Advertisement

David R. Boyd lecture in trauma care and emergency medical systems: “The Surgical Complications of Toxins”

  • Lewis R Goldfrank
    Correspondence
    Reprint Address: Lewis R. Goldfrank, MD, Emergency Medical Services, Bellevue Hospital Center, First Avenue and 27th Street, New York, NY 10016
    Affiliations
    Department of Emergency Medicine, Bellevue Hospital Center and New York University Medical Center and Department of Medicine, New York University School of Medicine. New York, New York, USA
    Search for articles by this author

      Abstract

      Toxins have had major roles in our societies for thousands of years. Interactions between surgeons, both generalists and subspecialists, and those caring for poisoned patients have been extensive throughout history. The advancement of the science of toxicology, the development of regional poison control centers, the development of emergency medicine, and the development of the subspecialty of medical toxicology have led to more appropriate and creative interactions between medical toxicologists, emergency physicians, and surgeons. This article will review the diverse interfaces between the medical toxicologist and the surgeon.

      Introduction

      Throughout the history of mankind, surgeons have used their skills to evaluate the effects of toxins. A few of these historic examples will serve as an introduction to a review of the current complex problems that subspecialty and general surgeons treat in conjunction with emergency physicians and medical toxicologists. At the beginning of the nineteenth century, the earliest advances in gastrointestinal decontamination were attributed to several surgeons. Philip Physick, Baron Guillaume Dupuytren, and Edward Jukes in the United States, France, and England, respectively, performed basic experiments on gastric lavage for the removal of poisons (
      • Burke M.
      Gastric lavage and emesis in the treatment of ingested poisons a review and a clinical study of lavage in ten adults.
      ,
      • Moore S.W.
      A case of poisoning by laudanum, successfully treated by means of Jukes’s syringe.
      ).
      Physick in 1805 demonstrated the use of a stomach tube with a brandy and water lavage fluid for the removal of opium. Dupuytren and Jukes attempted comparable experiments with long flexible sounds (
      • Burke M.
      Gastric lavage and emesis in the treatment of ingested poisons a review and a clinical study of lavage in ten adults.
      ).
      Exposures to toxins such as household caustic agents and industrial explosions have frequently brought patients to otolaryngologists and ophthalmologists. Chevalier Jackson, an early twentieth century otolaryngologist, appreciated the grave injuries associated with household acids and bases leading to severe gastrointestinal injuries. His efforts were critical in mandating the addition of a poison warning to these products in the Federal Caustic Poison Act of 1927 (
      • Taylor H.M.
      A preliminary survey of the effect which lye legislation has had on the incidence of esophageal stricture.
      ).
      A comparable event for environmental toxicology occurred at the Union Carbide carbaryl plant in Bhopal, India in 1984. This enormous civilian disaster occurred when an exothermic reaction led to the release of 24,000 kilograms of methyl isocyanate. In addition to the 2500 deaths, thousands of burns and grave corneal injuries occurred leading to ophthalmologic evaluation (
      • Varma D.R.
      • Guest I.
      The Bhopal accident and methyl isocyanate toxicity.
      ).
      Occupational exposures throughout history have led to surgical interventions. Conceivably the first and best-reported occupational cancer was described by Sir Percivall Pott in 1775, who described the high incidence of scrotal cancer among chimney sweeps long exposed to tar and soot (
      • Hunter D.
      ). More recent occupational neoplasms relate to asbestos workers and their development of mesotheliomas and lung cancer (
      • Corn J.K.
      • Starr J.
      Hisotrical perspective on asbestos policies and protective measures in World War II shipbuilding.
      ,
      • Murray R.
      Asbestos a chronology of its origins and health effects.
      ) and those working with synthetic chemicals such as polyvinyl chloride, which in the monomer form, vinyl chloride, has resulted in angiosarcomas (
      • Falk H.
      • Creech J.L.
      • Health C.W.
      • et al.
      Hepatic disease among workers at a vinyl chloride polymerization plant.
      ).
      Other events we now recognize at the interface of surgery, emergency medicine, and medical toxicology include the injury to almost 1000 individuals following a hydrofluoric acid release from a Texas petrochemical plant in 1987 and the hundreds of deaths in the Coconut Grove night club fire in 1943 where many died from carbon monoxide exposure as well as thermal injury (
      • Wing J.S.
      • Sanderson L.M.
      • Brender J.D.
      • et al.
      Acute health effects in a community after a release of hydrofluoric acid.
      ,
      • Faxon N.W.
      • Churchill E.D.
      The Coconut Grove disaster in Boston.
      ).
      These events and many others form the basis for our collaborative relationships, the antidotes, the science, and in many instances legislative and public health advances.

      The development of medical toxicology

      During the post World War II period in this country and throughout the world, there has been an expansion in access to new medications and chemicals. In addition, the international nature of our society has exposed all of us to natural products, both indigenous and imported species, and their associated problems never previously imagined. These dramatic changes led to the first American Poison Control Center in Chicago in 1953. By 1958 the American Association of Poison Control Centers had been established and by 1968 the American Academy of Clinical Toxicology had been developed.
      The development of diverse occupations for toxicologists led to further epidemiologic and scientific investigation, public and medical education, and a technological revolution. The earliest poison centers relied on a card based data system, moved to a microfilm system, and now most centers rely on integrated computer based analysis containing information on almost all products: natural or man made, medicinal or industrial, and alternative or allopathic.
      The evolution of the science of medical toxicology led to the development of fellowships, faculty, training programs, and organized links to the specialties of emergency medicine, pediatrics, and preventive medicine. Medical toxicology was approved by the American Board of Medical Specialties in 1992 and the Accreditation Council on Graduate Medical Education in 1998. A rigorous subspecialty examination is given biannually by the American Board of Emergency Medicine for graduates of fellowships in medical toxicology sponsored by pediatrics, preventive medicine, and emergency medicine.

      The role of the surgeon in medical toxicology

      The major part of this article will be divided into numerous relatively artificial sections. Although many textbooks of toxicology are divided by pharmacological and toxicological characteristics, some are organized by organ systems or presenting problems. As the purpose of this article is to address those toxicologic problems most relevant to surgeons, the sections will include parenteral substance use, inhalational and insufflational substance use, alcohol and drugs as they relate to traumatic events, occupational risks, envenomations, suicide, complications of gastrointestinal decontamination, toxins leading to organ transplantation, and substance withdrawal. The discussion will not address in any substantial detail alcohol and tobacco although all other toxins have a minimal surgical and societal impact when compared with that of alcohol and tobacco (
      • Hoffman R.S.
      • Goldfrank L.R.
      The impact of drug abuse and addiction on society.
      ).

      Parenteral substance use

      The parenteral use of drugs causes local and systemic toxicity and infections (
      • Cherubin C.E.
      The medical sequelae of narcotic addiction.
      ,
      • Cherubin C.E.
      • Sapira J.D.
      The medical complications of drug addiction and the medical assessment of the intravenous drug abuser 25 years later.
      ,
      • Moustoukas N.M.
      • Nichols R.L.
      • Smith J.W.
      • et al.
      Contaminated street heroin relationship to clinical infections.
      ). Diverse surgical interventions are necessary subsequent to patient exposure to contaminants and adulterants (
      • Pollard R.
      Surgical implications of some types of drug dependence.
      ,
      • Eisman B.
      • Lam R.C.
      • Rush B.
      Surgery on the narcotic addict.
      ,
      • Tinckler L.F.
      • Baratham G.
      Opium addiction and surgery.
      ,
      • Kantor T.G.
      • Cantor R.
      • Tom E.
      A study of hospitalized surgical patients on methadone maintenance.
      ). Adulterants to cocaine, heroin, and amphetamines include corn starch, flour, talc (magnesium silicate) (
      • Arnett E.N.
      • Battle W.E.
      • Russo J.V.
      • Roberts W.C.
      Intravenous injection of talc-containing drugs intended for oral use.
      ), sodium bicarbonate, various sugars [maltose, lactose], quinine, local anesthetics [lidocaine, procaine], heavy metals [lead, arsenic, mercury], and other active ingredients such as phencyclidine, lysergic acid diethylamide, and phenylpropanolamine (
      • Shannon M.
      Clinical toxicity of cocaine adulterants.
      ). The primary drug chosen by the patient has substantial potential toxicity when injected intravenously (i.v.), intraarterially, intramuscularly (i.m.), or subcutaneously (s.c.). In addition, these injections are almost invariably contaminated by local cutaneous bacteria or diverse organisms admixed during preparation.
      The local injury from injection may result in venous scarring (“tracks”), limiting venous access and resulting in chronic lymphedema, necessitating s.c. injections by these individual in the future, and facilitating cutaneous infections. These local infections include cellulitis (frequently of the hand and forearm), lymphangitis, abscesses, and necrotizing fasciitis. These individuals with or without prolonged narcosis (opioids, ethanol, sedatives) and pressure on an extremity may develop a compartment syndrome (
      • Torrens C.
      • Marin M.
      • Mestre C.
      • et al.
      Compartment syndrome and drug abuse.
      ) necessitating a fasciotomy or they may develop a peripheral neuropathy [“Saturday Night Palsy”]. These injection site injuries may lead to systemic manifestations of disease in the form of bacterial endocarditis (
      • Chambers H.F.
      • Korzeniowski O.M.
      • Sande M.A.
      Staphylococcus aureus endocarditis clinical manifestations in addicts and nonaddicts.
      ,
      • Levine D.
      • Crane L.
      • Zervos M.
      Bacteremia in narcotic addicts at the Detroit Medical Center. II. Infectious endocarditis A prospective comparative study.
      ). Although endocarditis can be directly linked to the number of contaminated injections, there is an increased incidence of endocarditis associated with the use of cocaine by any route. This added risk appears to be related to the direct endothelial injury resulting from utilizing cocaine (
      • Chambers H.F.
      • Morris D.L.
      • Tauber M.G.
      • Modin G.
      Cocaine use and the risk for endocarditis in intravenous drug abusers.
      ).
      Both tetanus and wound botulism are more prevalent among parenteral drug users (
      • Cherubin C.E.
      The medical sequelae of narcotic addiction.
      ,

      Wound botulism—California 1995. MMWR 1995;44:889–92.

