Clinical Toxicology最新文献

Introduction: Consensus guidelines for out-of-hospital assessment and triage of paracetamol (acetaminophen) exposure were published in 2006. Changes in the healthcare system, paracetamol ingestion trends, and availability of paracetamol-containing products necessitate an update to these guidelines. Updated guidelines were created for out-of-hospital management of paracetamol exposure in the United States and Canada.

Methods: A modified Delphi consensus methodology was used to create a decision framework to evaluate clinical aspects of care related to paracetamol overdose in the out-of-hospital setting. Twenty-one panelists were selected by four clinical toxicology societies (America's Poison Centers®, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association for Poison Centres and Clinical Toxicology) to participate as panelists. Guidelines were collected from most poison centers in the United States and Canada, and systematic collection and review of medical literature was conducted.

Results: The panel developed a guideline for out-of-hospital management of paracetamol exposure that encompasses acute and repeated supratherapeutic ingestion patterns. Acute ingestion is defined as any ingestion presenting within 24 h of initial ingestion, regardless of ingestion pattern. Repeated supratherapeutic ingestion is defined as an exposure that occurs over a period of 24 h or more. This guideline emphasizes the importance of obtaining accurate history. When ingestion history is determined as accurate, dosage and ingestion pattern are used to decide treatment referral. It is recommended that patients be referred to the emergency department if their ingestion amount is: (1) ≥200 mg/kg or 10 g (whichever is less) within 24 h; (2) ≥150 mg/kg/24 h or 6 g/day (whichever is less) within 48 h; (3) ≥100 mg/kg/24 h or 4 g/day (whichever is less) for more than 48 h.

Discussion: The need for standardizing the out-of-hospital assessment and triage of paracetamol exposure is pressing. Despite the availability of acetylcysteine, some patients develop fatal liver failure due to missed diagnoses and delays in treatment. Failure to recognize cases requiring acetylcysteine is associated with significant morbidity and mortality.

Conclusion: This consensus statement provides evidence-based guidance for out-of-hospital management of paracetamol ingestion to standardize healthcare facility referral criteria for paracetamol exposed patients.

Introduction: Metformin is a biguanide medication thought to contribute to increased insulin sensitivity. It does not induce insulin release or act via insulin receptors, so it is not considered a common cause of hypoglycemia, even in overdose. However, massive metformin overdoses may be associated with severe hypoglycemia as well as hypothermia.

Methods: Four patients who had hypoglycemia after metformin overdoses are presented. None had access to other diabetic medications or a known diagnosis of diabetes mellitus.

Results: Severe hypoglycemia (blood glucose concentration <2.2 mmol/L [<39.6 mg/dL]) in all patients was diagnosed on presentation or within 9 h of initial presentation. Peak serum lactate concentrations were observed after hypoglycemia in each patient. Three patients developed hypothermia. Three patients received extracorporeal therapy; hemodialysis (one), continuous kidney replacement therapy (one), both modalities (one). One patient died. The remainder were discharged home within 2-6 days of presentation.

Discussion: The complex mechanisms of metformin may explain the observed progression of manifestations following large metformin overdoses.

Conclusion: Large metformin ingestions exceeding 60 g can be associated with critically low serum glucose concentrations concurrently with or preceding increases in serum lactate concentrations. Hypothermia may also occur. Further study is needed to determine the exact mechanisms and true incidence of this manifestation, which may be underrecognized.

Background: Propanil toxicity is characterised by severe prolonged methaemoglobinaemia, cyanosis, acidosis, and progressive end-organ dysfunction. In vitro studies report propanil-induced kidney toxicity, which has not been studied clinically. This study determined the incidence of acute kidney injury and of methaemoglobinaemia after propanil self-poisoning and reported the diagnostic performance of novel and traditional biomarkers of acute kidney injury.

Methods: Sixty-seven previously healthy patients were recruited following acute propanil self-poisoning, between October 2010 and October 2014. Concentrations of serum biomarkers and urine biomarkers normalised for urine creatinine excretion were measured. Plasma and urine concentrations of propanil, its main metabolite 3,4-dichloroaniline, the antidote methylthioninium chloride (methylene blue), and methaemoglobin levels were measured.

Results: Kidney biomarkers were measured in 52 of the 67 patients, with 40% developing acute kidney injury (stage 1 [32%] and stage 2 [8%]). Blood methaemoglobin levels were recorded in 23 patients. Normalised urine biomarker concentrations of kidney injury molecule-1, trefoil factor 3, neutrophil gelatinase-associated lipocalin and beta₂ microglobulin increased in patients who developed acute kidney injury, but only trefoil factor 3 and cystatin C showed a significantly predicted acute kidney injury at 16-24 h and 8-16 h post-ingestion, respectively. In contrast, serum creatinine concentrations had a very good diagnostic performance throughout the 24 h post-ingestion period, with area under the receiver operating characteristic curve values of 0.79-0.96. Blood methaemoglobin levels were higher in patients with acute kidney injury and correlated with plasma propanil and 3,4-dichloroaniline concentrations. Concentrations of serum creatinine, urine beta₂ microglobulin, and trefoil factor-3 significantly correlated with plasma and urine concentrations of propanil, 3,4-dichloroaniline, and methylthioninium chloride.

