Clinical Profile and Outcome of Poisoned Pediatric Patients Admitted To Poison Control Center , Ain Shams University Hospitals during the Year 2012

Childhood poisoning comprises a significant component of injury-related morbidity and mortality all over the world and exerts a huge amount of pressure on the resources of the health care system as well as the workload on the health care staff. Early and accurate diagnosis and management of poisoning decrease the risk of morbidity and mortality. Therefore, study of manifestations and severity of poisoning by variable agents, effects of treatments and outcome is essential to assess the impact of poisonous substances and the effectiveness of treatment. Aim of the study: this study aims to determine the clinical profile, management and outcome of acutely poisoned children admitted to Poison Control Center (PCC), Ain Shams University Hospitals during a one year period starting from 1/1/2012 to 31/12/2012. Methods: The collected data from the cases’ medical records included: age, gender, delay time, pre-consultation treatment, clinical manifestations, findings of investigations, place and period of hospitalization, received treatment in the PCC and the outcome. Results: adolescence where the most frequent age group in this study and female gender was more prominent than male gender. Delay time was significantly increased in non-survivors than survivors. The proportion of deaths in group of patients who received pre-consultation treatment was significantly higher than that in patients who didn’t receive any treatment before arrival to the PCC. Faulty management in the form of induction of emesis by salty water intake was found in 2.6% of the cases; 7.7% of these cases were died. Most cases presented with unremarkable changes in vital signs and gastrointestinal manifestations (mainly nausea and vomiting) were the most frequent manifestations in the cases. Hypoglycemia, hyponatremia, hypokalemia and metabolic acidosis were the most common abnormalities found in laboratory investigations. Sinus tachycardia was the most common abnormality found in ECG. Most of the included cases in this study were admitted in the inpatient section (83 %). The majority of the cases (75%) were hospitalized for short period that didn’t exceed 24 hours. Higher PSS was associated with longer hospital stay periods. Corrosives, followed by pesticides were the most frequent cause of prolonged hospitalization (≥4 days). Emergency managements were indicated in 11% of the cases and procedures for gastric decontamination were done for 1296 cases (87.3%). All cases received supportive and symptomatic treatments. Atropine was the most frequent antidote that was used either alone or with toxogonin. The overall mortality ratio was 2.2%. Preschool age group had the greatest mortality ratio (3.7%), followed by infant group (3.6%). Hypernatremia had the highest case fatality rate (100 %), followed by CO poisoning (28.6%). Conclusion: Gastrointestinal manifestations (mainly nausea and vomiting) were the most frequent manifestations. Hypoglycemia, hyponatremia, hypokalemia and metabolic acidosis were the most common abnormalities found in laboratory investigations. Sinus tachycardia was the most common abnormality found in ECG. Corrosives, followed by pesticides were the most frequent cause of prolonged hospitalization. Atropine was the most frequently used antidote. The overall mortality was 2.2%. Hypernatremia had the highest case fatality rate (100 %). Recommendations: Increasing public awareness of the first aid measures in childhood poisoning is crucial to avoid complications of faulty measures. Also, it is important to increase public awareness of the services of the information center in the PCC as it presents guidance about management of poisoned cases. Ongoing childhood poisoning surveillance is needed to track its effects and risk factors and to monitor the impact of appropriate interventions.


Introduction
hildhood poisoning comprises a significant component of injury-related morbidity and mortality all over the world.According to the WHO world report on child injury prevention, acute poisoning accounts for an estimated 45,000 deaths annually in children and young people under the age of 20 years (Holder et al., 2008).
Acute poisoning in children represents one of the most common medical emergencies encountered in young children, and accounts for a significant proportion of emergency room visits for the adolescent population (Aqeel et al., 2009).It exerts a huge amount of pressure on the resources of the health care system as well as the workload on the health care staff (Randev et al., 2011).
Early and accurate diagnosis and management of poisoning decrease the risk of morbidity and mortality.Therefore, study of manifestations and severity of poisoning by variable agents, effects of treatments and outcome is essential to assess the impact of poisonous substances and effectiveness of treatment.
This study aims to determine the clinical profile, management and outcome of acutely poisoned children admitted to Poison Control Center (PCC), Ain Shams University Hospitals during a one year period starting from 1/1/2012 to 31/12/2012.

