests were utilized to analyse the parametric and non-parametric variables respectively. p-values of <0.05 were recognized as statistically significant.

RESULTS

Majority of patients were young adults aged 21-30 years (42.2%), with a male predominance (62.2%) and mean age of the patients was 30.8 ± 9.98 years as depicted in table 1.

Table 1: Age and Sex Distribution of Organophosphorus (OP) poisoning Patients

Most cases included the consumption of poison alone (74.8%), followed by poison coupled with alcohol (20%). The most prevalent agent involved was Chlorpyriphos (34.07%) and Monocrotophos 4(2.96) being least. Majority OP poisoning cases were due to intentional exposure (98.5%) and only 2 (1.48%) cases accidental.

Table 2: Time Interval from Exposure to Admission

Table 2 shows that, majority of patients were admitted within 6 hours of exposure (76.29%).

Figure 1: Bar Diagram depicting frequency of clinical features in OP poisoning study subjects

Figure 1 depicts pinpoint pupils (37.04%) as the most prevalent clinical sign identified, followed by profuse secretions (34.07%).

Table 3: Outcome according to severity grading in Peradeniya organophosphorus poisoning (POP) score during hospital stay

Table 3 shows that, majority cases were mild (POP Score 0-3), with 104 survivors and 1 fatality. Moderate cases (POP Score 4-7) had 4 survivors and 1 fatality. Severe cases (POP Score 8-11) reported 13 survivors and a considerably higher number of deaths at 12.

Table 4: Distribution of study participants ECG Changes with Severity of Poisoning according to POP score

Table 4 shows that particular ECG abnormalities were more prominent in specific severity categories. QTc prolongation was the predominant ECG alteration exhibiting diverse survival rates reported in 76 cases, with 53 (70%) in mild cases, 10 (13%) in moderate cases, and 13 (17%) in severe cases. This suggests that QTc prolongation is a common finding across all severity levels. Other ECG changes, such as ST elevation and inverted T waves, were also found across different severity levels with variable frequency. ST elevation and T-wave inversions were noted in 20 and 13 cases, respectively. Severe cases had a greater incidence of significant ECG alterations, such as atrial fibrillation and ventricular tachycardia, both resulting in 100% fatality rate.

Table 5: Association of ECG changes with study participants regarding their duration of hospital stay

Table 5 depicts that ST Elevation, Inverted T, and QTc prolongation exhibit considerable variations in the duration of hospital stays across different severity levels of OP poisoning, signifying that these ECG alterations are crucial indicators of poisoning severity. Low Voltage, Ventricular Tachycardia, Extra Systole, and Atrial Fibrillation exhibit no significant differences, indicating that these alterations are minimally affected by the severity of poisoning concerning the length of hospital stay.

Low Voltage, ST Elevation, Inverted T Waves, Atrial Fibrillation and Ventricular Tachycardia were primarily associated with severe cases, with different periods of hospital stay, showing that significant ECG abnormalities correspond with prolonged hospitalization in fatal situations. QTc Prolongation stands out due to its statistical significance (p-value = 0.005), underscoring its relevance as a significant prognostic indicator in OP poisoning. Hence, patients with QTc prolongation are likely to have more severe outcomes and longer hospital stays. Prolonged PR Interval and Extra Systole were not detected in deceased patients, indicating that these ECG abnormalities might not be as essential in the context of fatal OP poisoning outcomes.

Table 6: Association of ECG Changes with Hospital Stay Duration in Survivors

Table 5 depicts that ST elevation and T wave inversion were strongly associated to poisoning severity (p=0.045 and p=0.030, respectively).  QTc prolongation also showed a high connection with severity (p=0.005).  However, prolonged PR interval and extra systole had no difference substantially between severity levels.  This implies that whereas ST elevation, T wave inversion, and QTc prolongation are strongly associated with the severity of OP poisoning; prolonged PR interval and extra systole had not shown such significant changes.  These findings underscore the relevance of ECG monitoring in OP poisoning cases, notably ST elevation, T wave inversion, and QTc prolongation, which are strong indications of severity and can aid in prognosis.

The present study indicated that OP poisoning was more prevalent among younger persons aged 21-30 years (42.2%) and 31-40 years (31.1%) coinciding with earlier researches like Singh et al.8 and Kamath et al.1 Male predominance (62.2%) observed in present study aligned with the results of Banday et al.9 and Pradeep et al.10 and can be linked with more involvement in agricultural employment, easy accessibility of pesticides and self-harm attempts.

Majority of cases involved the consumption of poison alone (74.8%) and a lesser proportion taking poison together with alcohol (20%). Similarly, study by Paul et al.11 reported high rate of intentional poisonings. Alcohol used possibly increases the poison’s lethality or indicated underlying alcohol dependency.

The clinical signs of OP poisoning in the study included increased salivation, miosis, muscle fasciculations, and respiratory distress, which are indicative of acute cholinergic crisis caused by OP chemicals. These findings correlate with studies by Tripathy et al.5 and Shivaraj et al.12, and underscore the importance of detecting these clinical markers for early diagnosis and management.

