HYPOKALAEMIA IN ORGANOPHOSPHOROUS COMPOUND POISONING.
Organophosphorous compounds (OP) are one of the most commonly used insecticides in India and Asia.  They are the most commonly used agents for poisoning in India due to their easy availability. In some instances, severe poisoning may occur as an occupational hazard.  It is not a common health issue in developed nations, because access to poisons are restricted. Insecticides being used as suicidal agents, especially OP compounds, is an important public health problem worldwide and its incidence keep raising. 
Mechanism of action of OP compound is by inhibiting acetylcholinesterase (AchE) at muscarinic and nicotinic receptors. The commonly measured cholinesterases are butyrylcholinesterase (BuChE) and red cell cholinesterase. BuChE is produced in the liver. It is secreted into blood to metabolise xenobiotics. The latter is found in RBCs (PchE). Inhibition of these enzymes serves as the marker of poisoning. [3,4] Enzyme inhibition in RBCs will predict AchE inhibition at synaptic levels in acute poisoning. Hence, determination of PchE level is used for screening as well as for the diagnosis of OP poisoning so that proper and immediate intervention is possible. 
Although, we have understood the mechanism of OP toxicity as a result of cholinesterase inhibition, various health effects following exposure to OP are yet to be completely understood. It is apparent that although inhibition of cholinesterase plays a key role in OP toxicity, there are other factors which are important like individual susceptibility and direct effects of OP on tissues.  Electrolyte imbalances are one among the contributing factors for the severity of OP poisoning. In acute OP poisoning, the most common cause of mortality is respiratory failure as a result of respiratory muscle paralysis.  Hypokalaemia is also a frequent finding in OP poisoning either due to GI loss or through excessive secretions. Associated hypokalaemia increases muscle weakness. Hence, hypokalaemia can be considered as an important factor in the poisoning. 
MATERIALS AND METHODS
Following ethical clearance, a cross-sectional study was conducted in Department of Medicine, Victoria and Bowring and Lady Curzon Hospitals attached to Bangalore Medical College and Research Institute from February 2016 to June 2017. Patients with definitive history of OP poisoning were taken into the study. Patients with kidney disease, Heart disease and patients who are already on diuretics are excluded from the study. As soon as the patient is received, clinical features were observed and noted with severity assessment as per Proudfoot classification  (Table 4) along with measurement of serum potassium ion ([K+]) concentration and PChE level. The serum [K+] levels of less than 3.5 mmol/L were considered as hypokalaemia.  The PChE level was measured. The normal values of PChE range from 5320 to 11700. Data were analysed using descriptive statistics and unpaired student 't' test. Data were analysed using SPSS software (version 17).
In this study, 50 OP poisoned patients (32 men, 18 women) were enrolled with median age of 30 +/- 0.56 years in men and 30 +/- 0.12 years in women. Chlorpyrifos was the commonest type (26%) of OP compound consumed followed by dichlorvos (24%), quinalphos (14%), methyl parathion (8%) and others (Table 2).
Baseline Clinical Features
Clinical manifestations of the patients are summarised in Table 3. The most common clinical manifestation was respiratory distress (50%) followed by neck muscle weakness/ fasciculations (44%), miosis (40%) and diaphoresis (30%). A total of 28 cases presented with one or more severe clinical features according to Proudfoot's classification (Table 4).
Serum Potassium Alterations in Severe Cases Among severe cases, 56% (20 out of 28) developed hypokalaemia. Among all patients, 44% (22 cases) had muscle weakness or fasciculation with mean serum [K+] of 3.39 [+ or -] 0.60 showing that as the serum [K+] level decreases below 3.5 mmol/L, these alarming signs can be recognised. The ventilatory support was required at the mean serum [K+] of 3.48 [+ or -] 0.61 mmol/L. No Fatality was noted. For these conditions, the correlation of the clinical effects and serum [K+] was significant (P < 0.05).
Plasma Cholinesterase Levels in Severe Cases
Among the cases with severe clinical features, the PChE level was remarkably reduced except in two cases. The relation between PChE and clinical manifestations was assessed independently at the time of presentation. As it is shown in Table 5, muscle weakness, fasciculation and respiratory distress were associated with marked suppression of PChE (>50%). For those patients with severe clinical effects, considerable reduction in serum [K+] was also evident (Table 5). Among those who required ventilatory support had the lowest PChE levels (1187 +/- 0.15 IU/L).
