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Biomedical subjects

L R Goldfrank

Publications and source records attributed to L R Goldfrank.

At least 19 recordsLinked to original sources
PubMed1995

The poisoned patient with altered consciousness. Controversies in the use of a 'coma cocktail'.

OBJECTIVE: In the assessment and management of the potentially poisoned patient with altered consciousness, the most consequential and controversial interventions occur during the first 5 minutes of care. In this review article, the risks and benefits of standard diagnostic and therapeutic interventions are presented to guide clinicians through this critical period of decision making. DATA SOURCES: Data for discussion were obtained from a search of English-language publications referenced on MEDLINE for the years 1966 to 1994. Older literature was included when pertinent. Search terms included poisoning, overdose, toxicity, naloxone, glucose, thiamine, and flumazenil. STUDY SELECTION: Only large trials were used for determinations of diagnostic utility and efficacy. Small trials, case series, and case reports were reviewed extensively for adverse effects. DATA EXTRACTION AND SYNTHESIS: Trials were reviewed for overall methodology, inclusion and exclusion criteria, sources of bias, and outcome. CONCLUSION: Analysis favors empirical administration of hypertonic dextrose and thiamine hydrochloride to patients with altered consciousness. Although rapid reagent test strips can be used to guide this therapy, they are not infallible, and they fail to recognize clinical hypoglycemia that may occur without numerical hypoglycemia. Administration of naloxone hydrochloride should be reserved for patients with signs and symptoms of opioid intoxication. Flumazenil is best left for reversal of therapeutic conscious sedation and rare select cases of benzodiazepine overdose.

Consciousness↗
PubMed1995

Emergency medicine.

A survey determined that Medicaid recipients had limited access to outpatient care other than the care received at emergency departments. Recent advances in our understanding of trauma call into question how fluid resuscitation should be performed in the field.

Emergency Medicine↗
PubMed1992

Effect of nitric oxide on mitogenesis and proliferation of cerebellar glial cells.

In the brain, nitric oxide (NO) has been identified as a messenger molecule and a mediator of excitatory amino acid-induced neurotoxicity. In this study, the effects of NO on serum-induced mitogenesis and cell proliferation of the cerebellar glial cells were assessed. NO-generating agent, S-nitroso-N-acetylpenicillamine (SNAP) increased intracellular cyclic guanosine monophosphate (cGMP) levels. Furthermore, 2 chemically dissimilar NO-generating agents, SNAP and sodium nitroprusside (SNP) inhibited serum-induced thymidine incorporation and cell proliferation. The antimitogenic effect of NO was mimicked by 8-bromo-cGMP and blocked by hemoglobin, a known inhibitor of NO. The effect of NO was not cytotoxic, since the cells were not stained with Trypan blue and did not show increased release of lactate dehydrogenase in the culture supernatants. However, NO-treated cells showed decreased conversion of tetrazolium to blue formazan suggesting that NO inhibited mitochondrial activity in the glial cells. These results demonstrate that NO inhibits serum-induced mitogenesis and cell proliferation of cultured rat cerebellar glial cells.

Animals↗
PubMed1992

Bretylium tosylate and electrically induced cardiac arrhythmias during hypothermia in dogs.

The effect of bretylium tosylate on plasma catecholamines and on electrically induced arrhythmias was evaluated in anesthetized hypothermic dogs. Bretylium at a dose of 7.5 mg/kg was administered prior to cooling from 37 degrees C to 27 degrees C. During cooling, the ventricular arrhythmia threshold (VAT) in control animals decreased from 10.1 +/- 1.9 to 4.4 +/- 1.3 impulses, while the VAT in bretylium-treated animals increased from 9.8 +/- 2.9 to 23.2 +/- 2.7 impulses. Catecholamine levels increased during cooling in all animals. In control animals, the epinephrine/norepinephrine ratio was unchanged, but in animals treated with bretylium tosylate, the ratio increased more than 10-fold (from 0.48 +/- 0.1 to 5.49 +/- 0.32 at 29.9 degrees C). The demonstrated increase in catecholamine levels during hypothermia suggests that the protection offered by bretylium tosylate against cardiac arrhythmias is not explained by modification of catecholamine levels, and is more likely due to an alteration of the electrophysiologic properties of cardiac tissues.

Animals↗
PubMed1992

Update in medical toxicology.

