Use of phentolamine for cocaine-induced myocardial ischemia.
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Biomedical subjects
Publications and source records attributed to R S Hoffman.
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Methemoglobinemia is an uncommon cause of cyanosis. A 28-year-old male presented to the emergency department cyanotic and short of breath after exposure to noxious automobile fumes. He did not improve with the administration of 100% oxygen therapy. The initial arterial blood gas with cooximetry was: pH of 7.38, PaCO2 of 43 mm Hg, PaO2 of 118 mm Hg, measured oxygen saturation of 70%, and a methemoglobin level of 24.8%. Methylene blue was given (2 mg/kg intravenously) and the patient's symptoms resolved. On the following day he was discharged home without complication. A comprehensive review of the literature revealed no reported cases of methemoglobinemia secondary to accidental exposure to exhaust fumes.
STUDY OBJECTIVE: To determine whether plasma cholinesterase (pseudocholinesterase) activity is a marker for severe cocaine toxicity. DESIGN: A prevalence study in a cohort of cocaine users. SETTING: A large urban emergency department. PARTICIPANTS: During a three-month period in 1989, 187 patients who presented to the ED on 191 consecutive occasions with signs and symptoms consistent with cocaine intoxication were prospectively enrolled in the study protocol. METHODS AND MEASUREMENTS: All patients had plasma cholinesterase activity determined by the electrometric method. The patients who were cocaine positive were stratified into one of two groups: life-threatening toxicity (LT) and non-life-threatening toxicity (NLT), based on a predetermined set of criteria. Cocaine-negative patients served as controls for the LT group if criteria were otherwise met. RESULTS: Mean (+/- SD) plasma cholinesterase activities for the LT, NLT, and control groups were 682 +/- 277, 904 +/- 279, and 1,058 +/- 385 Michel units/L, respectively. All three groups were significantly different from each other (P less than .05 by analysis of variance). CONCLUSION: The data suggest that decreased plasma cholinesterase activity is associated with increased risk of life-threatening cocaine toxicity.
STUDY OBJECTIVE: To determine the reliability of a recently developed electrochemical meter to rapidly (within 60 seconds) measure blood alcohol concentration (BAC) in the emergency department. DESIGN: A prospective study comparing the meter data with that of immunoassay and gas chromatography criterion standards undertaken during a ten-week period. SETTING: Adult ED of a municipal hospital. PARTICIPANTS: Three hundred eighty-three consecutive patients with altered mental status or suspected alcohol intoxication. INTERVENTIONS: Each patient underwent routine phlebotomy, and blood samples were obtained for meter and immunoassay BAC determinations. The first 60% of patients also underwent gas chromatography BAC determination. RESULTS: Two hundred nineteen patients (60%) had BAC detectable by both meter and immunoassay. BAC measurement by the meter correlated strongly with immunoassay and gas chromatography determinations (Pearson's correlation coefficient, r = .94; P less than .00000001 for both correlations). CONCLUSION: The electrochemical meter provides a rapid and reliable BAC measurement in the ED.
The combination of tetracaine, epinephrine, and cocaine has gained wide acceptance as a topical anesthetic agent for use on pediatric dermal lacerations in the ED. This is despite the fact that the optimal dose and formulation have yet to be determined. TAC can be applied painlessly to wounds and is about as effective as lidocaine infiltration for anesthetizing pediatric facial and scalp lacerations. It is relatively ineffective on lacerations located elsewhere or in adults. The most commonly used TAC solution contains high concentrations of cocaine, tetracaine, and epinephrine, drugs that individually can cause serious toxicity if absorbed in sufficient amounts. In addition, the three components of TAC may interact to potentiate their intrinsic toxicities. The deliberate and inadvertent application of TAC to mucous membranes has caused status epilepticus and two pediatric deaths. The risk of toxicity from misapplication of TAC is heightened because TAC is most effective and therefore most widely used on pediatric facial and scalp lacerations. Cocaine is also absorbed after TAC is applied to dermal lacerations and may cause toxicity by this route. Until additional research is performed to establish the minimum effective dose of TAC and its potential toxicity and until FDA approval is granted, we do not think that it can be recommended as the drug of choice for pediatric facial and scalp lacerations in the ED. If TAC is administered, a maximum dose of 2 to 3 mL of the "half-strength" formula proposed by Bonadio and Wagner should be used, and application should be performed by medical personnel, using a soaked gauze or cotton ball. Care should be taken to make sure none of the solution comes in contact with mucous membranes, and TAC should not be applied to lacerations involving the vermillion border of the lip or the lip itself. Close medical monitoring of the patient is essential to detect signs of toxicity. Research on other topical agents such as tetracaine with epinephrine is also needed. Although anesthetizing wounds painlessly remains a worthy goal, exposing patients to added and unknown risks and increasing the cost of health care is unacceptable.
