领域：学术论文 · 自然科学

Comparison between pediatric and adult acute natural cannabinoids toxicity: A 5-year retrospective study with special consideration of acute synthetic cannabinoids toxicity
Abstract
Acute cannabinoids toxicity is an alarming toxicological problem. The current study aimed to compare children and adults with acute natural cannabinoids toxicity and highlight cases with acute synthetic cannabinoids (SCs) toxicity. This retrospective cross-sectional study was conducted on patients with acute cannabinoids toxicity admitted to Tanta University Poison Control Center from January 2019 to December 2023. Socio-demographic, toxicological, clinical, and laboratory data were retrieved from patients’ medical records. Patients were divided into a pediatric group (≤ 18 years) and an adult group (> 18 years). Out of 106 patients, 68 were children and 38 were adults. Impaired consciousness level and bradypnea were more significantly reported in children (P < 0.001, 0.007, respectively). Low oxygen saturation, tachycardia, hypokalemia, and leukocytosis were more significantly reported in adults (P < 0.001, for each). Delay time from exposure to medical intervention and potassium level were significantly valid to predict complications in children (Adjusted odds ratio: 1.393 and 4.139, respectively). Delay time to medical intervention and oxygen saturation were significant risk factors for prolonged hospital stay in children (Adjusted odds ratio: 1.255 and 0.677, respectively). Acute SCs toxicity was observed only in four cases presented mainly with seizures, tachycardia, hypertension, tachypnea, and hypoxemia. It could be concluded that natural cannabinoids toxicity is more prevalent than SCs. Presentation of acute natural cannabinoids toxicity exhibits variations between children and adults. Delay time to medical intervention, as well as potassium and oxygen saturation levels are significant risk factors for complications and prolonged hospitalization in children.

Keywords: Acute cannabis poisoning, Synthetic cannabinoids, Prediction, Outcomes

1. Introduction
Over the last decades, substance abuse has emerged as a significant health issue that strongly affects all countries. As defined by the World Health Organization (WHO), substance abuse is the hazardous use of psychoactive substances, including alcohol and illicit drugs with substantial risk of morbidity and premature death [1].

As other countries, Egypt is witnessing increasing rates of substance abuse while the exact prevalence is unavailable, most probably due to substantial social stigma and underreporting [2]. Some reports highlight the magnitude of the problem; in 2016, about 6.8 % of Egyptians aged above 15 years were involved in substance abuse [3]. Furthermore, in 2022, the Egyptian Ministry of Social Solidarity estimated that about 5.9 % of the total population consumed illicit drugs [4].

Globally, cannabis ranks third among abused substances after alcohol and tobacco as it is widely cultivated and trafficked with an ancient history of both medicinal and recreational uses [5], [6] . The annual prevalence rate of cannabis consumption has been estimated to be nearly 2.5 % of the global population [7]. In Egypt, different reports are available considering the prevalence of cannabis abuse. For example, it was reported that more than 9 % of Egyptian students are using bango and 3 % are depending on hashish [8].

Despite the fact that recreational cannabis use is known to be associated with a low risk of acute toxicity, recent reports indicate an increase in the potency of cannabis preparations, potentially leading to more visits to poison control centers due to accidental acute toxicity [9]. Furthermore, accidental ingestion of cannabis by children is also reported even in developed countries especially with legalization of medical and recreational marijuana [10]. Although it is an alarming toxicological problem, data regarding acute cannabis toxicity is still limited [11].

It is worth mentioning that the term cannabinoid refers to chemical substances that interact with cannabinoid receptors, producing effects similar to those of the Cannabis plant [12]. Depending on the source of production, cannabinoids are divided into endocannabinoids, phytocannabinoids and synthetic cannabinoids. The first group (endocannabinoids) is produced by mammalians while the second group (phytocannabinoids) is extracted from the cannabis plant and includes the most psychoactive Δ9-tetrahydrocannabinol (Δ9-THC) and non-psychoactive component cannabidiol. The third group involves a number of synthetic cannabinoids (SCs) which are sold for recreational use [13].

Toxicity from natural cannabinoids (marijuana) including hashish and bango can result from inhalation, smoking, or ingestion [14], [15], [16]. Manifestations are diverse depending on the patient’s age, cannabis potency, route of exposure, and combination with other psychoactive substances [17].

Basic treatment of acute cannabis toxicity is mainly supportive to keep a patent airway with adequate ventilation and circulation. Children presented with apnea and risk of aspiration need to be intubated and mechanically ventilated. However, those who are presenting with lethargy, rapid electrolytes and arterial blood gases, as well as random blood sugar measurement is considered. For patients with mild toxicity, benzodiazepine may be enough to control anxiety and agitation [18].

Regarding SCs, they are designer drugs with variable structure and potencies that mimic the psychoactive properties of Δ9-THC. In Egypt, they are traded under different names including strox and voodoo [16]. In 2014, they were added to Schedule No. 1 of the Egyptian Drugs Act [19]. Synthetic cannabinoids acquired their popularity because they are easily manufactured, so they are more accessible at low prices compared to cannabis. Additionally, they are not detected by standard toxicology screening for natural cannabis [15].

Despite the cannabomimetic effects of SCs, their side effects cannot be expected and may be more serious than the natural cannabis [20]. Acute toxicity could be due to Δ9-THC and additives like anticholinergic agents and ketamine [21]. However, acute strox intoxication is manifested by visual and auditory hallucinations, fright, speech impairments, and paranoia leading to aggressive behavior [22], [15]. It may also cause loss of concentration, delirium, vomiting, and fainting, as well as extreme fear of death and fatal convulsions [23]. Pupillary dilatation, tachycardia, flushed dry skin, and other anticholinergic toxidrome were also reported. In severe cases, lethal cardiovascular collapse and deep coma could occur [24]. Supportive and symptomatic care is the main line considered in the treatment of acute strox toxicity [25].

