Gaëtan

Aleman Gaëtan D'

Étude des cas d'intoxications et d

ouverte pluridisciplinaire HAL, est destinée au dépôt

STUDY OF CASES OF INTOXICATION AND ACCIDENTAL EXPOSURE TO FOREIGN BODIES IN THE PEDIATRIC EMERGENCY CARE UNIT OF NANTES UNIVERSITY HOSPITAL BETWEEN 2018 AND 2020

Introduction:

Toxic agent and foreign body exposure in pediatric population is a global issue of public health care, in the world with a major impact on health economics [START_REF] Gummin | Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 37th Annual Report[END_REF][START_REF] Hoffman | Ingestion of Caustic Substances. Longo DL, éditeur[END_REF][START_REF] Jepsen | Poisoning in children[END_REF][START_REF] Mintegi | Emergency visits for childhood poisoning: a 2-year prospective multicenter survey in Spain[END_REF]. The annual registry of the American Association of Poison Control Centers (AAPCC) showed that there are 36,503 severe intoxications and nearly 68,000 ingestions of foreign bodies per year in the United States, with children under 18 years old [START_REF] Gummin | Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 37th Annual Report[END_REF].

Young children are particularly affected by accidental exposure. When we look at the whole French population in 2010 the incidence of poisoning was approximately 0.1%, and 1.2% for children under 5 years old [START_REF] Bouilly | Les accidents de la vie courante aux urgences en France métropolitaine en 2010 selon l'enquête Epac[END_REF]. Indeed, during their first years of life, children discover their environment, and they are exposed to many objects and products that are more or less dangerous without being aware of the danger. Whereas when children become older, this issue is more related to voluntary intention in the context of psychiatric pathology [START_REF] Hoffman | Ingestion of Caustic Substances. Longo DL, éditeur[END_REF]. This lack of risk perception is responsible for the accidental ingestion of toxic products or drugs that children may find in their immediate environment in 98% of cases [START_REF] Mintegi | Emergency visits for childhood poisoning: a 2-year prospective multicenter survey in Spain[END_REF][START_REF] Masson | Pediatric Poisoning Hazards: An Analysis of 3.8 Million Exposure Incidents A Report from the American Association of Poison Control Centers[END_REF]7). In developed countries, poisoning accounts for around 7% of all accidents in children under 5 years and in about 2% of all childhood deaths (3). In France, calls for child poisoning accounted for nearly 50% of the activity of French Poison Control Centers (PCC); out of 187,028 calls, 86,478 refered to children under 10 years of age with a peak between 1 and 4 years old; out of which 40% were related to accidental drugs ingestion [START_REF] Masson | Pediatric Poisoning Hazards: An Analysis of 3.8 Million Exposure Incidents A Report from the American Association of Poison Control Centers[END_REF].

Lack of risk perception also leads to the insertion of foreign bodies in the nose, ears, eyes or even more frequently by ingesting foreign body. In France, the incidence of foreign bodies accidental insertion in natural orifice was approximately 5 to 7 % of the everyday life accidents of children aged from 1 to 7 years old in 2010 [START_REF] Bouilly | Les accidents de la vie courante aux urgences en France métropolitaine en 2010 selon l'enquête Epac[END_REF].

Prevention programs have been developed in France since 1983, which have led to a decrease of 50% in poisoning mortality in 20 years [START_REF] Lamireau | Epidemiology of poisoning in children: a 7-year survey in a paediatric emergency care unit[END_REF]. The mortality rate in the children population remained low around 10 deaths per year in France (9). Nevertheless, this avoidable issue is responsible for visits in the pediatric emergency care unit, leading to a conventional hospitalization rate of 18.7% and a rate of hospitalization in intensive care unit of 1 to 2% [START_REF] Brissaud | Intoxication grave par médicaments et/ou substances illicites admise en réanimation : spécificités pédiatriques[END_REF][START_REF] Santiago | Intoxications Working Group of the Spanish Society of Pediatric Emergencies. Epidemiology of acute pediatric poisonings in Spain: a prospective multicenter study from the Spanish Society of Pediatric Emergency Medicine[END_REF].

The majority of studies are global epidemiological analyses, with data from poison control centers or specialized services. There are few studies based on the real practice of a pediatric emergency service. And often the issue of accidental ingestions of toxic products is separated from drugs ingestions and foreign body exposure accidents.

In the absence of recent data, the objective of our work was to describe the population of children who consulted a pediatric emergency department, for the following reasons: accidental ingestion of a foreign body, drug or toxic product, as well as accidental insertion of a foreign body in the nose, ears or eyes and describe their management in a pediatric emergency department.

Methods:

Study design

We performed a retrospective unicentric observational study. We included:

• All children under 6 years old,

• Who were cared for in the Pediatric Emergency Care Unit (PECU) of Nantes University Hospita between January 1, 2018, and December 19, 2020,

• With exposition to foreign bodies by different ways, per os, intra nasal, intra auricular and intra ophthalmic,

• Who suffered ingestion of toxic products and drugs.

We excluded:

• Children who suffered a carbon monoxide inhalation,

• Collective food poisoning,

• Adverse effects of any therapeutic dose medication.

Data collection and research strategy

Data were collected from the patient records in the hospital database using anonymized data files. Two databases were cross-referenced to select patients:

• The information system medicalization program (PMSI) selected the files with the International Classification Disease 10 (ICD). The ICD 10 is an international classification for coding medical procedures according to recommendations of the World Health Organization.

