Abstract
Background
Organophosphorus poisoning is a major health hazard in developing countries. We conducted a study to compare the Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) scoring system and Peradeniya Organophosphorus Poisoning Scale in predicting the complications, ventilator requirement and mortality in patients of Acute Organophosphorus Poisoning.
Methodology
A prospective observational study was done on 100 patients above 18 years of age, presenting with alleged history of consumption of organophosphorus compounds. The patients were evaluated for the required details to calculate the APACHE II score and Peradeniya Organophosphorus Poisoning Scale and were followed up till discharge or mortality to identify the complications, ventilator requirement and mortality. This data was tabulated using Excel and analyzed using SPSS software to look for correlation between the scores and the outcome.
Results
The mean age of our patients was 33.64 ± 12.99 years. The APACHE II cutoff score for complications, ventilator requirement and mortality was ≥ 7 (sensitivity 94.3%, specificity 96.9%, Area under Receiver Operator Characteristic (ROC) 0.99, p < 0.01), ≥9 (sensitivity 86.7%, specificity 82.4%, Area under ROC 0.91, p < 0.01) and ≥16 (sensitivity 85.7, specificity 96.8%, Area under ROC 0.98, p < 0.01) respectively. Similarly, the Peradeniya Organophosphorus Poisoning Scale cutoff was for complications, ventilator requirement and mortality was ≥ 3 (sensitivity 80%, specificity 92.3%, Area under ROC 0.90, p < 0.01), ≥3 (sensitivity 80%, specificity 75.3%, Area under ROC 0.85, p < 0.01) and ≥7 (sensitivity 85.7%, specificity 97.8%, Area under ROC 0.99, p < 0.01) respectively.
Conclusion
Both APACHE II and POPS demonstrated good predictive performance for adverse outcomes in acute organophosphorus poisoning. Both scores showed excellent discrimination for mortality, with no statistically significant difference between their AUCs.
Keywords: Acute physiology and chronic health evaluation II score, Organophosphorus poisoning, Peradeniya Organophosphorus Poisoning Scale, Pesticide poisoning, Outcomes
Introduction
Pesticide poisoning is one of the most common toxicological emergencies in the developing world. Every year, millions of people are exposed to pesticides due to their occupation and improper storage practices [1]. Suicide is also the most common form of poisoning in the developing world. In underdeveloped countries, especially in Asia, suicide by poisoning is one of the biggest challenges to the healthcare system. In India, incidence of suicidal OP poisoning is noted to be 10 to 43% [2] with a mortality rate upto 20 to 70%.
Many of the patients present to hospitals in rural areas, which are frequently understaffed or underequipped to see hundreds of sick patients. Early detection and categorization of severity is very important for immediate treatment and early referral to higher center for better and aggressive care. There have been many studies into the use of serum cholinesterase levels in OP poisoning and their incidence of neurological syndromes [3, 4]. These studies showed that serum cholinesterase can be used as a diagnostic marker, with minimal role in finding the prognosis [5, 6]. However, it is expensive and not readily available at rural centers where most cases of OP poisoning present. Thus, it is essential to evaluate the value of alternate methods like clinical scoring systems for severity and outcome prediction.
The Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) score is a widely used physiological scoring system for assessing disease severity and predicting outcomes in critically ill patients. Although it was not specifically developed for poisoning, APACHE II has also been evaluated as a prognostic tool in clinical toxicology. A recent study demonstrated its utility in predicting adverse outcomes, including the need for intensive care unit admission, mechanical ventilation, and mortality in acutely poisoned patients [7]. Previous studies have also demonstrated the prognostic value of APACHE II in patients with organophosphorus poisoning [8–10]. The Peradeniya Organophosphorus Poisoning Scale (POPS) is used to assess the severity of OP intoxication [11, 12]. It consists of six parameters like pulse rate, respiratory rate, pupil size, fasciculations, level of consciousness, and seizure activity, taken at initial presentation. Each of these is given a score of 0 to 2 based on the value [12]. Although both APACHE II and the Peradeniya Organophosphorus Poisoning Scale (POPS) have been individually evaluated for prognostication in organophosphorus poisoning, evidence directly comparing their predictive performance within the same patient population remains limited. APACHE II incorporates multiple physiological and clinical parameters, whereas POPS is a simpler, organophosphorus-specific bedside scoring system [12, 13]. A direct comparison may therefore help determine whether the simpler POPS provides prognostic performance comparable to the more comprehensive APACHE II score in the emergency setting. Hence, the present study aimed to compare the prognostic performance of APACHE II and POPS in predicting complications, requirement for mechanical ventilation, and mortality in patients with acute organophosphorus poisoning.
