Prognostic significance of poison‑related factors and consumption patterns in acute aluminum phosphide poisoning

Abstract

OBJECTIVES: The prognosis of acute aluminum phosphide poisoning is usually based on toxidrome features, with little focus on poison related factors. We aimed to study the prognostic significance of poison related factors, consumption patterns, and time delays to treatment.

METHODS: We performed a prospective cohort study in an academic hospital in North India in patients aged ≥ 13 with aluminum phosphide poisoning from July 2019 to December 2020. During data collection, a particular emphasis was made on the poison formulation, the ingested dose, the reconstitution of poison, vomiting, and time intervals to initiate various treatments. The primary outcome was inhospital mortality.

RESULTS: Fifty eight patients were enrolled (median age, 32 years; 37 males). The mean dose of the ingested poison was 6.56 (±5.42) g. The predominant formulation of poison was pellet (n = 41), followed by powder (n = 16). Twenty patients performed reconstitution of poison before consumption, and 13 stirred the poison while reconstituting. All patients but three developed vomiting after consumption. Inhospital mortality (n = 23, 39%) was significantly high with a higher ingested dose (P < 0.001), nonstirred reconstitution before consumption (P = 0.042), fewer vomiting episodes (P = 0.010), a delay in detection of the victim by someone (P = 0.001), and delayed initiation of intravenous fluids (P = 0.043). The secondary outcomes (shock and requirement of vasopressor or ventilation) remained unaffected by the stirring in the reconstitution group.

CONCLUSIONS: Poison related factors and time intervals determine early risk stratification at admission in aluminum phosphide poisoning.

Introduction

Aluminum phosphide is widely used as a fumigant pesticide against insects and rodents to preserve stored grains in the agricultural economies of low and middle income countries (LMICs). Because of its easy availability, it remains a common agent for acute poisoning in these communities. Because of rapid systemic toxicity and the unavailability of a specific antidote, acute aluminum phosphide poisoning is associated with a mortality rate of 40%–80%.[1 5] The predominant manifestation of severe toxidrome is cardiotoxicity or circulatory failure.[6 8] Early recognition of systemic toxicity and immediate high quality supportive care remain the mainstay of management.

The toxic dose is approximately 150–500 mg for an average built adult.[9 11] The toxicity is primarily mediated by phosphine gas released from aluminum phosphide. Consumption of poison from a freshly opened container causes high toxicity because “exposed” forms lose their potency from reaction with atmospheric moisture with subsequent phosphine release.[10] Conversion into powder formulation usually results in lesser toxicity than the tablet or pellet form.

The prognosis of acute aluminum phosphide poisoning is usually based on clinical and laboratory features such as severe metabolic acidosis, refractory shock, cardiorespiratory failure requiring mechanical ventilation, or the presence of stupor or coma (low Glasgow Coma Scale [GCS]).[12 20] These toxidrome features are considered accurate and reproducible in predicting mortality. Furthermore, scoring tools based on these variables, such as the PGI score (representing low pH, low GCS score, and impaired or low systolic blood pressure), Acute Physiologic Assessment and Chronic Health Evaluation II score, or the Sequential Organ Failure Assessment score have demonstrated excellent predictive abilities.[21 24] In contrast, the influence of poison related factors on prognosis is less well studied. They are often the only available factors in primary health care settings in LMICs. Moreover, the baseline parameters determine rapid triaging and identifying patients who need priority for intensive care unit admission. Therefore, this study aimed to evaluate the effect of poison related factors on prognosis in aluminum phosphide poisoning.

Material and Methods

Study design

This is a prospective cohort study conducted at the medical emergency department (ED) of a tertiary care hospital and an apex referral center in North India from July 2019 to December 2020. About 100–120 patients are admitted daily to the ED of this 1948 bedded hospital from a large population of North India.[25,26] The age criterion for admission to our adult medical emergency is ≥13 years. The institutional ethics committee approved the study (No.: INT/IEC/2019/002071, date October 10, 2019). We obtained written informed consent from all study patients or legally authorized representatives. There was no funding source for the study.

