Efficacy of hexafluorine for emergent decontamination of hydrofluoric acid eye and skin splashes.

Hexafluorine is an amphoteric, hypertonic, polyvalent compound for decontaminating hydrofluoric acid (HF) eye and skin splashes. In a German metallurgy facility during the period of 1994-1998, all eye or skin splashes with 40% HF alone or with a 6% HF/15% HNO3 mixture were initially decontaminated with Hexafluorine within 2 min following the splash at the accident site by the victims themselves or co-workers who witnessed the accident. Eleven workers using 40% HF or a 6% HF/15% HNO3 mixture sustained eye (2 cases) or skin (10 cases) splashes (1 combined) during 1994-1998. Hexafluorine was used within 2 min, and a second Hexafluorine decontamination was done on arrival at the plant infirmary. No further medical or surgical treatment was needed, no workers developed chemical burns, and none lost work time. These II cases demonstrate the efficacy of Hexafluorine in decontaminating HF or combined HF/HNO3 splashes.

Computer modeling and computational toxicology in new chemical and pharmaceutical product development.

A theoretical basis for use of computer modeling and bioinformatics resources including the internet in decisions about whether to attempt synthesis and toxicology testing of new chemical or pharmaceutical products is described. Steps in the process include: (1) identification of a potentially efficacious chemical or pharmaceutical product; (2) structure-activity relationship (SAR) modeling; (3) synthesis methods and cost screening; (4) market screening for potential revenues; (5) regulatory impacts screening; (6) toxicology modeling and screening; (7) decision making about whether to attempt synthesis and testing. Some such computer modeling and screening processes are already in use. Others may reasonably be expected to be adopted in the near future. More development of structure-activity and structure-toxicity databases and therapeutic and toxicity molecular endpoints computerized libraries remains to be done. The internet is a rapidly developing source of information, but there are major problems with time-effectiveness, quality control, 'junk information' (misinformation), and deliberate 'disinformation'.

Hydrogen sulfide poisoning: an antidotal role for sodium nitrite?

In 2 separate incidents, 6 patients were poisoned with hydrogen sulfide (H2S) in sewer gas. In the first incident, mixing acid- and sodium hydroxide-based drain cleaners in a confined space resulted in 4 poisonings and 2 deaths. Three would-be rescuers were seriously poisoned and 1 died. Two survivors had neurological sequelae. Sodium nitrite appeared to have some clinical efficacy in 1 case. The second incident involved 2 patients working on a pump in a sewage pond. A patient lying on a raft close to the pond surface was seriously poisoned; sodium nitrite was clinically efficacious and this patient survived without developing neurological sequelae. Sodium nitrite deserves further clinical study as a potential H2S antidote.

Pulmonary dysfunction in survivors of acute paraquat poisoning.

Five patients survived acute paraquat ingestion, despite developing restrictive pulmonary dysfunction. Of these, 2 patients with documented long-term follow-up had progressive functional improvement. A literature review revealed 29 other patients surviving restrictive pulmonary dysfunction following acute paraquat poisoning. Some patients who survive an acute paraquat poisoning may develop pulmonary fibrosis, yet progressively improve over time.

Hydroxocobalamin as a cyanide antidote: safety, efficacy and pharmacokinetics in heavily smoking normal volunteers.

The safety, efficacy and pharmacokinetic parameters of 5 g of hydroxocobalamin given intravenously, alone or in combination with 12.5 g of sodium thiosulfate, were evaluated in healthy adult men who were heavy smokers. Sodium thiosulfate caused nausea, vomiting, and localized burning, muscle cramping, or twitching at the infusion site. Hydroxocobalamin was associated with a transient reddish discoloration of the skin, mucous membranes, and urine, and when administered alone produced mean elevations of 13.6% in systolic and 25.9% in diastolic blood pressure, with a concomitant 16.3% decrease in heart rate. No other clinically significant adverse effects were noted. Hydroxocobalamin alone decreased whole blood cyanide levels by 59% and increased urinary cyanide excretion. Pharmacokinetic parameters of hydroxocobalamin were best defined in the group who received both antidotes: t1/2 (alpha), 0.52 h; t1/2 (beta), 2.83 h; Vd (beta), 0.24 L/kg; and mean peak serum concentration 753 mcg/mL (560 mumol/L) at 0-50 minutes after completion of infusion. Hydroxocobalamin is safe when administered in a 5 gram intravenous dose, and effectively decreases the low whole blood cyanide levels found in heavy smokers.