Methodology
Study design and objectives
We conducted a prospective observational study between December 2023 and May 2024 at a tertiary center in Southern India. The objective was to assess the prognostic value of APACHE II scoring system and Peradeniya Organophosphorus Poisoning scale (POPS) in predicting the outcomes in terms of mortality, ventilator requirement and complications in patients presenting with organophosphorus poisoning. The study was approved by the institute ethics committee and was conducted and written according to STROBE guidelines.
Study setting, inclusion and exclusion criteria
At our tertiary care center, we receive around 200 cases of organophosphorus poisoning per year. Patients aged ≥ 18 years, acute organophosphorus poisoning diagnosed based on a history of organophosphorus compound exposure or ingestion obtained from the patient or accompanying bystander, together with clinical features consistent with an organophosphorus cholinergic toxidrome, and provision of informed consent were included for participation in the study. We used consecutive sampling method for inclusion.
Patients were excluded from the study if there was suspected co-ingestion with substances other than organophosphorus compounds, presence of features of atropinization at the time of presentation, alleged history of trauma, sepsis prior to presentation. Patients who left the hospital against medical advice before inpatient admission or before collection of the required blood samples were also excluded.
Sample size calculation
Sample size calculation: The sample size was calculated using the formula n = Z2p(1 – p) / d2, where p was the expected mortality following acute organophosphorus poisoning. Based on a previous study by Raveendra et al., which reported a mortality of 16%, p was taken as 0.16 [14]. At a 95% confidence level (Z = 1.96) and an absolute precision of 7.5%, the calculated sample size was approximately 92 patients. Considering feasibility and to ensure an adequate sample, 100 patients were included in the study.
Study methods and data collection
All patients were clinically evaluated on arrival with detailed history and thorough clinical examination. About 10 cc of blood was drawn from the patients and tested for complete blood count, renal function tests, liver function tests, arterial blood gases and serum electrolytes. A semi-structured questionnaire was used to record all the data. The reports of investigations were followed up and added to the questionnaire after admission. The data was tabulated using Microsoft Excel.
APACHE II score
The APACHE II score was calculated at the time of initial presentation to the emergency department. The score comprised three components: the Acute Physiology Score, age points, and chronic health points. The Acute Physiology Score included 12 physiological variables: body temperature, mean arterial pressure, heart rate, respiratory rate, oxygenation, arterial pH, serum sodium, serum potassium, serum creatinine, hematocrit, total white blood cell count, and Glasgow Coma Scale. Each variable was assigned points according to the APACHE II scoring system, and these were combined with the age and chronic health points to obtain the total APACHE II score. Higher scores indicated greater severity of illness [15].
Peradeniya Organophosphorus Poisoning Scale (POPS)
The Peradeniya Organophosphorus Poisoning Scale (POPS) was calculated at the time of initial presentation to the emergency department. The scale consists of six clinical parameters: pupil size, respiratory rate, heart rate, fasciculations, level of consciousness, and seizures. Each parameter was scored according to the original POPS criteria, with a total score ranging from 0 to 11. Based on the total score, the severity of poisoning was classified as mild (0–3), moderate (4–7), or severe (8–11) [12].
Plasma cholinesterase levels were measured as part of the biochemical evaluation. Plasma cholinesterase was measured on Day 1 and subsequently on Day 5. The Day 1 plasma cholinesterase level was used in the initial assessment of poisoning severity.
