3 - Medical Evaluation of Psychiatric Patients and the Acute Treatment of Psychotropic Drug Overdose

Editors: Shader, Richard I.

Title: Manual of Psychiatric Therapeutics, 3rd Edition

Copyright 2003 Lippincott Williams & Wilkins

> Table of Contents > 3 - Medical Evaluation of Psychiatric Patients and the Acute Treatment of Psychotropic Drug Overdose

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Medical Evaluation of Psychiatric Patients and the Acute Treatment of Psychotropic Drug Overdose

Richard I. Shader

Judith E. Tintinalli

Suzanne R. White

The incidence of medical problems in psychiatric patients depends on their age and the presence of comorbid conditions. In addition, the likelihood of occurrence of specific disorders can vary with the psychiatric setting in which the patient is seen. Acute medical problems can coexist with psychiatric problems, thereby compounding the difficulty of making a correct diagnosis. For example, in patients with preexisting psychotic disorders or dementia, identifying a superimposed delirium can be difficult (see Chapters 5 and 12). Substance abuse, especially of alcohol, cocaine, or heroin, coexists in patients with psychiatric disorders, and signs of intoxication, overdose, and/or withdrawal must be distinguished from the features of psychiatric illness (see Chapters 9, 10, 11, 12). Violent patients or patients who self-mutilate are subject to injuries. As psychiatric patients age, disorders common to an aging population, such as diabetes mellitus, coronary artery disease, cerebrovascular disease, and renal insufficiency, should be expected. The adverse effects and drug interactions of prescribed psychoactive drugs or herbal medications should be considered in the medical evaluation of elderly psychiatric patients. Finally, medical problems may have gone undetected during prepsychiatric admission screening, or they can develop during psychiatric hospitalization. The goal of this chapter is to provide a framework for the recognition, diagnosis, treatment, and appropriate referral, when necessary, for psychiatric patients with acute medical problems.

I. Prepsychiatric Admission Medical Evaluation

The accuracy and completeness of the medical evaluation of psychiatric patients seen in emergency departments or ambulatory settings are variable. Standards for pretransfer evaluation should be developed between the transferring medical facility and the accepting psychiatric facility. Medical evaluation should include documentation of the following:

  • Vital signs and drug allergies;

  • Medical history, including gynecologic and reproductive history for women;

  • General physical examination;

  • Screening neurologic examination, including mental status (see Chapter 2) and evaluation for focal findings;

  • Results of any laboratory and imaging studies;

  • Description of any acute treatment;

  • Listing of current medications and dosage;

  • Discharge instructions, including recommendations for the type and interval of, as well as need for, follow-up medical care.

Experience has taught that history alone has a greater than 90% sensitivity for the detection of acute medical conditions in psychiatric patients. Consequently, the medical screening evaluation for psychiatric patients is generally quite basic. Pelvic or rectal examinations are not done unless directed by a chief complaint relative to these body systems. Most studies support the use of clinical judgment in the selection of laboratory or imaging studies, and most of the time, these studies are not needed for medical evaluation. No clinical evidence suggests that routine toxicology testing is needed for medical evaluation because most patients provide accurate self-reports of substance abuse.

II. Acute Medical Conditions in the Psychiatric Setting

The psychiatric facility should be prepared to identify medical emergencies and to provide basic life support (BLS) until a more experienced team arrives.

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Both physicians and nurses in the psychiatric setting should know how to activate the local Emergency Medical Services (EMS) system and should be well informed about its treatment capabilities. Protocols should be in place to determine which conditions can be treated in-house through consultation and which conditions should instead be transferred to an appropriately staffed medical facility for further stabilization and evaluation. Options for transfer to another facility for emergency and elective conditions should be outlined and delineated in a transfer protocol procedures manual.

For those settings in which the psychiatric facility is located within a general hospital, all clinical staff should be familiar with the procedures for activating the in-house cardiac arrest team and should know how to obtain in-house emergency medical or surgical consultation.

III. Treatment of Acute Medical Conditions in the Psychiatric Setting

A complete list of acute medical conditions and their evaluation, treatment, and disposition is beyond the scope of this manual. However, contemporary advances have resulted in a number of time-limited treatments for acute conditions, such as acute myocardial infarction (AMI) and acute stroke. Identifying acute medical conditions as soon as possible is important. A general categorization of selected acute symptoms includes the following:

  • Cardiac arrest

  • Alterations in vital signs

  • Altered mental status or coma

  • Shortness of breath

  • Chest pain

  • Abdominal pain

  • Hearing or visual loss

  • Acute neurologic signs or headache

  • Fever

  • Acute injury

A. Cardiac Arrest

The acute management of a cardiac arrest is the same whether it oc-curs in the home, community, or hospital setting. The American Heart Association has delineated the following response steps as the Chain of Survival:

  • Activate the EMS system (call 911).

  • Begin cardiopulmonary resuscitation (CPR).

  • Assess cardiac rhythm and defibrillate.

The best survival after a cardiac arrest is seen in the group of patients with a witnessed arrest, bystander CPR, and immediate defibrillation. Psychiatric facilities should attempt to meet these goals by developing a simple and straightforward system that includes health care provider administered CPR and immediate defibrillation.

Instructions for CPR can be found readily at http://www.learncpr.org/ and for advanced cardiac life support (ACLS) at http://www.cpr-ecc.org/. In the absence of a portable external defibrillator (see discussion below), psychiatric facilities should have a plan for managing cardiac arrest that includes up-to-date training for staff in the application of bystander CPR. At a minimum, they should be able to do the following:

  • Determine unresponsiveness and call for help;

  • Open the airway (use head tilt or jaw thrust);

  • Give two slow breaths if the patient is found to be breathless;

  • Determine pulse status, and, when a pulse is present, continue rescue breathing at 10 to 12 breaths per min;

  • Perform chest compressions when no pulse is elicited, and continue rescue breathing (15 compressions and then two breaths for one rescuer; 5 compressions and then one breath for two rescuers).

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A number of options exist for acute airway management, including bag-mask ventilation, an esophageal obturator airway, a laryngeal mask airway, and endotracheal intubation. The simplest method for a psychiatric setting might well be the use of bag-mask ventilation. This method can be used until personnel with more experience at airway stabilization arrive. Wall-mounted containers with a bag and mask can be placed at key areas for easy access in an emergency. Posters describing the application of the chest or abdominal thrust for removal of upper airway foreign body obstruction may be similarly posted.

Another consideration in psychiatric facilities is the installation of automatic external defibrillators (AEDs). These devices are now commonly found in airports, shopping malls, and even gambling casinos. Directions for its use are clearly presented on the device itself, and nonmedical personnel have been effectively trained in its application.

Basic CPR and the use of AEDs should be available. ACLS steps, such as definitive airway management and advanced pharmacologic care, are not likely to be available in some psychiatric settings, and these patients should be deferred to the local EMS system or an in-house cardiac arrest team.

B. Alterations in Vital Signs

Giving general parameters for abnormal vital signs is difficult, but the presence of symptoms and abnormal vital signs usually suggests the need for emergency evaluation. Parameters for abnormal vital signs include fever (above 38 C [100.4 F]), hypotension (systolic blood pressure <100 mm Hg), hypertension (systolic blood pressure >160 mm Hg, diastolic blood pressure >90 mm Hg), tachycardia (pulse rate [PR] >120 beats per min [bpm]), bradycardia (PR <60 bpm), and hypoxia (oxygen saturation at room air <90%). Severe pain has been suggested as the fifth vital sign. The value of vital signs as triage variables in themselves has been questioned; usually the presence of other serious signs and symptoms, rather than an isolated determination of vital signs, raises the question of an acute medical condition.

C. Alterations in Mental Status or Coma

The Glasgow Coma Scale (GCS) can be used as a rough parameter of abnormal mental status for adults. A normal GCS rating is 15. Table 3.1 provides the elements of the GCS.

Although the GCS was developed for trauma evaluation, using it serially provides one objective way of describing a change in the level of consciousness as one aspect of mental status. Loss of attention, hallucinations, disorientation, and decreased arousal are other signs of altered mental status. The differential diagnosis of altered mental status is complex, including central nervous system (CNS) hemorrhage, infarction, space-occupying lesions, infections, and toxic-metabolic conditions. Although preparations should be

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made to transfer the patient for medical evaluation, the following steps can be taken:

TABLE 3.1. GLASGOW COMA SCALE

Eye opening
   4 Spontaneous
   3 To speech
   2 To pain
   1 No response
Motor response
   6 Follows commands
   5 Localizes pain
   4 Withdrawal to pain
   3 Decorticate flexion
   2 Decerebrate extension
   1 No response
Verbal response
   5 Alert and oriented
   4 Disoriented conversation
   3 Speaking but nonsensical
   2 Moans or unintelligible sounds
   1 No response
The Glasgow Coma Scale is available for download at http://www.trauma.org/

  • Obtain vital signs and maintain airway and oxygen saturation at more than 90% with supplemental oxygen;

  • Establish intravenous (i.v.) access;

  • Determine a bedside glucose; if less than 60, administer 25 g glucose i.v.;

  • Administer 2 mg of naloxone i.v. when a narcotic overdose is a possibility.