• The hospital search database. It is a data warehouse, managed by the epidemiological service of Nantes University Hospital, that allows you to search for keywords in hospitalization reports, emergency room summaries or biological and imaging test reports.

The files were selected in these databases via different strategies:

• Hierarchical nodes: all files from the PECU with foreign bodies exposure and ingestion of drug or toxic product were selected from PMSI,

• Data mining with following keywords: "intoxication" "toxic" "ingestion" "foreign body" "cannabis" "drug" "button battery" for hospital search database.

After selecting the patients, we collected the following data:

Circumstances and mechanism of the accident: Age and sex; date of the accident; motivation for consulting in the emergency care unit (visualized accident, suspected accident, or an unsuspected accident i.e. reason unrelated to our studying accidents that led to a visit in the PECU); the mechanism of the accident (per os, intra nasal, intra auricular, or intra ophthalmic); the place of the accident (home, school, or other public places, parks, restaurant…); the class of foreign bodies, toxic products, and drugs.

Stratified analysis

We performed a stratified analysis on the presence or absence of symptoms following the accident. We considered as symptomatic any child who presented symptoms before hospital consultation and/or at the PECU.

Statistical analysis

The descriptive statistical analysis was performed with the "tableone" package of the R® software version 6.1.2. Concerning the stratified description of symptomatic and nonsymptomatic children (see 4.B), the statistical tests used to compare asymptomatic and symptomatic children were the chi² test for binary and categorical variables (or Fisher's exact test if non-parametric) as well as the 1-way ANOVA test for continuous variables (or Krustal-Wallis test if non-parametric) with verification of the hypothesis of homogeneity of variances.

The 1-way ANOVA test was equivalent to the Student test in this case.

Data management followed the French Data Protection Authority recommendations. Due to its retrospective and non-interventional design, signed informed consent was waived.

Results:

Study population

Between January 1, 2018, and December 19, 2020, we extracted 783 files from the PMSI and 1380 files from the hospital search database. After the duplicate exclusions, 1852 were retained; among them, 878 were excluded. The files excluded are represented in the flowchart below (figure 1). To conclude, 974 files were finally selected for our study.

Population characteristics and circumstances data

Among the study population, 521 were boys, 453 girls (odd ratio M/F: 1,15). The average age of children was 3 years old; 398 (41%) were symptomatic, 574 (59%) aymptomatic (table 1). This increase was relatively steady in the number of events registered, which is reflected in an increasing and linear trend, i.e. a gradual increase in the trend in number of cases reported per month of about +20 cases over 3 years. The place of accident was known in 668 files (68.6%). Among these 668 files, 582 accidents (87.1%) occurred at home.

Accident circumstances were known in 962 files (98.8%). Among these 962 files, 592 (60.8%)

were visualized by witnesses or suspected (346, 35.5%). When the accident was not visualized by witnesses but only suspected, the accident was further confirmed in only 10% of cases. In our analysis, we considered as confirmed a foreign body found radiographically or in the PECU.

We also considered as confirmed a suspicion of accidental ingestions of toxic products or drugs with a positive research of toxics.

More rarely, children were admitted to the PECU without any notion of accidental exposure (24 children (2.5%)) and most of them were symptomatic (22 children (91.7%)). In these cases, the main family of symptoms was neurological symptoms with 15 children out of 22.

Clinical onset

Symptomatic children were younger than asymptomatic (2.76 years old vs 3.29 years old, p< 0.001). We did not see significant differences on the gender of the child.

For the symptomatic children, the way was mainly per os (84.2% p< 0.001), and for the asymptomatic children it was more frequently intra nasal or intra auricular accidents (35.4%, 11.5% p< 0.001). Nb: a child could present different types of symptoms following the accident this was why our total of clinical signs was higher than our symptomatic children.

Respiratory and ENT symptoms, related in 272 (68.3%) files, were the most common clinical symptoms.

Digestive symptoms were reported in 124 cases (31.1%) and neurological symptoms in 37 of cases (9.3%). No cardiological symptom was found.

On the arrival at the PECU, only 91 of symptomatic children (22.9%) still presented symptoms during the medical examination.

Agents exposure • Foreign body accident

Exposure to a foreign body was by far the most frequent reason for consultation at the PECU (816 children (83.8%)). The class of foreign bodies is described in table 3. The other category included unknown foreign body (no information in the medical file) with nearly 60 files and also glass fragment, tissue…

Accidents related to a food exposure were significantly more often symptomatic (26.1% vs.

8.9% p<0.001), as were coin ingestions (10.2% vs. 6.4% p<0.001). Conversely, children who ingested a button battery were more often asymptomatic (12.6% vs. 3.3% p<0.001).

• Medical drugs exposure Nb: a child swallowed 2 drugs during the study period.

Ninety four accidental drug intoxications in children under 6 years old were recorded. With one child who swallowed two drugs. The main class was analgesic ingestion 38 (40%) (33 paracetamol, 5 tramadol), followed by 9 anxiolytics intoxications (9.5%) and cardiotropic with 9 cases (9.5%). Children were more often asymptomatic after drug ingestion (12.2% vs 6% p= 0.002). The analgesic category was mainly asymptomatic as well as the cardiotropic drug.

The other class included various drugs like: antibiotic, proton pump inhibitors, levothyroxine, zinc, potassium…

• Toxic agent exposure Hospitalization was required for 132 (13.6%) children, intensive care unit (ICU) for 7 (0.7%) children. The hospitalization rate was higher in the symptomatic group (23.9% vs 6.4% p< 000.1) as well as the hospitalization in intensive care unit (1.8% vs 0 p<000.1). The discharge rate was logically higher in the asymptomatic group (93.6% versus 74.4% p<0.001).