All patients were treated according to the standard line of management of OP poisoning which included decontamination, blockade of muscarinic hyperactivity with atropine or glycopyrrolate, reversal of cholinesterase inhibition with oxime nucleophiles (pralidoxime), and correction of metabolic abnormalities. In unconscious patients, the adequate airway was maintained by endotracheal intubation, and ventilatory support was given, whenever indicated. All patients were monitored till death/ discharge. The treatment protocol was determined by the treating team and not altered for the study.
Data analysis
Qualitative data was represented in the form of frequency and percentage. Association between qualitative variables was assessed by Chi-Square test. Quantitative data was represented using Mean ± SD. Analysis of Quantitative data between the two groups was done using unpaired t-test if data passed ‘Normality test’ and by Mann-Whitney Test if data failed ‘Normality test’. ROC analysis was done to find the cutoff score above which complications, ventilator requirement and mortality could be predicted. The optimal cut-off values were determined using the Youden index. For mortality prediction, the areas under the ROC curves (AUCs) of APACHE II and POPS were compared using DeLong’s test for paired correlated ROC curves. A p-value < 0.05 was taken as level of significance. Results were graphically represented where deemed necessary. SPSS Version 26.0 was used for most analysis and Microsoft Excel 2021 for graphical representation.
Results
We received around 124 patients of organophosphorus poisoning during the study period, of whom, 24 were excluded, 7 patients with signs of atropinization, 4 patients were in sepsis, 3 patients didn’t consent to be part of the study and 10 left the hospital against medical advice before drawing the required blood samples.
We recruited 100 study subjects with a mean age of 33.64 ± 12.99 years with 76% cases 40 years or below. The patient flow diagram is represented in Fig. 1. There was a male predominance with 59% males to 41% females. Most common compound consumed was found to be Chlorpyrifos (39%) followed by tribufos (31%), diazinon and malathion (16 and 12%). Vomiting (82%) was the most common symptom followed by muscle weakness (31%) and convulsions (27%). Respiratory distress was seen in 25% cases. Ventilator requirement was seen among 15% with a mortality of 7%. The baseline characteristics of the study subjects are elaborated in Table 1. The severity status of all patients was assessed with APACHE II Scale and Peradeniya Organophosphorus Poisoning Scale and elaborated in Table 2.
Fig. 1.
Patient flow diagram of the study. *Patients who left the hospital against medical advice before drawing the blood sample or inpatient admission
Table 1.
Baseline clinical characteristics of study subjects at presentation
| Variable | N | % |
|---|---|---|
| Age group | ||
| </=20 | 17 | 17.00% |
| 21–40 | 59 | 59.00% |
| 41–60 | 24 | 24.00% |
| >60 | 0 | 0.00% |
| Sex | ||
| Female | 41 | 41.00% |
| Male | 59 | 59.00% |
| Compound | ||
| Chlorpyrifos | 39 | 39.00% |
| Tribufos | 31 | 31.00% |
| Diazinon | 16 | 16.00% |
| Malathion | 12 | 12.00% |
| Parathion | 2 | 2.00% |
| Symptoms | ||
| Muscle weakness | 31 | 31.00% |
| Convulsions | 27 | 27.00% |
| Respiratory Distress | 25 | 25.00% |
| Fasciculation | 13 | 13.00% |
| Lacrimation | 12 | 12.00% |
| Diarrhea | 7 | 7.00% |
| Vomiting | 82 | 82.00% |
| Examination Findings | ||
| Fever | 36 | 36.00% |
| Tachycardia | 27 | 27.00% |
| Raised BP | 6 | 6.00% |
| Tachypnea | 25 | 25.00% |
| Constricted Pupil | 37 | 37.00% |
N indicates the number of subjects
Table 2.