The illicit use of cocaine continues in epidemic proportions. Despite the incidence of life-threatening complications from cocaine use, little is known of the individual determinants of cocaine toxicity. In vitro analysis demonstrating that cocaine is poorly metabolized by the serum of patients with low plasma cholinesterase (PCh) activity (succinylcholine sensitivity) led to the hypothesis that altered PCh activity might modulate cocaine toxicity. An in vivo mouse model was created to test this theory. Mice were pretreated s.c. with either parathion [a mixed plasma and red blood cell cholinesterase (RBCCh) inhibitor], tetraisopropyl pyrophosphoramide (a selective PCh inhibitor) or placebo, and cholinesterase activity was determined at 24 hr. Incremental doses of i.p. cocaine were administered in a controlled and blinded fashion, and lethality was observed. Ten mg/kg s.c. parathion produced a mean suppression of 68 +/- 9 and 61 +/- 8% of PCh and RBCCh activity, respectively. One mg/kg s.c. tetraisopropyl pyrophosphoramide produced a mean suppression of 78 +/- 3 and 9 +/- 8% of PCh and RBCCh activity, respectively. Each pretreatment produced a statistically significant increase in cocaine lethality throughout the dose-response curve. Our results suggest that PCh activity is an important determinant of cocaine toxicity. This effect appears to be independent of either RBCCh activity or manifestations of organophosphate intoxication.
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Cocaine use and abuse continue to overwhelm urban economic, social, and health care systems. Patients frequently present to the emergency department with life-threatening manifestations of cocaine use, including trauma, acquired immune deficiency syndrome, psychomotor agitation, and cardiovascular collapse. Adequate treatment of the cocaine-intoxicated patient requires a critical understanding of the risk-to-benefit ratios for pharmacologic, toxicologic, and surgical or obstetric interventions. The pharmacologic and physiologic bases for the vascular manifestations of cocaine toxicity and experimental evidence for treatment strategies are reviewed.
Whole bowel irrigation with polyethylene glycol electrolyte lavage solution has been recommended as an adjunct to traditional overdose management. Although combined activated charcoal and whole bowel irrigation could enhance the efficacy of both modalities, this improvement remains largely speculative. An in vitro experiment was designed to determine whether polyethylene glycol electrolyte lavage solution alters the adsorption of theophylline to activated charcoal. Theophylline was agitated with activated charcoal in either water or polyethylene glycol electrolyte lavage solution, at each of three activated charcoal:theophylline ratios; 1:1, 3:1, and 10:1. The concentration in the supernatant was determined by high pressure liquid chromatography, and the maximal adsorptive capacity of activated charcoal for theophylline was calculated from the Langmuir equation. The percent of theophylline adsorbed by activated charcoal in water was 16 +/- 4%, 67 +/- 5%, and 97 +/- 3% for the 1:1, 3:1, and 10:1 ratios, respectively. This was decreased to 17 +/- 5%, 37 +/- 3%, and 62 +/- 2% when polyethylene glycol electrolyte lavage solution was added. A statistical difference (p less than 0.05) occurred at the 3:1 and 10:1 activated charcoal:theophylline ratios. Similarly the maximal adsorptive capacity was decreased 23% from 264 mg/g to 203 mg/g when polyethylene glycol electrolyte lavage solution was added to activated charcoal prior to theophylline. Polyethylene glycol electrolyte lavage solution significantly decreases adsorption of theophylline to activated charcoal in vitro. In vivo studies are required to confirm these findings. If activated charcoal is to be used clinically for theophylline toxicity, the authors suggest the possibility of larger quantities of activated charcoal, and administering activated charcoal in a slurry of water before the initiation of whole bowel irrigation.
A retrospective analysis of sedative-hypnotic overdoses reported to the New York City Poison Control Center (NYCPCC) for the years 1988 and 1989 was performed to evaluate the effects of the triplicate benzodiazepine (BZ) prescription program on the incidence and severity of sedative hypnotic overdoses. Although total BZ overdoses fell slightly, from 1,294 in 1988 to 1,265 in 1989, a statistically significant increase in non-benzodiazepine (NBZ) sedative-hypnotic overdoses, from 111 in 1988 to 144 in 1989, was noted. No difference in clinical outcomes between the two years could be demonstrated. These results suggest that the restriction of BZ failed to reduce the incidence or severity of sedative-hypnotic overdose, largely because of the substitution of similar nonrestricted agents.
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Gastrointestinal drug smuggling is a common problem in many major cities. Though the majority of cases never require medical attention, the "body-packer" frequently presents with life-threatening symptoms of intoxication, including seizures and cardiorespiratory collapse, as well as mechanical obstruction from the ingested drug packets. The risk to asymptomatic smugglers may vary with packaging materials, and remains unknown. Lack of controlled studies, and variations in packaging materials and clinical outcomes have prevented formulation of a consistent management strategy. Current recommendations for asymptomatic body-packers vary from immediate surgical removal, to use of laxatives, to observation. The authors present the first reported case of an asymptomatic cocaine body-packer treated with whole bowel irrigation with polyethylene glycol electrolyte lavage solution. This strategy was safe, well tolerated, resulted in the rapid elimination of drug packets from the gastrointestinal tract, and facilitated assessment by contrast radiography. The potential benefits and limitations for the use of whole bowel irrigation in this difficult problem are discussed.
Over 28 million Americans have admitted to abusing a substance in the last year alone, at a direct purchase price of over 79 billion dollars. Substance abuse and addiction have grave consequences on our existing social systems, effecting crime rates, hospitalizations, child abuse, and child neglect, and are rapidly consuming limited public funds. The intravenous drug abuser represents the fastest growing vector of HIV virus. This report focuses on the social and economic implications of substance abuse and addiction and discusses the merits and limitations of several popular solutions to the problem.