Among the 7 children hospitalized in ICU, 3 had tramadol intoxication, 1 had swallowed cannabis, 1 buprenorphine, 1 a piece of meat, and 1 had methemoglobin poisoning following a meal with home-cooked beets (rich in nitrate) and sausages (rich in sulfite).

One patient presented sequels at a distance from ingestion with oesophageal stenosis, while all the others recovered without sequel. Biological tests were performed on 62 (6.4%) children, 50 (5.1%) children had blood or urine toxicity test. These tests were positive for 36 (3.7%) children.

• Further examinations (table 7)

Medical imaging was performed in 417 (42.8%) cases. Symptomatic children had more examinations than asymptomatic and notably X-rays (50.5% vs 29.7% p< 0.001). Brain CTs scans and cerebral MRIs were only performed for symptomatic patients.

Six cerebral CTs scans were prescribed after 1 toxic ingestion, 2 cannabis intoxications and 3 tramadol intoxications and 2 cerebral MRIs for 1 child who swallowed tramadol and 1 lormetazepam, all because of the presence of neurological symptoms.

All the 96 endoscopic examinations were performed for diagnostic and therapeutic purposes.

• Medical intervention (table 7)

A foreign body was removed in the PECU in 219 (22.5%) cases. It was removed by a surgeon in 83 (8.5%) cases, under local anesthesia in the ENT or ophthalmologic department in 65 (6.7%) cases and under general anesthesia in the operating room in 18 (1.8%) cases. Activated charcoal was prescribed in 10 cases (1%), antidote in 2 cases (0.2%). But these results were probably overestimated, some accidents were considered as unconfirmed because they were not verifiable (for example, ingestion of toxic products not detectable by a toxicology test i.e. household products, or a toxicology test not performed in the PECU).

Accidents linked to foreign body exposure were the first cause of accidents whereas in the activity reports of the AAPCC, ingestion of foreign bodies was only found in fourth position of the pediatric calls [START_REF] Gummin | Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 37th Annual Report[END_REF]. But when we looked at the national report of accidents of everyday life, which was based on the activity of 5 French emergency services, the occurrence of foreign bodies exposures was higher than the ingestion of drugs and toxic products in the pediatric population [START_REF] Bouilly | Les accidents de la vie courante aux urgences en France métropolitaine en 2010 selon l'enquête Epac[END_REF]. We could find an explanation by the fact that poison centers are less often called for accidents related to foreign bodies.

What are the consequences of these accidents?

In the different clinical symptoms, we firstly found respiratory symptoms, then digestive symptoms. Neurological symptoms were in the third position. When we looked at the other main studies, we saw that in foreign bodies ingestion, digestive and respiratory symptoms were the most common symptoms (24-26), and in the drugs ingestion studies most of the symptoms presented by children were neurological symptoms [START_REF] Mintegi | Emergency visits for childhood poisoning: a 2-year prospective multicenter survey in Spain[END_REF][START_REF] Brissaud | Intoxication grave par médicaments et/ou substances illicites admise en réanimation : spécificités pédiatriques[END_REF]. Therefore, it was because we had a major part of foreign bodies ingestion in our study that we saw the respiratory and digestive symptoms appearing first.

There was no great differences between symptomatic and asymptomatic children in these foreign bodies accidents. Other studies focusing on foreign bodies ingestion found mostly symptomatic patients [START_REF] Kurowski | Caustic Ingestions and Foreign Bodies Ingestions in Pediatric Patients[END_REF][START_REF] Turgut | Prevalence of attention deficit hyperactivity disorder (ADHD) in children presenting with foreign body ingestion[END_REF]. However these studies were designed with different profiles of children. They were selected in specialized services, surgery services for most of them, and only via the per os way which was different from our emergency care unit population. We could see that button batteries represented almost 9% of our population, and even if we found that they were mostly asymptomatic, serious complications were reported, especially esophageal lesions [START_REF] Varga | Analysis of Complications After Button Battery Ingestion in Children[END_REF]. It was therefore important to listen to the parents in order to remove these button batteries as soon as possible.

We saw that most of drug ingestions were asymptomatic (70%); in literature, around 70.8% of poisoned children were asymptomatic (4). Some experts have evaluated the part of poisoning non-diagnostic around 40%, mostly linked to this asymptomatic population [START_REF] Michaud | Ingestion de corps étrangers chez l'enfant. Recommandations du Groupe francophone d'hépatologie, gastroentérologie et nutrition pédiatriques[END_REF].

The main class was analgesic as in a Spanish study [START_REF] Mintegi | Emergency visits for childhood poisoning: a 2-year prospective multicenter survey in Spain[END_REF]. Tramadol poisoning had led 3 children in intensive care unit. Many recent studies showed that even though pediatric tramadol fatalities were rare, some could lead to death (29,30). Therefore the French authorities had decided to limit the prescription for tramadol in April 2020 [START_REF]Tramadol par voie orale : l'ANSM rappelle les nouvelles règles de prescription et délivrance[END_REF].

Toxic products were more frequent in symptomatic patients. The largest family was household cleaning products. Then we had cannabis ingestions which were significantly more symptomatic (a child who had to be taken to intensive care following ingestion of cannabis).

