Successful Management of Carbamate Poisoning among Children : Case Report from Gaza Strip

A bad management of pesticide marketing and use resulted in using extreme toxic pesticides inside houses for controlling public health insects such as cockroaches. A child of two years old was poisoned with pesticide residues after application of pesticides at home for cockroach control. The child with a semi-conscious status was brought to the European hospital in south Gaza with his father along with the empty container of pesticide which was used at home. It appeared that Carbaryl (a carbamate insecticide) was the reason for poisoning. In the intensive care unite the child was washed out with clean water and his cloths were removed to reduced the possible hazards. Blood analysis showed that moderate inhibition of acetylcholinesterase (AChE) on addition became more sever on due time. Then the child was given several doses of atropine but without any improvement in AChE activity. Then the child was given Obedoxim as an antidote. This resulted in significant improvement of AChE activity. The child continued to receive Obedoxim every day until AChE activity reached the normal range. Blood analysis did not show any traces of Carbaryl. It is recommended to give Obedoxim to the carbamate immediately when someone is poisoned instead of atropine for successful management of the poisoned case.


Introduction
Pesticide poisoning in Gaza became quite common due to bad management of pesticide poisoning.However, poisoning in Gaza was occurred due to occupa-Occupational Diseases and Environmental Medicine tional activity of pesticides such as application of pesticides in farms and/or in houses [1] [2] [3].
Recent reports showed the use of pesticide container as a domestic tool among farm community.This attitude may expose the farm community to health risks such as occurrence of poisonous case among farmers [4].So far toxicity of pesticides among population in Gaza has been documented.For instance long term toxicity [5] [6] [7], acute toxicity [8], accidental toxicity [9], and suicidal attempts [10].
It is obvious that the abovementioned work poorly investigated the toxicity among children, or the investigation of toxicity among children remains on its primary stages.Furthermore, it is urgently needed to document a case of poising among children to be a scientific guide for successful management for poisoning among children around the world.Therefore, the author of this study devoted his efforts to present a poisonous case among children below three years old.

Case Report
Mr. Angheem A, a young child, 3 years old, losing conciousness at home while his father was spaying Carbaryl (an insecticide) in the house garden using ultra low volume technique.The father brought the child to the European hospital at 4:50 PM with a history of semi-conciousness.It appeared that the father used ultra-low volume technique at a windy day.
Carbaryl is an insecticide, belonging to the chemical group carbamate compounds.It has the following chemical name: 1-naphthalenyl-methylcarbamate.Its chemical structure is shown in Figure 1.It is poorly soluble in water (120 mg/L) and highly soluble in organic solvents [26].The lethal dose that is required to kill 50% of the tested organism (LD50) varies according to the tested animal.It is classified as class II of toxicity [27].So far its long term application has been shown to create health problems among farmers [28].
The child was admitted in the intensive care unit (ICU) where physical investigations such as blood pressure, temperature, and oxygen saturation were measured immediately.Blood samples were contentiously collected from the patient for complete blood chemistry (CBC) and acetylcholinesterase (AChE) activity were determined according to the international well know Ellman method [29].

Medical Treatment
The poisonous case was managed following the procedure described by Palestinian Authority Ministry of Health [30].In this protocol, the cloths of child were removed and his skin was washed with warm water containing some soups to enhance removal of poison residue from the skin.Then gastric lavage was not conducted because the child was unconscious.Then blood samples were collected for complete blood chemical analysis, and for acetylcholinesterase (AChE) activity determination and for liver enzymes.These steps were repeated every day to monitor the level of AChE.The child was given 10 mg atropine in 500 mL normal saline solution every 6 h, at a late stage double dose of Atropine was given to the patient.After three days stay in the ICU, the patient was given 75 mg Obedoxim in 50 mL saline solution every 6 hr along with other medical drugs (Diclofen (75 mg) intra muscular injection; Cefazoline (100 mg/8 hr); Zantac (50 mg/8 hr); Intra venues injection; Pramine (10 mg/12 hr); Intra venues injection; Obedoxim (75 mg/50 mL)) to stop the clinical symptoms such as vomiting, diarrhea.

Results
Table 1 shows values of some blood parameters from time of admission in the ICU on 9/2/2018 up to the release date from the hospital on 24/2/2018.Comparing with the reference range, it appeared that HGB is reduced from 10.It appeared from these stages that AChE activity was slightly inhibited on admission date then became severely inhibited in due time and reached the maximum inhibition percentage on the seventh day of treatment, then inhibition percentages reduced (Figure 2).So far, the inhibition percentage is reduced to a lower level and reached to the lowest inhibition percentage due to medical treatment with Obedoxim.
On the other hands levels of ALT, AST and ALP were reduced from high levels 29, 66, and 484 u/L to lower levels 14, 35, 326 u/L respectively.These data indicated that Carbaryl inhibit the production of these enzyme.