      ). Routine immunization [with diphtheria tetanus toxoid and tetanus immune globulin] of parenteral drug users when appropriate or immunization history is in doubt will diminish the risk of Clostridium tetanus infections. Meticulous care of wound sites with incision and drainage of abscesses and necrotic tissue will decrease available anaerobic sites for growth of both C. botulinum and C. tetanus.
      Wound sites such as cellulitis, abscesses, and fasciitis necessitate radiographic assessment as retained needles or parts thereof may represent ongoing infectious risks. Rare contaminants such as arsenic, mercury, thallium, and other heavy metals will be visualized by plain radiography. Evaluation of the potential benefit or success of surgical removal can be facilitated by radiographic study. There are probably no sites protected from infection in parenteral drug use. Additional examples such as epidural abscesses, osteomyelitis, and septic arthritis may necessitate immediate surgical intervention (
      • Chandrasekar P.H.
      • Narula A.
      Bone and joint infections in intravenous drug abusers.
      ).
      Cardiovascular injury is not limited to infection. Local arterial and venous injuries result from direct trauma resulting in wall injury, aneurysmal dilatation, clot formation, and vascular obliteration. Pseudoaneurysms and arteriovenous fistulas typically occur following femoral artery or subclavian artery injury. These injuries may result from multiple injections by an individual in the femoral triangle or by a “technician in a shooting gallery” injecting into the subclavian artery (
      • Grund J.P.
      • Friedman S.R.
      • Stern L.X.
      • et al.
      Syringe-mediated drug sharing among injecting drug users patterns, social context, and implications for transmission of blood-borne pathogens.
      ). Attempts at subclavian vein injection also result in pneumo- and hemothoraces.
      A more common cause of pneumothorax in a substance user is associated with barotrauma. This mechanical injury occurs from deep inhalation, Valsalva maneuver, and reflex coughing. Those individuals insufflating nasal cocaine, amphetamines, or other drugs, or smoking “crack” cocaine, marijuana, heroin or other drugs may present with cough, shortness of breath, and a chest pain syndrome. These individuals are at high risk for pneumothorax, pneumomediastinum, and pneumopericardium (
      • Haim D.Y.
      • Lippman M.L.
      • Goldberg S.K.
      • Walkenstein M.D.
      The pulmonary complications of crack cocaine a comprehensive review.
      ,
      • Leitman B.S.
      • Greengart A.
      • Wasser H.J.
      Pneumomediastinum and pneumopericardium after cocaine abuse.
      ,
      • Shesser R.
      • Davis D.
      • Edelstein S.
      Pneumomediastinum and pneumothorax after inhaling alkaloidal cocaine.
      ).
      When evaluating the patient who insufflates cocaine, a meticulous inspection of the nares may reveal epistaxis, muscosal atrophy, or actual nasal septal perforation. Sinusitis is a common finding in those who recurrently insufflate and wound botulism has been reported from this “ideal” anaerobic site. Although these complications to the nasal mucosa result from repetitive and excessive use of cocaine, the single therapeutic application of cocaine of 2 mg/kg body weight to the nasal mucosa has resulted in ischemic cardiovascular complications (
      • Lange R.A.
      • Cigarroa R.G.
      • Yancy C.W.
      • et al.
      Cocaine-induced coronary-artery vasoconstriction.
      ). The therapeutic use of cocaine does increase the risk to those with underlying cardiovascular disease and cannot be guaranteed to be safe in any individual.
      A gastrointestinal manifestation of chronic heroin, methadone, tricyclic antidepresssant (
      • Ross J.P.
      • Small T.R.
      • Lepage P.A.
      Imipramine overdose complicated by toxic megacolon.
      ), or phenothiazine use is pseudoobstruction or apparent toxic megacolon (
      • Arnett E.N.
      • Battle W.E.
      • Russo J.V.
      • Roberts W.C.
      Intravenous injection of talc-containing drugs intended for oral use.
      ). These individuals typically have long standing dependency, chronic constipation, hypoperistaltism, a distended abdomen, and a massively distended bowel gas pattern, radiographically.

      Alcohol and drugs as they relate to trauma

      The enormous number of investigative advances in research methodology (
      • Soderstrom C.A.
      • Dischinger P.
      • Smith G.
      • et al.
      Psychoactive substance dependence among trauma center patients.
      ,
      • Soderstrom C.A.
      • Cowley R.A.
      A national alcohol and trauma center survey missed opportunities, failures of responsibility.
      ,
      • Rivara F.P.
      • Mueller B.A.
      • Flinger C.L.
      Drug use in trauma victims.
      ), the focus on cost for society, the enhancement of social services for primary and secondary victims (
      • Fuller M.G.
      • Diamond D.L.
      • Jordan M.L.
      • et al.
      The role of a substance abuse consultation team addressing the problem of hospitalized substance abusers.
      ,
      • Gentilello L.M.
      • Donovan D.M.
      • Dunn C.W.
      • et al.
      Alcohol interventions in trauma centers current practice and future directions.
      ,
      • Holt A.
      • Stewart I.C.
      • Dixon J.M.
      • et al.
      Alcohol and the emergency service patient.
      ,
      • Pories S.E.
      • Gamelli R.L.
      • Vacek P.
      • et al.
      Intoxication and injury.
      ), the legal and legislative action, as well as education for community, students, residents, and faculty demonstrate the commitment of emergency physicians and trauma surgeons and their coworkers to participate in preventive public health measures to limit the societal risks suggested by the following data (
      • Hoffman R.S.
      • Goldfrank L.R.
      The impact of drug abuse and addiction on society.
      ,
      Institute of Medicine, National Academy of Sciences
      ,
      • Gentilello L.M.
      • Duggan P.
      • Drummond D.
      • et al.
      Major injury as a unique opportunity to initiate treatment in the alcoholic.
      ,
      • Rivara F.P.
      • Jurkovich G.J.
      • Gurney J.G.
      • et al.
      The magnitude of acute and chronic alcohol abuse in trauma patients.
      ,
      • Dunn C.W.
      • Donovan D.M.
      • Gentilello L.M.
      Practical guidelines for performing alcohol interventions in trauma centers.
      ,
      • Lowenstein S.R.
      • Weissberg M.P.
      • Terry D.
      Alcohol intoxication, injuries, and dangerous behaviors, and the revolving emergency department door.
      ,
      • Soderberg R.
      The effects of alcohol abuse on readmission for trauma.
      ,
      • Soderstrom C.A.
      • Smith G.S.
      Alcohol’s effect on trauma outcomes—A reappraisal of conventional wisdom.
      ,
      • Longabaugh R.
      • Minugh A.
      • Nirenberg T.D.
      • et al.
      Injury as a motivator to reduce drinking.
      ,
      • Jurkovich G.J.
      • Rivara F.P.
      • Gurney J.G.
      • et al.
      The effect of acute alcohol intoxication and chronic alcohol abuse on outcome from trauma.
      ).
      Many of our organizational and political advances date to the 1966 National Academy of Sciences Report, Accidental Death and Disability: The Neglected Disease of Modern Society (

      Committee on Trauma and Committee on Shock, National Academy of Sciences. Accidental death and disability: the neglected disease of modern society. Washington, DC: National Academy Press; 1966. Public Health Service publication 1071-A-13.

      ). These efforts have led to a broader analysis of trauma (
      • Soderstrom C.A.
      • Dailey J.T.
      • Kerns T.J.
      Alcohol and other drugs an assessment of testing and clinical practices in U.S. trauma centers.
      ,
      • Jurkovich G.J.
      • Rivara F.P.
      • Gurney J.G.
      • et al.
      Effects of alcohol intoxication on the initial assessment of trauma patients.
      ) including that associated with suicides, homicides (
      • Wieczorek W.F.
      • Welte J.W.
      • Abel E.L.
      Alcohol, drugs and murder a study of convicted homicide offenders.
      ), vehicular [car, motorcycle, bicycle] crashes (
      • Higgins J.P.
      • Wright S.W.
      • Wrenn K.D.
      Alcohol, the elderly, and motor vehicle crashes.
      ,
      • Colquitt M.
      • Fielding L.P.
      • Cronan J.F.
      Drunk drivers and medical and social injury.
      ,
      • Waller J.A.
      Management issues for trauma patients with alcohol.
      ,

      Alcohol-related traffic fatalities—United States: 1982–1989. MMWR 1990;39:889–92.