There was a recent alert from the French National Drug Authority on this issue to alert practitioners of the significant increase in the number of these accidental ingestions [START_REF]Augmentation du nombre d'intoxications au cannabis par ingestion accidentelle chez les enfants -Point d'Information -ANSM : Agence nationale de sécurité du médicament et des produits de santé[END_REF].

How to manage these accidents?

We found similar rates of hospitalization than in other studies [START_REF] Mintegi | Emergency visits for childhood poisoning: a 2-year prospective multicenter survey in Spain[END_REF][START_REF] Brissaud | Intoxication grave par médicaments et/ou substances illicites admise en réanimation : spécificités pédiatriques[END_REF][START_REF] Santiago | Intoxications Working Group of the Spanish Society of Pediatric Emergencies. Epidemiology of acute pediatric poisonings in Spain: a prospective multicenter study from the Spanish Society of Pediatric Emergency Medicine[END_REF]. Symptomatic ingestion of toxic products and drugs led to the most serious consequences with 6 hospitalizations out of 7 in intensive care unit. Therefore, a symptomatic accident may lead significantly more to hospitalization, thus, it is why we should be very careful during our medical interview and our clinical examination to look out for symptoms after the accident. The diagnosis of poisoning was sometimes not evoked at the time of admission to the PECU but only found after complementary examinations. It was particularly the case children with unexplainable neurological signs.

Accidental pediatric intoxications, beyond the clinical consequences for the child, require medical management combining a diagnostic approach and clinical monitoring. In our study we found a lower radiography rate, compared to other studies (24,28). This was explained by our population which included foreign body ingestion as well as foreign body insertion in ear, nose and eyes, as well as toxic product and drug ingestion, consequently less eligible to radiography. The 2 cerebral MRIs and 5 of the 7 cerebral CTs scans made, were prescribed after a symptomatic ingestion of drugs or toxic products that could have been detected in a urinary test. This urinary test could have given practicians a very quick answer about the ingested drugs; this may be due to the sometimes lengthy response time for the results of these samples and the impossibility or delay of analysis in the absence of urine.

The rate of surgery [START_REF] Chung | A Review of Pediatric Foreign Body Ingestion and Management[END_REF]24) and fibroscopic examinations [START_REF] Chung | A Review of Pediatric Foreign Body Ingestion and Management[END_REF]24,[START_REF] Dereci | Foreign body ingestion in children[END_REF] was quite similar to other studies. In the asymptomatic population, which was more concerned by foreign bodies in ear and nose, foreign body was more often extracted in the PECU. In the symptomatic group, where most of accidents were per os, they needed more investigations, to find out where the foreign body was located, and to extract it when possible and necessary.

We noted that activated charcoal was given to 10 children, who had a drug ingestion. The activated charcoal was much more frequent in other studies 8.3 % (8) and even more in a Spanish cohort around 60% depending on the center (4). However, many studies showed that activated charcoal had not demonstrated strong benefits, especially when the ingestion had taken place more than 1 hour ago in asymptomatic children [START_REF] Lapus | Activated charcoal for pediatric poisonings: the universal antidote?[END_REF][START_REF] Osterhoudt | Activated charcoal administration in a pediatric emergency department[END_REF]. In our study we were not able to have the length of time between the accident and the admission in the PECU. We also found that antidote have been prescribed for only 2 children, maybe this result is underestimated due to the retrospective character of our study.

One child had sequels after the accident: which was an esophageal stricture after ingestion of a toxic product. No death was registered during the 3 years of our study. In a Spanish cohort there were also few complications: one death with a carbon monoxide inhalation and 6 sequels after caustic ingestion with also esophageal stenoses [START_REF] Mintegi | Emergency visits for childhood poisoning: a 2-year prospective multicenter survey in Spain[END_REF].

How to prevent ?

These poisonings and accidental ingestions could be avoided through targeted and appropriate information and prevention actions for the general public and health professionals. It is essential to promote prevention by adopting good habits in the family circle: make sure that they are inaccessible for children (for example, storing drugs, toxic products and small foreign body out of reach of children, avoiding deconditioning, using secured pharmacy, closed drawer...).

Other preventive measures have demonstrated their efficiency, such as the use of safety caps and the securing of packaging [START_REF] Rodgers | The Safety Effects of Child-Resistant Packaging for Oral Prescription Drugs[END_REF]. Future work in this area should therefore lead to improvements in the prevention of the occurrence of sometimes serious events in a particularly vulnerable population; i.e. by identifying areas of prevention and thus developing more relevant information and prevention campaigns for the general public, the medical community, public health actors and health authorities.

Limitations, strengths and perspectives of our study

Our study had limitations. Firstly, it was a retrospective study and biases could be related to a lack of information in the medical files. Secondly, it was an unicentric study and the results represented only the population consulting in Nantes University Hospital. However, the size of the sample is one of the strong points of this study, with more than 900 cases of children included; similarly, the methodology of the inclusions, exploiting the PMSI and the hospital search database at the same time, make it possible to include an exhaustive number of children.

Our study was performed during the lockdown related to the COVID 19 pandemic. The impact of COVID and lockdown on the dynamics of pediatric poisonings was not the objective of our study. However, results do not seem to show a major change in the dynamics of these events that is associated with lockdown, and thus with school closures. It seems to be more an increase throughout the year of this problematic. Our results were consistent with an American study conducted in 2020, which also found no "lockdown" effect on a potential increase in hospitalisations due to pediatric poisonings [START_REF] Levine | Evaluating the impact of home quarantine during the coronavirus pandemic on pediatric exploratory ingestions[END_REF][START_REF] Lelak | COVID-19 and Pediatric Ingestions[END_REF]. The hypotheses considered were an increased vigilance of adults in charge of children and/or a fear of catching COVID on the way to the hospital. A qualitative study among parents could be informative in this context.

