Overdose with sustained-release lithium preparations

Two cases of overdose with sustained-release lithium preparations are presented. Initial serum lithium levels were in the therapeutic or subtherapeutic range. Subsequent levels were in the toxic range. These cases illustrate the potential danger of delayed toxicity with ingestion of these agents.     

Reversal of orphenadrine-induced ventricular tachycardia with physostigmine

A 3-year-old boy developed confusion, generalized tonic-Tonic seizures, and sustained ventricular tachycardia following ingestion of an unknown quantity of orphenadrine (Norflex). Although refractory to precordial thump, synchronous cardioversion, and lidocaine, the ventricular tachycardia was reversed by intravenous admiinistration of the tertiary acetylcholinesterase inhibitor physostigmine. We discuss the underlying physiology and manifestations of anticholinergic overdose, the specific manifestations of orphenadrine overdose, and the current recommendations refarding the utilization and toxicity of physostigmine in the treatment of anticholinergic syndromes and orphenadrine intoxication.     

Chlorambucil overdose: Accidental ingestion of an antineoplastic drug

A 22-month-old, 10 kg child ingested 32 mg of chlorambucil and developed irritability, myoclonic-like muscle jerks, an exaggerated startle reflex, vomiting, and EEG changes within a few hours. The neurologic symptoms improved overnight, and the patient was discharged at about 28 hours postingestion. During the three weeks of follow-up, mild bone marrow suppression occurred and resolved. A normal EEG was reported at 33 weeks postingestion.     

Central anticholinergic syndrome in a child: A case report

A 2-year-old boy developed classical signs and symptoms of the central anticholinergic syndrome after ingesting twenty 4-mg tablets of the antihistamine cyproheptadine (Periactin). His symptoms were dramatically reversed by the intravenous administration of physostigmine. The physiology of the anticholinergic system and physostigmine are discussed along with the indications, toxicity, and dosing of physostigmine.     

COVID‐19 and toxicity from potential treatments: Panacea or poison

Since December 2019, coronavirus disease (COVID‐19) has been increasingly spreading from its origin in Wuhan, China to many countries around the world eventuating in morbidity and mortality affecting millions of people. This pandemic has proven to be a challenge given that there is no immediate cure, no vaccine is currently available and medications or treatments being used are still undergoing clinical trials. There have already been examples of self‐medication and overdose. Clearly, there is a need to further define the efficacy of treatments used in the management of COVID‐19. This evidence needs to be backed by large randomised‐controlled clinical trials. In the meantime, there will no doubt be further off‐label use of these medications by patients and practitioners and possibly related toxicity.     

Atrioventricular block following overdose of decongestant cold medication

A 24-year-old man developed high-degree atrioventricular (A-V) block with a pulse rate of 40 beats per minute and hypertension following an overdose of a combination decongestant cold medication that contained phenylpropanolamine, phenylephrine, chlorpheniramine, and phenyltoloxamine. The patient was treated with ipecac, activated charcoal, and cathartics in the emergency department (ED). After his admission to the coronary care unit, the A-V block gradually resolved to sinus rhythm with periods of second-degree block, Mobitz types I and II. No treatment was required. The patient had a normal sinus rhythm and normal blood pressure prior to discharge.     

Ultrasonic toxicity study

Ultrasound in a delivery format similar to that used clinically in pulse echo diagnostic techniques (1 MHz frequency range, 1000 Hz pulse repetition frequency—peak spatial and temporal intensities and pulse width are larger than those used clinically) has been applied to the male mouse testicles, non-pregnant female mouse ovaries and pregnant mouse uterus at day 8 of gestation. The time average spatial peak intensity for a 20 sec irradiation period at each matrix site for onset of adult mortality in the males and non-pregnant females is essentially 70 W/cm². These data are for a focused beam having a 6 dB beam width of 2 mm. For the pregnant animals, adult mortality begins at 23 W/cm². Significant changes in litter size occur for similar intensity levels. When anomalies which occur in controls are significantly increased for irradiated animals (a striking feature of this study is the almost total lack of appearance of anomalies in irradiated animals which are not present in controls), this increased incidence is not always presented in a unidirectional manner as a function of increasing average intensity. As the average intensity levels are increased in grades to 180 W/cm² there is generally an increased incidence of a given bioeffect. There are, however, some notable exceptions to this generalization. When a 6 dB beam width of 4 mm is used with the pregnant animals the adult mortality begins at 8 W/cm².     

Emergency burn treatment in Denmark

Historically, bum treatment in Denmark has included several unique elements. Current Danish treatment includes prolonged tap water irrigation of burns, which largely replaces the use of narcotics for pain control in both the inpatient and outpatient settings. Burns on hands and feet are dressed for maximum mobility. Other burns are left open. Mortality is 10% to 15% below expectations.     