Subjects and Methods
This retrospective study was carried out on all acutely poisoned children of both sexes, aged ≤ 18 years old who were admitted to PCC, Ain Shams University Hospitals, during one year period starting from 1/1/2012 to 31/12/2012.
An official permission was taken from the director of the PCC.The approval of The Local Research Ethics Committee was obtained.All personal data were kept anonymous to ensure confidentiality of records.
The medical records of the pediatric patients were revised and the following data were obtained: 1. Age and gender 2. Delay time in hours.3. Pre-consultation treatment (at hospital or at home) 4. Clinical manifestations: the routine clinical examination of poisoned cases includes recording of vital signs as well as systematic general examination of all body systems.Cases were categorized as cases with normal vital functions or abnormal according to the normal ranges of vital signs in children (Hutchison et al., 2008 andSchafermayer, 2012).-Reed'sclassification of the level of consciousness (Chadha, 2003) was used for grading of coma in cases with disturbed level of consciousness.
5. Findings of investigations: cases were categorized to normal/abnormal according to the reference ranges.
6. Place and period of hospitalization.7. Received treatment in the PCC 8. Outcome of the case, either recovery and discharge or death.9. Severity of poisoning all cases were categorized according to severity of poisoning using poisoning severity score (PSS) (Persson et al., 1998).Statistical analysis of the data was done using Statistical package for Social Science (SPSS) version 19 software.Chi-square test was used for comparison of frequencies of qualitative variables between groups.Spearman correlation test was used to assess the strength of association between grades of PSS (as ordinal categorical variable) and delay time (continuous variable).Non-parametric test (Mann-Whitney test) was used for comparison of delay time between two groups since its distribution was not normal.All measured (P) values were two-sided.P<0.05 was considered significant.

Results
This study included 1,521 children who were admitted to the PCC and represented about 22% of the total pediatric cases.For comparison of poisoning between age groups; the included cases were subdivided into: infants (less than one year old), toddlers (1 : <3 years old), preschool age group (3 : <6 years old), school age group (6: <12 years old) and adolescents (12: 18 years old) (Kail, 2004).
Figure (1) shows the gender distribution in age groups of the included cases.Adolescents represented the most frequent age group among the admitted pediatric cases, followed by toddlers.Female gender was predominant in the adolescent and school age groups while male gender was predominant in younger age groups.This difference was statistically significant.
The delay time in the included cases ranged from 1 to 24 hours.Mann-Whitney test revealed significant increase in the median of delay time in nonsurvivors than that in survivors (table (1)).Spearman correlation test revealed non-significant correlation between delay time and severity of poisoning (table (2)).
There were 63 cases (4.1%) who received treatments before arrival to the PCC either at home or at another health care facility (figure (2)).Specific treatment was the most frequent pre-consultation treatment; it included atropine injection (20 cases), toxogonin injection (6 cases) and antivenom (2 cases).This was followed by gastric decontamination; gastric lavage (13 cases) and ingestion of activated charcoal (4 cases).