ECG alterations are crucial in OP poisoning, offering valuable prognostic information. The study revealed substantial ECG abnormalities, including prolonged QTc intervals, T wave inversion, and low voltage complexes. Prolonged QTc Interval was the most prevalent ECG abnormality and was substantially related with increased mortality and longer hospital stays. Studies by Yurumez et al.13 and Shadnia et al.14 revealed similar findings, underscoring its significance in determining the severity of poisoning. T wave Inversion suggested myocardial involvement and may reflect underlying myocardial ischemia or direct myocardial damage owing to OP poisoning similar to findings of Makwana et al.15 and Tripathy et al.5 Low Voltage Complexes highlights the cardiotoxic effects of OP chemicals and may imply myocardial inflammation or invasion. Taromsari et al.16 reported similar non-specific ST-T changes, including low voltage. The pathophysiology behind these changes could be multifactorial, involving direct myocardial toxicity, autonomic dysfunction, and electrolyte disturbances.

The Peradeniya Organophosphorus Poisoning (POP) score was used to determine the degree of poisoning for timely and appropriate interventions. Higher POP scores were substantially related with increased mortality, the need for mechanical ventilation and longer ICU stays. This finding is consistent with investigations by Kamath et al.1 and Raveendra et al.17

Yurumez et al. (2009) found that QTc prolongation was the most prevalent anomaly, followed by sinus tachycardia and ST-T alterations in OP poisoning patients.13 Present study similarly revealed QTc prolongation as a prominent ECG alteration, indicating its significance in determining the severity of poisoning. Shadnia et al. (2009), investigated the predictive usefulness of the QTc interval in OP poisoning and found that prolonged QTc was related with increased mortality and longer hospital admissions.14 Present study findings corroborate this, underscoring the importance of the QTc interval as a prognostic marker. Paul et al. (2012), found prolonged QTc interval, sinus tachycardia and T wave inversion as prevalent ECG abnormalities in OP poisoning. and also emphasized the possibility for significant cardiac complications, underlining the need for continuous ECG monitoring11, similar to the present study findings. Taromsari et al. (2013), identified sinus tachycardia and non-specific ST-T changes as the most common ECG abnormalities in OP poisoning.16 The present study likewise identified these irregularities, suggesting that such alterations should be considered significant and demand strict monitoring. Tripathy et al. (2018), found that QTc prolongation and hypokalemia were related with increased morbidity and mortality5 in consistent with the present study identifying these factors as essential in predicting patient outcomes. Kamath et al. (2021), reported that higher scores were related with worse outcomes.1 The present study supports the use of the POP score as an effective tool for prognostication.

Effective management entails quick detection of symptoms, supportive care, and the use of specialized antidotes. Atropine counteracts the muscarinic effects of high acetylcholine, and oximes revive blocked acetylcholinesterase. The combination of atropine and oximes is well-established in the management of OP poisoning, as reported by Eddleston et al.2 and Pawar et al.18 Benzodiazepines were used to treat seizures and alleviate anxiety and muscle fasciculations. This technique is backed by research such as those by Dickson et al.19 and McDonough et al.20 Mechanical ventilation was indicated for patients with severe respiratory distress and those with intermediate symptoms. This highlights the need for comprehensive supportive care in handling severe OP poisoning cases, as underlined by Eddleston et al.21

The study underlines the necessity of early detection, ongoing monitoring, risk stratification, and thorough management in OP poisoning cases. Further research is needed to explore the mechanisms of cardiotoxicity in OP poisoning and to develop more effective treatment regimens.

The present study had few limitations. A small sample size of 135 patients may impede the generalizability of the findings. The study was conducted at a single tertiary care hospital, potentially restricting its application to other contexts. The retrospective design may increase recall bias and limit the capacity to prove causality. Additionally, the study primarily focused on the acute phase of OP poisoning and lacked long-term follow-up of patients.

The present study underlines the relevance of early assessment utilizing the POP score and ECG monitoring in predicting outcomes for organophosphorus compound (OPC) poisoning. QTc prolongation is a crucial prognostic sign requiring careful treatment. The high frequency of intentional poisoning needs public health measures addressing socio-economic and mental health issues.  Education on safe handling and regulation of OPCs is vital for preventing accidental poisonings.  Robust methods for early diagnosis and management of cardiac problems can improve outcomes and minimize death in OPC poisoning cases.

Recommendations:

The present study emphasizes the importance of using the POP score and ECG for assessing poisoning severity and cardiotoxicity indicators, developing OPC poisoning protocols, monitoring electrolyte levels, ensuring rapid ICU admission, fostering a multidisciplinary approach, educating the public about OPC risks, and promoting research to understand OPC-induced cardiotoxicity and develop better treatments.

Ethical clearance: Obtained from the Institutional Ethics Committee with letter no.-IEC/2022/8629-18.

Source of Support: Nil

Conflict of Interest: None.

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