Pediatric carbon monoxide toxicity

We report a series of 28 pediatric carbon monoxide exposures. Sixteen patients (57%) were judged to have potentially toxic carboxyhemeglobin (COHb) levels (greater than 15%). In this group the range of COHb blood levels was 16.7% to 44.0% (mean = 26.5%). An unusually high incidence of syncope (56.3%, 9/16) and lethargy (68.7%, 11/16) was observed. Every patient with a COHb level ≥ 24% experienced syncope; a marked departure from published adult values. lethargy was reported at a mean COHb concentration of 25.9%. All patients with levels over 25016 COHb, neurologic findings, acidosis, or syncope were considered candidates for hyperbaric oxygen therapy (HB0T). No morbidity from HBOT was encountered. Eighty-nine percent (25/28) of the patients are reportedly doing well, with no late sequelae identified. Delayed neurologic sequelae in three patients include chronic headaches, memory difficulties, or decline in school performance.     

Baclofen overdose: defining the spectrum of toxicity

Objectives: To describe the spectrum of toxicity of baclofen in overdose, and investigate dose‐related clinical effects. Methods: Consecutive baclofen overdoses were identified from a prospective database of all poisoning admissions presenting to a regional toxicology service. Ingestion was corroborated on more than one occasion and from multiple sources. Demographic, clinical and outcome variables were extracted for each presentation for a retrospective review, and the data sets were divided into high dose (≥200 mg) and low dose (<200 mg) groups for comparison of clinical effects. Results: There were 23 presentations, of which eight patients ingested baclofen alone. Seizures were reported in four cases, a decreased level of consciousness (GCS < 9) occurred in eight patients and delirium was recorded in eight patients. Five patients had miosis and seven patients had dilated pupils, 13 patients had absent or depressed reflexes. The only arrhythmias were sinus bradycardia in six patients and sinus tachycardia in five. Hypertension occurred in 13 patients and hypotension in one. The reported total ingested dose of baclofen was known in 19 patients (Mean 630 mg, SD 730 mg; 80–2500 mg). A higher ICU admission rate, rate of mechanical ventilation and prolonged length of stay occurred in those ingesting 200 mg or more. Coma, delirium and seizures occurred only with doses of 200 mg or more, and hypertension was more common with higher doses. Conclusions: Baclofen overdose causes mainly neurological effects and excepting hypertension cardiovascular effects were uncommon. Doses greater than 200 mg were predictive of patients developing delirium, coma and seizures, requiring long hospital admissions and ICU admission.     

Acute transverse myelitis in the emergency department: A case report and review of the literature

Acute transverse myelitis (ATM) is a neurologic condition that presents with bilateral lower extremity weakness and sensory loss associated with bowel and bladder dysfunction. Whereas the time of onset may be hours to days, the time to either partial or complete recovery may require months. The etiology is varied and may be idiopathic. Laboratory and radiographic evaluation may be nonrevealing. Corticosteriods have been used for treatment, but their efficacy is controversial. As illustrated by this case report, the essential aspect of the initial management of ATM is the elimination of potentially treatable causes.     

The safety of high-dose insulin euglycaemia therapy in toxin-induced cardiac toxicity

Context: High-dose insulin euglycaemia (HIE) is recommended in the management of toxin-induced cardiac toxicity, with increasing insulin doses now being used. We aimed to investigate the safety of HIE in toxin-induced cardiac toxicity.

Methods: This was a retrospective review of cases from two clinical toxicology units. Demographics, toxin(s) ingested, clinical effects, investigations (serum glucose, electrolytes), treatments (insulin, glucose, electrolyte replacement), length of stay (LOS) and outcomes were extracted from the patients’ medical records. Associations between insulin and glucose/electrolyte homeostasis were explored by comparing insulin administration and glucose or electrolyte concentrations and replacement.

Results: There were 22 patients (12 females), median age 57 years (15–88 years) treated with HIE. There were 12 beta-blocker, six calcium channel blocker and three combined beta-blocker and calcium channel blocker ingestions. A total of 19 patients had a systolic blood pressure?<80mmHg and 18 patients required inotropes in addition to HIE. There were three deaths. Despite glucose and electrolyte replacement, 16 patients (73%) developed hypoglycaemia (Reference range [RR]?There was no apparent association between insulin dosing and severity of hypoglycaemia or hypokalaemia, or in glucose or potassium replacement. Median insulin loading dose was 80U (range 50–125?U) and the median maximum insulin infusion rate was 150?U/h (range 38–1500?U/h). Median glucose infusions rates were 37.5g/h (range 4–75g/h). There was no apparent association between insulin and glucose administration. Glucose was administered for a median of 18h after ceasing insulin. The duration of glucose administration after ceasing insulin increased with the rate and total insulin administered during HIE.

