Payal Sud

The synthetic cannabinoid withdrawal syndrome.

Background:Little is known about the effects of synthetic cannabinoids. There has been only one previous report of a withdrawal syndrome from synthetic cannabinoids. We report two cases of a withdrawal syndrome from prolonged habitual use of synthetic cannabinoids. Discussion:Withdrawal from delta-9-THC has been described as a syndrome of anxiety, myalgias, chills, and anorexia. Synthetic cannabinoids are potent than delta-9-THC and thus the withdrawal syndrome is similar but more severe; however the symptoms do not seem to improve with delta-9-THC. The differences in presentation could be due to the fact that synthetic products may contain several heterogeneous compounds, including amphetamine-like substances. Conclusions:The acute withdrawal syndrome appears to be characterized mainly by anxiety and tachycardia in the absence of any neurological findings or electrolyte disturbances. We describe two patients with symptoms consistent with withdrawal presumably due to synthetic cannabinoid use. The most appropriate treatment for such patients remains unknown, however benzodiazepines are a reasonable first line approach and quetiapine may have some efficacy.

Assessment of serum S100B and neuron specific enolase levels to evaluate the neurotoxic effects of organic solvent exposure.

In the article by Z u ng u n et al., 1 the authors postulate that S100B and neuron-specifi c enolase levels can be used as markers of subclinical nervous system dysfunction in patients exposed to organic solvents. We commend the authors for attempting to fi nd objective markers of dysfunction after solvent exposure, however, we have some concerns regarding the study. The authors state that there is a statistically signifi cant difference in S100B levels between a group of workers exposed to organic solvents and a control group. The control group was reported to have no exposure to organic solvents, but this was not verifi ed through laboratory testing. Also, relevant baseline characteristics of the two groups, besides the age, creatinine and AST/ALT, are not provided. Additionally, although the difference in the median values of S100B is quoted as statistically signifi cant ( p 0.036), it does not seem clinically relevant when the ranges are compared (0.03 – 0.19 vs. 0.03 – 0.14). Finally, the only objective differences reported in Table 3 include positive EMG fi ndings in those exposed. As the population studied involves welders, it is quite possible that this fi nding is simply the result of another work-related disease such as carpal tunnel syndrome. In conclusion, although the authors have put in signifi cant efforts to fi nd a method of monitoring the effects of exposure to organic solvents, their fi ndings do not support these tests as likely to be clinically useful.

Randomized controlled study on the use of multiple-dose activated charcoal in patients with supratherapeutic phenytoin levels

In the article by Skinner et al., 1 a prospective randomized control study was performed to compare management of patients with supratherapeutic phenytoin levels by either observation alone or with multi-dose activated charcoal (MDAC). The authors state in their statistical power analysis that 19 patients would be needed in order for the data to have validity. However, only 15 patients completed the study. Further, the study excluded critically ill patients, whose participation would have allowed the evaluation of MDAC for supratherapeutic phenytoin levels in patients who need treatment the most. It is likely that a retroactive consent would have allowed their inclusion. Additionally, since study included only male patients with chronic overuse the data obtained cannot be widely extrapolated. Allowing more time to collect data or inclusion of another hospital into the study may have broadened the study and improved its external validity. Furthermore, the study ’ s control and experimental groups had dissimilar initial phenytoin concentrations. The authors correctly commented that this is a potential confounder. The two outliers in the control group that had concentrations of 47.6 mg/L and 45.6 mg/L, respectively (in Table 1 and Fig. 2), maintained a high phenytoin level for greater than 100 hours. This exceeds the time listed in ‘ The Time to Study Completion ’ column of Table 1. These two results skew the data and merit further discussion. These results could explain the lack of statistical signifi cance between the study ’ s subgroups of greater than or less than 40 mg/L at initial concentration. Removing these two outliers reveals very little difference between the control and experimental groups as a whole, leading one to question the effi cacy of MDAC in patients with phenytoin overdose. Lastly, the major question that arises from the study is: what is the utility and safety in reducing phenytoin concentrations? Phenytoin toxicity rarely leads to permanent neurological damage and drastically lowering levels may be detrimental to the patient, raising the risk for seizure and complicating redosing. In conclusion, we commend the authors ’ efforts in investigating the management of phenytoin toxicity. However, it is not yet clear that MDAC is safe, or necessary, in the management of patients with phenytoin toxicity.

Intravenous Droperidol or Olanzapine as an Adjunct to Midazolam for the Acutely Agitated Patient: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial

their hospitals board psychiatric patients for whom appropriate treatment resources could not be found, sometimes for days. The situation is so dire that EDs are now being designed and configured to house psychiatric patients awaiting placement (personal communication, Martin Batt, Isgenuity, August 2012). Given our small sample size, our results probably cannot be generalized. However, given that Massachusetts was the model for national health care reform and the greater Boston area has more psychiatric offerings than many other locales, the difficulty of accessing psychiatric services in most other parts of the United States is likely worse than what we found in our study. Emergency personnel and psychiatric patients deserve better.