D. Shortness of Breath

The differential diagnosis of shortness of breath is broad. Distinguishing cardiac causes from pulmonary causes is often extremely difficult. About one-third of patients with AMI complain of shortness of breath as the most prominent symptom. One should begin by obtaining an oxygen saturation level. If this is less than 90% on room air, supplemental oxygen can be given at 2 L per min, unless the patient has known chronic obstructive pulmonary disease. Auscultation of the chest can be helpful to distinguish rales, wheezes, or decreased breath sounds if present. Chest x-ray (CXR) is necessary to determine conditions such as pneumonia, effusion, pneumothorax, or hemothorax; CXR should be negative in patients with bronchitis or asthma. For known asthma patients, standing orders for the administration of nebulized albuterol can be developed. The dose of albuterol (5 mg in 5 mL of saline) is administered in a nebulized solution; another approach consists of administering four puffs from a metered dose inhaler every 20 min. Additionally, while preparations are made to transfer the patient for more thorough medical evaluation, the following can be done:

  • Obtain vital signs and maintain oxygen saturation at more than 90% with supplemental oxygen unless patient has known chronic obstructive pulmonary disease;

  • Establish i.v. access, if possible;

  • Obtain an immediate CXR and electrocardiogram (ECG). Make sure copies of both are provided if the patient is transferred to another unit or facility for care.

E. Chest Pain

Signs and symptoms of coronary artery disease as a cause of chest pain can occur at any time in adulthood. Although risk factors, such as hypercholesterolemia, hypertension, diabetes, or smoking, are associated with coronary artery disease, their presence or absence does not assist in making the diagnosis of acute coronary ischemia or AMI in the individual. About one-third of patients, most often women or patients with diabetes mellitus, with an AMI have atypical signs, such as weakness or shortness of breath. In addition, patients without chest pain who develop an AMI have about a twofold greater in-hospital mortality rate. Furthermore, differentiating musculoskeletal causes of chest pain from other severe disorders besides acute coronary ischemia or AMI can be difficult; these include pulmonary embolism, myocarditis, pericarditis, and aortic dissection. Patients with chest pain, acute weakness, or shortness of breath deserve serious attention whether these symptoms are believed to be typical or atypical of cardiac ischemia or not. Contemporary time-dependent treatment modalities include thrombolytics, angioplasty, beta-blockers, platelet inhibitors, and anticoagulants. Their use is beyond the scope of this chapter.

While preparations are made to transfer the patient for medical evaluation, the following can be done:

  • Provide supplemental oxygen and i.v. access, if possible;

  • Administer aspirin (160 to 325 mg chewable);

  • Obtain a stat CXR and ECG, if possible;

  • Arrange for EMS transport using advanced life support;

  • Make additional copies of the CXR and ECG to accompany the patient.

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F. Abdominal Pain and Gastrointestinal Bleeding

Improved diagnostic and imaging techniques allow the clinician to make accurate and more rapid diagnoses for abdominal pain. A useful general rule is that abdominal pain persisting for 6 hours or more or abdominal pain accompanied by nausea, vomiting, or diarrhea should receive emergency evaluation. Patients with prior abdominal surgery who develop acute abdominal complaints should be viewed as having a suspected small bowel obstruction until proven otherwise. Upper or lower gastrointestinal (GI) bleeding always requires emergency evaluation, unless the patient describes only small streaks of blood in the vomitus or stool. In such patients, elective ambulatory evaluation can be considered. Causes of acute abdominal pain stratified by age are listed in Table 3.2. Transfer orders should include the following:

  • Nothing by mouth (eating will complicate condition if operative intervention becomes necessary; certain studies such as gallbladder ultrasound require 6 hours of fasting to visualize the gallbladder properly);

  • Intravenous access, if possible;

  • Supplemental oxygen;

  • Transport using advanced life support.

G. Hearing or Visual Loss

Acute hearing loss can result from simple causes, such as cerumen impaction, or from serious disorders. Visual loss can be from neurologic or ophthalmic causes. Neurologic causes include stroke, migraine, and ocular problems (e.g., retinal detachment, acute glaucoma).

H. Acute Neurologic Signs and Headache

The American Heart Association and the National Institute of Neurological Disorders emphasize the following signs of stroke in their public education programs:

  • Alteration in consciousness;

  • Intense headache or any headache associated with a decreased level of consciousness, neurologic deficit, and severe neck or facial pain;

  • Aphasia (incoherent speech or difficulty understanding speech);

  • Facial weakness or asymmetry;

  • Incoordination, weakness, paralysis, or sensory loss in one or more limbs;

  • Visual loss;

  • Dysarthria (slurred or indistinct speech);

  • Intense vertigo, double vision, unilateral hearing loss, nausea, vomiting, photophobia, or phonophobia.

TABLE 3.2. LIKELY CAUSES OF ACUTE ABDOMINAL PAIN BY AGE COHORT

Final Diagnosis Under 50 Yr of Age (%) Greater Than or Equal to 50 Yr of Age (%)
Biliary tract disease 21 6
Nonspecific abdominal pain 16 40
Appendicitis 15 32
Bowel obstruction 12 2
Pancreatitis 7 2
Diverticular disease 6 <0.1
Cancer 4 <0.1
Hernia 3 <0.1
Vascular 2 <0.1
Acute gynecologic disease <0.1 4
Other 13 13
From Gallagher J. Acute abdominal pain. In: Tintinalli J, Kelen G, Stapczynski S, eds. Emergency medicine: a comprehensive study guide. New York: McGraw-Hill, 2000:497 515, with permission.

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Some clinicians believe that thrombolytic therapy is indicated only if it can be initiated in the first 2 to 3 hours after an acute ischemic stroke. Evaluation of possible acute stroke includes imaging modalities, such as computed tomography and magnetic resonance imaging, and often requires neurologic consultation. Differential diagnosis of acute severe headache includes a hypertensive emergency, a subarachnoid or intracerebral hemorrhage, or meningitis. Transfer to an emergency medical facility is warranted for any of these acute signs or symptoms. Strict criteria for the management of hypertension in acute stroke have not been defined, and caution is recommended. Conservative guidelines for acute hypertension treatment in acute stroke include treatment only if the systolic blood pressure exceeds 220 mm Hg or if the diastolic blood pressure exceeds 130 mm Hg. Overly aggressive lowering of blood pressure is believed to expand the ischemic stroke penumbra and to convert transitional ischemic areas to infarcted areas.

Transfer orders should include the following:

  • Supplemental oxygen and monitoring of vital signs;

  • Intravenous access, if possible;

  • Nothing by mouth to avoid potential aspiration;

  • ECG and CXR, if possible; send copies with transfer.

I. Fever

The development of fever should prompt an investigation for the common infectious disorders.

  • Respiratory tract infections. Upper respiratory tract and pharyngeal infections and bronchitis are common causes of fever, and these are usually easily diagnosable by signs and symptoms.

    Clinical signs and symptoms of fever, cough and sore throat, myalgias, and its epidemic nature usually lead to the diagnosis of influenza, although rapid viral diagnostic testing may be increasingly available. Influenza vaccine is the best method to prevent outbreaks and morbidity. The course of the disease is reduced if treatment is begun within 48 hours of symptom onset. Treatment through inhalation is with zanamivir, two puffs twice a day for 5 days. However, this treatment plan requires some manual dexterity. Oral treatment choices include oseltamivir, which is effective against both influenza A and B (75 mg orally [p.o.] twice a day for 5 days).

    Pneumonia is readily diagnosed by CXR. Outpatient treatment is with azithromycin (standard azithromycin dose-pak [500 mg p.o. on day 1, then 250 mg p.o. on days 2 to 5]) or levofloxacin (500 mg per day p.o.). Hospital admission should be considered if the patient appears toxic or hypoxic (oxygen saturation <90%) or if he or she has significant comorbidities, such as diabetes mellitus or steroid administration.

  • Urinary tract infections. Cystitis (lower urinary tract infection [UTI]) is characterized by urinary frequency, urgency, suprapubic pain, and hematuria. Pyelonephritis usually manifests as fever and flank pain. Lower UTI symptoms may not be present. A urinalysis and urine culture should be obtained. Cystitis can be treated with 3 to 7 days of trimethoprim-sulfamethoxazole (also Bactrim DS or Septra DS; 1 tablet p.o. twice a day) or ciprofloxacin (500 mg p.o. twice a day). Pyelonephritis is termed uncomplicated in young or middle-aged otherwise healthy individuals, and it is generally treated with ciprofloxacin (500 mg p.o. twice a day for 10 to 14 days). Pyelonephritis is termed complicated in the elderly, in those with renal insufficiency or structural kidney abnormalities, in those who are immunocompromised or toxic, and in those with renal calculi or sickle cell disease. Complicated pyelonephritis requires inpatient treatment.

    Prostatitis may be evidenced by lower abdominal or rectal pain, back pain, and fever. Signs of cystitis are often not present. Treatment usually

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    consists of 2 to 4 weeks of ciprofloxacin (500 mg p.o. twice a day). Any patient with prostatitis who appears toxic requires inpatient treatment.

  • Meningitis. Bacterial meningitis is an uncommon disorder, but its serious morbidity requires early diagnosis and treatment. In adults, computed tomography is often performed before lumbar puncture, and antibiotics should be given as soon as the diagnosis is suspected. Treatment is generally with ceftriaxone (2 g i.v.); when the presence of resistant Streptococcus pneumoniae is suspected, vancomycin (15 mg per kg i.v.) is also added. Ampicillin (2 g i.v.) can be added when Listeria is suspected. To cover all diagnostic possibilities, some emergency department clinicians recommend the use of acyclovir (10 mg per kg i.v.) to treat potential herpes simplex encephalitis as well. Steroids are not recommended.