CONCLUSION

Throughout this study, we pointed out the importance of accidental ingestion and foreign body accidental insertion in ear nose and eye, with 974 in three years, representing around 1% of all the visits in our studying period.

These emergencies consultations generated additional examinations, a significant waiting time in the PECU, and hospitalizations in significant proportions. We have seen that symptomatic children were requiring the most examinations and hospitalizations, and in this population the per os way was predominant.

Most of these accidents took place at home in the presence of witnesses, so it is essential to improve prevention and education of parents on this issue. To improve these primary prevention measures, a prospective study is required to better understand these accidents.

This study is the first step of a research project, a future prospective and multicentric cohort of accidental ingestions in children, initiated by Nantes University Hospital. It will allow a better identification of the determinants, and a much more exhaustive collection of data. For example, more precise circumstantial data (in which room of the house, time of ingestion), the socialeconomic level of the families victims of these accidents, a more detailed analysis of the therapeutics (fibroscopy, surgery), the length of stay in the pediatric emergency room as well as the length of hospitalization. This broad follow-up will also allow us to set up primary prevention measures, at the level of parents, practitioners, but also at the level of the product manufacturers. It will also help us to trigger more effective care for children victims of these -Méthode: Nous avons réalisé une étude unicentrique rétrospective descriptive. Nous avons inclus tous les enfants de moins de 6 ans, ayant consulté aux urgences pédiatriques de Nantes entre 2018 et 2020 pour une ingestion accidentelle médicamenteuse ou de produits toxiques, ainsi que les enfants ayant été exposés à des corps étrangers par voie per os, intra nasale, intra auriculaire ou intra ophtalmique.

-Résutats: 974 enfants ont été inclus, l'âge moyen des enfants était de 3 ans (écart type: 1,55 ans), 53,5% des enfants étaient des garçons, 87 % des accidents avaient eu lieu au domicile de l'enfant, 83,8% des cas étaient secondaires à une exposition per os, intra nasale, intra auriculaire ou ophtalmologique des corps étrangers, 9,7 % à des intoxications médicamenteuses et 7,5% à des ingestions de produits toxiques. 40,9% des enfants étaient symptomatiques, 42,8% des enfants ont eu un examen d'imagerie, 6,7 % un bilan biologique. 85,7% des enfants sont rentrés à domicile, 13,6% ont été hospitalisés dans le service de pédiatrie générale, 0,7% dans une unité de soins intensifs pédiatrique. La population d'enfants symptomatiques était plus jeune (2,76 ans), avec plus fréquemment des ingestions per os (84,2%), les examens complémentaires étaient plus fréquents, ainsi que les hospitalisations (pédiatrie conventionnelle (23,9%) ou soins intensifs (1,8%)).

-Conclusion: Avec plus de 300 consultations par an, ce travail souligne la fréquence des recours aux urgences pédiatriques des enfants de moins de 6 ans pour suspicion d'ingestion, d'inhalation et d'exposition involontaires à des corps étrangers, médicaments et ou de toxiques. Aux vues de ces résultats, il semble important de sensibiliser les personnes en charge d'enfants en bas âge, à ces accidents domestiques afin de pouvoir les prévenir et diminuer leur nombre.

MOTS-CLES : URGENCES PEDIATRIQUES, INTOXICATIONS ACCIDENTELLES, CORPS ETRANGERS, PRODUITS TOXIQUES

⎯⎯⎯⎯

  Présentée et soutenue publiquement le 14 janvier 2022 ⎯⎯⎯⎯ Etude des cas d'intoxications et d'expositions accidentelles aux corps étrangers aux urgences pédiatriques du CHU de Nantes entre 2018 et 2020 ⎯⎯⎯⎯ Président : Professeur Christèle Gras Le Guen Directeurs de thèse : Docteur Karine Levieux, Docteur David Boels,TABLE DES MATIERES REMERCIEMENTS .................................................................................................................. TABLE DES MATIERES ......................................................................................................... STUDY OF CASES OF INTOXICATION AND ACCIDENTAL EXPOSURE TO FOREIGN BODIES IN THE PEDIATRIC EMERGENCY CARE UNIT OF NANTES UNIVERSITY HOSPITAL BETWEEN 2018 AND 2020 ................................................................................. Introduction: ............................................................................................................................ Methods: ................................................................................................................................. Results: .................................................................................................................................... Discussion: ............................................................................................................................ CONCLUSION ........................................................................................................................ BIBLIOGRAPHY .................................................................................................................... SERMENT D'HIPPOCRATE ................................................................................................. RESUME ..................................................................................................................................

  Clinical symptoms: ENT (ear, nose, throat) or respiratory symptoms; digestive symptoms; neurological symptoms; other clinical symptoms; symptoms persistence in the PECU. Medical care: Biological analyses, blood or urinary toxicology research, X rays, CT or MRI scans. Treatments such as activated charcoal, gastric fibroscopy and ENT fibroscopy (technique for search and remove the foreign body), surgery, and the further patient orientation (discharged or hospitalized).