Retrospective Chart Review of Synthetic Cannabinoid Intoxication with Toxicologic Analysis

Introduction Use of synthetic cannabinoids (SC) has recently emerged as a new drug epidemic. Our emergency departments (EDs) received a surge of SC users presenting with lethargy and bradycardia, contrasting prior reports of SC-induced tachycardia and agitation. Our goal was to describe these novel presentations and characterize the compounds. Methods We present a case series of patients with SC intoxication who presented to our toxicology service covering two tertiary care EDs between 2/11/2015 and 6/23/2015. A retrospective chart review recorded initial vital signs, chief complaint and clinical course. Urine, blood and xenobiotic samples were analyzed using either liquid chromatography/mass spectrometry or gas chromatography/mass spectrometry. We compared resulting spectra against databases containing numerous SCs or metabolites and scored based on a reference comparison. Results Between 2/11/2015 and 6/23/2015, we identified 141 visits. Males comprised 139 visits (age range 21–68 years; median 35, interquartile range 20). Sixty-eight percent presented with lethargy or loss of consciousness. Hypotension (SBP <90 mmHg) and bradycardia (HR<60 bpm) were seen in 10% and 24% of visits, respectively. While most patients were discharged after observation, three were admitted to the intensive care unit and seven to telemetry. Admissions were for vital sign instability, bradycardia requiring pacing, prolonged sedation and respiratory failure requiring mechanical ventilation. Laboratory analysis revealed SC in the XLR-11 family in 18/36 drug, 9/12 blood, and 23/31 urine samples. Carboxamide indazole derivative (CID) family compounds were detected in 13/36 drug samples, 21/31 urine samples, but no blood samples; 11/31 drug samples contained both XLR-11 and CID. Other compounds detected included PB-22 and nicotine. No JWH compounds, opiates, imidazoline receptor agonists, benzodiazepines or other sedative-hypnotics were detected. Conclusion Unlike their predecessors, novel SC may be associated with significant central nervous system depression and bradycardia. While prior reports indicated that SC mostly contained JWH compounds, none were detected in these samples. The most commonly identified compounds in this series were CID and alkyl SC derivatives, such as INACA compounds and XLR-11. These tend to be full agonists at the cannabinoid receptor and are presumably more potent. The lack of other depressants suggests that the clinical findings are due to the combination of these compounds and not coingestants or adulterants. SC intoxication should be considered for patients with undifferentiated psychomotor depression and bradycardia.

Hand Compartment Syndrome Due to N-acetylcysteine Extravasation

N-acetylcysteine (NAC) is the antidote for acetaminophen (APAP)-induced hepatotoxicity. Both intravenous (IV) and oral (PO) NAC formulations are available with equal efficacy. Adverse events from either preparation are rare. We describe a hand compartment syndrome after extravasation of NAC requiring emergent fasciotomy during phase three of treatment for suspected APAP toxicity. Extravasation injuries leading to compartment syndrome are rare. It is unclear whether IV NAC induced a direct tissue-toxic insult, or functioned as a space-occupying lesion to cause a compartment syndrome. Compartment syndrome from extravasation of NAC is possible. In cases where IV access is difficult, PO NAC is an alternative.

A Massive Overdose of Dalfampridine

Multiple sclerosis (MS) is an immune mediated inflammatory disease that attacks myelinated axons in the central nervous system. Dalfampridine (4-aminopyridine) was approved by the Food and Drug Administration in January 2010 for treatment of MS. Our patient was a 34-year-old male with a history of MS, who was brought to the emergency department after being found unresponsive. His current medications were valacyclovir, temazepam, dalfampridine (4-AP) and a tysabri intravenous (IV) infusion. Fifteen minutes after arrival the patient seized. The seizures were refractory to benzodiazepines, barbiturates and phenytoin. The 4-AP level was 530ng/mL (25ng/mL and 49ng/mL). The patient stopped seizing on hospital day 3 and was discharged 14 days later with normal mental status and neurologic exam. 4-AP is a potassium channel blocker that blocks the potassium ion current of repolarization following an action potential. The blockade of the potassium channel at the level of the membrane widens the action potential and enhances the release of acetylcholine, thus increasing post-synaptic action potentials. The treatment of patients with 4-AP overdose is supportive. Animal data suggest that patients with toxic levels of 4-AP may respond to phenytoin. Our case illustrates the highest recorded level of 4-AP in an overdose. Our patient appeared to be refractory to a combination of high doses of anticonvulsants and only improved with time.

Profound Shock after Initiation of Clozapine Therapy

Clozapine, a tricyclic dibenzodiazepine, is an atypical antipsychotic with dopaminergic, muscarinic, histaminic and serotonergic activity that has been used in the treatment of schizophrenia [1]. Although prescribers commonly recognize the hematologic adverse effect agranulocytosis its cardiac side effects, such as myocarditits, are less often considered [2]. A retrospective analysis of an Australian reporting system of patients with recent initiation of clozapine found an incidence of myocarditis about 1 in 500 young adults [3]. Studies since this publication have demonstrated incidences ranging from 0.015% to 8.5%. This compares to an estimated incidence of clozapine-induced agranulocytosis of between 3.8% and 8% [4]. A case definition for clozapine-related myocarditis used by Ronaldson et al described the syndrome as “any new symptoms of myocarditis within 45 days of commencing clozapine with histologic or clinical signs of cardiac dysfunction with either laboratory or radiographic evidence of myocardial pathology or congestive heart failure in the absence of alternative plausible schizophrenia” [5].