Ibuprofen overdose in adults.

A prospective study of 63 ibuprofen overdose cases in adults (14 years or older) reported to the Rocky Mountain Poison and Drug Center between March 1987 and February 1988 was done to determine the incidence of renal injury and utility of timed plasma levels. No serious toxicity was noted. No CNS or other significant toxicity was seen with ingestion of less than 3 g. Two patients with normal serum creatinines had minor elevations of the blood urea nitrogen after ingesting 4 and 4.8 g. Timed plasma levels (125 total) from patients without coingestants from this study (48) and previously published reports (77) were compared with a previously described nomogram. The resulting nomogram revision may be useful in determining which initially asymptomatic patients are likely to remain so. Renal function tests are not routinely required for patients ingesting less than 6 g. Four h of observation is sufficient for asymptomatic patients not requiring psychiatric admission. Plasma ibuprofen levels are not required for proper patient management.

Fluoride ingestion in children: a review of 87 cases.

All cases of fluoride ingestion in children younger than 12 years old reported to the Rocky Mountain Poison Center between January 1 and December 31, 1986, were retrospectively reviewed. Eighty-seven cases were identified. Eighty-four cases involved accidental ingestion of dental fluoride products in the home (tablets, drops, rinses) in children 8 months to 6 years old. Two older children (8 and 9 years old) became symptomatic after fluoride treatment by a dentist. A 13-month-old child died after ingesting an unknown amount of sodium fluoride insecticide, the only insecticide exposure in our series. Postmortem total serum calcium value was 4.8 mg/dL (normal 8.8 to 10.3). No other patients had serious symptoms or sequelae. Twenty-six (30%) of 87 became symptomatic, with gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain) in 25 patients and drowsiness in 1. Only 3 patients became symptomatic later than 1 hour after ingestion. Analysis of data from 70 cases with sufficient information revealed that as the amount of fluoride ingested increased, the percentage of patients with symptoms increased. Not including the fatal case, 6 patients had serum calcium levels measured, and all were normal. Children who ingested up to 8.4 mg/kg of elemental fluoride in dental products had mild and self-limited symptoms, mostly gastrointestinal.

Hyperbaric oxygen treatment for carbon tetrachloride poisoning.

Carbon tetrachloride (CCl4) undergoes hepatic reductive metabolism to trichloromethyl (.CCl3) and peroxytrichloromethyl (CCl3OO.) free radicals, toxic intermediates which may initiate hepatocellular damage. Recent investigations have demonstrated a potential role for hyperoxia and hyperbaric oxygen as therapeutic interventions for CCl4 poisoning. Elevated oxygen concentrations in vitro and in vivo reduce lipid peroxidation and hepatotoxicity. In vivo studies of hyperbaric oxygen following administration of CCl4 in a rat model have shown improved survival and decreased hepatotoxicity. Case reports of human poisoning, with potentially lethal ingested doses of CCl4, also suggest a potential role for treatment with hyperbaric oxygen. Hyperoxia may act by altering the metabolism of CCl4. These studies and case reports support the recommendation that 100% normobaric and hyperbaric oxygen should be treatment considerations for CCl4 poisoning.

Plants and mushrooms of abuse.

The plants described earlier are only a few of those that can be misused. Most have effects similar to those of more popular synthetic drugs but can cause unpleasant side effects and unpredictable results. Identification of the offending botanic agent can be problematic. These plants are still used because most are legal to possess, and they do produce desired hallucinogenic and stimulant effects. Because the active ingredients are similar pharmacologically to agents such as LSD and amphetamine, required treatment is often similar. The challenge for the Emergency Department physician is to recognize the potential for abuse of these botanic agents, their probable side effects, and the need for appropriate, usually supportive, treatment. There are many more plants with abuse potential than can be discussed in detail in an article of this size. Table 1 lists a number of other agents that might be misused. Phenylamine hallucinogens occur in several species and include N,N-dimethyltryptamine (DMT), N-monomethyltryptamine (MMT), 5-methoxy-N-N-dimethyltryptamine (5-MeO-DMT), 5-methoxy-N-monomethyltryptamine (5-MeO-DMT), 5-methoxy-N-monomethyltryptamine (5-MeO-MMT), 5-hydroxy-N-N-dimethyltryptamine (bufotenine or 5-H-DMT), and N,N-dimethyltryptamine-N-oxide (DMT-N-oxide).

