Deliberate Fingolimod Overdose Presenting with Delayed Hypotension and Bradycardia Responsive to Atropine

Introduction

Fingolimod is an immunomodulating agent used in multiple sclerosis (MS). It is a sphingosine-1-phosphate (S1P) receptor agonist prescribed for relapsing forms of MS to delay onset of physical disability. As fingolimod is known to cause first-dose bradycardia, telemetry is recommended for the first 6 h post-dose. We present the first reported case of deliberate fingolimod overdose requiring atropine administration for bradycardia and hemodynamic instability.

Case report

A 33-year-old woman ingested 14 mg of fingolimod and 2 g of phenoxymethylpenicillin. After presenting to the emergency department 19 h later, she was initially hemodynamically stable (heart rate (HR) 60, blood pressure (BP) 113/89 mmHg). Two hours later, she then developed bradycardia (HR 48) and hypotension (87/57 mmHg). Despite intravenous fluids, stabilisation was only achieved after administration of atropine (300 μg). She was then admitted to the intensive care unit (ICU) for further monitoring where another episode of bradycardia and hypotension required atropine. She was monitored in the ICU for 48 h and then discharged on day 5 with no further episodes.

Discussion

Fingolimod is known to cause bradycardia in the first 6 h post first therapeutic dose. Following intentional overdose, onset of bradycardia occurred at 21 h post-ingestion and was associated with hypotension. Atropine was successful in treating bradycardia and associated hypotension.     

Mortality and care of eating disorders

Introduction

Eating disorders (EDs) are considered serious mental illnesses, with one of the highest lethality among psychiatric disorders, even though the issue of mortality due to these conditions is still controversial. The present study was aimed at comparing the mortality rate in a cohort of ED patients representative of the geographic area with that of the age and gender-matched general population of central Italy.

Methods

Patients were enrolled between 1994 and 2018, among those attending the eating disorders treatment network of the Florence area (EDTN), which is a regional multidisciplinary treatment reference center for EDs covering the clinical population of the metropolitan Florence area (Italy). The life status of participants was determined through linkage with the Regional Mortality Registry.

Results

A total of 1277 individuals with EDs were included, including 368 with Anorexia Nervosa (AN), 312 with Bulimia Nervosa (BN), and 597 individuals with Binge Eating Disorder (BED). Twenty-two patients (1.72%) died, during a median follow-up of 7.4 years. The mortality rates among ED patients did not significantly differ from that of the general population of the same age and sex with a Standardized Mortality Ratio (SMR) of 1.19, 95% CI 0.79–1.81. Only among BN patients, the mortality was significantly increased after 10 years from clinical evaluation (SMR 11.24, 95% CI 3.62–34.84).

Conclusion

The low mortality in EDs, compared to published studies, might be due to the EDTN treatment strategy, based on a large network which makes an integrated multidisciplinary team available for almost all the patients with EDs of the geographical area.     

Hemostasis and fibrinolysis in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a systematic review

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with microthrombosis, which can result from activated hemostasis, inhibited fibrinolysis, or both. We systematically searched the PUBMED and EMBASE databases to identify hemostatic or fibrinolytic parameters that can be used for the prediction or diagnosis of DCI, or that inform on the pathogenesis of DCI and may serve as treatment targets. We included 24 studies that fulfilled predefined criteria and described 39 biomarkers. Only one study fulfilled predefined criteria for high quality. Since no parameter on admission was associated with DCI and in none of the included studies blood was drawn at the time of clinical deterioration, none of the studied parameters can presently be used for the prediction or diagnosis of DCI. Regarding the pathogenesis of DCI, it was shown that compared with patients without DCI those with DCI had higher levels of von Willebrand factor and platelet activating factor in plasma 5 to 9 days after aSAH, membrane tissue factor in cerebrospinal fluid 5 to 9 days after aSAH, and D-dimer in plasma 11 to 14 days after aSAH. Confirmation in high-quality studies is needed to investigate whether these parameters can serve as targets for new intervention studies.     

Management of anticoagulated patients in dentoalveolar surgery: a clinical comparative study

This prospective, comparative, clinical study analyzed the postoperative bleeding risk of patients on anticoagulation therapy (AT) who were undergoing toot     

Smoking does not alter the dose-requirements and the pharmacodynamics of rocuronium

PURPOSE: Controversial data about the effect of smoking on the dose-requirements and the pharamcodynamics of rocuronium have been reported recently. This study was conducted to evaluate the dose-requirements and the pharmacodynamics of rocuronium in smokers using target controlled infusion. METHODS: The dose-requirements of rocuronium for 60 min relaxation, using target controlled infusion, given under intravenous anaesthesia with propofol, fentanyl and nitrous oxide was studied in 37 smokers and 37 non-smokers. Initially 450 microg x kg(-1) rocuronium were administered, neuromuscular effects were quantified by recording the single twitch response of the adductor pollicis muscle after ulnar nerve stimulation using a force transducer, and the neuromuscular block was kept at 80% by target controlled infusion throughout the procedure. RESULTS: The dose-requirements for one hour relaxation were 867 +/- 116 microg x kg(-1) x hr(-1) for smokers (S) and 839 +/- 149 microg x kg(-1) x hr(-1) for non-smokers (NS). The duration to 10% and the spontaneous recovery from 25% to 75% of the control twitch response also showed no differences between S (17.2 +/- 3.4 min, 10.6 +/- 0.9 min) and NS (18.9 +/- 4.3 min, 10.9 +/- 3.2 min), as well as maximum block, onset time and infusion rate. CONCLUSION: Smoking does not alter the dose-requirements for rocuronium and no effects on the onset time, degree of block, time to maximum block, duration 10% and spontaneous recovery index were observed.