    Meningococcal prophylaxis should be given to close contacts. Regimens include ciprofloxacin (500 mg p.o.) and rifampin (600 mg p.o.), twice a day for 4 days, or ceftriaxone (250 mg intramuscularly [i.m.]) as a single dose.

    Aseptic or viral meningitis is the most common CNS infection in the United States. It is most commonly due to enterovirus or echovirus. Symptoms include fever, headache, vomiting, eye pain, nausea, photophobia, and myalgia. The diagnosis is made by lumbar puncture. Antibiotics are withheld unless bacterial meningitis is being considered.

  • Cellulitis. Cellulitis is another common infection that is characterized by fever and localized erythema, edema, and tenderness. It is most common in the lower extremities and in those patients with venous or arterial insufficiency. If the patient is nontoxic, treatment with oral cephalexin (500 mg, four times a day) for 10 to 14 days is usually sufficient.

  • Acute injury. The spectrum of acute injury care is beyond the scope of this manual, but a few principles can be described here. Any injury resulting in persistent pain, loss or limitation of function, or inability to bear weight or walk unaided requires emergency evaluation.

    Head injuries resulting in change in mental status or loss of consciousness, however brief, need emergency medical evaluation. Cervical spine immobilization should be provided until EMS personnel arrive. Temporary methods for cervical spine immobilization can be as simple as rolled towels or blankets placed on opposite sides of the head and securely taped to the stretcher or bed to prevent head and neck movement.

    Lacerations in which the epidermis is gaping generally require suturing. Lacerations around important functional areas, such as the face, eyes, and joints, require emergency evaluation. The appeal of synthetic glues is great, but their application is limited to small nongaping lacerations that are not near the eyes and that are not subject to skin tension. Most lacerations will require suturing or stapling. After suturing, instructions should be provided for the timing of suture removal. Staples require a separate instrument, a staple remover; if the institution does not have these in stock, the patient may have to be returned to the emergency facility for staple removal.

    Distal limb injuries, such as those involving the arms, hands, legs, or feet, require emergency evaluation and possibly radiography if attempted function causes pain. Punctures to the hands or feet should be medically evaluated to determine if radiographs or antibiotics are needed and to evaluate the need for tetanus toxoid.

IV. Abuse and Assault

Victims of violent acts, such as robbery or unprovoked assault by strangers, or accidents probably comprise the largest group of individuals who experience the emotional impact of trauma; their experiences, unfortunately, have not been systematically studied. Data are emerging about some forms of abuse and assault, particularly in the following three distinct epidemiologic groups: children, domestic partners, and the elderly or impaired. Although signs and symptoms

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of abuse and assault in these three groups are obtained when medical histories are taken, corroboration by physical evaluation and imaging studies is often essential. This is yet another reason for why a medical examination is complimentary to psychiatric evaluation.

A. Children and Youths

  • Sexual abuse is often suspected when the child complains of symptoms referable to the genitourinary tract, such as vaginal discharge or bleeding, dysuria, urethral discharge, or symptoms of urinary tract infection (see Chapter 27). Other symptoms include inappropriate sexually oriented behavior, nightmares, regressive behaviors, or bedwetting. Frequently, sexual abuse is suspected at a time remote from the actual episodes. When seen acutely, children need evaluation for acute genitourinary tract injury. Children with any suspicion of sexual abuse should be referred to pediatricians trained in this area because familiarity with the prepubertal genital examination and the legal process of evidence collection is necessary. Teaching or children's hospitals are the best sources for these services.

  • Physical abuse of children often presents with a constellation of the following signs: injuries incompatible with the alleged mechanism; multiple bruises, abrasions, bites, or lacerations of different ages or in disparate locations; cigarette or scalding burns; twisting (spiral) fractures of long bones; intracranial or retinal hemorrhage in infants; or facial injuries in older children. To identify a systematic pattern of injuries when abuse is suspected, radiographs of long bones, ribs, clavicles, fingers, toes, pelvis, and the skull (skeletal survey) are usually obtained. Social Services or the hospital child abuse team should be notified if one has suspicion of abuse, and the child can be hospitalized and placed in protective custody as mandated by law or when otherwise appropriate.

B. Adults

  • Sexual assault (see Chapter 27). Incidents of acute sexual assault are usually reported to the police, and part of the emergency department evaluation includes crisis intervention and referral for counseling services. However, many patients prefer to put the acute episode behind them, and they do not seek counseling. It may be weeks, months, or years later that unresolved issues with the assault present with symptoms such as nonspecific anxiety, depression, hyperventilation, concerns about sexually transmitted diseases or human immunodeficiency virus, pelvic pain, nightmares, relationship difficulties, or sleep disturbances. In addition, issues may surface in adulthood for those who have experienced sexual assault as children or who have grown up in households with an alcoholic or abusive parent. Consequently, psychiatric assessment of adults should always include questions about past or current sexual or physical assault or abuse, especially in those with symptoms for which no organic cause can be identified.

  • Domestic partner violence. Victims of partner violence rarely present with a chief complaint of partner violence. Patients usually present to the emergency department with acute injuries, and an astute health care team should be aware of the patterns of partner violence and of the situational response to an acute battering episode. Health care professionals at every level of the health care delivery system from emergency care to primary care to consultative services should be alert to the signs and symptoms of partner violence so that they can identify the syndrome and can encourage counseling at every patient encounter.

    A number of the following signs and symptoms should raise suspicion of partner violence:

    • Pregnant women with an unexplained pattern of injury, especially to the abdomen;

    • Injuries to the face, head, and neck with an unexplained pattern of injury;

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    • Any injury that is inconsistent with the alleged mechanism;

    • Injuries suggesting a posture defensive to blows, such as forearm bruises or fractures;

    • Multiple injuries in various stages of healing;

    • Any substantial delay between the time of acute injury and of presenting for treatment;

    • Noncompliance with important follow-up care, such as for fracture or dental care;

    • Visits to multiple care providers or emergency departments for injuries.

      Other signs and symptoms include depression and suicidal behavior, pelvic pain, or repetitive visits for complaints for which no clear basis can be found.

      The partner's behavior during the encounter can also be a clue. Excessively caring behavior and an insistence to remain with the patient throughout the interview are two suspicious signs.

      Unfortunately, a common response by a battering victim is the denial of abuse. The high frequency of denial has led clinicians to see denial as a feature of the partner abuse syndrome. Reasons for denial include the victim-patient's concern that violence will escalate if the battering is acknowledged, fears for the safety of any children or other family members, the victim's economic dependence on the partner, and/or a basic affection for the partner and a belief that these behaviors can and will spontaneously change. When suspicion is high, alternatives for safety, even hospital admission, should be explored. The patient should always be asked if children have been battered and if the patient has concerns about the children's safety. Child Protective Services or the Child Abuse Team should be notified if any concerns about the welfare of the children are present. Keep in mind that the expected victim response is to deny battering and to return to the battering environment. As more is learned about battering victims, the fact that numerous offers for help must be extended before victims are able to free themselves from their situation has become clear. For any individual health care encounter, predicting if the patient is close to, or far from, problem resolution is not possible. Therefore, continued persistence and encouragement to seek care at every encounter are important; the cumulative effect of such urgings will be important.

    • The elderly and impaired. Abuse in the elderly and impaired is difficult to determine, in part because of the complex psychosocial dynamic and also because the victim may be unable to corroborate the suspicions. The same principles that apply to the identification of child or adult abuse apply to the diagnosis of elder or impaired abuse. Reasons for the difficulty in arriving at an unequivocal diagnosis of abuse in the elderly or impaired include the following:

  • Any behavioral signs and symptoms associated with elder abuse, such as depression, confusion, withdrawal, anxiety, or helplessness, may be a part of progressive dementia (see Chapter 5);

  • Mentally retarded persons or patients who are psychotic may not be able to communicate effectively;

  • Physical deterioration in the elderly may lead to frequent falls, resulting in multiple fractures and bruises of different ages;

  • Skin fragility associated with aging can result in dramatic epidermal tears from trivial injury;

  • Determining whether injuries are a consequence of battering or are secondary to agitated or violent behavior in a demented or psychotic patient can be difficult;

  • Falls and injuries may be consequent to alcohol abuse or the misuse of prescribed sedative or anxiolytic agents, which can mimic or mask battering;

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  • The caretakers or health care professionals responsible for care may not be aware of techniques to handle behavioral problems; they are just doing the best they can.

C. Treatment

Acute medical problems should be treated promptly. Specialists in geriatric psychiatric care or in the care of mentally retarded adults or children should be consulted. Often admission to specialized units can result in changes in medication to improve behavior. Social workers can arrange for a more appropriate environment, either in the patient's own home, a living-assisted community, or an institution.

V. Acute Overdose

In 2000 in the continental United States, an estimated 601,776 drug-related emergency department visits occurred. That clinicians have at least some familiarity with the care of a patient after an acute overdose is essential. The United States Department of Health and Human Service's Substance Abuse and Mental Health Administration maintains a useful website (http://www.samsha.gov) for data on emergency department visits due to drug ingestions; their toll-free number is 1-800-729-6686.