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Induction of emesis by salty water was found as faulty management given to 39 cases, 3 cases of them (7.7%) were died.
Figure (3) shows the number of deaths in relation to pre-consultation treatment of the included cases.The proportion of deaths in group of patients who received pre-consultation treatment was significantly higher than that in patients who didn't receive any treatment before arrival to the PCC.
Table (3) shows severity of poisoning according to PSS grading in relation to causative agents of poisoning in the studied cases.Pesticides were the most frequent agent (477 cases, 31.4%),followed by cardiopulmonary drugs (383, 25.2%) and drugs acting on CNS (205, 13.5%).
Laboratory investigations included investigations for assessment of the patients' general conditions and specific investigations for assessment of the effects of the poisonous agent.Table (6) shows serum levels of electrolytes and blood sugar level.The most common abnormalities were hypokalemia (697 cases, 45.8%), followed by hypoglycemia (194 cases, 14.6%), hyponatremia (60 cases, 3.9%).
Blood gases tests had been done for 330 cases; table (7) shows that, metabolic acidosis was the most common abnormality as it was found in 75 cases (22.7%), followed by rrespiratory acidosis (45 cases, 13.6%).
Table (8) shows specific toxicological tests that were done for 487 cases (32% of all cases).Pseudo-cholinesterase level in blood was the most frequent performed specific test (351 cases, 72.1%).
Regarding the place of admission in the PCC, most of the cases were admitted in the inpatient section (1262 cases, 83 %) and 259 cases (17%) were admitted in the intensive care unit (ICU).Table (10) shows the place of admission in relation to age groups of the included cases.Chi-square statistical analysis showed that, the proportion of admitted cases to ICU was significantly smaller in both adolescents and infants than in other age groups.
Most of the cases were hospitalized for short duration not exceeding 24 hours (1141 cases, 75%) and 21.5% (326 cases) were admitted for period ranged from 1:4 days.Only 54 cases (3.5%) were hospitalized for a period ≥ 4 days.Table (11) shows durations of hospital stay in relation to severity of poisoning (according to PSS grades).Severe cases (PSS grades 3 and 4) represented the majority of patients who needed hospitalization for long period (≥ 4 days) (48 cases, 88.9%).
Table (12) shows the poisonous agents responsible for prolonged hospitalization period (≥ 4 days).Corrosives, followed by pesticides, were the most common cause of prolonged hospital stay (29.6% and 24.1% respectively).All of the cases were presented with moderate to severe toxicity (PSS grades 2 and 3) and 35.2% (19 cases) of them died.
Procedures for gastric decontamination were done for 971 cases (65.4% of the cases with oral route of exposure).Induction of emesis by syrup of ipecac was the most frequent method, followed by activated charcoal administration (figure (5)).
Regarding supportive treatment, all admitted cases received maintenance intravenous fluids.Table (14) shows that, medications for treatment of gastric irritation (histamine receptor type II (H2) blockers, proton pump inhibitors (PPIs)) and anti-emetics were the most frequent supportive treatment given to the admitted cases (856 cases, 56.3%).Blood transfusion was indicated for two cases; corrosive and snake poisoning.
The outcome of the cases was determined as recovery and discharge from the PCC or death.The percentage of mortality in the admitted cases was 2.2% (33 cases).Figure ( 6) shows percentages of mortality in age groups of the included cases.Preschool age group had the greatest percentage (3.7%),followed by infants (3.6%).
Table ( 16) shows case fatality rates of poisonous agent in the studied cases.Hypernatremia had the highest case fatality rate (100 %), followed by CO poisoning (28.6%).