Study participants

All patients aged ≥13 years diagnosed with acute aluminum phosphide poisoning based on a history of compound ingestion with the presence of clinical features consistent with the toxidrome were enrolled. Patients who had consumed multiple compounds and those with a history of doubtful consumption of aluminum phosphide were excluded from the study. No case was excluded after recruitment.

Data collection

Sociodemographic details, route of exposure, the intention of poisoning, and baseline clinical parameters were recorded. A particular emphasis was made on the poison formulation and the ingested dose, reconstitution of poison before ingestion, vomiting episodes, and time delay in contact with the health care facility and the initiation of primary care. The data regarding poison related factors and various time intervals were collected from the patients or the primary caregivers if the patients were unfit to answer. Basic laboratory investigations included blood gas analysis, lactate, complete blood count, serum electrolytes, renal and liver function tests, international normalized ratio, electrocardiography, and chest X ray.

The management of the study patients was according to the standard intuitional protocol [Figure 1]. Gastric lavage with 0.9% saline was done in patients who had ingested the compound 1–2 h before admission. The shock was managed with intravenous fluids and vasopressors. Noradrenaline was the initial vasopressor of choice. After initial resuscitation, the patients were shifted to an ED observation unit or intensive care unit based on the severity of the toxidrome and followed up throughout their hospital stay. The outcome (died or survived) and length of hospital stay were documented.

Figure 1. Management protocol for acute aluminum phosphide toxicity at our center (PGIMER, Chandigarh, India). a GIK protocol: Insulin regular loading dose of 0.5–1 IU/kg, followed by 0.5 IU/kg/h infusion (can be increased up to 10 IU/kg/h). Dextrose 0.5–1 g/kg loading dose, followed by 0.5–1 g/kg/h infusion; maintaining plasma glucose level between 140 and 180 mg/dL. IV K supplementation to maintain normal serum levels; monitoring levels every 8 h along with continuous ECG, b MgSO4 protocol: Loading dose 3 g over 3 h infusion, followed by 1.0-1.5 g every 6 h. ARDS: Acute respiratory distress syndrome, BP: Blood pressure, CBC: Complete blood count, CRRT: Continuous renal replacement therapy, CXR: Chest X‑ray, ECG: Electrocardiography, ECMO: Extracorporeal membrane oxygenation, GIK: Glucose‑insulin‑potassium, IABP: Intra‑aortic balloon counterpulsation, INR: International normalized ratio, IV: Intravenous, LFT: Liver function test, NS: Normal saline, PT: Prothrombin time, RFT: Renal function test, RRT: Renal replacement therapy

Outcomes

The primary outcome was to study the effect of the following factors (available at admission) on inhospital mortality – (a) poison formulation (e.g., tablet and sachet), (b) the ingested dose (in grams), (c) additives used during consumption (e.g., water, alcohol, and juice), (d) reconstitution of poison before consumption and stirring with a spoon for reconstitution, (e) presence of vomiting and the total number of episodes, and (f) time elapsed in contact with the health care facility and the initiation of treatment, i.e., gastric lavage and intravenous fluid administration.

The secondary outcomes were to detect the effect of reconstitution of the poison before ingestion on (a) the presence of shock on admission, (b) the requirement of vasopressors during hospitalization, and (c) the requirement of ventilation (e.g., noninvasive or invasive mechanical ventilation) during hospitalization.

Statistical analysis

Statistical analysis was performed using the SPSS software version 22.0 (SPSS Inc., Chicago, IL, USA). The categorical variables were presented as frequencies and analyzed using Chi square or Fisher’s exact test. Quantitative variables were expressed in the form of the mean (± standard deviation [SD]) and median (interquartile range [IQR]) as applicable. The normality of quantitative variables was assessed using Kolmogorov–Smirnov test. For normally distributed variables, between group comparisons were made using the unpaired Student’s t test. Mann-Whitney test was used for nonnormally distributed variables. Univariate analysis was performed to find factors associated with mortality. A two sided P <0.05 was considered statistically significant.