A. General Approach

The ABCs (Airway, Breathing, and Circulation) of resuscitation and stabilization take precedence over all other aspects of drug overdose management. In the patient with altered mental status, cervical spine protection and treatment with oxygen, naloxone, glucose, and thiamine are important aspects of early care. Next, the patient should be completely disrobed to allow a careful physical examination. This may uncover occult trauma or may suggest a specific toxic syndrome (i.e., anticholinergic, opioid) or toxidrome. A core temperature should be obtained. When hyperthermia is noted, aggressive evaporative cooling (mist and fan) should be carried out.

Once the patient is stabilized, attempts should be made to obtain a complete history. For example, information from family, friends, or EMS personnel may assist with exact substance identification, the time of ingestion, current medication use, allergies, past medical events, and the circumstances surrounding the exposure. Attention can then be directed toward patient decontamination, laboratory evaluation, enhancement of drug elimination, and, occasionally, the administration of specific antidotes.

No less important than the initial treatment of the poisoned patient is the continuing provision of supportive care and appropriate disposition. In general, after the diagnosis and initial treatment is established, appropriate disposition may include transfer to a medical unit, observation, and patient and family education in poison prevention. Exposure to some intoxicants (e.g., monoamine oxidase inhibitors [MAOIs]) requires prolonged medical observation. Definitive therapy includes appropriate referral for follow-up care.

Although general management guidelines such as those discussed below should be readily available, a Regional Poison Control Center should be contacted early in the treatment of any poisoning or overdose. Within the United States, the closest center can be reached by calling 1-800-222-1222; in California, call 1-800-876-4766.

  • External decontamination. Ocular or skin exposure to chemicals should be treated with immediate water irrigation, which should be carried out by staff wearing adequate skin and respiratory protection.

  • GI tract decontamination.

    • Gastric emptying. As the time following an ingestion lengthens, the value of measures used to empty the stomach decreases. Recovering significant amounts of toxin 1 hour or more after the ingestion is unusual. Gastric emptying is contraindicated after the ingestion of caustic substances or hydrocarbons.

    • Induced emesis. In health care facilities, the use of syrup of ipecac is no longer recommended, and it may in fact delay the administration

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      of charcoal. Other historic methods of stimulating emesis (apomorphine, lobeline, zinc sulfate, copper sulfate, potassium antimony tartrate, sodium chloride, powdered mustard, mechanical means) are never indicated, and they are potentially hazardous.

    • Gastric lavage. This procedure is time consuming and uncomfortable for the patient, and it may cause morbidity. Recovery of intact pills or large particles of undissolved poison is unlikely. Clinical studies do not show an improved outcome with this method of decontamination, and no indication for a role for routine use in poisoning exists. It may be considered for the patient who has ingested a life-threatening amount of a toxic substance within 1 hour of the presentation to the clinician, if he or she has not already vomited. Contraindications include an unprotected airway or the ingestion of corrosive substances or hydrocarbons.

      When gastric lavage is used, the following procedure can be followed. An unresponsive patient should have endotracheal intubation before gastric lavage to prevent reflux and aspiration of gastric contents. (Note: The endotracheal tube cuff should be briefly deflated during the actual passage of the orogastric tube to reduce the risk of esophageal laceration at the site of the cuff.) A conscious adult patient is placed first in the left lateral decubitus position. The lubricated tip of a French orogastric tube (size 36 or 40) is placed into the posterior pharynx. With the placement of a bite block between the patient's posterior molars, the tube is easily advanced into the stomach. If the left lateral head-down position does not result in a prompt return of gastric contents, auscultation of the stomach while 50 mL of air is injected into the proximal end of the tube verifies that the distal end is in the stomach. Gastric lavage is performed by repeated injection and withdrawal of 250 to 300 mL of water or isotonic saline until the lavage fluid is clear. Hypertonic saline should not be used.

      These instructions do not apply to the pediatric patient.

    • Activated charcoal (e.g., activated charcoal USP, Norit-A, Superchar, Actidose). This charcoal can adsorb and can prevent absorption of significant quantities of a wide variety of substances, including many psychotropic agents. Studies in volunteers show that activated charcoal is most effective when given within 1 hour of ingestion. Its administration should be considered after the recent ingestion of a potentially toxic amount of a substance that is known to adsorb to charcoal. Substances that do not adsorb well to activated charcoal include some metals, hydrocarbons, alcohols, and pesticides. One half to 1 g per kg of activated charcoal suspended in water (frequent stirring is important) is given by mouth or is administered through an orogastric or nasogastric tube. The first dose of activated charcoal is often given with sorbitol, although cathartics have not been shown to be beneficial. Additional doses of activated charcoal may be considered for certain situations (see below).

    • Whole bowel irrigation (Golytely). Balanced polyethylene glycol solutions are isoosmotic. These solutions allow for mechanical cleansing of the gut without the risk of fluid or electrolyte imbalance. Potential indications for whole bowel irrigation include the ingestion of (a) massive amounts of a toxic substance, (b) metals (e.g., lithium, iron) because they do not adsorb to activated charcoal, (c) sustained-release preparations, (d) wrapped packages of cocaine or heroin, (e) large pills or foreign bodies, and (f) concretions. The dose of polyethylene glycol solution is 2 L per h until the rectal effluent is clear in adults. For children, 40 mL per kg per h is used.

  • P.28


  • Enhanced elimination of intoxicants

    • Multidose charcoal. Serial doses of activated charcoal can be used to enhance drug elimination. Consider this method for significant intoxications with carbamazepine, dapsone, phenobarbital, quinine, or theophylline. Limited studies in volunteers suggest a possible role for the use of multidose charcoal in poisonings from amitriptyline, dextropropoxyphene, digitoxin, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin, piroxicam, salicylates, and sotalol.

    • Urinary alkalinization. Drugs that are weak acids tend to ionize in solution. Trapping the drug in its ionized form in the renal tubule can enhance the renal excretion of a few drugs. This requires manipulation of the urinary pH through the administration of i.v. sodium bicarbonate. By this method, the reabsorption of salicylates, phenobarbital, and chlorpropamide is reduced. The technique of urinary alkalinization should not be confused with the antiquated practice of forced diuresis, which relied on the administration of high volumes of fluid to maintain high urinary flow rates and which was fraught with hazardous side effects, such as cerebral and pulmonary edema. The most important therapeutic manipulation is now known to be that of urinary pH and not of the volume of urinary output. To institute urinary alkalinization, an indwelling Foley catheter is inserted, and urine outputs and pH are measured hourly. Sodium bicarbonate can be given either by bolus or by infusion to achieve a urinary pH of 7.5. A general approach involves the administration of sodium bicarbonate, 1 to 2 mEq per kg, by bolus, followed by a dose of 100 to 150 mEq per L added to each L of i.v. fluids (dextrose 5% water solution [D5W]) that is infused at approximately 1.5 times the maintenance fluid rate. (Note: For daily [24-h] maintenance fluid requirements, the rates are 100 mL per kg for the first 10 kg of body weight, 50 mL per kg for the second 10 kg, and 20 mL per kg for each additional kg of body weight.) Close monitoring of volume status and serum electrolytes, especially potassium and calcium, is necessary. Patients with congestive heart failure, cerebral edema, renal failure, or hypernatremia may not be candidates for this therapy. (Note: Acidification of the urine to ion trap weakly basic drugs, such as phencyclidine and amphetamines, was conducted historically; because rhabdomyolysis often complicates such intoxications, urinary acidification places the patient at an unacceptable risk for myoglobinuric renal failure, and thus it is no longer used.)

    • Peritoneal dialysis. This method of enhanced elimination is not used unless hemodialysis is unavailable.

    • Hemodialysis. The physical characteristics of the intoxicant determine whether it will be amenable to dialysis. The substance must be able to cross the dialysis membrane freely, and it should have a molecular weight below 500 Da, high water solubility, low protein binding, and a small volume of distribution (less than 1 L per kg). Although hemodialysis has been recommended for a wide variety of intoxications, clear benefits outweigh the risk for only a small number of substances. Examples include salicylates, phenobarbital, methanol, ethylene glycol, lithium, and certain metals. Renal failure in a patient who has ingested a drug for which the kidney is a major organ for elimination is another potential indication for hemodialysis. Hemodialysis can also be used for the treatment of a refractory acid base imbalance, an electrolyte disturbance, or a volume-overload state.

    • Charcoal hemoperfusion. This technique interposes a cartridge filled with activated charcoal or resin beads into the dialysis circuit. These beads are able to adsorb drugs with a low volume of distribution,

      P.29


      even if they are lipid soluble or are highly protein bound. Few well-studied indications for its use are available, but it has been applied in the setting of theophylline or carbamazepine toxicity or overdosing. Complications related to hemoperfusion include thrombocytopenia, leukopenia, reduced glucose and calcium levels, and hemorrhage secondary to heparinization.

B. Identification, Evaluation, and Treatment of Intoxication from Specific Psychotropic Agents

  • Conventional antipsychotic agents. Phenothiazines and butyrophenones accounted for 6,825 reported poisonings in the United States in 2000. These agents are pharmacologically complex, and they impact muscarinic, -adrenergic, histaminergic, and dopaminergic receptors, as well as cardiac potassium and sodium channels. Toxicity may be seen after acute overdose or as an idiosyncratic reaction related to therapeutic use.

