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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 2  |  Page : 94-98

A study of serum amylase as a probable prognostic marker in acute organophosphorus poisoning


Department of Internal Medicine, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India

Date of Submission21-Oct-2020
Date of Decision19-Nov-2020
Date of Acceptance21-Nov-2020
Date of Web Publication21-Apr-2021

Correspondence Address:
Dr. C N Mohan
#312/A 6th Main, 4th Block, 3rd Stage, Basaveshwaranagar, Bengaluru - 560 079, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajim.ajim_79_20

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  Abstract 


Background and Objectives: Organophosphate compounds are frequently used for homicidal and suicidal purposes, organophosphates account for as many as 80% of pesticide-related hospital admissions. This study was done to estimate serum amylase and plasma cholinesterase (ChE) in acute organophosphorus (OP) poisoning, to correlate serum amylase with plasma ChE levels and to study serum amylase levels as a probable prognostic marker in acute OP poisoning. Materials and Methods: The study was conducted at the hospitals attached to Bangalore Medical College and Research Institution, Bangalore, from November 2017 to May 2019, 110 cases of OP poisoning were selected based on inclusion and exclusion criteria. Patients were grouped accordingly based on ChE levels into mild, moderate, and severe. Serum amylase levels were estimated on admission, at 48 h, and at outcome either recovery or clinical deterioration. Serum amylase was used as a marker to assess severity in acute OP-poisoning cases, to predict ventilator requirement and mortality, and also for prognostication. Results: In our study, a total of 110 acute OP-poisoning cases were included. The mean serum amylase levels at admission, 48 h, and the outcome were 54.81, 54.44, and 53.35 among the nonintubated group, respectively, and 152.23, 152.67, and 141.13 among the intubated group, respectively, with a significant P value (0.000*). This shows that patients who were intubated had elevated mean serum amylase levels (>90 U/l) in comparison to patients who were not intubated. Sixty-three patients had normal amylase levels on day 1 (≤90 U/l) (normal value of serum amylase as per the laboratory was 28–90 U/l) and 47 patients had raised amylase levels on day 1 (>90 U/l). Among 47 patients with raised amylase level, 18 patients died and there were no deaths in the normal amylase level group with P = 0.00* which is statistically significant. Raised serum amylase correlated well in predicting ventilator requirement and mortality in patients with OP poisoning. Conclusion: Serum amylase can be used as a reliable biochemical marker as it is easily available, relatively cheap, and it also predicts the requirement for intubation and mortality in acute OP-poisoning cases. Increased amylase levels on admission imply poorer outcome and increased risk of mortality, and thereby, it can be used as an alternative marker to predict clinical outcome and for prognostication.

Keywords: Cholinesterase, organophosphorus poisoning, serum amylase


How to cite this article:
Raveendra K R, Mohan C N. A study of serum amylase as a probable prognostic marker in acute organophosphorus poisoning. APIK J Int Med 2021;9:94-8

How to cite this URL:
Raveendra K R, Mohan C N. A study of serum amylase as a probable prognostic marker in acute organophosphorus poisoning. APIK J Int Med [serial online] 2021 [cited 2021 Jun 12];9:94-8. Available from: https://www.ajim.in/text.asp?2021/9/2/94/314202