      ,
      • Reyna T.M.
      • Hollis H.W.
      • Hulsebus R.C.
      Alcohol-related trauma.
      ), falls, penetrating trauma from stabbings and gun shot wounds, fires (
      • Haum A.
      • Perbix
      • Hack H.J.
      • et al.
      Alcohol and drug abuse in burn patients.
      ), drownings, pedestrian injuries, child abuse, domestic violence, elder abuse, and the impact on the young (
      • Mannenbach M.S.
      • Hargarten S.W.
      • Phelan M.B.
      Alcohol use among injured patients aged 12 to 18 years.
      ) and elderly (
      • Higgins J.P.
      • Wright S.W.
      • Wrenn K.D.
      Alcohol, the elderly, and motor vehicle crashes.
      ).
      Ethanol remains the leading individual toxicologic cause for traumatic deaths (

      Sixth Special Report to Congress on Alcohol and Health. Department of Health and Human Services, National Institute on Alcohol Abuse and Alcoholism. DHHS pub. No. ADM 87–1519. 1987.

      ,
      • Landen M.G.
      • Beller M.
      • Funk E.
      • et al.
      Alcohol related injury death and alcohol availability in remote Alaska.
      ). Ethanol is associated with 50% of traffic fatalities, 50% of deaths by fire, 67% of drownings, 67% of homicides, and 35% of suicides (
      • Crouch D.J.
      • Birky M.M.
      • Gust S.W.
      • et al.
      The prevalence of drugs and alcohol in fatally injured truck drivers.
      ,
      • Maio R.F.
      Alcohol and injury in the emergency department opportunities for intervention.
      ,
      • West L.J.
      • Maxwell D.S.
      • Noble E.P.
      • Solomon D.H.
      Alcoholism.
      ). In a 1975 Dallas study of fatal motor vehicle crash victims, it was determined that 15% of all drivers, passengers, and pedestrians had positive toxicologic studies for illicit drugs alone or a combination of alcohol and drugs (
      • Garriott J.C.
      • DiMaio V.J.M.
      • Zumwalt R.E.
      • Petty C.S.
      Incidence of drugs and alcohol in fatally injured motor vehicle drivers.
      ). In a study of marijuana using students, twice as many had motor vehicle crashes in the 6–12 months prior to a marijuana conviction than a control group (
      • Smart R.G.
      Marijuana and driving risk among college students.
      ).
      Evidence continues to expand for the association between substance use and severe trauma (
      • Marzuk P.M.
      • Tardiff K.
      • Leon A.C.
      • et al.
      Fatal injuries after cocaine use as a leading cause of death among young adults in New York City.
      ). In New York City, Marzuk reported that 18.2% of those involved in motor vehicle crash fatalities were found to have utilized cocaine (
      • Marzuk P.M.
      • Tardiff K.
      • Leon A.C.
      • et al.
      Prevalance of recent cocaine use among motor vehicle fatalities in New York City.
      ). Lindenbaum and colleagues, in a study of urban trauma, found that 74.5% of the patients had toxicologic tests positive for illicit or prescription drugs, more than 50% of which included cocaine (
      • Lindenbaum G.A.
      • Carrol S.F.
      • Daskal H.
      • et al.
      Patterns of alcohol and drug abuse in an urban trauma center the increasing role of cocaine use.
      ). Similarly, Sloan et al. when analyzing trauma patients showed that 34% had marijuana present in urine toxicologic studies (
      • Sloan E.P.
      • Zalenski R.J.
      • Smith R.F.
      • et al.
      Toxicology screening in urban trauma patients. Drug prevalence and its relationship to trauma severity and management.
      ). Brookoff and coworkers showed that greater than 50% of reckless drivers who were not intoxicated with alcohol were intoxicated with other drugs, particularly marijuana and cocaine (
      • Brookoff D.
      • Cook C.S.
      • Williams C.
      • Mann C.S.
      Testing reckless drivers for cocaine and marijuana.
      ). Whereas other studies have similar findings, most minor traumatic events also leading to substantial disability including slips, falls, hand injury, and other work-related events, have been neglected with regard to rigorous toxicology study (
      • Becker B.
      • Woolard R.
      • Nirenberg T.D.
      • et al.
      Alcohol use among subcritically injured emergency department patients.
      ,
      • Loiselle J.M.
      • Baker M.D.
      • Templeton J.M.
      • et al.
      Substance abuse in adolescent trauma.
      ). Many of these events occur because of the individual’s loss of perception of risk or loss of eye-hand coordination. These injuries represent another component of the unrecognized consequences of substance abuse.
      A commonly criticized characteristic of these studies relates to the power of the analytic techniques such as breath analyzers for alcohol and urine and blood testing for other toxins. These studies can only substantiate an association between drug use and trauma, as it is not certain whether it is the toxin or a drug related behavior that is responsible for the event (
      • Soderstrom C.A.
      • Dischinger P.
      • Smith G.
      • et al.
      Psychoactive substance dependence among trauma center patients.
      ,
      • Loiselle J.M.
      • Baker M.D.
      • Templeton J.M.
      • et al.
      Substance abuse in adolescent trauma.
      ,
      • Brookoff D.
      • Campbell E.A.
      • Shaw L.M.
      The underreporting of cocaine-related trauma drug abuse warning network reports versus hospital toxicology tests.
      ).
      Many investigators have attempted to look at correlates between drugs and shock, severity of injury, and mortality (
      • Thal E.R.
      • Bost R.O.
      • Anderson R.J.
      Effects of alcohol and other drugs on traumatized patients.
      ). These results have been equivocal and confounding variables seem to often outweigh clarity – regarding the toxin’s effects on cognition, injury severity, autonomic and other compensatory responses.
      Although the cost analysis must be redone for current dollars, in 1989 the Centers for Disease Control: Cost of injury in the United States report showed that each injury death cost over $300,000 in terms of lost productivity. To place this in perspective, it is six times greater than that associated with death due to heart disease and eight times greater than that due to stroke (

      Centers for Disease Control. Cost of injury in the United States. Report to the US Congress. October, 1989.

      ). Injury severity analyses, metabolic and hemodynamic monitoring, and the improvement in the quality of surgical intensive care have improved analysis and the acute survival of these patients (
      • McGill V.
      • Kowal-Vern A.
      • Fisher S.G.
      • et al.
      The impact of substance abuse on mortality and morbidity from thermal injury.
      ).
      A broader base for interventions, a greater commitment to help, the recognition of need, the benefit of brief interventions, and the appreciation of the special opportunities of intervention during a prolonged hospitalization for a drug or alcohol using trauma victim have documented efficacy in reducing consumption (
      • Dunn C.W.
      • Donovan D.M.
      • Gentilello L.M.
      Practical guidelines for performing alcohol interventions in trauma centers.
      ,
      • D’Onofrio G.
      • Bernstein E.
      • Bernstein J.
      • et al.
      Patients with alcohol problems in the emergency department, Part 2 intervention and Referral.
      ).