Discussion: Severe methaemoglobinaemia can impair oxygen delivery and may cause acute ischaemic kidney injury. The poor diagnostic performance of novel biomarkers may be attributed to non-renal factors influencing creatinine concentration or an unusual site or mechanism of nephrotoxicity after propanil poisoning.

Conclusions: Patients with propanil self-poisoning exhibited reversible kidney injury diagnosable using serum creatinine concentrations within 4 h. Although other biomarkers were increased, they were not effective for early diagnosis.

Introduction: Ivabradine was approved for use in the United States in 2015 for the management of heart failure. It acts through inhibition of sodium channels found in cardiac myocytes (the "funny" pacemaker current, I_f), which reduces heart rate without significantly affecting inotropy.

Methods: We queried the National Poison Data System^® for reported ivabradine exposures from April 15, 2015-December 31, 2023. Age was stratified into child (0-5 years), adolescent (6-17 years), adult (18-64 years) and geriatric (65+ years). Other descriptive statistics gathered included patient sex, management site, and medical outcome as coded by America's Poison Centers^®.

Results: There were 240 ivabradine exposures, with 55.0% managed on-site and not transferred to a healthcare facility. The most common reported symptom was bradycardia, reported in 36 patients (15.1%). There were 139 cases that were followed to a known outcome. Within this cohort, 60%, 14%, and 27% of patients suffered no effect, minor effect, or moderate effect, respectively. Exposures in children comprised 18.8% of cases; none required intervention. Intentional self-harm exposures comprised 17.1% of all cases and were more likely to have worse outcomes. Five adult patients received intensive therapy (endotracheal intubation, vasopressors, cardiac pacing, hemodialysis). There were no reported deaths from ivabradine exposure.

Discussion: This study has limitations. First, our data source was limited by being retrospective and incomplete; we could only study the information that was reported to poison centers, and exposures were not confirmed by laboratory testing. It is possible that cases without further follow-up had other treatments and clinical effects not reported here. Finally, reports to poison centers likely underestimate the true number of ivabradine exposures.

Conclusion: Adults with unintentional, asymptomatic exposures to ivabradine may be candidates for home monitoring. In ivabradine exposures refractory to medical management, clinicians should consider cardiac pacing or other supportive measures as a temporizing measure.

Introduction: In November 2020, Oregon passed Measures 109 and 110 altering the legal landscape for psychoactive substances by regulating psilocybin use and decriminalizing possession of Schedule I substances. This coincided with the growth of the commercial nootropic (cognitive enhancers) mushroom industry, including products such as mushroom gummies marketed for "legal highs." Despite these product claims, concerns have been raised about their safety profile. Our study aimed to assess the accuracy of labeling of these products and quantify their psychoactive contents.

Methods: Eight gummy products were procured from seven different smoke and vape shops in Portland, Oregon. Gummy samples were homogenized and analyzed using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Products were screened for psychoactive compounds, including psilocybin, psilocin, and their analogues, as well as for purported Amanita muscaria derivatives. Quantitative analysis of identified compounds was performed using isotope dilution.

Results: Neither ibotenic acid nor muscimol, the active components of Amanita muscaria, were detected in the two products claiming to contain Amanita muscaria extracts. However, these products contained psilocin and tryptamine derivatives. One product labeled as psilocybin-free tested positive for psilocybin. Another sample claiming to be nootropic contained undisclosed Δ9-tetrahydrocannabinol. Overall, seven of the eight products contained psilocin, and six contained 4-acetoxy-N,N,dimethyltryptamine. Other detected compounds included various tryptamine congeners and kavalactones.

Discussion: Labeling was inaccurate and inconsistent in many of the products examined. Users are likely to experience psychoactive symptoms considering the concentrations of xenobiotics determined. Serotonergic effects are expected from products containing tryptamine derivatives, including those inaccurately labeled as containing Amanita muscaria extracts.

Conclusions: The labeling of psychoactive mushroom gummies we tested was overall inaccurate. Products suggesting Amanita muscaria content instead contained serotonergic tryptamines, including some which falsely claimed to be free of psilocybin.

Introduction: The persistent increase in the use of 3,4-methylenedioxymetamfetamine has led to an increase in emergency department presentations. Our aim was to study the most frequent reasons for admission to the intensive care unit of critically ill patients with 3,4-methylenedioxymetamfetamine intoxication and to describe their complications, management and outcome.