  Introduction Top


Pesticides are chemical compounds that are used in agriculture to kill pests that harm crops including insects, rodents, fungi, and unwanted plants (weeds) and to kill vectors of disease, such as mosquitoes. By their nature, these agents are potentially toxic to other organisms, including humans, and need to be used with caution and disposed of safely.[1] Organophosphorus (OP) compounds and carbamates are the two groups of cholinesterase (ChE) inhibiting pesticides that frequently produce human toxicity.[2] Worldwide, an estimated 3,000,000 people are exposed to organophosphate or carbamate agents each year, with up to 3,00,000 fatalities.[3],[4] About 2,00,000 population succumb to OP poisoning in rural Asia where intentional self-harm is common and extremely harmful OP insecticides are widely used in agriculture and therefore easily available in the households.[5],[6] In India, a total of 12,602 persons (consisting of 8007 farmers/cultivators and 4595 agricultural laborers) involved in the farming sector have committed suicide during 2015, in which 7566 were male and 441 were female.[7] Kamath et al. reported 34% incidence of OP poisoning among poisoning cases in 1964 from G. T. Hospital, Bombay.[5] Singh et al. reported a 19.23% incidence of OP poisoning from G. B. Pant Hospital,[8] New Delhi. Khosya and Meena reported that pesticides were the major cause of poisoning, a study done in Rajasthan.[9] Insecticides group which constituted 30.65% was the most common cause of poisoning, of which OP poisoning accounted for 17.39% of cases.[9] Acetylcholinesterase (AChE) activity in human blood reflects the activity of synaptic AChE, the target enzyme of anticholinesterases; majority of OP compounds inhibit plasma Butyrylcholinesterase (BuChE) faster than erythrocyte AChE; thereby, accurate information about the exposure of an individual to OPs can be obtained by measurement of both AChE and BuChE. Since BuChE found in the plasma and AChE is bound to the erythrocyte membrane, to determine the activity of each enzyme, erythrocytes and plasma either have to be separated or one has to apply selective substrates and/or inhibitors to assay only one enzyme in the presence of the other. However, there are no known substrates or inhibitors that are fully selective for either AChE or BuChE. On the other hand, it is difficult to achieve full separation of erythrocytes from plasma without loss of some of the activity. In the acute phase of OP poisoning, serum ChE activity is usually depressed within a few hours to few days and is also restored to normal levels quickly.[10] About 3% of the population have a genetic variation manifested by a serum ChE deficiency. Pregnancy, acute (or) chronic inflammatory conditions, neoplasia, use of certain drugs (succinylcholine, codeine, and morphine), malnutrition, and liver disease are conditions that also affect serum ChE levels, but the depression caused by these conditions is not as great as that caused by organophosphate insecticide. Serum amylase on the other hand is a easily available, accessible and cost effective biochemical marker of acute OP poisoning, various studies show that there is an increased incidence of pancreatitis and its related complications after consumption of OP compound when compared to the general population. There is an elevated serum amylase level in these patients. Although the exact mechanisms for its occurrence are not known, the following mechanisms have been suggested: OP insecticides raise the intraductal pressure and exocrine pancreatic flow, this increase in pressure leads to extravasation of pancreatic fluid and increased pancreatic exocrine flow could be due to direct cholinergic hyperstimulation of pancreatic acinar and ductal cells. It is observed that there are pancreatic interstitial edema, acinar cell vacuolization, elevated serum amylase, and lipase levels following ingestion of OP poisoning.[11],[12]


  Materials and Methods Top


This prospective study was conducted between November 1, 2017, and May 31, 2019, it included a total of 110 confirmed OP-poisoning patients admitted to Victoria Hospital and Bowring and Lady Curzon Hospital, attached to Bangalore Medical College and Research Institute. After obtaining clearance from the institute ethical committee, written informed consent was obtained; patients were selected after satisfying the inclusion and exclusion criteria, and individuals who had consumed any other poison, alcohol, or known pancreatic or salivary gland disorders were strictly excluded from the study.

Patients were initiated on protocol-based management, initial management included maintenance of airway, breathing, and circulation. Injection atropine 1-3mg bolus given intravenously, depending on the severity assessed by clinical examination. Patient's also received injection pralidoxime 2g intravenously over 20-30mins, followed by 0.5-1g/hour intravenous infusion given for next 48 hours. The patient was re evaluated every 5 min, the dosage of atropine was doubled if there was no sign of atropinization in the form of heart rate more than 80 beats per minute, pupillary dilatation, drying of axilla, and clear chest, once the patient is clinically showing signs of atropinization then the patient will be started on atropine infusion of 0.02–0.08 mg/kg/min to maintain atropinization. The stomach wash contents were sent to forensic laboratory analysis, for medicolegal purposes. Relevant blood investigations were sent. Serum amylase levels and plasma ChE levels were measured at the time of admission and serum amylase and plasma ChE levels were correlated. Patients were grouped under three groups based on Proudfoot Classification:[13] Group 1 – mild (<10% reduction of PChE levels 4050–4499 U/L), Group 2 – moderate (10%–50% reduction of PChE levels: 2250–4049 U/L), and Group 3 – severe (more than 50% reduction of PChE levels <2249 U/L), the normal levels of plasma ChE were 4500–11,000 U/l. Serum amylase levels was measured again at 48 h of admission and at the time of outcome (death or clinical recovery) to study serum amylase as a probable prognostic factor in acute OP poisoning. Statistical analysis was performed using the Statistical Package for the Social Sciences version 20 (IBM SPASS statistics [IBM corp. Armonk, NY, USA released 2011]). Descriptive statistics of the outcome variables were calculated by mean, standard deviation for quantitative variables. Inferential statistics such as Chi-square test was used for categorical variables, Kruskal–Wallis test was used to compare the mean ChE levels among the groups (mild, moderate, and severe), and Spearman's correlation was performed to correlate ChE and amylase levels. The level of significance is set at 5%, P < 0.05 was taken as significant.