Complications, severity, ventilator requirement and mortality of the study subjects during the course of the study
| Variable | N | % |
|---|---|---|
| Complications | ||
| Kidney Injury | 10 | 10.00% |
| Death | 7 | 7.00% |
| Heart Failure | 5 | 5.00% |
| Depression | 5 | 5.00% |
| Sepsis | 4 | 4.00% |
| Pancreatitis | 3 | 3.00% |
| Stroke | 2 | 2.00% |
| Ataxia | 2 | 2.00% |
| Cardiomyopathy | 2 | 2.00% |
| Polyneuropathy | 1 | 1.00% |
| None | 65 | 65.00% |
| Severity of Poisoning (Proudfoot Classification) | ||
| Mild | 59 | 59.00% |
| Moderate | 14 | 14.00% |
| Severe | 27 | 27.00% |
| Ventilator Requirement | ||
| No | 85 | 85.00% |
| Yes | 15 | 15.00% |
| Mortality | ||
| No | 93 | 93.00% |
| Yes | 7 | 7.00% |
| Total | 100 | 100.00% |
N indicates the number of subjects
APACHE II score and outcome
There was a significant association between APACHE II score and complications, ventilator support and mortality. Mean APACHE II score in cases with and without complications was 13.4 and 4.12 respectively (p < 0.01). The mean score in cases with and without ventilator requirement was 14.8 and 6.06 respectively (p < 0.01). Mean APACHE II score in cases who did not survive was 18.71 as compared to 6.52 in cases who survived (p < 0.01).
On ROC analysis, APACHE II score showed a definite correlation with complications, ventilator requirement and mortality. APACHE II score of ≥ 7 predicted complications with a sensitivity of 94.3% and specificity of 96.9% with area under ROC of 0.99 (0.99–1.00) and p value of <0.01. Similarly, a score of ≥ 9 predicted ventilator requirement with sensitivity and specificity of 86.7% and 82.4% respectively with area under ROC of 0.91 (0.86–0.97) and p value of <0.01. APACHE II score ≥ 16 predicted mortality with sensitivity and specificity of 85.7% and 96.8% respectively with area under ROC of 0.98 (0.95–1.00) and p value of <0.01. (The ROC analysis and graphs are detailed in Table 3 and Figs. 2a, 2b and 2c).
Table 3.
ROC analysis of APACHE II cutoff score to look for sensitivity and specificity in predicting complications, ventilator requirement and mortality
| Test Result Variable(s) | APACHE II Cut-off value | Sensitivity (%) | Specificity (%) | Area | SE | p- value | Asymptotic 95% Confidence Interval | |
|---|---|---|---|---|---|---|---|---|
| Lower Bound | Upper Bound | |||||||
| Complications | 7 | 94.3% | 96.9% | 0.995 | 0.004 | <0.01* | 0.987 | 1 |
| Ventilator requirement | 9 | 86.7% | 82.4% | 0.914 | 0.029 | <0.01* | 0.857 | 0.971 |
| Mortality | 16 | 85.7% | 96.8% | 0.977 | 0.014 | <0.01* | 0.949 | 1 |
* p < 0.05 was considered statistically significant
Fig. 2.
ROC graphs of APACHE II and POPS scores in depicting the sensitivity and specificity of the scores in identifying severity of OP poisoning. Graphs showing (a) complications, (b) ventilator requirement and (c) mortality with APACHE II score. Graphs showing (d) complications, (e) ventilator requirement and (f) mortality with POPS score
Peradeniya Organophosphorus Poisoning Scale and outcome
There was also a significant association between the severity of OP poisoning as assessed by POP score and complications, ventilator requirement and mortality. Complication rate in cases of mild, moderate and severe category of POP score was 10.4, 80 and 100% respectively (p < 0.01). Similarly, ventilator requirement in cases of mild, moderate and severe category of POP score was 4.5, 24 and 75% respectively (p < 0.01). Mortality rate in cases of mild, moderate and severe category of POP score was 0, 4 and 75% respectively (p < 0.01).
Similar to APACHE II score, on ROC analysis, POP scale also showed a correlation with complications, ventilator requirement and mortality. POPS score of ≥ 3 predicted complications with a sensitivity and specificity of 80% and 92.3% respectively with area under ROC of 0.90 (0.83–0.97) and p value of <0.01. A score of ≥ 3 also predicted ventilator requirement with sensitivity and specificity of 80% and 75.3% respectively with area under ROC of0.85 (0.75–0.94) and p value of <0.01. POPS score ≥ 7 predicted mortality with sensitivity and specificity of 85.7% and 97.8% respectively with area under ROC of 0.99 (0.98–1.00) and p value of <0.01. (The ROC analysis and graphs are detailed in Table 4 and Figs. 2d, 2e and 2f). Pairwise comparison of the ROC curves for mortality using DeLong’s test (Table 5) showed no statistically significant difference in discriminatory performance between POPS and APACHE II (AUC 0.995 vs. 0.977, respectively; difference in AUC, 0.0175; 95% CI, −0.0075 to 0.0425; Z = 1.37; p = 0.17).