Toxic effects of nonsteroidal anti-inflammatory drugs in overdose. An overview of recent evidence on clinical effects and dose-response relationships.

Nonsalicylate, nonsteroidal anti-inflammatory drugs (NSAIDs) can be divided into 4 chemical classes: acetic acids, fenamic acids, oxicams and propionic acids. Most NSAID overdoses result in a benign outcome. Of 50,614 exposures reported to poison centres in the United States in a 2-year period, 131 (0.26%) had a major outcome, with 10 deaths. Despite the generally mild effects reported in large patient series, isolated case reports have documented serious toxicity, such as seizures, hypotension, apnoea, coma and renal failure. The majority of these consequences occur after ingestion of substantial quantities by adults attempting suicide. Rarely, with ibuprofen and piroxicam, children who ingest small amounts in accidental exposure develop serious toxicity. Typical signs and symptoms of NSAID overdose include nausea, vomiting, headache, drowsiness, blurred vision and dizziness. Seizures are rarely documented across all NSAID classes, with the exception of mefenamic acid (where seizures occur in over one-third of cases), or following massive ingestion of other agents. Drugs in the propionic acid group have produced metabolic acidosis, respiratory depression and coma in severe cases. Ibuprofen is the agent with the most published data on overdose, probably because it is available without a prescription in many countries. Symptoms are unlikely after ingestion of 100 mg/kg or less, and are usually not life-threatening unless more than 400 mg/kg is ingested. There is some relationship between plasma concentrations and the potential for development of symptoms, but plasma concentrations have no impact on treatment decisions. Treatment of NSAID overdose is entirely supportive. Recent trends in emergency department procedures regarding gastric decontamination are evolving towards the recommended administration of activated charcoal without gastric emptying in patients presenting more than 1 hour after ingestion, although gastric lavage, followed by administration of activated charcoal, may be advisable in patients who present earlier. Home administration of syrup of ipecac is still recommended if treatment is given shortly after ingestion, with a few exceptions: for example, ipecac is contraindicated after ingestion of mefenamic acid or ibuprofen in amounts greater than 400 mg/kg. Urine alkalinisation and diuresis have been recommended to enhance the elimination of NSAIDs, based on a pKa in the range of 3 to 5. However, because the drugs are universally highly protein bound, with little unchanged renal excretion, this technique is not likely to be beneficial. Haemodialysis is also unlikely to enhance elimination, but may be required if oliguric renal failure develops. Multiple dose activated charcoal may be useful in enhancing elimination of NSAIDs with long half-lives, such as piroxicam and sulindac.

Methylene chloride exposure in furniture-stripping shops: ventilation and respirator use practices.

Four cases of serious methylene chloride (dichloromethane) poisoning, including fatalities, in small-scale furniture-stripping shops were reported to the Rocky Mountain Poison and Drug Center between 1984 and 1988. Adequate ventilation systems and use of recommended respirators may seem impractical or overly expensive to the operators of such shops. Twenty-one shops in the metropolitan Denver, Colorado area were surveyed. A half-facepiece respirator with organic vapor cartridges was worn at least part-time in 14 of 21 shops; none was worn in 7. In 10 of 21 shops, workers had experienced dizziness, headache, or nausea when stripping furniture. Current safety practices in small-scale furniture-stripping shops may be inadequate to keep methylene chloride exposure levels in compliance with latest recommendations, and serious or fatal overexposure can occur.

Cyanide poisoning successfully treated without 'therapeutic methemoglobin levels'.

A 24-year-old woman ingested an unknown amount of potassium cyanide in a suicide attempt. Coma and metabolic acidosis developed. Administration of the Lilly Cyanide Antidote kit (Eli Lilly and Co, Indianapolis) resulted in prompt resolution of symptoms and full recovery. Whole blood cyanide level was 13 micrograms/mL approximately one hour after ingestion. The highest measured methemoglobin level after sodium nitrite administration was 9.2%, demonstrating that attaining a "therapeutic methemoglobin level" of 25% is unnecessary to insure a satisfactory clinical outcome. Because severe hypotension or excessive methemoglobinemia can be caused by the sodium nitrite component of the Lilly kit, only enough to produce an acceptable clinical response should be administered.