  Results Top


In our study, 110 included patients who were admitted to the hospital with evidence of OP poisoning were divided into mild, moderate, and severe grades based on the ChE levels. Majority of them were male (n-81), males accounted for 69.2%, 53.8%, and 77.4% in mild, moderate, and severe grades, respectively and females accounted for 30.8%, 46.2%, and 22.6% in mild, moderate, and severe grades, respectively. The mean age distribution in years as included in the study was 35.92 in mild grade, 34.31 in moderate grade, and 36.73 in severe grade [Figure 1]. Most patients, 84.9%, belonged to age groups between 15 and 45 years. All had consumed the poison with suicidal intention, among them 86.36% had consumed the poison for the first time and others had a history of having consumed the poison for more than once. Dimethoate (72.72%) was the most common OP compound that was consumed which was followed by dichlorvos (22.72%) and parathion (4.54%) and there was no statistically significant correlation between the nature of OP compound and levels of amylase. About 54.54% of patients presented to the hospital within 12 h of consumption and other 45.54% after 12 h of consumption. Nearly 29.09% of patients had associated hypertension, 18.18% were diabetes, and 9.09% were obese. All these patients had a smell of OP compound at admission; excessive oral and nasal secretion was the most common presenting feature (81.81%), followed by difficulty in breathing (54.54%), abdominal pain (40.90%), fasciculations (18.18%), altered sensorium (9.09%), and seizures (4.54%). On examination, bradycardia was seen in 86.36%, pinpoint pupil in 63.63%, tachypnea in 54.54%, fasciculations in 45.54%, hypoxemia in 29.09%, poor cough reflex in 29.09%, neck muscle weakness in 18.18%, and poor Glasgow Coma Scale in 9.09%. Among 31 patients who had hypoxemia (29.09%), 12 patients had SpO2 85%–90%, 9 had SpO2 80%–84%, 6 had SpO2 75%–79%, and 4 had SpO2 70%–74%. The outcome variables that were observed in our study were type-I paralysis (45.54%), acute respiratory failure (29.09%), type-II paralysis (18.18%), aspiration pneumonitis (9.09%), acute kidney injury (9.09%), and multi-organ dysfunction syndrome (4.54%).
Figure 1: The mean serum amylase levels on admission

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The mean serum amylase levels on admission among mild, moderate, and severe grades in U/l (normal range: 28–90 U/l) were 45.85, 72.62, and 109.11, respectively [Figure 2]. The estimation of serum amylase and plasma ChE was done using a BECKMAN AU-480 colorimetric method. The mean serum amylase levels at 48 h among mild, moderate, and severe grades in U/l (normal range: 28–90U/l) were 46.00, 72.54, and 108.52, respectively [Figure 3]. The mean serum amylase levels at outcome either recovery, clinical deterioration, or death among mild, moderate, and severe grades in U/l (normal range: 28–90U/l) were 46.00, 75.54, and 100.89, respectively [Figure 4]. The mean serum amylase levels at admission, 48 h, and the time of clinical deterioration or discharge were 54.81, 54.44, and 53.35 among patients who were not intubated, respectively, and 152.23, 152.67, and 141.13 among patients who were intubated, respectively, with a significant P value (0.000*) [Figure 5]. Mortality was seen only in intubated patients, which was about 37.5% among patients who were intubated with a significant P value (0.00*) [Figure 6]. Patients who were intubated in view of respiratory failure had elevated mean serum amylase levels (>90 U/l) in comparison to patients who were not intubated. Among 47 patients who had raised amylase levels on admission, 18 of them succumbed to the complications of OP poisoning and none died in the normal amylase level group with P = 0.00* which is statistically significant. There was a statistically significant correlation between levels of ChE in severe grade with serum amylase that was estimated on day 1 and day 2 with a significant P value.
Figure 2: The mean serum amylase levels at 48 hours

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Figure 3: The mean serum amylase at the outcome

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Figure 4: Correlation of serum amylase on admission, 48 h, and at either recovery or death among patients who were intubated (serum amylase on admission, at 48 h, and at recovery or death) and non-intubated (serum amylase on admission, at 48 h, and at recovery)

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Figure 5: Mortality rate comparison among patients who were intubated versus who were not intubated

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Figure 6: Distribution of study sample based on cholinesterase levels into mild, moderate, and severe grades and gender distribution of the sample

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  Discussion Top


Acute OP poisoning is common in countries like India due to easy availability and accessibility to OP compounds. Most of these cases are reported from rural areas,[5],[6] timely shifting of these patients becomes crucial for initiation of early protocol-based management and identification of patients with a high risk of progression to respiratory failure at the first medical contact itself. Various clinical and laboratory parameters can be used to assess patients at risk, requiring ventilatory support, so that patients can be shifted to tertiary care centers at the right time, if the health-care facilities are limited. Patients admitted in critical care units and high-dependency units need to be monitored by daily clinical assessment and laboratory parameters that are easily available, reliable, and cost-effective. Plasma ChE is the most widely used biochemical parameter for prognostication in acute OP poisoning. This study was conducted to assess the correlation between serum amylase and plasma ChE levels in patients admitted with acute OP poisoning and to study the utility of serum amylase levels as a probable prognostic marker in acute OP poisoning.