Discussion
Hazard of poisoning by variable agents have been increased due to several factors such as rapid industrialization and exposure to hazardous chemical products, introduction of newer range of drugs for treatment, massive use of pesticides in agriculture and unhealthy dietary habits.(Kiran et al., 2008).Children are particularly at risk because of their curious and exploratory behavior (Vasavada and Desai, 2013).
This study showed a significant increase of the median of delay time in non-survivors than that in survivors.This agreed with Ozdemir et al., (2012) and Ramesha et al, (2009) who studied childhood poisoning in Turkey and India respectively and found an association between prolonged delay time and mortality as majority of deaths occurred in patients presented to the hospital with a delay time exceeding 8 hours.
The duration of pre-hospitalization period was found as a strong predictive factor of severity of poisoning.This was explained by the fact that, delayed treatment allows the suspected initial peak blood level of poison to induce irreversible tissue damage (Sam et al., (2009).
The current study found significant increase of mortality in patients who received pre-consultation treatment than that in patients who didn't receive any treatment before arrival to the PCC.This may be due to improper pre-consultation management as found by Veale et al. (2013) who reported that, poisoning had been misdiagnosed in prereferral hospitals in South Africa as organophosphate poisoning and atropine wrongly administered as the antidote in amitraz, glyphosate and aluminium phosphide poisoning.
The same findings were reported by El Masry and Azab, (2013) who studied inappropriate management and transfer of referred patients to the PCC, Ain Shams University Hospitals and found that, 52 cases received improper management that was either incorrect medications (40 cases) or faulty decontamination or resuscitation maneuvers (12 cases).
This study revealed faulty management in the form of induction of emesis by salty water that was given to 2.6% of the included cases (39 cases).The percentage of mortality among these cases was 7.7%.Similar findings were reported by El Masry and Azab, (2013) who found that, 9% of the cases with inappropriate management measures were given salty water for induction of emesis.Death in these cases is most probably due to hypernatremia which is a serious complication of intake of salty water (Su et al., 2010).
In this study, most of the included cases were admitted in the inpatient section.This agreed with Taghaddosinejad et al. (2012) who reported that, ICU admission is strictly limited to severe and life threatening poisoning.
The current study found most cases were presented with normal vital signs.The most common abnormalities were tachycardia, hypotension, tachypnea and hypothermia.This agreed with Alazab, (2012) who studied acute poisoning in children admitted to a University Hospital in Egypt and found the majority of cases presented with normal vital signs.He found that, hypotension, followed by tachypnea, was the most common abnormality in vital functions.
Theophylline was the most frequent cause of tachycardia and hypotension in this study while kerosene was the most frequent cause of tachypnea and organophosphorous compounds (OPC) were the most frequent cause of hypothermia (49 cases, 49%).
Theophylline may cause sinus tachycardia and tachypnea through its sympathomimetic action and positive chronotropic effect (this was evident in ECG, as sinus tachycardia was the most common abnormality).It may also cause hypotension due to increased beta-2 receptor stimulation (Aggarwal, 2012).Tachycardia and tachypnea can occur as a physiologic response to catecholamine release due to stress and anxiety (Viswanathan and Kollef, 2012).
Poisoned cases with kerosene are commonly presented with tachypnea and signs of respiratory distress due to chemical pneumonitis (Osterhoudt et al., 2006).
(OPC) may cause initial hypothermia due to direct CNS administration of cholinergic agonists in the region of the hypothalamus or cerebral ventricles (Moffatt et al., 2010).This study found that, cases presented with constricted pupils were more frequent than those presented with dilated pupils.This may be due to high prevalence of pesticides (mainly OPC and carbamates) as they were the most common non-medicinal poisonous agent in the included cases.They are commonly presented with constricted pupils due to the nicotinic action of the excess of acetylcholine in synapses and neuromuscular junctions (Rajendiran et al., 2009).
Mydriasis can result from increased sympathetic stimulation as in cases affected by cocaine, amphetamines and hypoglycemia or from inhibition of muscarinic cholinergic-mediated pupillary constriction secondary to exposure to anticholinergic agents (Perera et al., 2008).
In this study, gastrointestinal manifestations (mainly nausea and vomiting) were the most frequent manifestations among the included cases, followed by neurological manifestations.This agreed with previous studies on poisoned pediatric patients that found the common presenting systems symptomatology were digestive and CNS (Bhat et al., 2012 andShwe et al., 2013).
These can be explained by the prevalence of pesticides as they were the most common agents in the included cases.Vomiting in (OPC) toxicity occurs due to excessive muscarinic activity (Aggarwal, 2012).Neurological manifestations are common with (OPC) and carbamates due to their nicotinic action.The effects of excessive cholinergic stimulation at these sites are similar to that of a depolarizing neuromuscular blocker agent (succinylcholine) initially resulting in fasciculations, hypotonia or weakness (Clark, 2006).Also, respiratory manifestations are common with insecticide toxicity due to excessive stimulation of muscarinic receptors which leads to bronchorrhea and bronchospasm (Rajendiran et al., 2009).(OPC) toxicity can result in respiratory failure and development of cyanosis due to weakness of the respiratory muscles, paralysis of the respiratory center, bronchospasm and increased bronchial secretion (Prasad, 2010).
In this study, the most common abnormalities found in laboratory investigations were hypoglycemia, hyponatremia and hypokalemia.Pesticides were the most common causes of hypokalemia, hypoglycemia and hyponatremia.
In (OPC), excessive adrenergic influences on metabolism cause glycogenolysis with hyperglycemia and ketosis that are occasionally mistaken for diabetic ketoacidosis.Hypoglycemia can also occur, although the mechanism is unclear (Clark, 2006).Hypoglycemia can be caused by many drugs as beta blockers, oral hypoglycemic drugs and salicylate poisoning hyperinsulinism (Josefson and Zimmerman, 2009).