Figure 1 :

 1 Figure 1: Flowchart of the study, 2018-2020 Nantes PECU.

Figure 2 :

 2 Figure 2: Distribution of our population per year, 2018-2020 Nantes PECU, n = 974

  was symptomatic, symptoms were generally reported by the parents or direct witnesses of the accident.

  accidents. PRENOM : Gaëtan Titre de Thèse : Etude des cas d'intoxications accidentelles et d'expositions accidentelles aux corps étrangers aux urgences pédiatriques du CHU de Nantes entre 2018 et 2020 RESUME -Introduction: Lors de leurs premières années de vie, les enfants sont exposés dans leur environnement à de multiples objets et produits plus ou moins dangereux. Les ingestions, inhalations et intoxications accidentelles sont fréquemment responsables de consultations dans les services d'urgences pédiatriques voire d'hospitalisations. Notre objectif principal était de décrire les caractéristiques épidémiologiques ainsi que les modalités de la prise en charge des enfants de moins de 6 ans ayant consulté aux urgences pédiatriques du CHU de Nantes pour ces motifs.

Table 1

 1 Circumstances and mechanism of the accident, 2018-2020 Nantes PECU n = 974 :

	Variables	Modalities	Population n (%) Asymptomatic n (%) Symptomatic n (%)	p-value
	Effective		974	576	398
	Patients data
	Gender	Male	521 (53.5)	301 (52.3)	220 (55.3)	0.388
		Female	453 (46.5)	275 (47.7)	178 (44.7)
	Age (mean (SD))		3.08 (1.55)	3.29 (1.45)	2.76 (1.64)	<0.001
	General accident
	data
	Accident year	2018	224 (23.0)	124 (21.5)	100 (25.1)	0.346
		2019	348 (35.7)	214 (37.2)	134 (33.7)
		2020	402 (41.3)	238 (41.3)	164 (41.2)
	Accident place	Home	582 (87.1)	304 (86.9)	278 (87.4)	0.426
		School	40 (6.0)	24 (6.9)	16 (5.0)
		Public place (road, shop, restaurant)	21 (3.1)	8 (2.3)	13 (4.1)
		Other	25 (3.7)	14 (4.0)	11 (3.5)
	Accident	Visualized accident	592 (60.8)	377 (65.5)	215 (54.0)	<0.001
	circumstance	Suspected accident	346 (35.5)	186 (32.3)	160 (40.2)	<0.001
		Initially unsuspected accident	24 (2.5)	2 (0.3)	22 (5.5)	0.014
	Accident way	Oral route	630 (64.7)	295 (51.2)	335 (84.2)	<0.001
		Intra nasal	230 (23.6)	204 (35.4)	26 (6.5)
		Intra auricular	80 (8.2)	66 (11.5)	14 (3.5)
		Intra ocular	34 (3.5)	11 (1.9)	23 (5.8)
	Accident agent	Foreign body	816 (83.8)	483 (83.9)	333 (83.7)	0.868
		Drug	94 (9.7)	70 (12.2)	24 (6.0)	0.002
		Toxic product	65 (6.7)	24 (4.2)	41 (10.3)	<0.001
	We found an increase in the proportion of our accidents over the global population consulting
	the PECU: 0.62% in 2018 (224 accidents for 35,883 consultations), 0.98% in 2019 (348
	accidents for 35,406 consultations) and 1.6% in 2020 (402 accidents for 24,867 consultations).

NB: A child swallowed 1 foreign body and 1 drug (total of accident agent = 975), in accident place 306 files (31.4%) were without information, and in accident circumstance 12 files (1.2%) were without information.

Table 2 :

 2 Clinical symptoms, 2018-2020 Nantes PECU, n = 398

	Clinical symptoms	Symptomatic children n (%)
	Respiratory and ENT(ear, nose, throat) symptoms	272 (68.3)
	Penetration syndrom	45 (11.3)
	Oxygen requirement	4 (1.0)
	Cough	144 (36.2)
	Hypersialorea	59 (14.8)
	Digestive symptoms	124 (31.1)
	Vomiting	74 (18.6)
	Neurological symptoms	37 (9.3)
	Consciousness disorder	12 (3.0)
	Cerebellum syndrom	9 (2.3)
	Cardiological symptoms	0 (0.0)
	Persistant clinical symptoms in the PECU	91 (22.9)
	Total	433 (108.7)

Table 3 :

 3 Class of foreign bodies, 2018-2020 Nantes PECU n = 816

	Class of foreign bodies	Population n (%)	Asymptomatic n (%)	Symptomatic n (%)	p-value
	Toy	132 (16.2)	82 (17.0)	50 (15)
	Food	130 (15.9)	43 (8.9)	87 (26.1)
	Jewel	96 (11.8)	82 (17.0)	14 (4.2)
	Button battery	72 (8.8)	61 (12.6)	11 (3.3)	<0.001
	Coin	65 (8.0)	31 (6.4)	34 (10.2)
	Office material	61 (7.5)	37 (7.7)	24 (7.2)
	Plant	38 (4.7)	21 (4.3)	17 (5.1)
	Metallic hardware	34 (4.2)	18 (3.7)	16 (4.8)
	Magnet	11 (1.3)	9 (1.9)	2 (0.6)
	Other	177 (21.6)	99 (20.5)	78 (23.4)
	Total	816 (100.0)	483 (100.0)	333 (100.0)
	The most common foreign bodies were toys (132, 16.2%), food (130, 15.9%), button battery
	(72, 8.8%), coins (65, 8.0%), metallic hardware (nail, screw, metal) (34, 4.2%), non toxic plant
	(38, 4.7%), magnet (11, 1.3%).