      Occupational injuries, toxicology and the surgeon

      Several occupations place the worker at extreme risk for a toxicologic exposure necessitating surgical intervention. Three diverse tasks of significant importance have a unique clinical manifestation - pain out of proportion to the physical findings. Using a paint or grease gun under high pressure, working with hydrofluoric acid for rust removal, brick cleaning and etching microchips in the semiconductor industry, and the international transport of cocaine or heroin in human intestines [a body packer] may be associated with pain out or proportion to clinical findings.
      A grease or paint gun is used under high pressure (approximately 3000 pounds/square inch) to apply paints or grease to a surface or object (
      • Edlich R.F.
      • Rodeheaver G.T.
      • Edgerton M.T.
      Airless paint gun injuries an update.
      ,
      • Karlbauer A.
      • Gasperschitz F.
      High pressure injection injury a hand threatening emergency.
      ). A critical error occurs when the gun misfires or the employee touches the tip to determine the presence of a blockage in the gun’s delivery system. These individuals may initially have extreme pain, no discoloration of the skin, and normal motor function. A physician without prior experience with this surgical emergency may not recognize the need for removal of the specific hydrocarbon or paint through extensive exploration and debridement. A radiograph may be useful to define the extent of the distribution of the foreign material. If neglected these injuries rapidly progress to soft tissue, muscle, and tendon infections. This particularly important toxicologic problem led Edlich to report the risk to the Consumer Product Safety Commission, which ultimately led the manufacturers to take voluntary corrective action in changing the nozzle design of airless paint guns.
      Hydrofluoric acid injuries have become common in the semiconductor industry, the brick and rust cleaning industries, as well as in the glass etching industry. Hydrofluoric acid (HF) may cause life-threatening injury with seemingly trivial exposures. Although this acid is considered a weak acid due to its limited dissociation constant, its permeability coefficient allows it to deeply penetrate tissues prior to its dissociation. Small exposures with 100% anhydrous HF of merely 2.5% body surface area can result in lethal hypocalcemia, hypomagnesemia, and hypokalemia. Dermal, ocular, inhalational, and oral exposure can result in extensive tissue destruction (
      • Anderson W.J.
      • Anderson J.R.
      Hydrofluoric acid burns of the hand mechanism of injury and treatment.
      ). All of these exposures, when the surface area of contact is substantial, necessitate continuous patient monitoring and clinical decisions with regard to tissue viability. Many patients require transfer to burn units. The commonest occupational exposure occurs on the fingers and hands through unrecognized pinhole leaks in gloves. The delay to onset of pain is often inversely related to the length of exposure and HF concentration. Unfortunately, the initial visual appearance of the wound may be benign, even lacking the presence of hyperemia in the first several hours. Only the vigilant physician who understands the pathophysiology and recognizes the implication of the pain out of proportion to clinical findings will initiate rapid appropriate therapy. Shortly thereafter the tissue becomes hyperemic subsequently blanching with whitish discoloration and coagulative necrosis occurring as calcium is precipitated. The initial treatment includes removal of exposed clothing and irrigation of exposed tissues with water or saline. A topical gel of calcium (gluconate or chloride) in lubricating jelly [ex 25 mL of 10% calcium gluconate in 75 mL of sterile water soluble lubricant] can be applied to a small surface area (
      • Anderson W.J.
      • Anderson J.R.
      Hydrofluoric acid burns of the hand mechanism of injury and treatment.
      ). If the wound is large or in a finger pad not accessible to intradermal calcium injections, calcium gluconate can be delivered directly to the affected tissue by a radial or brachial artery infusion or by an i.v. Bier block. Recommendations for these infusions are 10 mL of 10% calcium gluconate in either 40 mL of D5W or normal saline given over 4 h (
      • Velvart J.
      Arterial perfusion for hydrofluoric acid burns.
      ). These procedures are usually done in collaboration with a plastic surgeon who may still need to perform extensive debridement although pain is usually rapidly ameliorated and tissue salvage appears to be substantial following calcium infusion (
      • Anderson W.J.
      • Anderson J.R.
      Hydrofluoric acid burns of the hand mechanism of injury and treatment.
      ,
      • Velvart J.
      Arterial perfusion for hydrofluoric acid burns.
      ).
      Management of body packers who typically transport large numbers of well constructed and firmly closed multiply layered wrappings of plastic or polyvinyl chloride bags of cocaine or heroin can be complex. Obvious cocaine or heroin overdose in a body packer leads to the use of a very high dose naloxone infusion [5–10 mg/h] for the individual transporting heroin, and operative removal of the bags, inspection of the site of package rupture for evidence of mucosal ischemia, as well as appropriate management of systemic cocaine intoxication [often doses of diazepam of 20–100 mg i.v.] for the cocaine packer. Most patients have ingested these bags in their native country and then taken a drug such as diphenoxylate to decrease peristalsis and prevent defecation prior to arrival in another country. When arrested in the United States or elsewhere, these individuals may be asymptomatic. Usually a treatment strategy can be negotiated with the prisoner who often fears the legal consequences more than the potential lethality of the ingestant. Our treatment is to perform an abdominal radiograph to determine the potential visibility and character of the bags. The patient is then given whole bowel irrigation with several liters of polyethylene glycol – electrolyte solution until the effluent is clear and the presumed number of ingested bags have been produced. This number is usually precisely known by the body packers. Following collection and a clear effluent, an upper gastrointestinal series with small bowel follow through can be easily performed to define the presence of any retained bags. Retained bags rarely are found in the stomach and if present can be removed with an endoscopic technique (
      • Hoffman R.S.
      • Smilkstein M.J.
      • Goldfrank L.R.
      Whole bowel irrigation and the cocaine body packer.
      ). Obstruction at the ileocecal valve or at the splenic flexure will necessitate laparotomy and enterotomy. These same principles of removal apply to massive suicidal ingestions from agents such as iron, bromides, barbiturates, or meprobamate, which may also be treated with endoscopic removal, whole bowel irrigation, or laparotomy when concretions and pill masses are formed (
      • Ambrose N.
      • Johnson M.
      • Burdon D.
      • et al.
      A physiologic approach of polyethylene glycol and a balanced electrolyte solution as bowel preparation.
      ,
      • Tenenbein M.
      Whole bowel irrigation for toxic ingestions.
      ,
      • Tenenbein M.
      Whole bowel irrigation as gastrointestinal decontamination procedure after acute poisoning.
      ).

      Complications of therapy for gastrointestinal decontamination

      In the last 10–15 years, syrup of ipecac and gastric lavage have been replaced by activated charcoal as the prime technique for managing overdoses (
      • Kulig K.W.
      • Bar-Or D.
      • Cantrill S.V.
      • et al.
      Management of acutely poisoned patients without gastric emptying.
      ). Several complications of these therapies may lead to surgical interventions. Emesis with syrup of ipecac has led to Mallory Weiss tears (
      • Tandberg D.
      • Liechty E.J.
      • Fishbein D.
      Mallory-Weiss syndrome an unusual complication of ipecac-induced emesis.
      ) and diaphragmatic rupture (
      • Robertson W.O.
      Syrup of ipecac associated fatality a case report.
      ). Gastric lavage with a large bore orogastric tube has caused esophageal tears and perforation and gastric perforation (
      • Askenasi R.
      • Abramowicz M.
      • Jeanmart J.
      • et al.
      Esophageal perforation an unusual complication of gastric lavage.
      ,
      • Wald P.
      • Stern J.
      • Weiner B.
      • et al.
      Esophageal tear following forceful removal of an impacted oral-gastric lavage tube.
      ,
      • Mafiani P.J.
      • Poole N.
      Gastrointestinal tract perforation with charcoal peritoneum complicating orogastric intubation and lavage.
      ).
      Activated charcoal, a fine black powder, has extensive adsorptive properties both preventing initial absorption of a toxin and also limiting enteroenteric recycling. There are the rarest of complications associated with this commonly utilized antidote, but bowel obstruction or pseudoobstruction has resulted from multiple dose activated charcoal use (
      • Brubacher J.R.
      • Levine B.
      • Hoffman R.S.
      Intestinal pseudoobstruction (Ogilvie’s syndrome) in theophylline overdose.
      ,
      • Flores F.
      • Battle W.S.
      Intestinal obstruction secondary to activated charcoal.
      ,
      • Gomez B.I.F.
      • Brent J.A.
      • Munoz D.C.
      • et al.
      Charcoal stercolith with intestinal perforation in a patient treated for amitriptyline ingestion.
      ,
      • Goulboume K.B.
      • Cisek J.E.
      Small bowel obstruction secondary to activated charcoal and adhesions.
      ,
      • Longdon P.
      • Henderson A.
      Intestinal pseudoobstruction following the use of enteral charcoal and sorbitol with mechanical ventialation with papaveretum sedation for theophylline poisoning.
      ,
      • Ray M.J.
      • Padin D.R.
      • Condie J.D.
      • Halls J.M.
      Charcoal bezoar. Small bowel obstruction secondary to amitriptyline overdose therapy.
      ,
      • Watson W.A.
      • Cremes K.F.
      • Chapman J.A.
      Gastrointestinal obstruction associated with multiple dose activated charcoal.
      ). These events can usually be avoided by solely utilizing single dose activated charcoal when the presumed toxin under treatment may result in decreased gut motility. The benefits of decreasing enteric absorption through repetitive dose activated charcoal should be evaluated collaboratively with a medical toxicologist.

      Thermal burns and smoke inhalation

      No discussion of thermal burns can neglect the fact that toxin use such as ethanol is commonly associated with fire related injury. In addition, these fires are typically initiated by smokers of cigarettes. Individual fire victims with and without thermal burns commonly also inhale diverse combustion products. These products are usually divided into simple asphyxiants [carbon dioxide, methane, and an oxygen depleted environment], irritants [chlorine, phosgene, acrolein, ammonia, and others] and the chemical asphyxiants of carbon monoxide (CO), hydrogen cyanide (HCN), hydrogen sulfide (H2S), and oxides of nitrogen [producing methemoglobin]. It is this last group that typically necessitates collaboration with a toxicologist.
      The potential therapeutic intervention for carboxyhemoglobin is appropriate for the other exposures, but the therapies for cyanide toxicity and methemoglobin formation are limited by the potential for simultaneous exposure to the other agents. The management of these individuals can be safely guided by interpretation of an arterial blood gas, a lactic acid and cooximetry determining carboxyhemoglobin, oxyhemoglobin, and methemoglobin. This approach will determine whether hyperbaric oxygen, the full cyanide antidote kit [amyl nitrite, sodium nitrite, and sodium thiosulfate) or methylene blue (for methemogloin) is indicated.

      Ingestion of acids and burns

      The role of surgery for patients who ingest caustic agents has changed over the last 25 years (
      • Meredith W.
      • Kon N.D.
      • Thompson J.N.
      Management of injuries from liquid lye ingestion.
      ). In great part these changes are related to controls established on maximal caustic concentrations available for sale to the general consumer, the utilization of childproof containers, and increasing public awareness of potential toxicity. These factors have limited the unintentional exposure of young children to these products so that the vast majority of grave exposures now occur in suicidal adults. The decision to perform surgery on patients who have ingested strong acids or bases is obvious when perforation is visualized radiographically or by endoscopy, or severe abdominal rigidity or hypotension ensues (
      • Safarti E.
      • Gossot D.
      • Assens P.
      • Celerier M.
      Management of caustic ingestion in adults.
      ). Many patients with none of this clinical evidence may be in danger of sepsis and delayed hemorrhage and already actually have necrosis and perforation.
      In certain strong base and many strong acid exposures, the initial clinical manifestations may be subtle and recognition of this early dissociation between grave tissue injury is essential to prevent further damage and death (
      • Horvath O.P.
      • Olah T.
      • Zental G.
      Emergency esophagogastrectomy for the treatment of hydrochloric acid injury.
      ,
      • Zargar S.A.
      • Kochar R.
      • Nagi B.
      • et al.
      Ingestion of corrosive acids spectrum of injury to upper gastrointestinal tract and natural history.
      ,
      • Wu M.H.
      • Lai W.W.
      Surgical management of extensive corrosive injuries of the alimentary tract.
      ). The extent of tissue injury will define essential management and disposition. Endoscopic evaluation is a standard diagnostic tool in the management of caustic ingestions. Patients should have this procedure performed within 12 h and no later than 24 h if its benefit is to be maximized. The surgical intervention may include laparotomy for evaluation of serosal surfaces and resection of necrotic tissue, and repair of perforation if indicated (
      • Ribet M.E.
      Esophagogastrectomy for acid injury.
      ). Laparoscopy has been utilized for tissue assessment but this does not allow complete visualization and can be misleading. Gastrostomy and enterostomy may be useful following esophageal or gastric injury (
      • Estrera A.
      • Taylor W.
      • Mills L.J.
      Corrosive burns of the esophagus and stomach a recommendation for an aggressive surgical approach.
      ,
      • Hwang T.L.
      • Shen-Chen S.M.
      • Chen M.F.
      Nonthoracotomy esophagectomy for corrosive esophagitis with gastric perforation.
      ,
      • Ochi K.
      • Ohashi T.
      • Sato S.
      • et al.
      Surgical treatment for caustic ingestion injury of the pharynx, larynx, and esophagus.
      ). Delayed surgical intervention can be used for strictures and gastric outlet obstruction.