Discussion
Carbaryl is an insecticide widely used in the field and at home for many species of insect control.It belongs to carbamate compound, a class of insecticides derived from the amid radical of carbonic acid [26].who found that drift of pesticide application using ultra low volume technique, in which it caused harmful effects to non-target organisms.In addition, ultra-low volume technique used the organic solvent to dissolve the technical materials of Carbaryl.This further enhanced the fast distribution of Carbaryl on the skin of poisoned cases.This agreed with Tomlin [26] who reported similar phenomenon.Furthermore, the data in Figure 1 clearly shows the chemical structure of Carbaryl, Atropine and Obedoxim contained aromatic groups.This property enables planar distribution of molecules and faster reaction with AChE.Additionally, it can be suggested that Carbaryl reacted with AChE producing a complex reaction type 2 [33].This is in accordance with the data in Table 1, which indicated the possible reaction of between Carbaryl and blood parameters.
This is evidenced from the data in Table 1, which showed high values of blood parameter on admission date and reduced to lower values on the release date, regardless to the fact that value of blood parameter is in the acceptable reference range.Moreover, it can be suggested that Carbaryl can be adsorbed on the surfaces of blood cells from a type of adsorption complex.This suggestion is in accordance with El-Nahhal and Safi [34] [35], who revealed the adsorption of some pesticides on biomaterials.Nevertheless, this type of surface reaction may occur due to chemical structure.This suggestion is in agreement with previous reports [36] [37] [38] which revealed the possibility of surface reactions of organic molecules in biological system.Moreover, El-Nahhal [33] characterized four type of surface reactions between organophosphorus insecticides and enzymes among them ionic interactions (Adsorption reaction).
That data in Figure 2, indicated three stages of poisoning.These are, stage a, low inhibition percentage, stage b, the highest inhibition percentage and stage c, reduced inhibition percentage (recovery stage).The explanation of these results is that, stage a indicates the distribution, partitioning and activation of Carbaryl molecules in the human body.Stage b indicated the formation of Carbaryl AChE complex due to reaction of activated Carbaryl molecules and AChE.Stage c indicated the degradation of Carbaryl AChE complex and formation of free AChE (recovery of poisoning).This explanation is in agreement with previous reports [1] [4] [10].
Exposure to Carbaryl molecules and its reaction with AChE, and recovery reactions can be modeled as follows: Carbary human body distribtion partitioning and activation + → [ ]

[ ]
Carbary-Obedoxim unine exctreation → (6) According to these models, Equation (1) represents distribution, partitioning and activation of Carbaryl.This step depends on the physicochemical properties of Carbaryl such as partitioning coefficients (Kow) water solubility.As long as the partitioning of Carbaryl is fast in the human body as long the toxicity appeared.For our case, the distribution of Carbaryl was not so fast accordingly appearance of inhibition was low.This is evidenced in Figure 2.
As long as activated Carbaryl molecules reached the target site (AChE) it reacted with it and formed Carbaryl-AChE complex Equation ( 2).This complex represents the inhibition status of AChE.As long as the inhibition status is stable, the poisoning case continued to be stronger due to accumulation of acetylcholine in the synaptic gaps and lack of effective medical treatment.As long as the medical treatment is not effective, Equation (3), no improvement would occur.This is obvious from the data in Figure 2, where maximum inhibition was observed for longer period with using atropine.Nevertheless, effective medical treatment as using Obedoxim as in Equations ( 4) and ( 5) which resulted in a formation of free AChE.Then Carbaryl-Obedoxim complex would be excreted from the body throughout urine system.This explanation is in accordance with Ref [33] who demonstrated the strength of reactions between pesticides and AChE.So far some chemical reactions are presented in Figure 3.It can be seen that the activated Carbaryl reacted with AChE forming an inhibited status of AChE, which responsible on the appearance of toxicity symptoms due to accumulation of acetylcholine in the synaptic gaps.Then the use of effective antidote Obedoxim is to free AChE from the complex and to excrete Carbaryl from the body.

Conclusion
Poisoning with Carbaryl showed three stages of poisoning, distribution and
Foot note: HGB = hemoglobin; where WBC = white blood count; RBC = red blood count; HCT = hematocrit; MCH = mean corpuscular hemoglobin; RDW = red blood distribution percent; LYM = lymphocyte cell percent; GRAN = granulocyte cell percent; MCV = mean corpuscular volume; MCHC = mean corpuscular hemoglobin concentration; PLT = platelet count.Occupational Diseases and Environmental Medicine admission date to acceptable reference range.So far, similar trends were observed with other blood parameters such as WBC, RBC, HCT.On the other hand, Figure2shows the inhibition status of acetylcholine esterase (AChE).Three stages of AChE activity levels were characterized.These stages are: stage a, stage b and stage c, where stage a shows low level of inhibition, stage b shows the maximum inhibition level and stage c shows the recovery level of the AChE due to treatment with atropine and Obedoxim.

Figure 3 .
Figure 3. Proposed schematic reactions of Carbaryl and AChE in the poisoned case and recovery reactions with using of Obedoxim.

Table 1 .
Selected blood indices during the medical treatment of the child.
1 on So far, ultra-low technique is a very dangerous method because it directly used the technical materials of Carbaryl without and water dilution.This technique may result in high atmospheric contamination of Carbaryl drift that may cause serious poisoning cases among population specially in the crowded areas or in houses closed to the rural areas where ultra-low volume technique are being applied.This is in accordance with El-Nahhal et al.[31] [32] Carbaryl is used in many countries without any restriction.It can be applied by either ultra-low volume technique or high-volume technique but both techniques are recommended for Figure 2. AChE activity levels.Phase a, b and c represent the initial status of AChE on admission time (few hours after poisoning), maximum inhibition level and recovery level, respectively.Percentage of AChE inhibitions were 11.4; 96.72% and 52.5% for the status on admission, maximum inhibition and recovery respectively.Y. El-Nahhal DOI: 10.4236/odem.2018.6300899 Occupational Diseases and Environmental Medicine field applications.