Considering that age could affect the characteristics of acute toxicity and the introduction of SCs into the market of substance abuse, this study aimed to compare clinical and laboratory findings of acute natural cannabinoids toxicity in the adults and pediatric group, together with highlighting cases presented with acute SCs toxicity.

2. Patients and methods
2.1. Study design and settings
The current retrospective cross-sectional study was conducted on all patients with acute cannabis or SCs toxicity who were admitted to Tanta University Poison Control Center (TUPCC) throughout five years from January 2019 to December 2023.

2.2. Ethical considerations
The current study was approved by our institution's ethics committee (approval code: 36264PR708/5/24) and followed the declaration of Helsinki. To secure confidentiality, patients’ data were coded for anonymous statistical analysis. The requirement for written informed consent was waived due to the retrospective nature of the study.

2.3. Eligibility criteria
All patients, males and females, with acute cannabis or SCs toxicity were included in the study. Diagnosis was based on definite history as reported from the patients or witnesses besides clinical assessment of the attending physician and urine screening test [26]. On the other hand, patients with known medical illnesses such as cardiovascular or neuropsychological diseases, renal or hepatic impairment, respiratory disorders such as asthma or chronic obstructive pulmonary disorders, and diabetes were excluded. Additionally, the current study excluded patients with mixed intoxication or those who received medical intervention before admission. Pregnant and lactating females were also excluded.

2.4. Data collection
The following variables were extracted from the medical records of each patient:

1.Socio-demographics: age, sex, and residence.
2.History of pre-existing medical disorders.
3.Toxicological data: name of substance, route, manner, and place of exposure, and delay time from exposure to medical intervention.
4.Findings of clinical examination:
•Vital signs: systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate (PR), respiratory rate (RR), temperature, and oxygen (O2) saturation.
•Level of consciousness using the Glasgow Coma Scale (GCS).
•Systemic examination: head & neck, neurological, chest, abdomen, skin, and extremities examination
•Electrocardiographic (ECG) findings
1.Results of laboratory investigations:
•Arterial blood gases (ABG): pH, partial arterial carbon dioxide pressure (PaCO2), partial arterial oxygen pressure (PaO2).
•Serum electrolytes: serum sodium (Na) and potassium (K) levels
•Serum random blood glucose level
•Glucose potassium (Glu/K) ratio was obtained by dividing serum random blood glucose level over serum potassium level
•Renal functions: blood urea nitrogen and serum creatinine.
•Liver enzymes: aspartate aminotransferase (AST) and alanine aminotransferase (ALT).
2.Outcome measures: mortality, intensive care unit (ICU) admission, and duration of hospital stay.
Patients were treated according to guidelines including emergency and supportive measures if indicated. Patients were divided according to their age into two groups: the pediatric group included patients whose age was 18 years or less and the adult group where the age of patients was above 18 years.

2.5. Statistical analysis
All data were tabulated and analyzed by the statistical package for the social sciences software program, IBM SPSS Statistics for Windows, version 27 (IBM Corp., Armonk, N.Y., USA). Categorical data were presented as numbers and percentages, while numerical data were first tested for normality by the Shapiro-Wilk test. Normally distributed numerical data were expressed as the mean ± standard deviation, while skewed numerical data were represented as median and interquartile range (IQR: 25th −75th percentiles). Comparisons between the studied groups were done by applying Pearson’s Chi-Square test for categorical data. When more than 20 % of cells have expected count of less than 5 Fisher’s Exact and Fisher-Freeman-Halton Exact tests was adopted instead of Pearson’s Chi-Square test. Normally distributed numerical data were compared by the Independent Samples T-test. Alternatively, Mann-Whitney U test was performed to compare skewed data. For determining risk factors of complicated outcome and prolonged hospital stay among the studied children group, univariable and multivariable logistic regression analyses were performed. As regards multivariable logistic regression, all variables that showed significant results in the bivariate analysis were selected as covariates. Results were presented as adjusted odds ratio (AOR) and 95 % confidence interval. P < 0.05 was considered statistically significant.

翻译考点：
考点 1："Acute cannabinoids toxicity" 应译为 "急性大麻素毒性"
考点 2："Impaired consciousness level" 应译为 "意识障碍"
考点 3："leukocytosis" 应译为 "白细胞增多症"
考点 4："Adjusted odds ratio" 应译为 "校正后比值比"
考点 5："Outcomes" 应译为 "临床结局"
考点 6："morbidity and premature death" 应译为 "发病率和过早死亡"
考点 7："prevalence" 应译为 "流行率"
考点 8："bango and hashish" 应译为 "班戈和哈希什"
考点 9："poison control centers" 应译为 "中毒控制中心"
考点 10："patent airway" 应译为 "保持气道通畅"
考点 11："intubated and mechanically ventilated" 应译为 "气管插管和机械通气"
考点 12："designer drugs" 应译为 "设计毒品"
考点 13："strox and voodoo" 应译为 "斯特罗 和 巫毒"
考点 14："cannabomimetic effects" 应译为 "拟大麻素作用"
考点 15："anticholinergic toxidrome" 应译为 "抗胆碱能毒性症候群"
考点 33："lethal cardiovascular collapse" 应译为 "致死性心血管衰竭"
考点 34："waived" 应译为 "豁免"
考点 35："Eligibility criteria" 应译为 "纳入标准"
考点 36："mixed intoxication" 应译为 "混合中毒"