      Envenomations

      Marine envenomations, or more specifically punctures of the lengthy spines of the sea urchin [Diadema spp], can result in painful muscle and joint injuries. Although these injuries are rare, the spines may necessitate surgical removal.
      Brown Recluse Spider [Loxosceles reclusa] bites are associated with local cutaneous necrosis. These lesions are initially painless; subsequently they blister, bleed, and ulcerate 2–8 h later. The initial intervention should include the use of dapsone, a leukocyte inhibitor. Surgical care should be delayed until primary granulation has occurred and delayed secondary closure with skin graft may be considered as valuable (
      • Rees R.
      • Campbell D.
      • Rieger E.
      • King L.E.
      The diagnosis and treatment of brown recluse spider bites.
      ,
      • Rees R.S.
      • Altenbern D.P.
      • Lynch J.B.
      • et al.
      Brown recluse spider bites a comparison of early surgical excision versus dapsone and delayed surgical excision.
      ).
      One of the most controversial debates regarding envenomation relates to the role of fasciotomy for patients envenomated by a specific group of crotalids—the rattlesnakes (
      • Garfin S.R.
      • Castilonia R.R.
      • Mubarak S.J.
      • et al.
      Rattlesnake bites and surgical decompression results using a laboratory model.
      ,
      • Glass T.G.
      Early debridement in pit viper bites.
      ). Surgery should not be considered in the management of elapids (coral snakes) nor in crotalids such as water moccasins and copperheads as tissue destruction will usually be limited and systemic manifestations are of greatest concern.
      Most agree that immediate excision of a bitten area to remove venom, extensive debridement, and fasciotomy are unnecessary. The early use of adequate amounts of antivenom may limit necrosis, edema, and the potential for the development of a compartment syndrome (
      • Wingert W.A.
      • Chan L.
      Rattlesnake bites in southern California and rationale for recommended treatment.
      ). There are infrequent indications for fasciotomy that may be necessary if antivenom use is delayed or inappropriate or appropriate antivenom is unavailable for the specific envenomation. Surgical debridement [for blisters, blebs, and necrosis] will be indicated several days following the initial envenomation.

      Toxins and the transplant surgeon

      The standard criteria that apply to any deceased person apply to patients succumbing who have been exposed to a toxin—if the organ under consideration is functional, it should be acceptable for removal and transplantation. It is unlikely that the quantity of almost any toxin in a particular organ will be sufficient to harm the patient to whom the organ will be transplanted when that toxin is distributed throughout the recipient.
      Patients who have intentionally or unintentionally ingested toxins resulting in hepatic, renal, or pulmonary disease may be candidates to receive new organs. Liver failure following Amanita phalloides, A. ocreata, Lepiota helveola, and L. brunneoincarnata, or other cyclopeptide-containing mushroom may necessitate liver transplantation (
      • Klein A.S.
      • Hart J.
      • Brems J.J.
      • et al.
      Amanita poisoning treatment and the role of liver transplantation.
      ,
      • Pinson C.W.
      • Daya M.R.
      • Benner K.G.
      • et al.
      Liver transplantation for severe Amanita phalloides mushroom poisoning.
      ,
      • Ramirez P.
      • Parilla P.
      • Sanchez-Bueno F.
      • et al.
      Fulminant hepatic failure after Lepiota mushroom poisoning.
      ,
      • Meunier B.C.
      • Camus C.M.
      • Houssin D.P.
      • et al.
      Liver transplantation after severe poisoning due to amatoxin containing Lepiota–report of three cases.
      ). Exposure to carbon tetrachloride and iron sulfate has also necessitated liver transplantation (
      • Nehoda H.
      • Wieser C.
      • Koller J.
      • et al.
      Recurrent liver failure with severe rhabdomyolysis after liver transplantation for carbon tetrachloride intoxication.
      ,
      • Kozaki K.
      • Egawa H.
      • Garcia-Kennedy R.
      • et al.
      Hepatic failure due to massive iron ingestion successfully treated with liver transplantation.
      ). Acetaminophen induced hepatotoxicity has led to the transfer for hepatic transplantation of numerous previously suicidal patients (
      • Clark R.
      • Thompson R.P.H.
      • Borirakchanyavat V.
      • et al.
      Hepatic damage and death from overdose of paracetamol.
      ,
      • Makin A.J.
      • Wendon J.
      • Williams R.
      A 7-year experience of severe acetaminophen-induced hepatotoxicity(1987–1993).
      ,
      • Bernal W.
      • Wendon J.
      • Rela M.
      • et al.
      Use and outcome of liver transplantation in acetaminophen-induced acute liver failure.
      ). Currently, the criteria to define those who cannot survive without surgery are inadequate. Most criteria are sensitive but inadequately specific. The current criteria are a pH < 7.30 following fluid and hemodynamic resuscitation or a PT ≥ 1.8 times greater than control, creatinine > 3.3 mg/dL, and grade III or IV hepatic encephalopathy (
      • Harrison P.M.
      • O’Grady J.G.
      • Keays R.T.
      • et al.
      Serial prothrombin time as prognostic indicator in paracetamol induced fulminant hepatic failure.
      ,
      • O’Grady J.G.
      • Wendon J.
      • Tan K.C.
      • et al.
      Liver transplantation after paracetamol overdose.
      ,
      • O’Grady J.G.
      • Alexander G.J.M.
      • Hayllar K.M.
      • et al.
      Early indicators of prognosis in fulminant hepatic failure.
      ).
      Lung transplantation has been performed on patients who have survived the acute exposure to paraquat, an herbicide that has specific toxicity for alveolar epithelial cells (
      • Walder B.
      • Brundler M.A.
      • Spiliopoulos A.
      • Romand J.A.
      Successful single-lung transplantation after paraquat intoxication.
      ). Most patients have died in spite of lung transplantation (
      • Kalmholz S.
      • Veith F.L.
      • Mollenkopf F.
      • et al.
      Single lung transplantation in paraquat intoxication.
      ,
      • Matthew H.
      • Logan A.
      • Woodruff M.F.A.
      • Heard B.
      Paraquat poisoning. Lung transplantation.
      ,
      • Saunders N.R.
      • Alpert H.M.
      • Cooper J.D.
      Sequential bilateral lung transplantation for paraquat poisoning. A case report.
      ).
      Renal transplantation has been performed for renal failure associated with the Cortinarius speciosissimus mushroom that has a toxin orellanine that results in interstitial nephritis and tubular damage (
      • Holmdahl J.
      • Blohme I.
      Renal transplantation after Cortinarius speciosissimus poisoning.
      ).

      Drug withdrawal and interactions

      Drug withdrawal from ethanol, sedative hypnotics, and opioids is a common occurrence on most surgical services. It is critical for the clinician to differentiate ethanol and sedative hypnotic withdrawal, which have quite similar characteristics, from opioid withdrawal. (
      • Hamilton R.J.
      Substance withdrawal.
      ) Untreated ethanol or sedative hypnotic withdrawal is life threatening, whereas opioid withdrawal is disagreeable but not life threatening. Ethanol or sedative withdrawal is readily differentiated from opioid withdrawal by the presence of a fever, an altered consciousness, and seizures in ethanol or sedative withdrawal. Ethanol withdrawal is acute in onset occurring as ethanol is metabolized by zero order kinetics through alcohol dehydrogenase in the liver. Sedative hypnotics may have delayed manifestations depending on the metabolic characteristics of the agents following the initiation of absolute or relative abstinence. Those sedative hypnotics with short half-lives may take 1–2 days to manifest withdrawal while other agents such as diazepam may take weeks for the more life-threatening withdrawal manifestations to become evident.
      Opioid withdrawal from short acting agents such as heroin will occur within hours, whereas withdrawal from methadone will take 1–2 days. The symptoms of abdominal cramps, nausea, diarrhea, dilated pupils, yawning, piloerection, and diaphoresis are present to varying degrees.
      Both of these groups of patients will require treatment for withdrawal so that their surgical care can be optimized. Active treatment for withdrawal with parenteral doses of opioids such as methadone with a long half life of 24–48 h will facilitate the overall management. Management of ethanol withdrawal prior to life-threatening manifestations should be active, with a drug such as diazepam with a long half life [20–70 h] and active metabolites with long half lives (
      • Saitz R.
      • Mayo-Smith M.F.
      • Roberts M.S.
      • et al.
      Individualized treatment for alcohol withdrawal. A randomized double blind controlled trial.
      ,
      • Sellers E.M.
      • Naranjo C.A.
      • Harrison M.
      • et al.
      Diazepam loading simplified treatment of alcohol withdrawal.
      ,
      • Wasilewski D.
      • Matsumoto H.
      • Kur E.
      • et al.
      Assessment of diazepam loading dose therapy of delirium tremens.
      ). These patients will need detoxification, rehabilitation and longterm follow up care.