Methods: This retrospective cohort study included all patients with confirmed or self-reported 3,4-methylenedioxymetamfetamine intoxication admitted to the intensive care of a tertiary care hospital in Amsterdam between 2010 and 2020.

Results: Seventy-four patients (73% male) were included. Three patients (4%) died. The most common reason for intensive care admission was a threatened airway (n = 35, 47%) due to trismus, which led to respiratory acidosis in 25 patients (71%). Two patients developed aspiration pneumonia, and one patient developed a pneumothorax. Seventeen patients (39%) presented with hyponatraemia, of whom 65% were treated with hypertonic saline, leading to a median serum sodium concentration correction of 13 mmol/L (IQR 7-15 mmol/L) after 8 h. Lastly, eight patients (11%) presented with hyperthermia of whom seven patients received cooling therapy. All displayed secondary complications, such as rhabdomyolysis, acute kidney injury, acute liver injury, acute liver failure and disseminated intravascular coagulation. Patients with a temperature <39 °C did not develop complications of hyperthermia.

Discussion: Unlike other studies, trismus was the most common reason for intensive care unit admission in our study. Trismus, or its treatment with benzodiazepines, may lead to respiratory acidosis. The median correction of the serum sodium concentration in our population was greater than advised in the European guideline. The occurrence of osmotic demyelination was not reported.

Conclusion: The three most common complications of 3,4-methylenedioxymetamfetamine use necessitating intensive care admission were a threatened airway due to trismus, hyponatraemia and hyperthermia. Severe complications can arise, especially in patients presenting with hyperthermia. Although the majority of patients included in this study made a full recovery, 4% died.

Introduction: Hemodialysis has an essential role in the treatment of certain poisoned patients, both by enhancing the elimination of select poisons and correcting underlying fluid, electrolyte, and acid-base disturbances. We sought to identify barriers to the performance of hemodialysis when it was recommended by our poison center.

Methods: Data from a single United States poison center were retrospectively queried for adult patients for whom the poison center recommended intermittent hemodialysis for poison removal. The primary outcome was the performance of intermittent hemodialysis within 12 h of the poison center recommendation, which we defined as timely hemodialysis. Univariable and multivariable logistic regressions were performed to assess the effect of the following variables on this outcome: age group, patient sex, time of day of the recommendation, day of week of the recommendation, year of the recommendation, hospital location, and poison category.

Results: A total of 535 patient encounters were analyzed. The majority (72%) of patients had intermittent hemodialysis performed within 12 h of when it was recommended. The multivariable analyses showed that the odds of receiving recommended intermittent hemodialysis within 12 h were significantly lower when the recommendation was made during the nighttime (OR: 0.660; 95% CI: 0.442-0.987) compared to daytime and during the weekend (OR: 0.605; 95% CI: 0.398-0.918) compared to weekdays.

Discussion: Intermittent hemodialysis is resource-intensive and requires specialized equipment and personnel, which is likely less available outside of regular business hours. This study is limited by its retrospective nature and may not be generalizable to other poison centers.

Conclusion: Patients for whom our poison center recommended intermittent hemodialysis during non-weekday times had lower odds of receiving timely hemodialysis. Hospital administrators and healthcare providers should be aware of this potential treatment obstacle for poisoned patients and identify the specific barriers involved in order to facilitate timely hemodialysis.

Background: Pediatric nephrologists are rare in the United States; many children with poisoning needing extracorporeal treatments may not have timely access to care. This study compared outcomes in children receiving extracorporeal treatments for poisoning at centers with and without a pediatric nephrologist.

Methods: This was a retrospective cohort study of all patients aged ≤17 years reported to an American poison center covering three upper midwestern states during 2000-2024.

Results: We identified 72 patients: 54 received extracorporeal treatments at a hospital with pediatric nephrologists, and 18 patients aged 14-17 years (minimum weight, 35 kg) received extracorporeal treatments at hospitals staffed solely by adult nephrologists. The most common responsible poisons were toxic alcohols (10/18, 55%) and salicylates (4/18, 22%). Children receiving extracorporeal treatments from adult nephrologists more commonly (P <0.001) received intermittent hemodialysis (18/18, 100%) compared to pediatric nephrologists (31/54, 57%). Conversely, children treated by pediatric nephrologists more commonly (P <0.05) received continuous kidney replacement therapy (28/54, 52%) compared to adult nephrologists (0/18). We found no difference (P = 0.1) in mortality between the children treated by pediatric nephrologists (9/54, 17%) compared to those treated by adult nephrologists (0/18).

Discussion: Teenage children commonly received hemodialysis from adult nephrologists for poisoning and had similar outcomes to those treated by pediatric nephrologists.

Conclusions: These data suggest adult nephrologists can successfully perform extracorporeal treatments for poisoning in teenage children.