Results

Participants and baseline characteristics

A total of 58 patients were enrolled in the study. The median age was 32 years (range: 16–80 years), and most patients were 21–40 years (n = 35, 60%). Table 1 shows the patients’ baseline sociodemographic, clinical, and laboratory characteristics. The intention of the poisoning was mainly suicidal (n = 55, 95%), followed by accidental (n = 2) and homicidal (n = 1).

Table 1. Baseline sociodemographic, clinical, and laboratory characteristics of patients with acute aluminum phosphide poisoning (n=58)

Table 1. Contd...

The predominant formulation of poison consumed was pellet (n = 41, 71%) [Table 2]. The mean ± SD (95% CI) dose of the ingested poison was 6.56 ± 5.42 (5.17–7.96) g. At least one third (n = 20) of patients gave a history of reconstitution of toxin (i.e., exposed form) before consumption and 13 of them stirred the poison while reconstituting. All patients but three developed vomiting after consumption. The median time elapsed for someone to find the victim and contact the first health care facility was 30 min and 1 h, respectively. The median time interval between poison consumption and initiation of gastric lavage was 1.25 h [Table 2].

Table 2. Effect of poison‑related factors and consumption patterns on mortality in aluminum phosphide poisoning (n=58)

Treatment and outcomes

During hospitalization, 40 (69.0%) patients needed vasopressor support for hypotension(vasopressors – single in 26, two in 13, and three in 1 patient). Ventilation was required in 33 (56.9%) patients in the form of invasive mechanical ventilation (n = 24) and oxygen supplementation through a venturi mask (n = 9). Four patients received renal replacement therapy for advanced azotemia or refractory metabolic acidosis. Inhospital mortality was 39% (n = 23). The median duration of hospital stay was 1 day (IQR: 4 h–2.375 days, range: 2 h–21 days).

Analysis of the outcomes

The primary outcome of this study was inhospital mortality, which was significantly high with a higher ingested dose (P <0.001), nonstirred reconstitution before consumption(P=0.042), less number of vomiting episodes after consumption (P = 0.010), a delay in detection of the victim by someone (P = 0.001), and delayed initiation of intravenous fluids (P = 0.043) [Table 2]. The secondary outcomes, i.e., shock at admission and requirement of vasopressor or ventilation during hospitalization, remained unaffected by the stirring with a spoon in the reconstitution group [Table 3]. The effect of baseline demographic, clinical, and laboratory characteristics on mortality is shown in Table 4.

Table 3. Effect of reconstitution of poison before consumption on secondary outcomes

Table 4. Effect of baseline demographic, clinical, and laboratory characteristics on mortality in aluminum phosphide poisoning (n=58)

Discussion

Determining prognosis at admission is crucial for rapid risk stratification or triaging patients with acute poisoning and identifying high risk patients for intensive care unit transfer in LMICs. Our study evaluates poison related factors and time intervals in detail. We found that the ingested dose, reconstitution of poison by stirring before consumption, number of vomiting episodes, and time delay to find the victim after ingestion or to administer intravenous fluids help provide prognosis at admission.