Table 4 :

 4 Class of drugs, 2018-2020 Nantes PECU, n = 94.

	Class of drugs	Population n (%)	Asymptomatic n (%)	Symptomatic n (%)	p-value
	Analgesic	38 (40.0)	31 (44.3)	7 (28.0)
	Anxiolytic	9 (9.5)	2 (2.9)	7 (28.0)
	Cardiotropic	9 (9.5)	9 (12.9)	0 (0.0)
	Anti-emetic	4 (4.2)	4 (5.7)	0 (0.0)	0.001
	Antipsychotic	4 (4.2)	2 (2.9)	2 (8.0)
	Antispasmodic	4 (4.2)	4 (5.7)	0 (0.0)
	Antidepressant	3 (3.2)	2 (2.9)	1 (4.0)
	Antihistaminic	3 (3.2)	3 (4.3)	0 (0.0)
	Hypnotic	2 (2.1)	0 (0.0)	2 (8.0)
	Anti-diabétic	2 (2.1)	2 (2.9)	0 (0.0)
	Opiate substitution therapy	2 (2.1)	0 (0.0)	2 (8.0)
	Nonsteroidal anti-inflammatory	2 (2.1)	2 (2.9)	0 (0.0)
	Corticosteroid	2 (2,1)	2 (2.9)	0 (0.0)
	Other	11 (11.6)	7 (10.0)	4 (16.0)
	Total	95 (100.0)	70 (100.0)	25 (100.0)

Table 5 :

 5 Class of toxic products, 2018-2020 Nantes PECU, n = 65.

	Class of toxic products	Population n (%)	Asymptomatic n (%) Symptomatic n (%)	p-value
	Household product	27 (41.5)	13 (54.2)	14 (34.1)
	Cannabis Petroleum by-product	12 (18.5) 2 (3.1)	1 (4.2) 0 (0.0)	11 (26.8) 2 (4.9)	0.001
	Cosmetic product	7 (10.8)	2 (8.3)	5 (12.2)
	Other	17 (26.2)	8 (33.3)	9 (22.0)
	Total	65 (100.0)	24 (100.0)	41 (100.0)

Table 6 :

 6 Orientation and clinical evolution, 2018-2020 Nantes PECU, n = 974:

	Variables	Modalities	Population	Asymptomatic	Symptomatic	p-value
			n (%)	n (%)	n (%)
	Orientation	Discharged home	835 (85.7)	539 (93.6)	296 (74.4)	<0.001
		Hospitalization in pediatric care	132 (13.6)	37 (6.4)	95 (23.9)
		Hospitalization in intensive care unit	7 (0.7)	0 (0.0)	7 (1.7)
	Clinical	Recovery	973 (99.9)	576 (100.0)	397 (99.7)	0.852
	evolution	Sequels	1 (0.1)	0 (0.0)	1 (0.3)
		Death	0	0	0

Table 7 :

 7 Medical care, 2018-2020 Nantes PECU, n = 974 :

	Variables	Modalities	Population	Asymptomatic	Symptomatic	p-value
			n (%)	n (%)	n (%)
	Further	Biological test	62 (6.4)	29 (5.0)	33 (8.3)	0.056
	examination	Toxic test (blood or urinary test)	50 (5.1)	21 (3.6)	29 (7.3)	0.017
		X-Ray	372 (38.2)	171 (29.7)
		ENT (ear, nose, throat) endoscopy	96 (9.9)	27 (4.
		Gastric fibroscopy	25 (2.6)
		Cerebral CT scan	7 (0.7)
		Cerebral MRI	2 (0.2)

SERMENT D'HIPPOCRATE

Au moment d'être admis à exercer la médecine, je promets et je jure d'être fidèle aux lois de l'honneur et de la probité.

Mon premier souci sera de rétablir, de préserver ou de promouvoir la santé dans tous ses éléments, physiques et mentaux, individuels et sociaux.

Je respecterai toutes les personnes, leur autonomie et leur volonté, sans aucune discrimination selon leur état ou leurs convictions. J'interviendrai pour les protéger si elles sont affaiblies, vulnérables ou menacées dans leur intégrité ou leur dignité. Même sous la contrainte, je ne ferai pas usage de mes connaissances contre les lois de l'humanité. J'informerai les patients des décisions envisagées, de leurs raisons et de leurs conséquences. Je ne tromperai jamais leur confiance et n'exploiterai pas le pouvoir hérité des circonstances pour forcer les consciences.

Je donnerai mes soins à l'indigent et à quiconque me les demandera. Je ne me laisserai pas influencer par la soif du gain ou la recherche de la gloire.

Admis dans l'intimité des personnes, je tairai les secrets qui me seront confiés. Reçu à l'intérieur des maisons, je respecterai les secrets des foyers et ma conduite ne servira pas à corrompre les moeurs.

Je ferai tout pour soulager les souffrances. Je ne prolongerai pas abusivement les agonies. Je ne provoquerai jamais la mort délibérément.

Je préserverai l'indépendance nécessaire à l'accomplissement de ma mission. Je n'entreprendrai rien qui dépasse mes compétences. Je les entretiendrai et les perfectionnerai pour assurer au mieux les services qui me seront demandés. J'apporterai mon aide à mes confrères ainsi qu'à leurs familles dans l'adversité.

Que les hommes et mes confrères m'accordent leur estime si je suis fidèle à mes promesses ; que je sois déshonoré et méprisé si j'y manque.

Discussion:

Who is exposed and how?

