Gabapentin dose and the 30-day risk of altered mental status in older adults: A retrospective population-based study.

Gabapentin is an effective treatment for chronic neuropathic pain but may cause dizziness, drowsiness, and confusion in some older adults. The goal of this study was to assess the association between gabapentin dosing and adverse outcomes by obtaining estimates of the 30-day risk of hospitalization with altered mental status and mortality in older adults (mean age 76 years) in Ontario, Canada initiated on high dose (>600 mg/day; n = 34,159) compared to low dose (≤600 mg/day; n = 76,025) oral gabapentin in routine outpatient care. A population-based, retrospective cohort study assessing new gabapentin use between 2002 to 2014 was conducted. The primary outcome was 30-day hospitalization with an urgent head computed tomography (CT) scan in the absence of evidence of stroke (a proxy for altered mental status). The secondary outcome was 30-day all-cause mortality. The baseline characteristics measured in the two dose groups were similar. Initiation of a high versus low dose of gabapentin was associated with a higher risk of hospitalization with head CT scan (1.27% vs. 1.06%, absolute risk difference 0.21%, adjusted relative risk 1.29 [95% CI 1.14 to 1.46], number needed to treat 477) but not a statistically significant higher risk of mortality (1.25% vs. 1.16%, absolute risk difference of 0.09%, adjusted relative risk of 1.01 [95% CI 0.89 to 1.14]). Overall, the risk of being hospitalized with altered mental status after initiating gabapentin remains low, but may be reduced through the judicious use of gabapentin, use of the lowest dose to control pain, and vigilance for early signs of altered mental status.

[Confusion caused by dietary supplement lithium orotate]. / Verwarring bij behandelaars door voedingssupplement lithiumorotaat.

A 38-year-old woman was referred to our hospital with pelvic inflammatory disease. She had been diagnosed as having a tubo-ovarian abscess, for which antibiotic therapy with metronidazole and levofloxacin was indicated. Because the patient was already taking lithium she was prescribed clindamycin instead of metronidazole, a drug that interacts with lithium. For the same reason, naproxen could not be prescribed to reduce pain. However, the lithium taken by the patient turned out to be a dietary supplement containing lithium orotate which she had obtained via the Internet. Because the serum lithium level proved to be below 0.05 mmol/l clindamycin was still replaced by metronidazole, and naproxen could be started.

Cerebral arterial gas embolism after pre-flight ingestion of hydrogen peroxide.

Cerebral arterial gas embolism (CAGE) is a feared complication of ambient depressurisation and can also be a complication of hydrogen peroxide ingestion. We present an unusual case of CAGE in a 57-year-old woman exposed to both of these risk factors. We describe her subsequent successful treatment with hyperbaric oxygen, despite a 72-hour delay in initial presentation and diagnosis, and discuss the safety of aero-medical transfer following hydrogen peroxide ingestions.

Differential physiological and behavioral cues observed in individuals smoking botanical marijuana versus synthetic cannabinoid drugs.