The dose of the poison consumed has historically been one of the most important prognostic factors in most toxidromes. Higher doses of aluminum phosphide lead to higher blood phosphine levels and subsequent inhibition of oxidative phosphorylation and anti oxidant enzymes, resulting in free radical damage.[10,27,28] Like most studies, the dose was significantly associated with mortality in our data.[14 16,27] The inhospital mortality was 39% in our study, with a mean ingested dose of 6.5 g. In contrast, in previous studies, the ingested dose varied from 1.2 to 5.1 g, with a mortality rate ranging from 30% to 60%.[9,18,26,29] The reason for this discrepancy may be multifactorial such as consumption of expired formulations that exert lesser toxicity, differences in the method of consumption, including reconstitution, and early institution of treatment. The dose taken into consideration in our study is the actual dose of formulation consumed by the patients. The composition of aluminum phosphide in standard tablet or granulation form available in North India is 56%. In contrast, the previous studies have either considered the effective dose of toxin or did not mention the toxin or formulation.[9,18,26,29] Although government protocols have dictated standardization of tablet and granulation formulations into 3 and 10 g, their easy accessibility to the general public makes aluminum phosphide a typical “suicide poison.”[6] More steps need to be taken to reduce the dose of formulations available in the market and restrict their availability to select groups.

Tablets or pellets are considered more toxic than powder or granules because of lower surface area, reduced exposure to the environment, and higher phosphine release in the body. We also found a severe toxidrome with tablet forms; however, it was not statistically significant. Similarly, reconstitution of the poison before ingestion (exposed form) resulted in better outcomes but did not reach a level of significance, as demonstrated in a few other studies.[9,15] The mortality was 1.9 times higher in patients who had ingested the nonreconstituted form. It was hypothesized that reconstitution with stirring leads to the escape of phosphine, resulting in a reduced systemic burden of the toxin. Although an association was demonstrated in our study, this interpretation is difficult to determine given the smaller sample size and the power of the reconstitution group. Moreover, stirring did not influence the incidence of shock and the requirement of vasopressor or ventilation in the reconstitution group. Future studies should elucidate and verify the prognostic significance of stirring.

Vomiting after consumption tends to remove the poison from the gastrointestinal tract before releasing phosphine, resulting in reduced systemic absorption of the toxin. Many studies demonstrated that the presence of vomiting, its early occurrence after consumption, and the number of episodes are associated with a less severe toxidrome.[16,27] In our study, patients with more vomiting episodes before admission had better outcomes than those with fewer.

Early recognition of a toxidrome and initiation of appropriate treatment are two essential factors in any poisoning because a delay worsens systemic toxicity.[30] In this study, the detection of the victim the first time after poison ingestion and initiation of intravenous fluid were two critical time intervals. Initial fluid resuscitation is often required to restore intravascular volume in acute aluminum phosphide poisoning as the toxin disrupts the vascular wall integrity, leading to congestion of vital organs, transudation of fluid into the serous cavities, and inadequate response to vasopressors.[10,27] The time intervals to contact the first health care facility and gastric lavage were also higher in the nonsurvivor group but were not significant. Overall, the time elapsed to reach the first health care facility after poison exposure was significantly less in our study compared to our center’s previous data of 2009 (1 h vs. 3 h).

Limitations

This study has three main limitations. First, a single center experience and tertiary hospital referral bias lack the generalizability of the results. Second, we caution that some poison related information and time intervals were collected from previous hospital records, and there could have been some differences in their subjective interpretation. Third, the sample size was relatively small, partly because of the coronavirus disease 2019 pandemic.[26] Therefore, we extended the patient enrollment period from 1 year to 1.5 years to increase the sample size. Our study incites larger multicentered studies, including primary health centers, to establish the prognostic role of poison related factors and time delays in aluminum phosphide poisoning.

Conclusion

Our study demonstrates the prognostic significance of poison related factors such as ingested dose, stirring for reconstitution, number of vomiting episodes, and time delay to the first detection of the victim or intravenous fluid administration. These factors are immediately available at admission and, along with toxidrome features, might improve early risk stratification of aluminum phosphide poisoning. The significant mortality and higher dose of ingested toxin in our study reflect easy access of the poison to the general public in our area and require tailored government regulations.

^† These authors (Lokhesh Chockalingam Anbalagan and Ashok Kumar Pannu) contributed equally to the manuscript and are the joint first authors.