In our study, patients who belonged to the severe category showed elevations in mean serum amylase levels compared to mild and moderate categories. In a similar study that was done by M E Sumathi et al.[14] that included 53 acute OP-poisoning cases, the patients were subdivided into three groups based on plasma ChE activity: Group 1 (20%–50% plasma ChE activity) included 12 patients, of which 6 patients (50%) had elevated serum amylase levels, among them 3 had increased lipase levels; Group 2 (10%–20% plasma ChE activity) included 15 patients, of which 7 (46.66%) had elevated serum amylase levels, among them 3 showed elevated serum lipase levels; and Group 3 (<10% plasma ChE activity) included 26 patients, among which 19 (73.04%) showed elevated serum amylase levels, of which 6 showed an elevation in serum lipase levels.

Patients who required mechanical ventilatory support had elevated mean serum amylase levels (>90 U/l) in comparison to patients who were not intubated. Among 47 patients who had raised serum amylase levels on admission, 18 of them succumbed to the complications of OP poisoning and there were no deaths in the normal amylase level group. A retrospective study done by Lee et al.[15] that included 121 patients with OP poisoning at Veterans General Hospital showed that 44 patients (36%) had elevated amylase levels (serum amylase >360 U/L). The finding of elevated amylase levels was closely related to clinical severity and presence of acute pancreatitis and septic shock. Another study done by N Matsumiya et al.[16] on 32 OP-poisoning patients admitted to the intensive care unit at Kyodo General Hospital, Ibaraki, Japan, in 1996, to analyze the incidence of respiratory failure showed that[16] these patients developed respiratory failure and received ventilator support. An increase in plasma amylase above the normal range was found in patients who developed respiratory failure.

A prospective study done by Sahin et al.[17] included 47 patients of acute OP poisoning admitted to the Emergency Department of the Yüzüncü Yõl Medical School Hospital from May 1999 to December 2000. Serum amylase, serum lipase, serum transaminases, lactate dehydrogenase, creatinine phosphokinase, potassium levels, leukocyte count and total hospitalization days were evaluated in this study. Four of 47 patients had obviously elevated amylase and lipase levels (amylase >300 U/L, lipase >60 U/L). Only two of the patients with amylase levels between 100 and 300 U/L also had elevated levels of lipase. None of the patients with normal amylase levels had elevated levels of lipase. A total of 12.76% were diagnosed with acute pancreatitis and these patients underwent ultrasound and computed tomography to confirm the diagnosis of acute pancreatitis. However, none of the patients in our study developed OP-poisoning-induced acute pancreatitis.


  Conclusion Top


Organophosphate compounds are frequently used for suicidal and homicidal purposes, they account for as many as 80% of pesticide-related hospital admissions. High mortality rates seen in developing countries are due to lack of hospital services in the vicinity, inadequate transport facility, increased patient to caregivers ratio, and finally nonavailability of definite antidote. Inhibition of BuChE, also called plasma ChE or pseudocholinesterase, does not give clear information about the clinical severity of the poisoning. Therefore, serum amylase can be used as an alternative biochemical marker as it is easily available, relatively cheap, and it also predicts the requirement of intubation and mortality in acute OP poisoning cases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Lee WC, Yang CC, Deng JF, Wu ML, Ger J, Lin HC, et al. The clinical significance of hyperamylasaemia in organophosphate poisoning. Hyperamylasaemia 1998;36:673-81.  Back to cited text no. 15
    
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Matsumiya N, Tanaka M, Iwai M, Kondo T, Takahashi S, Sato S. Elevated amylase is related to the development of respiratory failure in organophosphate poisoning. Hum Exp Toxicol 1996;15:250-3.  Back to cited text no. 16
    
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Sahin I, Onbasi K, Sahin H, Karakaya C, Ustun Y, Noyan T. The prevalence of pancreatitis in organophosphate poisonings. Hum Exp Toxicol 2002;21:175-7.  Back to cited text no. 17
    


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