    • Manifestations of acute overdose

      • Central nervous system effects. Aliphatic and piperidine phenothiazines (e.g., chlorpromazine, thioridazine, mesoridazine) tend to sedate more than do the higher potency piperazine phenothiazines, thioxanthenes, and butyrophenones (e.g., fluphenazine, perphenazine, trifluoperazine, thiothixene, and haloperidol) due to the greater antihistaminic and antimuscarinic effects of the former. However, any of these agents can cause coma and unresponsiveness after the ingestion of large amounts. Agitation, delirium, muscular rigidity, spasm, twitching, hyperreflexia, tremor, or seizures can also occur.

      • Cardiovascular effects. Hypotension results primarily from 1-adrenergic receptor blockade and vasodilation. A reflex tachycardia that is compounded by the antimuscarinic effects of these agents may result. Sodium channel blockade may cause QRS prolongation on ECG. Potassium channel blockade, which manifests as QTc prolongation, is a serious complication that may lead to ventricular dysrhythmias, such as torsade de pointes. QTc prolongation is most commonly associated with thioridazine and mesoridazine overdose, and it may have a delayed onset after an acute overdose.

      • Autonomic nervous system effects. Thermoregulatory impairment may cause hypothermia or hyperthermia. Antimuscarinic effects may manifest as hyperthermia, absence of sweating, dry mucous membranes, tachycardia, ileus, and urinary retention. Mydriasis is an expected finding as a result of the muscarinic blockade, but, because these agents cause concomitant potent -adrenergic receptor antagonism, the pupillary size generally is from pinpoint to midrange.

    • Treatment of acute overdose

      • Gastric lavage followed by the administration of activated charcoal should be considered soon after significant ingestions (see above).

      • ECG monitoring should be continuous for all patients because of the possibility of cardiac dysrhythmias. QRS widening beyond 100 ms should be treated with i.v. sodium bicarbonate, 1 to 2 mEq per kg bolus. Torsade de pointes should be treated with magnesium, 2 g i.v. bolus; i.v. potassium supplementation; isoproterenol; and transcutaneous or transvenous pacing. All class Ia (e.g., quinidine, disopyramide, procainamide), Ic (e.g., flecainide, encainide), and III (e.g., bretylium, amiodarone, sotalol) antidysrhythmics should be avoided.

      • Hypotension is treated with volume expansion with crystalloids. A bolus of isotonic saline (250 to 500 mL) is administered

        P.30


        over 30 minutes or less, as long as cardiac function is normal. When hypotension is refractory to a fluid bolus, the administration of vasopressors are indicated (e.g., direct-acting -adrenergic receptor agonists, such as norepinephrine and metaraminol, are the pressors of choice). Catecholamines having -adrenergic receptor activity (e.g., isoproterenol, epinephrine) can theoretically cause a further fall in blood pressure, and they may also further increase the heart rate.

      • Seizures should be treated with i.v. benzodiazepines (e.g., lorazepam [1 mg]), followed by barbiturates, if necessary. Phenytoin is not effective in controlling drug-induced seizures. Flumazenil and physostigmine should be avoided. Many causes of seizures exist, and different etiologies may coexist in poisoned patients. Therefore, all patients with seizures should be evaluated for metabolic, toxic, infectious, or structural causes. Treatment is indicated when seizures are repetitive or intractable or when they are associated with deteriorating vital signs. Emergency medical consultation is indicated for any patient with seizures.

      • Hypothermia and hyperthermia are treated symptomatically. The core temperature should be monitored, usually with rectal thermometer or urinary bladder probe. The initial treatment of mild hypothermia (32.2 C to 35 C [90 F to 95 F]) consists of the administration of heated humidified oxygen and passive external rewarming with heated blankets. The special warming devices or temperature-controlled water baths needed to heat i.v. fluids are beyond the scope of care expected in psychiatric settings. For patients with core temperatures below 35 C (95 F), transfer to an appropriate medical setting is essential. Other serious causes of hypothermia should be ruled out (e.g., hypoglycemia, thiamine deficiency, endocrinopathy). When evaluating patients with hyperthermia, sepsis and neuroleptic malignant syndrome (NMS) must be considered in the differential diagnosis. Hyperthermic patients should be transferred to an appropriate medical setting. Mild hyperthermia may be treated with cooling blankets, cool moist towels, or antipyretics. Drug-induced hyperthermia, however, usually is unresponsive to these measures; it requires aggressive evaporative cooling measures via mist and fan.

        Forced diuresis or extracorporeal elimination have no role in the treatment of acute overdose.

    • Idiosyncratic toxicities from antipsychotic agents

      • Acute dystonias. Although dopaminergic receptor antagonism accounts for many of the therapeutic effects of antipsychotic agents, it is also responsible for causing unwanted extrapyramidal reactions. Because of their antidopaminergic properties, antipsychotic agents are often associated with a variety of motor disorders involving acute involuntary muscle movements and spasms. Although any muscle group in the body can be involved, the most common manifestations are oculogyric crisis, trismus, torticollis, facial grimacing, and retrocollis. Rarely, rigidity, laryngospasm, dysphagia, dysphonia, or opisthotonus may occur.

        Treatment consists of diphenhydramine (50 mg i.m. or i.v.) or benztropine (2 mg i.m. or i.v.). Improvement generally occurs within seconds or within 15 to 30 minutes. These doses can be repeated in 30 minutes. Refractory dystonias may be treated with benzodiazepines (e.g., lorazepam [1 mg i.v.]). Even if the antipsychotic agent is discontinued, oral treatment

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        with either diphenhydramine or benztropine should be continued for the next 3 to 7 days as dystonias can recur.

      • Neuroleptic malignant syndrome. NMS is a rare, life-threatening syndrome that can occur with a variety of antipsychotic agents, including phenothiazines, butyrophenones, substituted benzamides, and thioxanthenes, at any time during treatment. MAOIs and lithium can also cause significant hyperthermia. NMS has most often been reported in association with the initiation of medication or with rapid dose escalation.

        Common signs and symptoms include hyperthermia, muscular rigidity, an altered level of consciousness, and autonomic instability. Body temperatures can exceed 40 C (104 F). Muscular rigidity can be localized, as in oculogyric crisis; generalized; or associated with opisthotonus. Mutism, disorientation, agitation, stupor, or coma can result. Diaphoresis, tachycardia, labile hypertension, or hypotension characterizes autonomic instability.

        Historically, the mortality rate for NMS was 30%; with the advent of the intensive care unit, mortality should not be expected. The complications are primarily pulmonary and renal. Deaths usually result from a failure to recognize the syndrome or from inadequate or delayed treatment and supportive therapy.

        The differential diagnosis for NMS includes sepsis, CNS infection, seizures, thyrotoxicosis, tetanus, strychnine toxicity, lithium toxicity, lethal catatonia, abrupt discontinuation of clozapine, heat stroke, cocaine toxicity, ecstasy (methylenedioxymethamphetamine [MDMA]) or other stimulant intoxication, salicylate toxicity, MAOI toxicity, anticholinergic toxicity, delirium tremens, sedative-hypnotic withdrawal, stiff man syndrome, and toxic serotonin syndrome.1

        Treatment for suspected NMS is as follows. The causative agent(s) should be discontinued, and the patient should be moved to an intensive care unit as soon as possible. Cooling should be initiated to reduce the hyperthermia, and airway and cardiovascular support should be provided as needed. Benzodiazepines can be given for muscular rigidity. For intubated patients, refractory rigidity can be treated with short-acting neuromuscular blocking agents (e.g., vecuronium [10 mg]) or with dantrolene sodium, which also acts peripherally in skeletal muscle (the initial dose of dantrolene is 1 mg per kg i.v. repeated every 5 minutes as necessary to a total dose of 10 mg per kg). The disadvantages of dantrolene include its high pH, which may lead to tissue necrosis with extravasation and hepatotoxicity, which is common. Bromocriptine, a centrally acting dopamine agonist that is available in an oral form, should be started as soon as possible to reverse the central antidopaminergic effects of the antipsychotic agent (the starting dose is 5 mg p.o.; then 2.5 to 10 mg four times a day until the symptoms resolve).

        As the comments on differential diagnosis noted, catatonia must be distinguished from NMS. Because affective disorders have a notable incidence among patients with NMS and because catatonia can also be comorbid with affective disorders, distinguishing between catatonia and NMS is of considerable importance. Catatonia may respond promptly to benzodiazepines, and, when necessary, electroconvulsive therapy (see Chapter 24) may be beneficial. Although bromocriptine may help in

        P.32


        NMS, it can precipitate manic symptomatology in patients with affective disorders. For these reasons, calling the NMSIS Hotline (1-800-NMS-TEMP [667-8367]; 315-428-9010 from outside the United States) may be prudent and clinically beneficial. This will give the caller access to a consultation with a psychiatrist who has extensive experience in both the treatment and differential diagnosis of NMS.

  • Atypical antipsychotic agents. These (clozapine, quetiapine, olanzapine, risperidone, and ziprasidone) are more selective for limbic than for extrapyramidal sites, and they also possess greater selectivity for dopamine-1 (D1) than for D2 receptors. In general, overdose results in less severe toxicity than with conventional antipsychotic agents, and extrapyramidal effects are less common. Clozapine and olanzapine have greater antimuscarinic and antihistaminic properties than do quetiapine, risperidone, or ziprasidone, and they are more likely to cause anticholinergic toxicity and sedation in an overdose. Seizures may also occur. All of these agents antagonize 1-adrenergic receptors, and they may cause hypotension and miosis. Conduction disturbances and QT prolongation can also occur.