      Conclusion

      This article has discussed many of the roles for toxicologists and surgeons. Many types of surgeons, burn, plastic, cardiovascular, pediatric, otolaryngologist, ophthalmologist, traumatologist, peripheral vascular, and transplant, and generalists all interface with medical toxicologists.
      The role of the medical toxicologist in the care of these complex clinical problems can be substantial and enhance the interdisciplinary effort. Many fine Regional Poison Centers and Medical Toxicology training programs have clinicians who can add essential toxicologic and pharmacologic information at the bedside. The combination of the unique reasoning of the medical toxicologists and surgeons will decrease morbidity and mortality for these patients.
      The public health implications for the care of these patients is that their physicians must cooperate to study improvements in care as well as preventive and rehabilitative strategies so as to alter public policy.
      There have been many consequential improvements in patient care including the routine use of thiamine [decreasing the incidence of Wernicke–Korsakoff syndrome], and the use of diphtheria – tetanus toxoid [decreasing the risk of tetanus]. The focus on the adverse effects of tobacco, ethanol, and substance use has led to more legal, social, and therapeutic interventions and recognition of the risk from exposure to substance users’ blood potentially transmitting hepatitis B [immunization of all health personnel—OSHA] and the similar risk of HIV exposure [post exposure prophylaxis] has decreased the risk of transmission following blood borne exposure.
      These toxic exposures result in increased costs to society in the hospital and post hospital phases and lead to family disruption, lost years of productivity, and ultimately utilize limited health resources. Each person must be evaluated from a molecular, clinical, and societal perspective so that we may consider our potential to change individual health practices and societal approaches to these patients. We must consider each encounter a unique and tragic human experiment and teachable moment for the patient, family, student, and staff. In so doing we will be developing a shared public health role for the surgeon, the medical toxicologist, and the emergency physician. (
      • Jaeger A.
      • Jehl F.
      • Flesch F.
      • et al.
      Kinetics of amatoxins in human posioning therapeutic implications.
      ,
      • Woodle E.S.
      • Moody R.R.
      • Cox K.L.
      • et al.
      Orthotopic liver transplantation in a patient with Amanita poisoning.
      )

      References

        • Burke M.
        Gastric lavage and emesis in the treatment of ingested poisons.
        Resuscitation. 1972; 1: 91-105
        • Moore S.W.
        A case of poisoning by laudanum, successfully treated by means of Jukes’s syringe.
        NY Med Phys J. 1825; 4: 91-92
        • Taylor H.M.
        A preliminary survey of the effect which lye legislation has had on the incidence of esophageal stricture.
        Ann Otol Rhinol Laryngol. 1935; 44: 1157-1158
        • Varma D.R.
        • Guest I.
        The Bhopal accident and methyl isocyanate toxicity.
        J Toxicol Environ Health. 1993; 40: 513-529
        • Hunter D.
        The diseases of occupations. 6th ed. Hodder Stoughton, London1978
        • Corn J.K.
        • Starr J.
        Hisotrical perspective on asbestos.
        Am J Indust Med. 1987; 11: 359-373
        • Murray R.
        Asbestos.
        Br J Indust Med. 1990; 47: 361-365
        • Falk H.
        • Creech J.L.
        • Health C.W.
        • et al.
        Hepatic disease among workers at a vinyl chloride polymerization plant.
        JAMA. 1974; 230: 59-63
        • Wing J.S.
        • Sanderson L.M.
        • Brender J.D.
        • et al.
        Acute health effects in a community after a release of hydrofluoric acid.
        Arch Environ Helath. 1991; 46: 155-160
        • Faxon N.W.
        • Churchill E.D.
        The Coconut Grove disaster in Boston.
        JAMA. 1942; 120: 1385-1388
        • Hoffman R.S.
        • Goldfrank L.R.
        The impact of drug abuse and addiction on society.
        Emerg Med Clin North Am. 1990; 8: 467-480
        • Cherubin C.E.
        The medical sequelae of narcotic addiction.
        Ann Intern Med. 1967; 67: 23-33
        • Cherubin C.E.
        • Sapira J.D.
        The medical complications of drug addiction and the medical assessment of the intravenous drug abuser.
        Ann Intern Med. 1993; 119: 1017-1028
        • Moustoukas N.M.
        • Nichols R.L.
        • Smith J.W.
        • et al.
        Contaminated street heroin.
        Arch Surg. 1983; 118: 746-749
        • Pollard R.
        Surgical implications of some types of drug dependence.
        Br Med J. 1973; 1: 784-787
        • Eisman B.
        • Lam R.C.
        • Rush B.
        Surgery on the narcotic addict.
        Ann Surg. 1964; 159: 748-757
        • Tinckler L.F.
        • Baratham G.
        Opium addiction and surgery.
        Br J Surg. 1966; 53: 576-583
        • Kantor T.G.
        • Cantor R.
        • Tom E.
        A study of hospitalized surgical patients on methadone maintenance.
        Drug Alcohol Dependence. 1980; 6: 163-173
        • Arnett E.N.
        • Battle W.E.
        • Russo J.V.
        • Roberts W.C.
        Intravenous injection of talc-containing drugs intended for oral use.
        Am J Med. 1976; 60: 711-718
        • Shannon M.
        Clinical toxicity of cocaine adulterants.
        Ann Emerg Med. 1988; 17: 1243-1247
        • Torrens C.
        • Marin M.
        • Mestre C.
        • et al.
        Compartment syndrome and drug abuse.
        Acta Orthop Belg. 1993; 59: 143-146
        • Chambers H.F.
        • Korzeniowski O.M.
        • Sande M.A.
        Staphylococcus aureus endocarditis.
        Medicine. 1983; 62: 170-177
        • Levine D.
        • Crane L.
        • Zervos M.
        Bacteremia in narcotic addicts at the Detroit Medical Center. II. Infectious endocarditis.
        Rev Infect Dis. 1986; 8: 374-396
        • Chambers H.F.
        • Morris D.L.
        • Tauber M.G.
        • Modin G.
        Cocaine use and the risk for endocarditis in intravenous drug abusers.
        Ann Intern Med. 1987; 106: 833-836
      1. Wound botulism—California 1995. MMWR 1995;44:889–92.

        • Chandrasekar P.H.
        • Narula A.
        Bone and joint infections in intravenous drug abusers.
        Rev Infect Dis. 1986; 8: 904-910
        • Grund J.P.
        • Friedman S.R.
        • Stern L.X.
        • et al.
        Syringe-mediated drug sharing among injecting drug users.
        Soc Sci Med. 1996; 42: 691-703
        • Haim D.Y.
        • Lippman M.L.
        • Goldberg S.K.
        • Walkenstein M.D.
        The pulmonary complications of crack cocaine.
        Chest. 1995; 107: 233-240
        • Leitman B.S.
        • Greengart A.
        • Wasser H.J.
        Pneumomediastinum and pneumopericardium after cocaine abuse.
        AJR. 1988; 151: 614
        • Shesser R.
        • Davis D.
        • Edelstein S.
        Pneumomediastinum and pneumothorax after inhaling alkaloidal cocaine.
        Ann Emerg Med. 1981; 10: 213-215
        • Lange R.A.
        • Cigarroa R.G.
        • Yancy C.W.
        • et al.
        Cocaine-induced coronary-artery vasoconstriction.
        N Engl J Med. 1989; 321: 1557-1561
        • Ross J.P.
        • Small T.R.
        • Lepage P.A.
        Imipramine overdose complicated by toxic megacolon.
        Am Surg. 1998; 64: 242-244
        • Soderstrom C.A.
        • Dischinger P.
        • Smith G.
        • et al.
        Psychoactive substance dependence among trauma center patients.
        JAMA. 1992; 267: 2756-2759
        • Soderstrom C.A.
        • Cowley R.A.
        A national alcohol and trauma center survey.
        Arch Surg. 1987; 122: 1067-1071
        • Rivara F.P.
        • Mueller B.A.
        • Flinger C.L.
        Drug use in trauma victims.
        J Trauma. 1989; 29: 462-470
        • Fuller M.G.
        • Diamond D.L.
        • Jordan M.L.
        • et al.
        The role of a substance abuse consultation team addressing the problem of hospitalized substance abusers.
        Gen Hosp Psych. 1994; 16: 73
        • Gentilello L.M.
        • Donovan D.M.
        • Dunn C.W.
        • et al.
        Alcohol interventions in trauma centers.
        JAMA. 1995; 274: 1043-1048
        • Holt A.
        • Stewart I.C.
        • Dixon J.M.
        • et al.
        Alcohol and the emergency service patient.
        Br Med J. 1980; 281: 638-640
        • Pories S.E.
        • Gamelli R.L.
        • Vacek P.
        • et al.
        Intoxication and injury.
        J Trauma. 1992; 32: 60-64
        • Institute of Medicine, National Academy of Sciences
        Broadening the base of treatment for alcohol problems. National Academy Press, Washington, DC1990
        • Gentilello L.M.
        • Duggan P.
        • Drummond D.
        • et al.
        Major injury as a unique opportunity to initiate treatment in the alcoholic.
        Am J Surg. 1988; 156: 558-561
        • Rivara F.P.
        • Jurkovich G.J.
        • Gurney J.G.
        • et al.
        The magnitude of acute and chronic alcohol abuse in trauma patients.
        Arch Surg. 1993; 128: 907-913
        • Dunn C.W.
        • Donovan D.M.
        • Gentilello L.M.
        Practical guidelines for performing alcohol interventions in trauma centers.
        J Trauma. 1997; 42: 299-304
        • Lowenstein S.R.
        • Weissberg M.P.
        • Terry D.
        Alcohol intoxication, injuries, and dangerous behaviors, and the revolving emergency department door.
        J Trauma. 1990; 30: 1252-1258
        • Soderberg R.
        The effects of alcohol abuse on readmission for trauma.
        JAMA. 1993; 270: 1962-1964
        • Soderstrom C.A.
        • Smith G.S.
        Alcohol’s effect on trauma outcomes—A reappraisal of conventional wisdom.
        JAMA. 1993; 270: 93-94
        • Longabaugh R.
        • Minugh A.
        • Nirenberg T.D.
        • et al.
        Injury as a motivator to reduce drinking.
        Acad Emerg Med. 1995; 2: 817-825
        • Jurkovich G.J.
        • Rivara F.P.
        • Gurney J.G.
        • et al.
        The effect of acute alcohol intoxication and chronic alcohol abuse on outcome from trauma.
        JAMA. 1993; 270: 51-56
      2. Committee on Trauma and Committee on Shock, National Academy of Sciences. Accidental death and disability: the neglected disease of modern society. Washington, DC: National Academy Press; 1966. Public Health Service publication 1071-A-13.