CONTEXT: Synthetic cannabinoid use has increased in many states, and medicinal and/or recreational marijuana use has been legalized in some states. These changes present challenges to law enforcement drug recognition experts (DREs) who determine whether drivers are impaired by synthetic cannabinoids or marijuana, as well as to clinical toxicologists who care for patients with complications from synthetic cannabinoids and marijuana. Our goal was to compare what effects synthetic cannabinoids and marijuana had on performance and behavior, including driving impairment, by reviewing records generated by law enforcement DREs who evaluated motorists arrested for impaired driving. METHODS: Data were from a retrospective, convenience sample of de-identified arrest reports from impaired drivers suspected of using synthetic cannabinoids (n = 100) or marijuana (n = 33). Inclusion criteria were arrested drivers who admitted to using either synthetic cannabinoids or marijuana, or who possessed either synthetic cannabinoids or marijuana; who also had a DRE evaluation at the scene; and whose blood screens were negative for alcohol and other drugs. Exclusion criteria were impaired drivers arrested with other intoxicants found in their drug or alcohol blood screens. Blood samples were analyzed for 20 popular synthetic cannabinoids by using liquid chromatography-tandem mass spectrometry. Delta-9-tetrahydrocannabinol (THC) and THC-COOH were quantified by gas chromatography-mass spectrometry. Statistical significance was determined by using Fisher's exact test or Student's t-test, where appropriate, to compare the frequency of characteristics of those in the synthetic cannabinoid group versus those in the marijuana group. RESULTS: 16 synthetic cannabinoid and 25 marijuana records met selection criteria; the drivers of these records were arrested for moving violations. Median age for the synthetic cannabinoid group (n = 16, 15 males) was 20 years (IQR 19-23 years). Median age for the marijuana group (n = 25, 21 males) was 20 years (IQR 19-24 years) (p = 0.46). In the synthetic cannabinoid group, 94% (15/16) admitted to using synthetic cannabinoids. In the marijuana group, 96% (24/25) admitted to using marijuana. Blood was available for testing in 96% (24/25) of the marijuana group; 21 of these 24 had quantitative levels of THC (mean + SD = 10.7 + 5 ng/mL) and THC-COOH (mean + SD = 57.8 + 3 ng/mL). Blood was available for testing in 63% (10/16) of the synthetic cannabinoid group, with 80% (8/10) of these positive for synthetic cannabinoids. Those in the synthetic cannabinoid group were more frequently confused (7/16 [44%] vs. 0/25 [0%], p ≤ 0.003) and disoriented (5/16 [31%] vs. 0/25 [0%], p ≤ 0.003), and more frequently had incoherent, slurred speech (10/16 [63%] vs. 3/25 [12%], p = 0.0014) and horizontal gaze nystagmus (8/16 [50%] vs. 3/25 [12%], p = 0.01) than those in the marijuana group. CONCLUSION: Drivers under the influence of synthetic cannabinoids were more frequently impaired with confusion, disorientation, and incoherent, slurred speech than drivers under the influence of marijuana in this population evaluated by DREs.

Accidental overdose in the deep shade of night: a warning on the assumed safety of 'natural substances'.

There is an increasing use of herbal remedies and medicines, with a commonly held belief that natural substances are safe. We present the case of a 50-year-old woman who was a trained herbalist and had purchased an 'Atropa belladonna (deadly nightshade) preparation'. Attempting to combat her insomnia, late one evening she deliberately ingested a small portion of this, approximately 50 mL. Unintentionally, this was equivalent to a very large (15 mg) dose of atropine and she presented in an acute anticholinergic syndrome (confused, tachycardic and hypertensive) to our accident and emergency department. She received supportive management in our intensive treatment unit including mechanical ventilation. Fortunately, there were no long-term sequelae from this episode. However, this dramatic clinical presentation does highlight the potential dangers posed by herbal remedies. Furthermore, this case provides clinicians with an important insight into potentially dangerous products available legally within the UK. To help clinicians' understanding of this our discussion explains the manufacture and 'dosing' of the A. belladonna preparation.

The safety of high-dose buprenorphine administered subcutaneously in cats.

The safety of a proprietary formulation of buprenorphine hydrochloride administered subcutaneously (SC) to young cats was investigated in a blinded, randomized study. Four cohorts of eight cats aged approximately 4 months were administered saline, 0.24, 0.72 or 1.20 mg/kg/day buprenorphine SC for nine consecutive days, representing 0×, 1×, 3× and 5× of the intended dose. Cats were monitored daily for evidence of clinical reactions, food and water intake and adverse events (AEs). Physical examinations, clinical pathology, vital signs and electrocardiograms (ECGs) were evaluated at protocol-specified time points. Complete necropsy and histopathologic examinations were performed following humane euthanasia. Four buprenorphine-treated cats experienced AEs during the study, two unrelated and two related to study drug administration. The two cats with AEs considered related to drug administration had clinical signs of hyperactivity, difficulty in handling, disorientation, agitation and dilated pupils in one 0.24 mg/kg/day cat and one 0.72 mg/kg/day cat. All of these clinical signs were observed simultaneously. There were no drug-related effects on survival, injection response, injection site inspections, body weight, food or water consumption, bleeding time, urinalysis, respiration rate, heart rate, ECGs, blood pressures, body temperatures, macroscopic examinations or organ weights. Once daily buprenorphine s.c. injections at doses of 0.24, 0.72 and 1.20 mg/kg/day for 9 consecutive days were well tolerated in young domestic cats.