    Treatment is supportive. Gastric decontamination should be considered, as outlined above. Continuous ECG monitoring is warranted. Hypotension should be treated with crystalloids; in refractory patients, crystalloids are followed by -adrenergic receptor agonists that act as vasopressors (e.g., norepinephrine).

  • Tricyclic antidepressants (TCAs) and other heterocyclic antidepressants

    • Epidemiology. In the United States, TCAs accounted for 13,848 poisonings in 2000, and they were the second largest category of drugs causing death. The agents that were most commonly implicated were amitriptyline, doxepin, imipramine, and nortriptyline. As with antipsychotic agents, these drugs are pharmacologically complex; they also harbor even greater toxicity in overdose. Their pharmacologic properties include the blockade of sodium and potassium channels and of 1-adrenergic, muscarinic, histaminergic, and -aminobutyric acid A receptors. The reuptake of biogenic amines, including serotonin and norepinephrine, also occurs.

    • Manifestations. Signs of overdose most commonly include CNS depression, seizures, hypotension, and cardiac dysrhythmias.

      • Central nervous system effects. The rapid onset of sedation, coma, and respiratory depression is most commonly seen. Myoclonic jerking is noted in up to 50% of patients and may be mistaken for tonic-clonic seizures. When seizures occur, they usually are brief and isolated, except for when amoxapine or maprotiline is the index drug; in these patients, seizures may be protracted. Agitation, delirium, and hallucinations are less common than are CNS depression and seizures.

      • Cardiac effects. Cardiac dysrhythmias due to TCAs are potentially fatal; they most commonly result from sodium channel blockade. QRS widening on the ECG (greater than 100 ms) indicates significant sodium channel blockade, and it is a predictor of seizures and cardiac dysrhythmias. Dysrhythmias are rate dependent (i.e., sodium channel blockade is more likely to occur in patients with tachycardia). Therefore, patients with tachycardia are not considered medically stable after a TCA overdose. QT interval prolongation stemming from potassium channel blockade may also be seen.

      • Hypotension. Hypotension resulting from -adrenergic receptor antagonism is common. In severe toxicity, hypotension

        P.33


        may also result from myocardial depression related to sodium channel blockade.

      • Anticholinergic effects. These are inconsistently observed; they may be masked by other drug effects. When present, antimuscarinic toxicity manifests as delirium, tachycardia, urinary retention, paralytic ileus, mydriasis, absent sweating, dry mucous membranes, and hyperpyrexia.

    • Treatment

      • Gastric decontamination, as discussed above (see section V.A.2), should be considered as soon as the patient's airway is secured.

      • Continuous ECG monitoring is mandatory.

      • Alkalinization of the serum by hyperventilation of the intubated patient and sodium bicarbonate administration is the initial treatment of choice for dysrhythmias, hypotension, or QRS widening greater than 100 ms. Sodium bicarbonate is given as a bolus of 1 to 2 mEq per kg, followed by repeat boluses or an infusion to maintain the blood pH at 7.5.

      • Hypotension is best treated initially with a crystalloid bolus, followed by sodium bicarbonate, if it is persistent. When hypotension is unresponsive to fluids, -adrenergic receptor agonist vasopressors (e.g., norepinephrine) may be indicated. Avoid vasopressors with -adrenergic receptor effects, as they may further accelerate heart rate.

      • Seizures are treated initially with benzodiazepines (e.g., lorazepam [1 to 2 mg i.v.]). In patients who are not hypotensive, barbiturates may be given for seizures refractory to benzodiazepines. Phenytoin is not an effective agent for seizure control. Noting that sodium bicarbonate does not have an impact on seizures is important; it may, however, be administered in an effort to protect the myocardium against the acidosis that may occur with protracted seizures, as acidosis enhances the binding of TCAs to sodium channels.

        Physostigmine, flumazenil, procainamide, disopyramide, quinidine, and -adrenergic receptor antagonists are contraindicated in the treatment of TCA overdoses. These agents may increase QRS widening, QT interval prolongation, or conduction disturbances.

  • Monoamine oxidase inhibitors

    • Epidemiology. MAOIs, such as phenelzine, tranylcypromine, isocarboxazid, selegiline, and moclobemide (although moclobemide is not available in the United States, it is available in Canada and some other countries), may be highly toxic in overdose. Fatal poisoning has occurred with as little as three to four times the therapeutic dose of tranylcypromine and with five to six times the therapeutic dose of phenelzine. In recent years, the clinical use of MAOIs has started to increase. As a result, overdoses have been seen more frequently. In 2000, 360 poisonings related to MAOIs were recorded in the United States. Many drugs can precipitate life-threatening drug interactions, when they are given to a patient taking MAOIs (see Tables 3.3 and 3.4 and Chapter 29 for drugs to be avoided).

    • Manifestations after overdose. Clinical signs and symptoms do not appear immediately after ingestion. The latent period can be as long as 12 hours. Signs of CNS and neuromuscular excita-tion then appear; these include confusion, agitation, delirium, diaphoresis, tachycardia, hyperreflexia, muscular rigidity, and seizures. Malignant hyperpyrexia is the usual terminal event. After the hyperadrenergic period, the clinical picture may unpredictably

      P.34


      P.35


      progress to one of catecholamine depletion with hypotension, bradycardia, and coma.

      TABLE 3.3. SOME INDIRECT-ACTING AND DIRECT-ACTING SYMPATHOMIMETIC AGENTS AND MONOAMINE OXIDASE INHIBITORS

      Avoid Use with Caution
      Amphetamines, dextroamphetamine Norepinephrine
      Other anorexiants (diet pills) Epinephrine
      Cough and cold preparations Isoproterenol
      Pseudoephedrine Caffeine
      Ephedrine Guarana ( natural caffeine)
      Phenylpropanolamine Theobromine (tea, chocolate)
      Ephedra (Ma huang) Theophylline
      Methyldopa Phenylephrine
      Reserpine Methoxamine
      Guanethidine Albuterol
      Methylphenidate Terbutaline
      Pemoline Clonidine, guanfacine
      Bretylium
      Dopamine
      Metaraminol

      TABLE 3.4. SOME DRUGS TO AVOID OR TO USE WITH EXTREME CAUTION IN PATIENTS TAKING MONOAMINE OXIDASE INHIBITORS

      Agent Effect
      Opioids Prolonged sedation
         Codeine Serotonin excess or toxic serotonin syndrome
         Meperidine
         Dextromethorphan
         Tramadol
      Antidepressants Serotonin excess or toxic serotonin syndrome
         Lithium
         Cyclic antidepressants
         Selective serotonin reuptake inhibitors
         Trazodone
         Nefazodone
         Bupropion
         Mirtazapine
         St. John's wort
         Levodopa
      Central nervous system stimulants Adrenergic crisis
         Theophylline, theobromine
         Caffeine, guarana
         Cocaine, ephedra
         Phenylcyclidine
         Tryptophan
      Hypoglycemic agents or insulin Potentiation of hypoglycemia
      Barbiturates, ketamine Prolonged sedation
      -Adrenergic receptor antagonists Increased blood pressure
      Phenothiazines Hyperthermia

    • Treatment. Management should begin immediately, preferably before the patient becomes symptomatic. Attention to the airway, cardiac monitoring, the establishment of i.v. access, gastric decontamination, and admission to a monitored setting are required. Pharmacologic treatment involves the use of titratable short-acting agents. Recommended therapeutic agents are as follows:

      • For hypertension nitroprusside or phentolamine;

      • For tachyarrhythmias benzodiazepines, esmolol, adenosine (for supraventricular tachycardias), and lidocaine (when ventricular);

      • For agitation benzodiazepines, short-acting neuromuscular blocking agents;

      • For hyperthermia aggressive cooling;

      • For hypotension direct-acting vasopressors (e.g., norepinephrine);

      • For seizures benzodiazepines, barbiturates (note: barbiturates may have prolonged effects);

      • For serotonergic symptoms, reduce dosage or stop and follow recommendations in section IV.B.5.c.(2).

  • Selective serotonin reuptake inhibitors (SSRIs) and other reuptake inhibitors

    • Epidemiology and manifestations. Although overdosing with SSRIs is comparatively common (e.g., 36,672 cases were reported in 2000), fatality is rare. Representative drugs include citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. The most common symptoms seen in overdose are sinus tachycardia, drowsiness, tremor, vomiting, and rarely seizures. Venlafaxine is a somewhat less selective inhibitor of biogenic amine reuptake, and it manifests greater toxicity in overdose. Venlafaxine is much more likely to cause seizures, serotonergic symptoms, hypertension, and tachycardia after overdose compared with the SSRIs. The sustained-release formulation (venlafaxine XR) currently is more commonly used; this may further complicate management.

    • Treatment. After an overdose, care is supportive. Gastric decontamination may be considered as discussed above (see section V.A.2). Cardiac monitoring should be instituted, and seizure precautions should be maintained. A high index of suspicion for coingestants should be maintained. A minimum period of 6 hours of cardiac monitoring is indicated for SSRIs after overdose. Those symptomatic at 6 hours should be admitted. At least a 24 hour period of monitoring is necessary after the ingestion of venlafaxine XR.