How to cite this article: Anbalagan LC, Pannu AK, Bhalla A, Dhibar DP, Sharma N. Prognostic significance of poison-related factors and consumption patterns in acute aluminum phosphide poisoning. Turk J Emerg Med 2023;23:88-95.

The Institutional Ethics Committee of Postgraduate Institute of Medical Education and Research, Chandigarh (India) approved the study (No.: INT/IEC/2019/002071, date October 1, 2019).

Written informed consent was taken from all study patients or a legally authorized representative (if the patient could not consent). The study patients were explained about confidentiality and their information will be used for educational purposes only.

LAC: Data curation (lead), formal analysis (supporting), and writing – original draft (lead).
AKP: Conceptualization (supporting), methodology (supporting), formal analysis (lead), writing – original draft (supporting), writing – review, and editing (lead).
AB: Conceptualization (lead), methodology (lead), writing – review, and editing (supporting).
DPD: Conceptualization (supporting) and methodology (supporting).
NS: Conceptualization (supporting) and methodology (supporting).

None declared.

None.

References

1. Pannu AK, Bhalla A, Vamshi V, Upadhyay MK, Sharma N, Kumar S. Changing spectrum of acute poisoning in North India: A hospital based descriptive study. Turk J Emerg Med 2022;22:192 9.
2. Mew EJ, Padmanathan P, Konradsen F, Eddleston M, Chang SS, Phillips MR, et al. The global burden of fatal self poisoning with pesticides 2006 15: Systematic review. J Affect Disord 2017;219:93 104.
3. Singh D, Dewan I, Pandey AN, Tyagi S. Spectrum of unnatural fatalities in the Chandigarh zone of North West India – A 25 year autopsy study from a tertiary care hospital. J Clin Forensic Med 2003;10:145 52.
4. Gupta SK, Peshin SS, Srivastava A, Kaleekal T. A study of childhood poisoning at national poisons information Centre, all India institute of medical sciences, New Delhi. J Occup Health 2003;45:191 6.
5. Chugh SN, Dushyant, Ram S, Arora B, Malhotra KC. Incidence & outcome of aluminium phosphide poisoning in a hospital study. Indian J Med Res 1991;94:232 5.
6. Anbalagan LC, Arora N, Pannu AK. Management of acute aluminum phosphide poisoning: Has anything changed? Drug Metab Lett 2021;14:106 16.
7. Gurjar M, Baronia AK, Azim A, Sharma K. Managing aluminum phosphide poisonings. J Emerg Trauma Shock 2011;4:378 84.
8. Pannu AK, Bhalla A, Gantala J, Sharma N, Kumar S, Dhibar DP. Glucose insulin potassium infusion for the treatment of acute aluminum phosphide poisoning: An open label pilot study. Clin Toxicol (Phila) 2020;58:1004 9.
9. Mathai A, Bhanu MS. Acute aluminium phosphide poisoning: Can we predict mortality? Indian J Anaesth 2010;54:302 7.
10. Anand R, Binukumar BK, Gill KD. Aluminum phosphide poisoning: An unsolved riddle. J Appl Toxicol 2011;31:499 505.
11. Etemadi Aleagha A, Akhgari M, Iravani FS. Aluminum phosphide poisoning related deaths in Tehran, Iran, 2006 to 2013. Medicine (Baltimore) 2015;94:e1637.
12. Sharma A, Dishant, Gupta V, Kaushik JS, Mittal K. Aluminum phosphide (celphos) poisoning in children: A 5 year experience in a tertiary care hospital from Northern India. Indian J Crit Care Med 2014;18:33 6.