Discussion: Despite the benefits of HIE in toxin-induced cardiac toxicity, it caused significant disruption to glucose and electrolyte homeostasis, although there were no apparent complications from this. There was no association by comparing the amount of insulin administered on adverse effects or glucose administered, suggesting higher doses of insulin are associated with no more adverse effects.     

The beginnings of urban ambulance service in the United States and England

Urban ambulance systems emerged in the second half of the 19th century as an outgrowth of military experiences in both Europe and America. Developing first in cities such as Cleveland and New York, these systems quickly adapted to the urban environment, and modifications in ambulance construction and procedures soon followed. Since first-aid texts for urban ambulances were rare, military texts on battlefield medicine were adapted to emergency medicine in civilian accidents.     

Attitudes about cancer pain: A survey of Wisconsin's first-year medical students

A brief questionnaire was administered to 317 first-year students at Wisconsin's two medical schools to assess their attitudes about cancer pain prior to their entry into medical school. Although the students had a realistic perspective of the prevalence and severity of cancer pain, they displayed a number of negative attitudes that if unchanged would contribute to future inadequate pain treatment. Students (a) greatly exaggerated the incidence of psychological dependence (addiction) in patients treated with opioid analgesics, (b) inappropriately timed maximal analgesic therapy to the duration of life expectancy, (c) felt that a majority of patients with cancer currently receive adequate or excessive analgesic therapy, and (d) believed that increasing pain was invariably related to the development of drug tolerance rather than to progression of the disease. Curricular efforts need to be directed at bringing about changes in students' negative attitudes about cancer pain and its management.     

Five-year multicenter retrospective review of cyclobenzaprine toxicity

Cyclobenzaprine (CBP) has a cyclic structure similar to amitriptyline. In overdose, CBP has been suggested to produce the cardiovascular and neurologic toxicity found with the cyclic antidepressants. To examine this possibility, a retrospective chart review of all cases of CBP exposure reported to five regional poison centers was performed for the years 1989–1993. There were a total of 750 charts identified for CBP exposure, of which 523 had data sufficient for evaluation. There were 121 polydrug ingestions leaving 402 pure CBP ingestions. Ages ranged from 7 mo to 77 yrs, with a mean of 20 yrs; 26% were 6 yrs or less. Females comprised 63% of the patient group. No deaths occurred. Dysrhythmias beyond sinus tachycardia were infrequent, and none were life-threatening. No seizures occurred. Common effects were lethargy, sinus tachycardia, and agitation, and both hypertension and hypotension were seen. All symptomatic cases with a known time of ingestion were symptomatic within 4 h of ingestion. Doses ingested ranged from 5–1000 mg, with a mean of 133 mg. Asymptomatic and symptomatic patients had a mean dose ingested of 45 mg and 183 mg, respectively. Treatment was primarily gastrointestinal (GI) decontamination and supportive care. Other therapies required were mechanical ventilation, dopamine, fluid bolus, sedation, and foley catheter. Symptoms requiring treatment beyond GI decontamination did not occur with ingestions less than 100 mg. In conclusion, cyclobenzaprine does not appear to produce the life-threatening cardiovascular or neurologic effects of the cyclic antidepressants in doses less than 1 g. Lethargy and anticholinergic effects are prominent, though serious toxicity is infrequent.     