        • Soderstrom C.A.
        • Dailey J.T.
        • Kerns T.J.
        Alcohol and other drugs.
        J Trauma. 1994; 36: 68-73
        • Jurkovich G.J.
        • Rivara F.P.
        • Gurney J.G.
        • et al.
        Effects of alcohol intoxication on the initial assessment of trauma patients.
        Ann Emerg Med. 1992; 21: 704-708
        • Wieczorek W.F.
        • Welte J.W.
        • Abel E.L.
        Alcohol, drugs and murder.
        J Criminal Justice. 1990; 18: 217-227
        • Higgins J.P.
        • Wright S.W.
        • Wrenn K.D.
        Alcohol, the elderly, and motor vehicle crashes.
        Am J Emerg Med. 1996; 14: 265-267
        • Colquitt M.
        • Fielding L.P.
        • Cronan J.F.
        Drunk drivers and medical and social injury.
        N Engl J Med. 1987; 317: 1262-1266
        • Waller J.A.
        Management issues for trauma patients with alcohol.
        J Trauma. 1990; 30: 1548-1553
      3. Alcohol-related traffic fatalities—United States: 1982–1989. MMWR 1990;39:889–92.

        • Reyna T.M.
        • Hollis H.W.
        • Hulsebus R.C.
        Alcohol-related trauma.
        Ann Surg. 1985; 201: 194-197
        • Haum A.
        • Perbix
        • Hack H.J.
        • et al.
        Alcohol and drug abuse in burn patients.
        Burns. 1995; 21: 194-199
        • Mannenbach M.S.
        • Hargarten S.W.
        • Phelan M.B.
        Alcohol use among injured patients aged 12 to 18 years.
        Acad Emerg Med. 1997; 4: 40-44
        • Higgins J.P.
        • Wright S.W.
        • Wrenn K.D.
        Alcohol, the elderly, and motor vehicle crashes.
        Am J Emerg Med. 1996; 14: 265-267
      4. Sixth Special Report to Congress on Alcohol and Health. Department of Health and Human Services, National Institute on Alcohol Abuse and Alcoholism. DHHS pub. No. ADM 87–1519. 1987.

        • Landen M.G.
        • Beller M.
        • Funk E.
        • et al.
        Alcohol related injury death and alcohol availability in remote Alaska.
        JAMA. 1997; 278: 1755-1758
        • Crouch D.J.
        • Birky M.M.
        • Gust S.W.
        • et al.
        The prevalence of drugs and alcohol in fatally injured truck drivers.
        J Forensic Sci. 1993; 38: 1342-1353
        • Maio R.F.
        Alcohol and injury in the emergency department.
        Ann Emerg Med. 1995; 26: 221-223
        • West L.J.
        • Maxwell D.S.
        • Noble E.P.
        • Solomon D.H.
        Alcoholism.
        Ann Intern Med. 1984; 100: 405-406
        • Garriott J.C.
        • DiMaio V.J.M.
        • Zumwalt R.E.
        • Petty C.S.
        Incidence of drugs and alcohol in fatally injured motor vehicle drivers.
        J Forensic Sci. 1977; 22: 383-389
        • Smart R.G.
        Marijuana and driving risk among college students.
        J Safety Res. 1974; 6: 155
        • Marzuk P.M.
        • Tardiff K.
        • Leon A.C.
        • et al.
        Fatal injuries after cocaine use as a leading cause of death among young adults in New York City.
        N Engl J Med. 1995; 332: 1753-1757
        • Marzuk P.M.
        • Tardiff K.
        • Leon A.C.
        • et al.
        Prevalance of recent cocaine use among motor vehicle fatalities in New York City.
        JAMA. 1990; 263: 250-256
        • Lindenbaum G.A.
        • Carrol S.F.
        • Daskal H.
        • et al.
        Patterns of alcohol and drug abuse in an urban trauma center.
        J Trauma. 1989; 29: 1654-1658
        • Sloan E.P.
        • Zalenski R.J.
        • Smith R.F.
        • et al.
        Toxicology screening in urban trauma patients. Drug prevalence and its relationship to trauma severity and management.
        J Trauma. 1989; 29: 1647-1653
        • Brookoff D.
        • Cook C.S.
        • Williams C.
        • Mann C.S.
        Testing reckless drivers for cocaine and marijuana.
        N Engl J Med. 1994; 331: 518-522
        • Becker B.
        • Woolard R.
        • Nirenberg T.D.
        • et al.
        Alcohol use among subcritically injured emergency department patients.
        Acad Emerg Med. 1995; 2: 784-790
        • Loiselle J.M.
        • Baker M.D.
        • Templeton J.M.
        • et al.
        Substance abuse in adolescent trauma.
        Ann Emerg Med. 1993; 22: 1530-1534
        • Brookoff D.
        • Campbell E.A.
        • Shaw L.M.
        The underreporting of cocaine-related trauma.
        Am J Public Health. 1993; 83: 369-371
        • Thal E.R.
        • Bost R.O.
        • Anderson R.J.
        Effects of alcohol and other drugs on traumatized patients.
        Arch Surg. 1985; 120: 708-712
      5. Centers for Disease Control. Cost of injury in the United States. Report to the US Congress. October, 1989.