OP compounds bind to acetylcholinesterase (AChE), preventing hydrolysis of acetylcholine and resulting in its accumulation in muscarinic and nicotinic receptors. Accumulation at nicotinic receptors results in muscle fasciculation and flaccid paralysis. Decrease in serum [K+] may alter neuromuscular junction activity by hyperpolarising the muscle and impairing their ability to develop the depolarisation necessary for muscle contraction. Balali-Mood et al revealed that hypokalaemia may aggravate muscular weakness due to inhibition of AChE by OP compounds.  We also found that reduction in serum [K+] aggravate the OP toxicity induced muscle weakness and paralysis. The patients in the present study developed severe signs and symptoms of nicotinic effects of OP as the [K+] reduced. More than 98% of total body potassium is intracellular, chiefly in the muscle; buffering of extracellular potassium by this large intracellular pool plays a crucial role in the regulation of plasma K+ concentration.  Changes in the exchange and distribution of intra- and extra-cellular K+ can thus lead to hypo- and hyperkalaemia. The resting membrane potential and functional activity of electrically excitable cells undergo significant alteration even due to minute change in extracellular potassium concentration.  In acute cases of OP poisoning due to strong nicotinic actions, respiratory distress, muscle weakness and paralysis sets in. In such conditions, hypokalaemia acts as an add-on to the clinical severity of OP poisoning.
It is a well-known fact that Hypokalaemia and Hyperkalaemia can cause muscle weakness and periodic paralysis. [12,13] Hypokalaemia manifests with lassitude, muscular weakness, loss of deep tendon reflexes, paralysis and death (which is usually due to cardiac arrhythmias and respiratory distress). 
Cause of death in both acute OP poisoning and hypokalaemia is usually muscular weakness and respiratory distress. [13,14,9,15,16] Hypokalaemia and paralysis are potentially reversible medical emergencies [12,13]; however, when these features were coupled with reduction of PChE, higher chance of morbidity were observed. Hence, the level of PChE and serum [K+] can be proposed as OP poisoning predictive markers.
Serum [K+] and PchE level are greatly reduced in patients with OP poisoning with severe clinical features. Hence, these biochemical markers can be considered predictors of outcome in OP poisoning. Physicians should consider hypokalaemia associated with reduced PchE level as alarming signs of poor prognosis in OP poisoned patients and the need for ICU admission and ventilatory support.
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Diwakar Tumkur Narasimhamurthy (1), Shubha Vishnu Hegde (2)
(1) Associate Professor, Department of Medicine, Bangalore Medical College and Research Institute, Bangalore.
(2) Postgraduate Student, Department of Medicine, Bangalore Medical College and Research Institute, Bangalore.
'Financial or Other Competing Interest': None.
Submission 29-08-2017, Peer Review 07-10-2017, Acceptance 12-10-2017, Published 19-10-2017.
Shubha Vishnu Hegde, PG girls Hostel, Victoria Hospital Campus, K R. Market, Bangalore.
Table 1. Demographic Features Gender No. of Patients Mean Age Male 32(64%) 30 +/- 0.56 yrs. Female 18(36%) 30 +/- 0.12 yrs. Table 2. Type of Compounds Consumed Compound Name No. Percentage % Chlorpyrifos 13 26 Dichlorvos 12 24 Quinalphos 7 14 Methyl Parathion 4 8 Monocrotophos 3 6 Parathion 3 6 Phorate 3 6 Dimethoate 2 4 Diazinon 1 2 Pantothenate 1 2 Profenofos 1 2 Table 3. Clinical Manifestations of OP Poisoning Patients (n= 50) Clinical Manifestations No. % Diaphoresis 15 30 Salivation 14 28 Bronchorrhoea 10 20 Vomiting 6 12 Neck muscle weakness 22 44 Fasciculations 22 44 Respiratory distress 25 50 Miosis 20 40 Seizures 1 2 Table 4. Proudfoot Classification- Assessment of Severity of Acute OP Poisoning  Mild Fatigue, Headache, Paraesthesia Clinical Nausea and Vomiting, Diaphoresis, Manifestations Salivation, Abdominal pain Diarrhoea, Able to ambulate Decline in <10% Serum PchE Moderate Symptoms of Mild poisoning + Clinical Miosis, General weakness, Manifestations Dysarthria, Fasciculations, Unable to ambulate Decline in 10-50% Serum PchE Severe Generalised Fasciculation, Marked Clinical Miosis, Flaccid paralysis, Manifestations Respiratory distress, Unconsciousness Decline in >50% Serum PchE Table 5. Mean Potassium and Mean PChE Levels in association with Severe Clinical Features of OP Poisoning Clinical Features Mean K+ Mean PChE Muscle weakness/ Yes 3.391+/-0.60 958.73+/-801.17 fasciculations No 3.84+/- 0.43 3192.44+/-2927.01 P value 0.003 0.001 Respiratory Yes 3.472+/-0.66 1006.17+/-836.04 Distress No 3.82+/-0.35 3413.04+/-3007.49 P value 0.025 0.001 Miosis Yes 3.635+/-0.54 1597.50+/-2039.598 No 3.653+/-0.56 2617.68+/-2721.184 P value 0.910 o.160 Ventilatory Yes 3.48 [+ or -] 0.61 1187.24+/-1525.83 support No 3.895+/-0.32 3743.15+/-3743.15 P value 0.008 0.001
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|Title Annotation:||Original Research Article|
|Author:||Narasimhamurthy, Diwakar Tumkur; Hegde, Shubha Vishnu|
|Publication:||Journal of Evolution of Medical and Dental Sciences|
|Date:||Oct 19, 2017|
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