Effects of remifentanil on processing of auditory stimuli: a combined MEG/EEG study.

Remifentanil (Ultiva(®)) is a potent ultra-short acting mu-opioid receptor agonist used for perioperative pain treatment and anaesthesia. So far, it is not known how sensitive the cognitive processing of auditory perception elicited by the mismatch negativity (MMN) paradigm is to opioids. The present exploratory study investigated how the opioid remifentanil modulates different stages of auditory processing as reflected in the MMN(m) and P3a(m). We recorded electroencephalography (EEG) and magnetoencephalography (MEG) during auditory stimulation under remifentanil or placebo infusion in 20 healthy participants. For the MMN, a gender effect was found for tones deviating in frequency (± 10%) from the standard tone. Remifentanil increased the amplitude of the frequency MMN at F3 in females but not in males. No effect of treatment was found for the MMN(m) or the novel P3a(m). These results suggest that while the bottom-up stimulus change detection system for auditory stimuli appears to be relatively insensitive to opioids, the automatic attention switch caused by the change detection seems to be modulated by the opioid system in females. The multiple deviant paradigm including novel sounds is a promising tool for investigating pharmacological manipulation of different stages of auditory processing. Furthermore, combining the two techniques will yield more specific information about the drug effects on MMN(m).

Cases from NACCT acute and intensive care symposium: altered mental status, seizures, and rash in a fumigation company employee.

CONTEXT: Methyl bromide is a halogenated aliphatic hydrocarbon that exists as a colorless gas or a volatile liquid. Methyl bromide historically had been used in fire extinguishers but is more commonly used as a gas fumigant for soil-borne diseases and pests. Methyl bromide is being phased out due to concerns for ozone depletion but can still be found. It is readily absorbed through the lungs while dermal absorption can also occur. Signs and symptoms of severe exposures include headache, respiratory distress, pulmonary hemorrhage, and seizures. In large pulmonary exposures, death can occur as rapidly as 1 h usually from respiratory failure. Methyl bromide can penetrate clothing and protective equipment presenting challenges to first responders. There is a debate over the mechanism of toxicity of methyl bromide and the role of hemodialysis and chelation in treatment. CASE DETAILS: A 22-year-old female employee of a fumigation company contacted emergency medical services (EMS) after opening a tank of compressed methyl bromide in her car. She was initially combative and confused. She underwent two water dermal decontaminations and was transported to the nearest tertiary center. She rapidly progressed to obtundation with seizure-like activity and dysrhythmias. Despite the supportive care and resuscitative efforts, she died approximately 1 h after her call to EMS. DISCUSSION: Methyl bromide exposures can be fatal, and this case highlights the difficulty in managing these acutely poisoned patients. Questions for consideration after this case include time spent on decontamination, use of adjunctive anti-epileptic drugs, role of chelation therapy, and the role of hemodialysis in the treatment of methyl bromide poisoning.

Ban Tu Wan hepatotoxicity.

Medications are thought to contribute to approximately 50% of the cases of acute liver failure in the USA. This number includes some herbal medications and supplements. However, little regulatory oversight of these later substances occurs. This report describes a case of fulminant hepatic failure secondary to Ban Tu Wan (a Chinese herb). We discuss the use of this herbal supplement and the relationship to drug-induced hepatitis.

The importance of drug-drug interactions as a cause of adverse drug reactions: a pharmacovigilance study of serotoninergic reuptake inhibitors in France.