Table 4.
ROC analysis of POPS cutoff score to look for sensitivity and specificity in predicting complications, ventilator requirement and mortality
| Test Result Variable(s) | POPS Cut-off value | Sensitivity (%) | Specificity (%) | Area | SE | p- value | Asymptotic 95% Confidence Interval | |
|---|---|---|---|---|---|---|---|---|
| Lower Bound | Upper Bound | |||||||
| Complications | 3 | 80% | 92.30% | 0.896 | 0.036 | <0.01* | 0.825 | 0.967 |
| Ventilator requirement | 3 | 80% | 75.30% | 0.848 | 0.048 | <0.01* | 0.753 | 0.943 |
| Mortality | 7 | 85.70% | 97.80% | 0.995 | 0.006 | <0.01* | 0.982 | 1 |
Abbreviations: ROC, receiver operating characteristic; AUC, area under the ROC curve; CI, confidence interval; SE, standard error; POPS, Peradeniya Organophosphorus Poisoning Scale. Statistical test: ROC curve analysis. p < 0.05 was considered statistically significant
Table 5.
Pairwise comparison of ROC curves of POPS and APACHE II for prediction of mortality using Delong’s test
| POP AUC | APACHE II AUC | Difference in AUC | 95%CI of difference | DeLong Z statistic | p value |
|---|---|---|---|---|---|
| 0.995 | 0.977 | 0.0175 | −0.00075 to 0.0425 | 1.37 | 0.17 |
Abbreviations: AUC, area under the receiver operating characteristic curve; CI, confidence interval; APACHE II, Acute Physiology, Age and Chronic Health Evaluation II; POPS, Peradeniya Organophosphorus Poisoning Scale. Statistical test: DeLong’s test for paired correlated ROC curves. p < 0.05 was considered statistically significant
Discussion
Organophosphates are among the frequently used pesticides and can result in serious morbidity and mortality. Our present study aimed to compare the APACHE II scoring system and Peradeniya Organophosphorus Poisoning (POP) Scale in predicting the complications, ventilator requirement and mortality in Acute Organophosphorus Poisoning.
Mean age of the study cases was 33.64 years with 76% cases were 40 years or below, with a male predominance. This is similar to a study by Raddi et al. [16] which showed majority of the patients in the age group of 21–30 years with a male predominance (58.75%). Other studies by Chintale et al. [17] and Gagarin et al. [18] showed a similar age and sex predominance. The patients of this age group are suspected to be stressful, emotionally weak and vulnerable to conflicts. Male patients are more prone to exposure to organophosphorus poisoning accidentally by occupation or by intention.
Chintale et al. [17] observed mild, moderate and severe poisoning in 50.73%, 22.79% and 18.38% respectively while mortality rate was 3.67%. Gagarin et al. [18] observed 40% cases with severe OP poisoning and mortality rate of 25%. In a study by Peter et al. [19], mechanical ventilation was required in 65.7% of the patients and the overall mortality rate was 13.1%. The mortality rate in the Jamal et al. [20] study was 9.7%. The variation could be explained by the severity of the poisoning and the variation in treatment protocols.
A significant association was observed between severity of OP poisoning as assessed by APACHE II score and associated complications, ventilator requirement & mortality. The difference in APACHE II score was statistically significant among the survivors (5.70 ± 3.01) and non survivors (19.57 ± 3.93) with p < 0.01 in a study by Adalarasan et al. [21]. Kim et al. [22] observed the sensitivity, specificity, and accuracy of APACHE II score in predicting mortality as 65.5%, 68.6%, and 67.9%. The study concluded that APACHE II can predict early in-hospital mortality of patients of OP poisoning. In the study by Peter et al. [19], overall AUC for mortality for APACHE-II was 0.77 (p < 0.01). In Jamal et al. [20] study, APACHE II score had a fair value for predicting death risk as indicated by ROC curve of 0.67 (CI. 0.512–0.833). Wu et al. [23] study observed the AUC for APACHE II for predicting mortality as 0.89 (p < 0.01).