With an average age of 3 years old and a strong male predominance, the population studied in our work was similar to the various studies which found a majority of boys under 4 years old [START_REF] Mintegi | Emergency visits for childhood poisoning: a 2-year prospective multicenter survey in Spain[END_REF][START_REF] Santiago | Intoxications Working Group of the Spanish Society of Pediatric Emergencies. Epidemiology of acute pediatric poisonings in Spain: a prospective multicenter study from the Spanish Society of Pediatric Emergency Medicine[END_REF][START_REF] Chung | A Review of Pediatric Foreign Body Ingestion and Management[END_REF][START_REF] Kurowski | Caustic Ingestions and Foreign Bodies Ingestions in Pediatric Patients[END_REF]. We have shown that these accidents were involved in about 1% of annual visits in the PECU of the Nantes university hospital, thus a non-negligible part of the activity of this hospital unit. In our study, we observed that the oral way was the most current accidental way, as found in other studies [START_REF] Oyama | Foreign Bodies of the Ear, Nose and Throat[END_REF][START_REF] Aksakal | Management of foreign bodies in the ear, nose and throat in children: a review of 829 cases from Northern Anatolia[END_REF]. These accidents of everyday life occurred more often in the children house. In an American study, nearly 80% of accidental poisoning in children were due to a lack of supervision [START_REF] Schillie | Medication overdoses leading to emergency department visits among children[END_REF]. However, in our study, accidents were visualised by those around the children in the majority of cases. This high proportion of visualized accident was also found in others studies [START_REF] Mintegi | Emergency visits for childhood poisoning: a 2-year prospective multicenter survey in Spain[END_REF][START_REF] Lamireau | Epidemiology of poisoning in children: a 7-year survey in a paediatric emergency care unit[END_REF].

In literature we found factors endogenous to children [START_REF] Raynal | Les intoxications du jeune enfant aux produits domestiques: rôle du pharmacien d'officine[END_REF]. Children under 6 years of age were in the midst of psychomotor development, discovering their environment, exploring it, and searching autonomy. These young children who are curious, spontaneously put everything they find in their immediate environment in their mouths without being aware of the danger of the product. As we had seen previously, in our study accidental intoxications occured more often in boys, which was also found in the literature with approximately 60% of accidental intoxications attributed to boys [START_REF] Brito | Accidental intoxication of the infant-juvenile population in households: profiles of emergency care[END_REF][START_REF]Les intoxications aiguës accidentelles de l'enfant : aspects épidémiologiques, étiologiques et évolutifs au CHU pédiatrique Charles-de-Gaulle de Ouagadougou (Burkina Faso[END_REF][START_REF] Franklin | Unintentional child poisonings treated in United States hospital emergency departments: national estimates of incident cases, population-based poisoning rates, and product involvement[END_REF][START_REF] Masson | Ingestion de corps étrangers aimantés chez l'enfant : enquête multicentrique française[END_REF]. Other factors such as personality, emotional development, the presence of any disability and hyperactivity also played a role in the occurrence of intoxication [START_REF] Turgut | Prevalence of attention deficit hyperactivity disorder (ADHD) in children presenting with foreign body ingestion[END_REF]. We also distinguished between exogenous factors directly linked to the child's environment, such as family factors (separated, blended family, etc.), cultural, socio-economic and material environment [START_REF] Masson | Tantivit, Phiuphong, Pattapong, Siripan. Foreign Body Ingestion in Pediatrics: Distribution, Management and Complications[END_REF]. In addition, an American study had shown that the mechanism of imitation of adult behaviour (taking a medicine in front of the child, for example) could account for around 20% of accidental poisoning by oral ingestion in children under 6 years of age [START_REF] Franklin | Unintentional child poisonings treated in United States hospital emergency departments: national estimates of incident cases, population-based poisoning rates, and product involvement[END_REF].

When the accident was not visualized by witnesses but only suspected, the accident was confirmed in only 10% of cases, maybe some emergency room visits and many additional examinations could be avoid. Our main objective was to describe the epidemiological characteristics and the management of children who consulted the pediatric emergency department of the Nantes University Hospital for these reasons.

-Methods: We conducted a single-center retrospective descriptive study. We included all children under 6 years who consulted the pediatric emergency department of Nantes between 2018 and 2020 for accidental ingestion of drugs or toxic products, as well as children who were exposed to foreign bodies by per os, intra nasal, intra auricular or intra ophthalmic way.

-Results: 974 children were included, the average age of the children was 3 years (SD: 1.55 years), 53.5% of the children were boys, 87% of the accidents took place in the child's home, 83.8% of the cases were secondary to per os, intra nasal, intra auricular or ophthalmic exposure to foreign bodies, 9.7% to drug intoxication and 7.5% to ingestions of toxic products. 40.9% of the children were symptomatic, 42.8% of the children had an imaging examination, 6.7% a biological workup. 85.7% of the children were discharged home, 13.6% were hospitalized in the general pediatric service, 0.7% in a pediatric intensive care unit. The population of symptomatic children was younger (2.76 years), with more frequent per os ingestions (84.2%), more frequent complementary examinations, and more frequent hospitalizations (conventional pediatrics (23.9%) or intensive care (1.8%)).

-Conclusion: With more than 300 consultations per year, this study highlights the frequency of pediatric emergency room visits for children under 6 years for suspected ingestion and involuntary exposure to foreign bodies, drugs, or toxic substances. In view of these results, it seems important to make people in charge of young children aware of these domestic accidents in order to prevent them and reduce their number.

KEYWORDS: PEDIATRIC EMERGENCIES, ACCIDENTAL POISONING, FOREIGN BODIES, TOXIC PRODUCTS