13. Bajwa SJ, Bajwa SK, Kaur J, Singh K, Panda A. Management of celphos poisoning with a novel intervention: A ray of hope in the darkest of clouds. Anesth Essays Res 2010;4:20 4.
14. Villa Manzano AI, Zamora López XX, Huerta Viera M, Vázquez Solís MG, Flores Robles GD. Mortality and factors associated with phosphide poisoning: Prospective cohort study Rev Med Inst Mex Seguro Soc 2019;57:156 61.
15. Hn M. Study of clinical profile and predictors of mortality in aluminium phosphide ppisoning. J Assoc Physicians India 2020;68:103.
16. Navabi SM, Navabi J, Aghaei A, Shaahmadi Z, Heydari R. Mortality from aluminum phosphide poisoning in Kermanshah province, Iran: Characteristics and predictive factors. Epidemiol Health 2018;40:e2018022.
17. Astaraki P, Ahadi M, Salehinejad F, Honardoost V. Fatalities due to poisoning with aluminum phosphide (Rice Pill) and methadone. Drug Res (Stuttg) 2022;72:82 5.
18. Louriz M, Dendane T, Abidi K, Madani N, Abouqal R, Zeggwagh AA. Prognostic factors of acute aluminum phosphide poisoning. Indian J Med Sci 2009;63:227 34.
19. El SarnagawyGN, AbdelnoorAA, AbuelfadlAA, El Mehallawi IH. Comparison between various scoring systems in predicting the need for intensive care unit admission of acute pesticide poisoned patients. Environ Sci Pollut Res Int 2022;29:33999 4009.
20. Nejad FT, Mohammadi AB, Behnoush B, Kazemifar A, Nahandi MZ, Dabiran S, et al. Predictors of poor prognosis in aluminum phosphide intoxication. IJT 2012;6:610 14.
21. Pannu AK, Bhalla A. A simple tool predicts mortality in aluminum phosphide self poisoning. Indian J Crit Care Med 2020;24:755 6.
22. Pannu AK, Bhalla A, Sharma A, Sharma N. “PGI Score”: A simplified three point prognostic score for acute aluminum phosphide poisoning. Indian J Crit Care Med 2020;24:790 3.
23. Pannu AK, Jhuria L, Bhalla A, Sharma N. PGI score: Prospective validation and correlation with SOFA, SAPS II, and APACHE II scores for predicting outcomes in acute aluminum phosphide poisoning. Toxicol Res (Camb) 2022;11:361 6.
24. Farzaneh E, Ghobadi H, Akbarifard M, Nakhaee S, Amirabadizadeh A, Akhavanakbari G, et al. Prognostic factors in acute aluminium phosphide poisoning: A risk prediction nomogram approach. Basic Clin Pharmacol Toxicol 2018;123:347 55.
25. Pannu AK, Saroch A, Kumar M, Behera A, Nayyar GS, Sharma N. Quantification of chronic diseases presenting in the emergency department and their disposition outcomes: A hospital based cross sectional study in North India. Trop Doct 2022;52:276 9.
26. Saini MK, Kumar H, Saini K, Behera A, Pannu AK, Soundappan K, et al. Impact of lockdown on medical emergency visits during the COVID 19 pandemic in India. Postgrad Med J 2022;98(e2):e112-4.
27. Singh SB. Aluminum phosphide poisoning. J Mahatma Gandhi Inst Med Sci 2015;20:15 9.
28. Hsu CH, Quistad GB, Casida JE. Phosphine induced oxidative stress in Hepa 1c1c7 cells. Toxicol Sci 1998;46:204 10.
29. Shadnia S, Sasanian G, Allami P, Hosseini A, Ranjbar A, Amini Shirazi N, et al. A retrospective 7 years study of aluminum phosphide poisoning in Tehran: Opportunities for prevention. Hum Exp Toxicol 2009;28:209 13.
30. Alnasser S, Hussain SM, Kirdi TS, Ahmed A. Aluminum phosphide poisoning in Saudi Arabia over a nine year period. Ann Saudi Med 2018;38:277 83.

The authors thank Mrs. Sunaina Verma for help in statistics.