POP scale also showed a significant association with complications, ventilator requirement and mortality. POP score of > 3 indicated a higher complication rate and ventilator requirement, while POPS > 7 indicated a higher mortality. Kamath et al. [24] concluded that patients in severe grade (22.1%) of POP scale needed ventilatory support (46.1%) & the mortality (30.8%) and amount of atropine (631.8 mg) was higher when compared to the patients with mild to moderate grade. Other studies [13, 25] conducted in similar patients also concluded that POP score at presentation is an effective tool to measure the severity of OP poisoning. In the present study, both POPS and APACHE II demonstrated excellent discriminatory ability for mortality. Although the AUC was numerically higher for POPS than for APACHE II (0.995 vs. 0.977), direct pairwise comparison using DeLong’s test demonstrated no statistically significant difference between the two scoring systems (p = 0.17). These findings suggest that both scoring systems had comparable discriminatory performance for mortality in this cohort.
Respiratory compromise is an important determinant of severity in acute poisoning. In organophosphorus poisoning, bronchorrhea, bronchospasm, respiratory muscle weakness, central respiratory depression, and aspiration may contribute to hypoxemia and the need for ventilatory support. Oxygenation is also incorporated as a physiological variable in the APACHE II score. Previous studies in acutely poisoned patients have highlighted the importance of oxygen saturation and other physiological parameters in predicting the need for endotracheal intubation and mechanical ventilation [26, 27].
Strengths of the study
The present study provides a prospective head-to-head comparison of APACHE II and POPS within the same patient cohort for predicting complications, mechanical ventilation requirement, and mortality in acute organophosphorus poisoning. Our study population was well-representative of the general population and had no loss to follow-up from the emergency department. This resulted in accurate measurement of the scoring systems and correlation to final outcome in the hospital, whether discharge or mortality.
Limitations
This study has several limitations. First, it was a single-center study with a relatively small sample size of 100 patients, which may limit the generalizability of the findings. Second, the number of mortality events was small, limiting the ability to perform reliable multivariable adjustment for mortality. Third, the estimated dose of organophosphorus compound consumed and the time interval between exposure and hospital presentation were not recorded; therefore, their potential confounding effects on clinical outcomes could not be adjusted for. Although age was recorded, the small number of mortality events limited reliable multivariable adjustment. Larger multicenter studies with adequate adjustment for potential confounding factors are required to validate these findings.
Conclusion
The study revealed significant correlation between complications, ventilator requirement and mortality in Acute Organophosphorus Poisoning and APACHE II scoring system and Peradeniya Organophosphorus Poisoning (POP) Scale. Both APACHE II and POPS demonstrated excellent discriminatory ability for predicting mortality in patients with acute organophosphorus poisoning. Pairwise comparison showed no statistically significant difference between the two scoring systems. POPS, being relatively simpler to assess, may provide a practical tool for early risk stratification; however, these findings should be validated in larger multicenter studies.
Acknowledgements
The authors acknowledge the help of Mr. Prasad, Biostatistician at Yashoda Hospital, Secunderabad for his help in the analysis of the study.
Author contributions
Authors GGT, SKC, SRG and VK conceptualized the study. GGT, SPS and PB conducted the study under the supervision of the other authors. GGT, SKC and VK wrote the manuscript with input from other authors. All authors reviewed the manuscript.
Funding
Not applicable.
Data availability
All the collected data related to the study is available with the corresponding author and can be shared on request.
Declarations
Ethical approval
The study was approved by the Research ethics committee, Yashoda Hospital, Secunderabad (Ethics approval reference number: DNBT/20/2023). All patients were included in the study after informed consent. All procedures were conducted according to the Good Clinical Practice guidelines and Declaration of Helsinki. All personal identifiers were removed and replaced with study identification numbers before statistical analysis.
Previous submissions
None.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All the collected data related to the study is available with the corresponding author and can be shared on request.