    • Toxic serotonin syndrome. Certain symptoms and signs have been recognized collectively as the toxic serotonin syndrome. Occurring only rarely after an overdose and more commonly when two or more proserotonergic agents are coingested, the clinical presentation is similar to NMS; it consists of mental status changes, autonomic dysfunction, and neuromuscular hyperexcitability. Common symptoms include mydriasis, nystagmus, anxiety, CNS depression, salivation, sweating, tachycardia, hypertension, diarrhea, piloerection, ankle clonus, rigidity, shivering, teeth chattering, and ataxia.

      Any combination of the following agents may precipitate the toxic serotonin syndrome: MAOIs, SSRIs, dextromethorphan, TCAs, bupropion, meperidine, amphetamines, trazodone, nefazodone, risperidone, tramadol, St. John's wort, buspirone, tryptophan, lithium, sibutramine, or MDMA.

      • Clinical features that differentiate toxic serotonin syndrome from NMS are (a) rapid onset after the administration of

        P.36


        an offending serotonergic agent, (b) lack of involvement of a dopamine antagonist, (c) greater likelihood of hyperreflexia and/or myoclonus in the lower extremities that is out of proportion to the upper extremities, (d) an increased incidence of diarrhea, and (e) improvement within 24 hours after onset and discontinuation of the proserotonergic agents.

      • Treatment is supportive and is similar to that for NMS with the following exceptions: dopamine agonists are not likely to be effective and the use of cyproheptadine (a 5-hydroxytryptamine 1A [5-HT1A] receptor antagonist) may be considered. The initial dose of cyproheptadine is 4 to 8 mg p.o.

  • Other antidepressants

    • Trazodone. This agent acts through serotonin reuptake inhibition and -adrenergic receptor antagonism. Overdoses are relatively common, with 12,656 cases reported in 2000 in the United States. After overdose, a mild toxicity, typically manifesting as CNS depression, is generally seen. Orthostatic hypotension, miosis, and priapism may occur from local -adrenergic receptor antagonism. Hypotension is best treated with crystalloid bolus; for patients unresponsive to volume expansion, an -adrenergic receptor agonist vasopressor (e.g., norepinephrine) is added. Very rarely, conduction disturbances are described on ECG.

    • Bupropion. In overdoses, this widely used biogenic amine uptake inhibitor has a toxicity profile similar to that of an SSRI. Common symptoms include sinus tachycardia, lethargy, and tremor. One unique feature of bupropion overdose is a greater propensity for generalized seizures (seen in >20% of overdoses), the onset of which may occur more than 6 hours after ingestion. Of note is the fact that most ingestions of bupropion now involve sustained-release formulations and therefore warrant prolonged monitoring.

    • St. John's wort. This agent is an over-the-counter herbal preparation that is commonly used to self-treat depression. Although its mechanism of action is still unknown, two of its putatively active components, hyperforin and hypericin, appear to be proserotonergic. Toxicity in overdose is rare; however, several patients have had seizures, and serotonergic symptoms have been reported. Its side effects include GI upset, photosensitization, fatigue, anxiety, and tremor.

      St. John's wort should not be combined with other serotonergic drugs (see V.B.5.c. above); herbal stimulants, such as Ma huang (ephedra); or cold preparations. Treatment is supportive. St. John's wort is an inducer of the gut transport protein p-glycoprotein or MDR1. When taken at therapeutic dosages or in overdoses, it may increase the presystemic extraction of other agents (e.g., digoxin or indinavir [see Chapter 29]).

    • Mirtazapine. Mirtazapine (Remeron) is a new antidepressant with noradrenergic and serotonergic effects. Through antagonism of the 2-adrenergic receptors, it promotes the release of norepinephrine and serotonin. It also antagonizes 5-HT2 and 5-HT3 receptors, allowing released serotonin to exert its effects on 5-HT1 receptors more fully. Clinical data following a significant overdose with mirtazapine are limited. Mirtazapine appears to enhance the CNS depression caused by other agents in overdose. Other findings include tachycardia, confusion, agitation, and nonspecific ECG changes. Potentially, serious interactions with MAOI or a toxic serotonin syndrome could occur with the use of mirtazapine. Management is supportive, and it should include cardiac monitoring.

  • Lithium carbonate or citrate

    • Epidemiology. In 2000, 4,663 poisonings related to lithium occurred in the United States. Lithium toxicity can develop slowly

      P.37


      during maintenance therapy or after acute overdose. Some factors that may lead to insidious lithium toxicity include (a) a failure to monitor plasma concentrations; (b) coadministration of diuretics, angiotensin-converting enzyme inhibitors, or nonsteroidal antiinflammatory drugs; (c) dietary sodium restriction; (d) aging and reduced glomerular filtration; and (e) dehydration. Serum lithium concentrations of greater than 1.5 mEq per L may be associated with toxicity, although levels after acute ingestion correlate very poorly with symptoms. Severe toxicity, especially in those on chronic therapy, may be seen at relatively low serum levels (approximately 2.5 mEq per L).

    • Manifestations. Early signs of lithium toxicity include nausea, tremor, drowsiness, thirst, behavioral changes, and muscle irritability. More severe poisoning produces coarse tremor, dysarthria, muscle fasciculations, twitching, rigidity, clonus, hyperreflexia, seizures, hyperpyrexia, obtundation, seizures, and coma.

    • Treatment

      • Gastric decontamination may be considered for recent significant ingestions. Lithium does not adsorb to activated charcoal, but activated charcoal may still be given if coingestants are a possibility. Whole bowel irrigation is indicated for recent large ingestions or after overdose with sustained-released products (see section V.A.2.e).

      • Cardiac monitoring is indicated. T wave flattening, U waves, bradycardia, conduction blocks, and ventricular dysrhythmias may be seen.

      • Restoration of sodium and water balance should begin with gentle hydration with normal saline.

      • Hemodialysis is highly effective because of lithium's lack of protein binding and its small volume of distribution. Indications for hemodialysis include severe neurotoxicity, moderate neurotoxicity and serum levels that do not decline by at least 20% in 6 hours, renal failure, and a serum lithium level greater than 4 mEq per L, even if the patient is asymptomatic.

        Rebound increases in serum levels may occur after hemodialysis. Neurologic recovery may lag behind declining serum levels due to slow equilibration between the intraneuronal and/or intracellular lithium concentrations and the plasma.

  • Anticholinergic agents. Anticholinergic agent exposure is extremely common in the United States, with 194,000 cases reported in 1998. Several agents already discussed TCAs, phenothiazines, and some atypical antipsychotic agents can cause antimuscarinic findings in overdose. Anticholinergic toxicity may also occur after drug overdose or as a side effect of medications used to combat motion sickness (e.g., scopolamine, meclizine), GI spasm (e.g., dicyclomine, propantheline), diarrhea (e.g., diphenoxylate and/or atropine), bladder instability (e.g., oxybutynin, tolterodine), skeletal muscle spasm (e.g., cyclobenzaprine, orphenadrine), asthma (e.g., ipratropium), parkinsonism (e.g., benztropine, trihexyphenidyl, amantadine), colds and allergies (e.g., diphenhydramine, chlorpheniramine, hydroxyzine, cyproheptadine, loratadine, fexofenadine, cetirizine), seizures (e.g., carbamazepine), or cardiac dysrhythmias (e.g., procainamide, quinidine). Recent outbreaks of anticholinergic toxicity have been encountered in both intentional abuse (e.g., Jimson weed, scopolamine-adulterated heroin) and malicious administration (e.g., scopolamine-tainted alcoholic beverages). The major morbidity and mortality associated with anticholinergic drug toxicity stem from hyperthermia and rhabdomyolysis caused by agitation and ineffective heat dissipation. Even patients taking these medications therapeutically may become ill under conditions of heat stress.

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    Peripheral antimuscarinic signs include dry skin and mucous membranes, thirst, blurred vision, mydriasis, tachycardia, hypertension, rash or flushing, hyperthermia, absent bowel sounds, and urinary retention. Central antimuscarinic receptor antagonism causes lethargy, anxiety, confusion, hallucination, coma, seizures, ataxia, and respiratory and circulatory collapse. The classic presentation can be remembered as hot as a hare, blind as a bat, red as a beet, dry as a bone, and mad as a hatter. Any ECG finding other than sinus tachycardia suggests either a massive exposure to anticholinergic agents or the presence of other cardiotoxic substances.

    Treatment of anticholinergic toxicity is based on supportive care and basic life support, establishment of an i.v. line, and cardiac monitoring. Physical restraint may be needed for the delirious patient (see Chapter 26). Once an airway is established, gastric decontamination may be considered as outlined above (see section V.A.2). Hyperthermia should be aggressively treated with evaporative cooling methods. Sedation should be carried out with benzodiazepines. Physostigmine (a tertiary ammonium compound) achieves anticholinesterase inhibition and reverses both central and peripheral anticholinergic effects because it crosses the blood brain barrier. Unfortunately, physostigmine may be as dangerous as it is beneficial. Its use may aggravate seizures and arrhythmias and may potentiate the toxicity of TCAs. Indications for its use include peripheral refractory seizures or hemodynamically unstable tachydysrhythmias that are unresponsive to conventional therapy. In general, physostigmine is a last resort medication. Initial doses range from 0.5 to 2 mg i.v. given over 5 to 10 minutes. Before its use, (a) a baseline ECG showing no conduction disturbances or axis deviation should be obtained; (b) the patient should have no history of exposure to other toxins with potential cardiac effect; (c) peripheral and central signs of antimuscarinic toxicity should be present; and (d) bronchospastic disease, vagotonic symptoms (especially bradycardia), intestinal and/or bladder obstruction, severe peripheral vascular disease (gangrene), diabetes mellitus, cardiovascular disease, and recent coadministration of succinylcholine should be excluded. Having atropine at the bedside as a precaution is important. Patients with mild anticholinergic poisoning should be observed for at least 6 to 8 hours; moderate to severe poisoning cases should be admitted to the critical care unit. Monitoring of creatine phosphokinase, transaminases, renal function, and coagulation studies is warranted.