Significant fluid, sodium and potassium concentration abnormalities commonly occur in the setting of xenobiotic exposure.Gastrointestinal losses may occur in the form of vomiting, diarrhea or bleeding.Renal fluid losses may result from increased glomerular filtration rate (inotropes) or impaired absorption (diuretics).Fluid losses also may occur through the skin as a result of sweating as in cases of sympathomimetics, cholinergics or salicylates poisoning or through the lungs as a result of bronchorrhea as in cholinergics (Charney and Hoffman, 2006).
Hypokalemia can result from acute theophylline toxicity due to influx of extracellular potassium into the intracellular compartment despite normal total body potassium content.Also, it is common finding in patients with toxicity from βadrenergic agonist activity (Jones and Alpern, 2014).(OPC) can cause hypokalemia due to excessive vomiting and diarrhea (Balali-Mood and Saber, 2012).
In this study, metabolic acidosis was the most common blood gases' abnormality caused most commonly by pesticides, followed by respiratory acidosis caused mainly by tramadol.
Respiratory acidosis can be primarily caused by the toxin as a result of central respiratory center depression (as in tramadol and opioid toxicity) (Sood et al., 2010) or a premorbid finding due to loss of respiratory compensation for the metabolic acidosis caused by other toxins as pesticides, theophylline or salicylate toxicity (Pearlman and Gambhir, 2009).
Respiratory alkalosis represents the earliest acid-base abnormality of salicylate and theophylline intoxication due to a direct stimulation of the respiratory center (Liamis et al., 2010).
In this study, most of the included cases were admitted in the inpatient department.This agreed with Veale et al., (2013) who studied poisoning in South Africa where most children were admitted for overnight observation while only 5% were admitted to the ICU.This can be explained by the fact that, ICU admission is strictly limited to severe and life threatening poisoning (Taghaddosinejad et al., 2012).
The present study revealed an association between increased severity of poisoning and prolonged duration of hospital stay.This agrees with Paterson et al., (2006) and Sam et al., (2009) who found an association between the increased duration of hospital stay and the significant mortality and morbidity of the poisoned cases.
Corrosives, followed by pesticides were the most frequent cause of prolonged hospitalization in thus study.This can be explained by the fact that, in cases with ingestion of corrosives, hospitalization is indicated for cases with severe or significant manifestation that need intensive care of complications until regaining of oral nutrition (Naik and Vadivelan, 2012).
Regarding the received treatment in the PCC, emergency managements were indicated in small percentage of the cases (11.3%).Poisoning with pesticides was the most frequent causative agent in cases indicated mechanical ventilation, followed by substances of abuse and poisonous gases.This agreed with El Masry and Tawfik, (2013) who found that, (OPC) was the most frequent cause of poisoning in cases required MV (30%), followed by tramadol (16%).
Gut decontamination of ingested poisons was performed in the majority of the cases by induction of emesis by syrup ipecac and administration of activated charcoal.Gastric lavage was done in small percentage of the included cases.
Although there is no evidence from clinical studies that emesis by ipecac improves the outcome of poisoned patient, yet its routine use is still present and should be prohibited (Yip et al., 2011) as syrup ipecac may cause aspiration, delay the administration or reduce the effectiveness of activated charcoal, oral antidotes, and whole bowel irrigation.
Therefore, recent guidelines of the European Association of Poisons Centers and Clinical Toxicologists as well as the American Academy of Pediatrics recommended that, ipecac should no longer be used routinely as a treatment strategy for treatment of pediatric poisoning (Chyka et al., 2005).
The wide use of ipecac in the PCC for gastric decontamination may be due to limited resources and unavailability of disposable gastric lavage tubes in the market in Egypt which makes ipecac an easier and safer method for gastric decontamination.
On the other hand, activated charcoal is a universal antidote for the majority of poisons (Michael, 2007).Yet, it is contraindicated after the ingestion of corrosive substances, surfactants, or liquid hydrocarbons, and whenever the respiratory tract has not been protected (by intubation) (Chyka et al., 2005).Symptomatic treatments were given to all of the included cases in the present study.Maintenance IV fluids, followed by medications for treatment of gastric irritation were the most frequent supportive treatment given to the admitted cases.Similar findings were reported by previous studies on childhood poisoning which found that, treatment in most of the cases was non-specific, including general decontamination and supportive-symptomatic therapy (Sahin et al., 2011, Müller andDesel, 2013).
Atropine, followed by oximes, was the most common antidote used in treatment of the included cases in this study .This is can be explained by high prevalence of poisoning by (OPC).
Regarding cases' outcome, this study found the percentage of mortality in the included cases 2.2%.Preschool age group had the greatest percentage of mortality while adolescents group had the smallest percentage.
Similar findings were reported by Bhat et al. (2012) who studied the profile of poisoning in children and adolescent in India and found the greatest mortality ratio in the preschool age group.Also, Haghighat et al., (2013) reported that, acute poisoning in both adults and children is often associated with morbidity rather than mortality.Half of mortalities were in the preschool age group with the highest mortality ratio.
Small proportion of mortality in adolescents group may be explained by predominance of suicidal poisoning in this group since most cases of suicidal attempts aim to draw attention rather than to inflict real harm or cause death.This is of course achieved by taking less toxic drugs in smaller amounts (Ozdemir et al., 2012).
(OPC) was the most frequent cause of mortalities, followed by CNS drugs.Hypernatremia had the greatest case fatality rate, followed by carbon monoxide poisoning.These findings are in accordance with Malangu and Ogunbanjo, (2009) and Haghighat et al., (2013) who found that, (OPC) accounted for the largest proportion of deaths in acutely poisoned cases Hypernatremia occurred as a complication of use of salty water for induction of emesis and was found to have the highest case fatality rate.It is known as a fatal complication as it results in brain edema and permanent brain damage (Bockenhauer et al., 2010).