Hydrofluoric acid dermal exposure.

A retrospective review of 237 consecutive cases of dermal exposure to dilute (6-11%) hydrofluoric acid (HF)- containing rust stain remover consumer products reported to the Rocky Mountain Poison and Drug Center during 1986 was done to evaluate the toxicity of these agents and the efficacy of topical treatment with calcium gluconate gel. In 148 cases (62%), failure to follow manufacturers' recommended safety procedures was the likely cause of exposure. 219 patients developed the following symptoms: dermal swelling, redness, or both (131, 55%); blistering (12, 5%); black discoloration under fingernails (12, 5%); or pain without reported dermal changes (64, 27%). Local complications were noted in 7 cases (3%) (infection, 4 cases; fingertip dermal necrosis, 3 cases). No systemic toxicity was noted. 116 patients (49%) received treatment with topical calcium gluconate gel; 53 were followed until complete resolution of symptoms. There appeared to be a relationship between earlier initial gel application and more rapid resolution of signs and symptoms. Some degree of dermal injury may be quite common following exposure to dilute (6-11%) HF-containing rust stain remover consumer products. Failure to follow manufacturers' recommended safety procedures may be responsible for many exposures. Treatment with topical calcium gluconate gel may be effective, and more rapid resolution of signs and symptoms may occur with earlier initiation of this therapy.

Cyanide and arsenic poisoning by intravenous injection.

A 29-year-old man was found unresponsive a few minutes after self-injecting undetermined amounts of potassium cyanide and sodium arsenite intravenously in a suicide attempt. Treatment with the Lilly Cyanide Antidote kit rapidly resolved the initial coma, despite a whole blood cyanide level of 4.4 micrograms/mL. A 12-hour urine arsenic collection begun on admission showed 10,065 micrograms arsenic/12 hr. The patient received intramuscular BAL initially, which was followed by two ten-day courses of oral D-penicillamine. Complications included upper gastrointestinal tract bleeding requiring transfusion, transient elevations of liver function tests, self-limited complaints of decreased vision with conjunctival hyperemia and photophobia, and an abscess at the injection site. Although specific antidote therapy completely resolved the cyanide toxicity, early and prolonged arsenic chelation did not prevent a mild sensory peripheral neuropathy from developing with onset about 17 days after self-injection.

Suspected cyanide poisoning in smoke inhalation: complications of sodium nitrite therapy.

A 78 year old man was found comatose, apneic, and asystolic after closed-space smoke inhalation. He was successfully resuscitated to pulse and blood pressure at the scene. A cyanide component to the poisoning was suspected and two 300 mg doses of sodium nitrite were administered, resulting in significant hypotension. Although high methemoglobin levels were not induced, when added to simultaneously obtained carboxyhemoglobin levels, the total amount of non-oxygen transporting hemoglobin remained nearly constant for about 4-1/2 hours before hyperbaric oxygen (HBO) therapy could be administered. The patient later died in multi-organ system failure. Admission whole blood cyanide level was only 0.34 mcg/mL. These sodium nitrite adverse effects can be avoided by slow intravenous infusion and by administering only recommended doses. In smoke inhalation victims with suspected cyanide poisoning, sodium thiosulfate should be administered first, and sodium nitrite withheld until after the patient is receiving HBO therapy. When available, hydroxocobalamin (which neither induces methemoglobinemia nor causes hypotension) may be the specific cyanide antidote of choice for victims of smoke inhalation.

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.

Ibuprofen overdose--a prospective study.

Of 61 cases of ibuprofen overdosage reported consecutively to the Rocky Mountain Poison and Drug Center from September 1985 through April 1986, 16 were excluded because of incomplete follow-up or concurrent medication ingestion. A toxic reaction developed in 7 (16%) of the remaining 45 patients. Nausea, vomiting, abdominal cramps, mild central nervous system depression, coma, tachycardia, apnea, metabolic acidosis with or without respiratory alkalosis, hematemesis, and oliguric renal failure were noted. Two of six adults had a toxic reaction, and one died. Among pediatric patients, 5/39 (13%) had a toxic reaction. Of patients whose ibuprofen ingestion was less than 104 mg per kg, none became ill. All patients in whom the time of ingestion was known (six of seven) and who had a toxic reaction did so within four hours of ingestion. An ibuprofen overdose, although usually benign, can occasionally produce serious toxicity.