Digoxin-specific antibody fragments in the treatment of digoxin toxicity

Context. Digoxin-specific antibody fragments (digoxin-Fab) are widely regarded as a safe and effective treatment for the management of acute and chronic digoxin poisoning. Calculated equimolar doses of digoxin-Fab are high, very expensive, and infrequently used. Objective. To review the pharmacology, efficacy, effectiveness, indications, safety and the dosage of digoxin-specific antibody fragments. Methods. Pubmed, Embase, Medline and Cochrane were searched from 1946 to May 2013 using the terms digoxin, digoxin-specific Fab, and digoxin antibody. Pharmacology and kinetics of digoxin and digoxin-Fab. Digoxin acts via inhibition of Na⁺/K⁺ ATPase. It has a narrow therapeutic index. Digoxin has 60–80% bioavailability, a mean plasma half-life of 40 h and a volume of distribution (Vd) of 5–10 L/kg and low protein binding (20%). A 40-mg vial of digoxin-Fab (DigiFab) binds 0.5 mg digoxin. Digoxin-Fab has a mean plasma half-life of 19–30 h and a Vd of 0.4 L/kg. The half-lives of both digoxin and digoxin-Fab are prolonged in renal failure to over 100 h. Efficacy and effectiveness of digoxin-Fab. There were no randomised clinical trials examining the use of digoxin-Fab for acute or chronic digoxin poisonings. Ten case series with a total of 2,080 patients have reported on the use of digoxin-Fab in digoxin poisoning. In three large case series of 430 acute and 1308 chronic poisonings, response rates to digoxin-Fab vary from 80–90% to 50%. The time for reversal of digoxin toxicity is reported to be 30–45 min. Studies with pharmacokinetic data showed that free digoxin concentration fell to almost zero within a few minutes following the administration of digoxin-Fab. Digoxin-Fab was used more frequently in acute than chronic digoxin poisoning with a higher reported success rate when used in acute overdose. It is sometimes recommended to use full neutralisation doses (based on serum concentration × Vd or ingested dose). It has also been proposed to use half this dose. Indications for digoxin-Fab. Patients who have life-threatening tachy–bradyarrhythmias, hyperkalaemia (> 6 mmol/L) or haemodynamic instability with an elevated digoxin concentration (> 2 μg/L or 2.6 nmol/L). The lowest effective digoxin-Fab dosing regimen has not been established. Safety of digoxin-Fab. Adverse events such as exacerbation of heart failure, increased ventricular rate and hypokalaemia are uncommon (< 10%). Recrudescence of digoxin toxicity and allergic reactions are infrequent. Digoxin-Fab dosing in acute poisoning. Digoxin load based on ingested dose will generally overestimate digoxin-Fab doses as bioavailability is 60–80%, and further reduced by vomiting and activated charcoal. Digoxin load based on concentration also will be overestimated when the concentration is taken before distribution is complete (around 6 h). Much smaller doses of digoxin-Fab can eliminate the digoxin in the central compartment (Vd ≈ 55 L). In imminent cardiac arrest, it may be justified to give a full neutralising dose. Otherwise, based on pharmacokinetic modelling, it is recommended to give 80 mg bolus digoxin-Fab, repeated as required according to clinical parameters because the onset of clinical response is usually rapid. Most patients would be expected to require a total of less than half of the calculated neutralising dose using this strategy. Digoxin-Fab dosing in chronic poisoning. Even if digoxin load is estimated following distribution (> 6 h), excessive neutralisation doses may still be calculated because of variation in Vd due to equations failing to account for lean body weight, age and renal failure. In practice, it is suggested to give 40 mg (1 vial) digoxin-Fab at a time and repeat after 60 min if patient is still symptomatic, sooner if patient is clinically unstable. In general, 40–120 mg (1–3 vials) should be sufficient. Conclusions. Digoxin-Fab is safe and indicated in all patients with life-threatening arrhythmias and an elevated digoxin concentration. However, calculated full neutralising doses of digoxin-Fab are expensive and may not be required. In acute poisoning, a small bolus of 80 mg, repeat if necessary, titrated against clinical effect, is likely to achieve equivalent benefits with much lower total doses. With chronic poisoning, it may be simplest to give 40 mg (1 vial) digoxin-Fab at a time and repeat after 60 min if there is no response.     

Pilocarpine for the treatment of refractory dry mouth (xerostomia) associated with botulinum toxin type B

A woman with spastic hemiparesis from a stroke was injected with botulinum toxin type B (BoNTB) at a dose of 10,000 U. Although this had the desired effect of a reduction in her spasticity, she also developed severe dry mouth, which became refractory to local remedies such as moist towels, lip balms, and throat lozenges. She was then given pilocarpine (a muscarinic agonist) at a dose of 5 mg, three times a day, to which she responded well. This report describes another treatment option in rare cases of severe dry mouth after administration of BoNTB.     

Phototherapy in the treatment of depression in the terminally ill

Research in affective disorders has shown that there is a clear link between mood and light exposure, and that exposure to bright wide-spectrum light (phototherapy) may be an effective antidepressant treatment in some clinical situations. Cancer patients, especially those in the terminal phase of illness, have a high incidence of depression. Furthermore, their mobility is often severely reduced, resulting in little exposure to direct sunlight. We report the use of phototherapy in three terminally ill patients to alleviate symptoms of depression.     

Malaria: Review of features pertinent to the emergency physician

Malaria is a health problem of growing concern to the emergency physician. Plasmodium vivax, P ovale, and P malaria infections are relatively benign and can be treated in an outpatient setting with oral chloroquine or amodiaquine. In contrast, P falciparum can present fulminantly, often resulting in death with multiple organ system failure. Although quinine historically has been the mainstay of therapy for severe falciparum malaria in the United States, and still is outside the U.S., quinidine gluconate as a continuous infusion is currently recommended as the agent of choice for severe P falciparum infection. In addition to the rapid administration of appropriate chemotherapeutic agents and the institution of aggressive supportive care, exchange transfusion may be utilized as a means of rapidly reducing the parasitemia and consequently, the mortality.