PURPOSE: To quantify the importance of drug-drug interactions (DDIs) in the occurrence of adverse drug reactions (ADRs) reported with serotoninergic reuptake inhibitors in a pharmacovigilance database. METHODS: All spontaneous reports of ADRs registered in 2008 by the Midi-Pyrénées PharmacoVigilance Centre that contained mention of one of the serotoninergic reuptake inhibitor (SRI) antidepressants marketed in France were reviewed. DDIs were identified according to the French National Drug Formulary (Vidal) and the interaction supplement of the French independent drug bulletin La Revue Prescrire. ADRs explained by DDIs were characterised. RESULTS: Among the 2,101 spontaneous reports recorded, 177 involved at least one SRI antidepressant. Among the 156 ADRs with at least one theoretical DDI, 41% (95% confidence interval 34-49%) could be explained by a DDI. The most frequent antidepressant involved in DDIs was escitalopram, followed by fluoxetine and citalopram. Among the 65 ADRs related to DDIs, 37 (52.9%) were "serious", mainly bleedings, confusion and falls, hyponatremia and serotoninergic syndromes. The most frequent drug interactions occurred with psychotropics (antipsychotics, benzodiazepines, among others), followed by antithrombotic agents (antagonists of vitamin K, antiplatelets), diuretics and angiotensin II antagonists. The group with ADRs related to DDIs was older than the group with ADRs not related to DDIs. ADRs were threefold more "serious" in the case of DDIs. CONCLUSION: Around 40% of ADRs reported with SRIs were related to DDIs. Most of these occurred after association with psychotropics, antithrombotics, or diuretics, especially in the elderly.

Salvia divinorum: exposures reported to a statewide poison control system over 10 years.

BACKGROUND: Salvia divinorum, a hallucinogenic herb, has in recent years become popular among teenagers and young adults. Salvia is presently marketed as a "legal" alternative to other drugs of abuse, but little is known about the clinical toxicity of this substance. OBJECTIVES: The purpose of this study is to describe the clinical and demographic features of this emerging substance of recreational abuse using data obtained from the records of a poison control center. METHODS: We performed retrospective review of exposures to the herbal hallucinogen Salvia divinorum as reported to the California Poison Control System (CPCS) over the last 10 years. Demographic and clinical data were collected and compiled from the computerized records of the CPCS for the search terms "salvia" and "sage." RESULTS: There were 37 exposures to S. divinorum and 96 exposures to non-hallucinogenic Salvia species. Eighteen (49%) of the exposures were to S. divinorum alone. Intentional Salvia exposures resulted in a variety of neurologic, cardiovascular, and gastrointestinal effects. Notably, the use of concomitant substances of abuse was associated with a high rate of complications and psychomotor disturbances. CONCLUSIONS: Intentional use of S. divinorum, whether alone or in combination with alcoholic beverages and other drugs, causes neurologic, cardiovascular, and gastrointestinal effects. This poison-center-based review helps to characterize the clinical toxicity of S. divinorum, but more clinical and pharmacologic research is warranted for this rapidly emerging substance of abuse.

Carbon monoxide toxicity with neurological and cardiac complications

A family suffered carbon monoxide toxicity, with cerebral and / or cardiac complications, while sleeping in the cabin on a recreational boat. This article describes a couple exposed to a malfunctioning air-conditioning system on the boat, which subsequently developed the unique combination of cerebral symptoms and a non Q/non-ST elevation myocardial infarction, with enzyme elevations and electrocardiographic abnormalities. This interesting complication of a myocardial infarction secondary to carbon monoxide toxicity, associated with neurological manifestations, is reviewed.

Carbon monoxide toxicity with neurological and cardiac complications.

A family suffered carbon monoxide toxicity, with cerebral and / or cardiac complications, while sleeping in the cabin on a recreational boat. This article describes a couple exposed to a malfunctioning air-conditioning system on the boat, which subsequently developed the unique combination of cerebral symptoms and a non Q/non-ST elevation myocardial infarction, with enzyme elevations and electrocardiographic abnormalities. This interesting complication of a myocardial infarction secondary to carbon monoxide toxicity, associated with neurological manifestations, is reviewed.