Conclusions
Delay time was significantly increased in nonsurvivors than survivors.Faulty management in the form of induction of emesis by salty water intake was found in 2.6% of the cases; 7.7% of these cases were died.Most cases presented with normal vital signs and gastrointestinal manifestations (mainly nausea and vomiting) were the most frequent manifestations in the cases.Hypoglycemia, hyponatremia, hypokalemia and metabolic acidosis were the most common abnormalities found in laboratory investigations.Sinus tachycardia was the most common abnormality found in ECG Most of the included cases in this study were admitted in the inpatient section (83 %).The majority of the cases (75%) were hospitalized for short period that didn't exceed 24 hours.Higher PSS was associated with longer hospital stay periods.
Emergency managements were indicated in 11% of the cases and procedures for gastric decontamination were done for 1296 cases (87.3%).All cases received supportive and symptomatic treatments.Atropine was the most frequent antidote that was used either alone or with toxogonin.

Recommendations
It is important to increase the public awareness of the first aid measures in childhood poisoning to avoid complications of faulty measures as induction of emesis by salty water.Also, it is important to increase public awareness of the services of the information center in the PCC as it presents guidance about management of poisoned cases.
Ongoing childhood poisoning surveillance is needed to track its effects and risk factors and to monitor the impact of appropriate interventions

Figure
Figure (1): Gender distribution in age groups of poisoned children, admitted to PCC, Ain Shams University Hospitals during the year 2012

Figure
Figure (3): Mortalities in pediatric poisoned patients admitted to PCC, Ain Shams University Hospitals during the year 2012 in relation to pre-consultation treatment.

Figure ( 5
Figure (5): Methods of gastric decontamination in children with oral route of exposure admitted to PCC, Ain Shams University Hospitals during the year 2012.

Figure ( 6
Figure (6): Percentage of mortality in age groups of pediatric poisoned patients admitted to PCC, Ain Shams University Hospitals during the year 2012.

Table ( 10): Chi-square statistical analysis comparing the place of admission between the age groups of the pediatric poisoned patients admitted to PCC, Ain Shams University Hospitals during the year 2012: Admission place Age group
Y: year(s), N: Number, (%): Percentage by age group, *: statistically significant.

Table ( 14): Supportive treatments received by the pediatric poisoned patients admitted to PCC, Ain Shams University Hospitals during the year 2012:
Percentage of the number of admitted cases.† PPIs: proton pump inhibitors, IV: intravenous.