This article examines some current issues in toxicologic care. First there is a review of the scope of pediatric poisonings and some aspects of initial management. Then there is a discussion of the decision-making process required to properly use gastric decontamination in the management of poisonings. Each of the common methods available--emesis, gastric lavage, activated charcoal, catharsis, and whole bowel irrigation--is discussed. Finally, several new and old antidotes are reviewed, namely naloxone, glucagon, bicarbonate, dimercaptosuccinic acid, digoxin-specific fab fragments, and flumazenil.

Antidotes↗
PubMed1992

Association between life-threatening cocaine toxicity and plasma cholinesterase activity.

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.

Adult↗
PubMed1992

Rapid quantitative determination of blood alcohol concentration in the emergency department using an electrochemical method.

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.

Adolescent↗
PubMed1992

Decreased plasma cholinesterase activity enhances cocaine toxicity in mice.

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.

Animals↗
PubMed1991

Antagonism of acute cocaine toxicity by buprenorphine.

The effect of buprenorphine pretreatment on the acute cocaine toxicity was assessed in male Swiss Webster mice. Buprenorphine pretreatment (0.15 or 0.30 mg/kg ip, 30 mins before) significantly attenuated the lethal effects of cocaine (60-140 mg/kg ip). The dose of cocaine which resulted in 50% mortality (LD50) in saline pretreated group was 100.61 mg/kg while the LD50 of cocaine in buprenorphine (0.15 and 0.3 mg/kg) pretreated groups were 113.57 and 118.16 mg/kg respectively. There was no significant change in the ratio of brain/plasma levels of cocaine in buprenorphine pretreated group when compared to the ratio from saline treated controls. Furthermore, neither naloxone (10 mg/kg ip, 15 mins before) nor naltrexone (3 mg/kg ip, 15 mins before) pretreatment affected the LD50 of cocaine. When tested 0.5, 1, 2, 4, 8 and 24 hrs after cocaine administration, sublethal dose of cocaine (80 mg/kg ip) injection resulted in significant increase in the plasma lactate dehydrogenase (LDH) levels. Buprenorphine pretreatment significantly attenuated cocaine-induced release of LDH. These results suggest that buprenorphine could be of potential advantage over naloxone in the management of cocaine and heroin ("speed ball") toxicity and in studies on the pharmacotherapy of cocaine-induced toxicity, LDH levels may be used as a biochemical marker to assess the protective effects of drugs.

Analysis of Variance↗
PubMed1991

The cardiovascular effects of cocaine.

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.

Adult↗
PubMed1991

Theophylline desorption from activated charcoal caused by whole bowel irrigation solution.

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.

Adsorption↗
PubMed1990

Whole bowel irrigation and the cocaine body-packer: a new approach to a common problem.

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.

Adult↗
PubMed1990

The impact of drug abuse and addiction on society.

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.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Opioids and designer drugs.

Despite the increasing use of other illicit drugs, opioid abuse, overdose, and the ensuing medical complications continue to pose management challenges for the emergency physician. Heroin use is increasing as abusers of cocaine seek a drug to prolong cocaine's effects while blunting the postcocaine depression. Clandestine chemists have created newer, more powerful compounds--designer drugs--whose potencies are many-fold that of the presently available opioids. Aggressive airway support and use of naloxone enable the emergency physician to salvage many of these patients, leaving the many medical complications of parenteral and inhalational use as the greatest management challenge.

Ambulatory Care↗
PubMed1990

Substance withdrawal.

As long as drug use and abuse persist in our society, a significant number of patients with various types of drug withdrawal will present to Emergency Departments. It is imperative that we recognize the signs and symptoms of drug withdrawal and render the appropriate treatments. Although it may be easy to recognize "skid row" alcoholics, a drug abuser with track marks on his (or her) arms or with a perforated nasal septum, the executive alcoholic, the elderly patient on chronic diazepam therapy, or the "blue collar" worker using cocaine may be more common and more elusive. Because most drug abusers use and can be dependent on multiple drugs, detoxification may need to proceed with one drug or one class of drugs at a time. Although our discussion has concentrated on the acute presentation and treatment of these symptoms for the emergency physician, we recognize that the acute treatment of withdrawal symptoms is only a small but vital part of withdrawal treatment. These patients will require chronic treatment, including social and psychologic counseling. As emergency physicians, by performing our jobs of recognition, stabilization, and counseling, we will fulfill the first critical link in the treatment of these patients.

Ambulatory Care↗