        • McGill V.
        • Kowal-Vern A.
        • Fisher S.G.
        • et al.
        The impact of substance abuse on mortality and morbidity from thermal injury.
        J Trauma. 1995; 38: 931-934
        • D’Onofrio G.
        • Bernstein E.
        • Bernstein J.
        • et al.
        Patients with alcohol problems in the emergency department, Part 2.
        Acad Emerg Med. 1998; 5: 1210-1217
        • Edlich R.F.
        • Rodeheaver G.T.
        • Edgerton M.T.
        Airless paint gun injuries.
        J Am Coll Emerg Phys. 1978; 7: 397-400
        • Karlbauer A.
        • Gasperschitz F.
        High pressure injection injury.
        J Emerg Med. 1987; 5: 375-379
        • Anderson W.J.
        • Anderson J.R.
        Hydrofluoric acid burns of the hand.
        J Hand Surg. 1988; 13: 52-57
        • Velvart J.
        Arterial perfusion for hydrofluoric acid burns.
        Hum Toxicol. 1983; 2: 233-238
        • Hoffman R.S.
        • Smilkstein M.J.
        • Goldfrank L.R.
        Whole bowel irrigation and the cocaine body packer.
        Am J Emerg Med. 1990; 8: 523-527
        • Ambrose N.
        • Johnson M.
        • Burdon D.
        • et al.
        A physiologic approach of polyethylene glycol and a balanced electrolyte solution as bowel preparation.
        Br J Surg. 1983; 70: 428-430
        • Tenenbein M.
        Whole bowel irrigation for toxic ingestions.
        J Toxicol Clin Toxicol. 1985; 23: 177-184
        • Tenenbein M.
        Whole bowel irrigation as gastrointestinal decontamination procedure after acute poisoning.
        Med Toxicol. 1988; 3: 77-84
        • Kulig K.W.
        • Bar-Or D.
        • Cantrill S.V.
        • et al.
        Management of acutely poisoned patients without gastric emptying.
        Ann Emerg Med. 1985; 14: 562-567
        • Tandberg D.
        • Liechty E.J.
        • Fishbein D.
        Mallory-Weiss syndrome.
        Ann Emerg Med. 1981; 10: 521-523
        • Robertson W.O.
        Syrup of ipecac associated fatality.
        Vet Hum Toxicol. 1979; 21: 87-89
        • Askenasi R.
        • Abramowicz M.
        • Jeanmart J.
        • et al.
        Esophageal perforation.
        Ann Emerg Med. 1984; 13: 146
        • Wald P.
        • Stern J.
        • Weiner B.
        • et al.
        Esophageal tear following forceful removal of an impacted oral-gastric lavage tube.
        Ann Emerg Med. 1986; 4: 401-407
        • Mafiani P.J.
        • Poole N.
        Gastrointestinal tract perforation with charcoal peritoneum complicating orogastric intubation and lavage.
        Ann Emerg Med. 1993; 22: 606-609
        • Brubacher J.R.
        • Levine B.
        • Hoffman R.S.
        Intestinal pseudoobstruction (Ogilvie’s syndrome) in theophylline overdose.
        Vet Hum Toxicol. 1996; 38: 368-370
        • Flores F.
        • Battle W.S.
        Intestinal obstruction secondary to activated charcoal.
        Contemp Surg. 1987; 30: 57-59
        • Gomez B.I.F.
        • Brent J.A.
        • Munoz D.C.
        • et al.
        Charcoal stercolith with intestinal perforation in a patient treated for amitriptyline ingestion.
        J Emerg Med. 1994; 12: 57-60
        • Goulboume K.B.
        • Cisek J.E.
        Small bowel obstruction secondary to activated charcoal and adhesions.
        Ann Emerg Med. 1994; 24: 108-110
        • Longdon P.
        • Henderson A.
        Intestinal pseudoobstruction following the use of enteral charcoal and sorbitol with mechanical ventialation with papaveretum sedation for theophylline poisoning.
        Drug Safety. 1992; 7: 74-77
        • Ray M.J.
        • Padin D.R.
        • Condie J.D.
        • Halls J.M.
        Charcoal bezoar. Small bowel obstruction secondary to amitriptyline overdose therapy.
        Dig Dis Sci. 1988; 33: 106-107
        • Watson W.A.
        • Cremes K.F.
        • Chapman J.A.
        Gastrointestinal obstruction associated with multiple dose activated charcoal.
        J Emerg Med. 1986; 4: 401-407
        • Meredith W.
        • Kon N.D.
        • Thompson J.N.
        Management of injuries from liquid lye ingestion.
        J Trauma. 1988; 28: 1173-1180
        • Safarti E.
        • Gossot D.
        • Assens P.
        • Celerier M.
        Management of caustic ingestion in adults.
        Br J Surg. 1987; 74: 146-148
        • Horvath O.P.
        • Olah T.
        • Zental G.
        Emergency esophagogastrectomy for the treatment of hydrochloric acid injury.
        Ann Thorac Surg. 1991; 52: 98-101
        • Zargar S.A.
        • Kochar R.
        • Nagi B.
        • et al.
        Ingestion of corrosive acids.
        Gastroenterology. 1989; 97: 702-707
        • Wu M.H.
        • Lai W.W.
        Surgical management of extensive corrosive injuries of the alimentary tract.
        Surg Gynecol Obstet. 1993; 177: 12-16
        • Ribet M.E.
        Esophagogastrectomy for acid injury.
        Ann Thorac Surg. 1992; 53: 738-742
        • Estrera A.
        • Taylor W.
        • Mills L.J.
        Corrosive burns of the esophagus and stomach.
        Ann Thorac Surg. 1986; 41: 276-283
        • Hwang T.L.
        • Shen-Chen S.M.
        • Chen M.F.
        Nonthoracotomy esophagectomy for corrosive esophagitis with gastric perforation.
        Surg Gynecol Obstet. 1987; 164: 537-540
        • Ochi K.
        • Ohashi T.
        • Sato S.
        • et al.
        Surgical treatment for caustic ingestion injury of the pharynx, larynx, and esophagus.
        Acta Otolarygol. 1996; 522: 116-119
        • Rees R.
        • Campbell D.
        • Rieger E.
        • King L.E.
        The diagnosis and treatment of brown recluse spider bites.
        Ann Emerg Med. 1987; 16: 945-949
        • Rees R.S.
        • Altenbern D.P.
        • Lynch J.B.
        • et al.
        Brown recluse spider bites.
        Ann Surg. 1985; 202: 659-663
        • Garfin S.R.
        • Castilonia R.R.
        • Mubarak S.J.
        • et al.
        Rattlesnake bites and surgical decompression.
        Toxicon. 1984; 22: 177-182
        • Glass T.G.
        Early debridement in pit viper bites.
        JAMA. 1976; 235: 2513-2516
        • Wingert W.A.
        • Chan L.
        Rattlesnake bites in southern California and rationale for recommended treatment.
        West J Med. 1988; 148: 37-43
        • Klein A.S.
        • Hart J.
        • Brems J.J.
        • et al.
        Amanita poisoning.
        Am J Med. 1989; 86: 187-193
        • Jaeger A.
        • Jehl F.
        • Flesch F.
        • et al.
        Kinetics of amatoxins in human posioning.
        J Toxicol Clin Toxicol. 1993; 31: 63-80
        • Woodle E.S.
        • Moody R.R.
        • Cox K.L.
        • et al.
        Orthotopic liver transplantation in a patient with Amanita poisoning.
        JAMA. 1985; 253: 69-70
        • Pinson C.W.
        • Daya M.R.
        • Benner K.G.
        • et al.
        Liver transplantation for severe Amanita phalloides mushroom poisoning.
        Am J Surg. 1990; 159: 493-499
        • Ramirez P.
        • Parilla P.
        • Sanchez-Bueno F.
        • et al.
        Fulminant hepatic failure after Lepiota mushroom poisoning.
        J Hepatol. 1993; 19: 51-54
        • Meunier B.C.
        • Camus C.M.
        • Houssin D.P.
        • et al.
        Liver transplantation after severe poisoning due to amatoxin containing Lepiota–report of three cases.
        J Toxicol Clin Toxicol. 1995; 33: 165-171
        • Nehoda H.
        • Wieser C.
        • Koller J.
        • et al.
        Recurrent liver failure with severe rhabdomyolysis after liver transplantation for carbon tetrachloride intoxication.
        Hepatogastroenterology. 1998; 45: 191-195
        • Kozaki K.
        • Egawa H.
        • Garcia-Kennedy R.
        • et al.
        Hepatic failure due to massive iron ingestion successfully treated with liver transplantation.
        Clin Transplant. 1995; 9: 85-87
        • Clark R.
        • Thompson R.P.H.
        • Borirakchanyavat V.
        • et al.
        Hepatic damage and death from overdose of paracetamol.
        Lancet. 1973; 1: 66-70
        • Makin A.J.
        • Wendon J.
        • Williams R.
        A 7-year experience of severe acetaminophen-induced hepatotoxicity(1987–1993).
        Gastroenterology. 1995; 109: 1907-1916
        • Bernal W.
        • Wendon J.
        • Rela M.
        • et al.
        Use and outcome of liver transplantation in acetaminophen-induced acute liver failure.
        Hepatology. 1998; 27: 1050-1055
        • Harrison P.M.
        • O’Grady J.G.
        • Keays R.T.
        • et al.
        Serial prothrombin time as prognostic indicator in paracetamol induced fulminant hepatic failure.
        Br Med J. 1990; 301: 964-966
        • O’Grady J.G.
        • Wendon J.
        • Tan K.C.
        • et al.
        Liver transplantation after paracetamol overdose.
        BMJ. 1991; 303: 221-223
        • O’Grady J.G.
        • Alexander G.J.M.
        • Hayllar K.M.
        • et al.
        Early indicators of prognosis in fulminant hepatic failure.
        Gastroenterology. 1989; 97: 439-445
        • Walder B.
        • Brundler M.A.
        • Spiliopoulos A.
        • Romand J.A.
        Successful single-lung transplantation after paraquat intoxication.
        Transplantation. 1997; 64: 789-791
        • Kalmholz S.
        • Veith F.L.
        • Mollenkopf F.
        • et al.
        Single lung transplantation in paraquat intoxication.
        NY State J Med. 1984; 84: 81-85
        • Matthew H.
        • Logan A.
        • Woodruff M.F.A.
        • Heard B.
        Paraquat poisoning. Lung transplantation.
        Br Med J. 1968; 3: 759-763
        • Saunders N.R.
        • Alpert H.M.
        • Cooper J.D.
        Sequential bilateral lung transplantation for paraquat poisoning. A case report.
        J Thorac Cardiovasc Surg. 1985; 89: 734-742
        • Holmdahl J.
        • Blohme I.
        Renal transplantation after Cortinarius speciosissimus poisoning.
        Nephrol Dial Transplant. 1995; 10: 1920-1922
        • Hamilton R.J.
        Substance withdrawal.
        in: Goldfrank L.R. Flomenbaum N. Lewin N.A. Goldfrank’s toxicologic emergencies. 6th edition. Appleton Lange, Norwalk, CT1998: 1127-1143
        • Saitz R.
        • Mayo-Smith M.F.
        • Roberts M.S.
        • et al.
        Individualized treatment for alcohol withdrawal. A randomized double blind controlled trial.
        JAMA. 1994; 272: 519-523
        • Sellers E.M.
        • Naranjo C.A.
        • Harrison M.
        • et al.
        Diazepam loading.
        Clin Pharmacol Ther. 1983; 34: 822-826
        • Wasilewski D.
        • Matsumoto H.
        • Kur E.
        • et al.
        Assessment of diazepam loading dose therapy of delirium tremens.
        Alcohol. 1996; 31: 273-278