  • CNS stimulants. Catecholamines are key neurotransmitters in the sympathetic nervous system. Epinephrine, norepinephrine, and dopamine are involved in the innervation of the skin, eyes, heart, lungs, GI tract, and exocrine glands. -Adrenergic and -adrenergic receptors are classified into certain subtypes as follows: 1 receptors are primarily peripheral, postsynaptic, and excitatory to smooth muscle and exocrine glands; 2 receptors are primarily central, presynaptic, and inhibitory, causing a decrease in catecholamine release; 1 receptors are primarily cardiovascular and excitatory; and 2 receptors primarily affect smooth muscle relaxation, insulin release, and gluconeogenesis. Receptor cloning suggests that this family of receptors is more complex; nevertheless, this limited classification system still has heuristic and clinical value. Most synthetic sympathomimetic agents are structurally similar to natural catecholamines. Predictably, the sympathomimetic toxidrome includes manifestations of CNS excitation, seizures, hypertension, tachycardia, hyperthermia, nausea, vomiting, diarrhea, and diaphoresis.

    • Cocaine produces its excitatory response by blocking the presynaptic reuptake of norepinephrine, serotonin, and dopamine and by stimulating their presynaptic release. Intoxication with cocaine is therefore characterized by excessive stimulation of the sympathetic

      P.39


      nervous system. In the United States, 5,000 cases of primary cocaine toxicity were reported to poison centers in 2000.

      • Manifestations. These include agitation and hyperactivity, tachycardia, hypertension, sweating, increased respirations, seizures, hyperthermia, acute psychosis, and occasionally chest pain.

      • Treatment. After initial stabilization and assessment for rapidly treatable causes of altered mental status, hyperthermia must be aggressively treated with evaporative cooling measures. Continuous core temperature monitoring should be used. Seizures should be treated with benzodiazepines or barbiturates. Phenytoin has no clear role in the management of drug-induced seizures. Benzodiazepines may be needed to control extreme agitation, and they have been shown to be safe in cocaine intoxication. Their use may also suffice for hypertension and tachycardia because they attenuate both the cardiac and central nervous system toxicity of cocaine when given in sedative dosages. For the management of hypertension unresponsive to sedation, -adrenergic receptor antagonists should be avoided because unopposed -adrenergic receptor-mediated vasoconstriction could result in increased blood pressure or coronary artery vasoconstriction. Hypertension could be managed with an -adrenergic receptor antagonist (e.g., phentolamine) or with other direct-acting vasodilators (e.g., nitrates, hydralazine, or nitroprusside). Dosage titration for sodium nitroprusside, starting at 0.5 g per kg per min, is used with the goal of reducing the mean arterial pressure by 30%. Administering maximally titratable agents in the treatment of cocaine-induced cardiovascular toxicity is generally desirable because the clinical picture is often dynamic. Myocardial ischemia should initially be managed with oxygen, aspirin, benzodiazepines, and vasodilators (e.g., nitrates, phentolamine). Dysrhythmias should be treated with benzodiazepines and sodium bicarbonate (if a wide QRS complex is present). Many tachydysrhythmias will terminate spontaneously with drug metabolism. Those associated with hypotension require cardioversion. For suspected ventricular dysrhythmias, either lidocaine or magnesium is a reasonable antidysrhythmic choice. Bretylium could theoretically accentuate catecholamine release, so it should not be used.

      • Complications. Myocardial infarction and ischemia, myocarditis, congestive heart failure, and ventricular and atrial arrhythmias have been reported. ECG findings of QT prolongation and QRS widening may occur. Bronchospasm, pneumonia, pneumothorax, pneumomediastinum, ischemic and hemorrhagic cerebrovascular accidents, rhabdomyolysis, renal failure, thrombophlebitis, abscess formation, hepatotoxicity, mesenteric ischemia, human immunodeficiency virus infection, and osteomyelitis are other complications.

    • Methylenedioxymethamphetamine (MDMA, ecstasy)

      • Manifestations. This illicit drug is currently one of the most widely abused drugs in the United States. Like other amphetamines, MDMA displaces biogenic amines from storage vesicles, ultimately inducing serotonin, norepinephrine, or dopamine efflux. However, MDMA stimulates a greater release of serotonin than of dopamine, which may explain its greater psychoactive effect compared with that of other unsubstituted amphetamines. Other actions occur through a false neurotransmitter effect, the prevention of monoamine reuptake, and

        P.40


        monoamine oxidase (MAO)-A and MAO-B inhibition. A commonly ingested dose is 75 to 100 mg. Higher doses may cause muscle spasms, involuntary bruxism, nausea, vomiting, dehydration, urinary retention, diaphoresis, restlessness, autonomic fluctuations, and hallucinations. Postrecreational let down effects include confusion, depression, sleep disturbance, anxiety, and paranoia; these effects may persist for weeks. Severe MDMA toxicity is not necessarily dose dependent, and it may occur after the ingestion of a single tablet. Serious complications include hyperthermia; the toxic serotonin syndrome (see section V.B.5), which is characterized by mental status changes, neuromuscular overactivity, autonomic instability, and diarrhea; hyponatremia; hypoglycemia; hepatic necrosis; renal failure; seizures; and intracranial hemorrhage.

      • General treatment. Unless a large recent ingestion is suspected, gastric decontamination has a limited role. Mortality correlates best with the degree of hyperthermia, and therefore aggressive cooling is indicated. Cardiac monitoring is also indicated. Other treatment follows the same principles as those for cocaine toxicity (see section V.B.9.a.(2)). Although dantrolene has been advocated for MDMA-intoxicated patients with temperatures above 41 C (105.8 F), others have found it to be of no benefit when the thermoregulatory mechanisms are overwhelmed. In the setting of catecholamine depletion from end-stage amphetamine toxicity, hypotension may be more responsive to direct-acting vasopressors (e.g., norepinephrine) than to dopamine. Treatment of hyponatremia related to MDMA toxicity depends on the determination of extracellular fluid volume status via physical examination, the measurement of central venous pressure or pulmonary capillary wedge pressure, and the assessment of urine electrolytes and osmolarity. In the absence of dehydration plus a history of excessive water intake, fluid restriction may be indicated. The use of hypertonic saline, mannitol, or loop diuretics may be considered for more severe cases. Forced acid diuresis, which historically was advocated to enhance the elimination of basic amphetamines, is no longer recommended.

      • Disposition and clinical relapse. With the advent of long-acting preparations and particularly potent substances such as methamphetamine, medical observation for at least 24 hours is often warranted. Patients with only mild symptoms usually can be discharged after about 6 hours; they should be provided with appointments for follow-up psychiatric and medical care. Follow-up care is essential because withdrawal symptoms, such as depression, increased appetite, nausea, diarrhea, cramps, restlessness, and headache, may occur within 2 or 3 days after the abrupt cessation of MDMA, cocaine, or amphetamines.

    • Hallucinogens include synthetic and naturally occurring compounds that can be divided into the following two groups: agents that cause true hallucinations (i.e., perceptions of things that do not exist) and psychedelic agents that cause altered perceptions (i.e., distorted images of things that do exist). With the latter, however, the person having the altered perception may have some degree of awareness that the perception is not real. PCP (phencyclidine), lysergic acid diethylamide (LSD), mescaline, certain mushrooms, jimsonweed, and amphetamine analogues may all produce alterations of reality. Most patients who use hallucinogens do not seek medical attention, which is evidenced by the relatively low number of cases reported to poison centers in 2000 (e.g., lysergic acid diethylamide, 1,024; mescaline, 229; PCP, 555).

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      • Manifestations. These include agitation (this may be extreme in PCP intoxication), hypertension, nystagmus, seizures, hyperthermia, rhabdomyolysis, tachycardia, coma, hallucinations, and acute psychosis.

      • Treatment. Initiate the ABCs. Treat agitation with benzodiazepines. When necessary, initiate rapid cooling through evaporative methods. If coingestants are suspected, gastric decontamination may be considered. Although acidification of the urine to enhance PCP elimination has been described historically, the amount cleared is small because the drug is 90% hepatically metabolized and is somewhat acid trapped in the stomach. The potential for myoglobinuric renal failure and worsening of systemic acidosis makes the use of acidification an unwarranted therapy. Nasogastric suction with multidose activated charcoal may be more beneficial.

        Most patients with hallucinogen exposure require only a quiet environment and possibly sedation with benzodiazepines. They can generally be discharged after a period of observation, once their mental status normalizes. Patients with cardiovascular complications, seizures, severe agitation, renal dysfunction, or hyperpyrexia should be admitted to a medical unit.

    • Alcohol (ethanol) is the most commonly abused drug in our society. In 2000, 36,869 exposures were reported to poison centers. Alcohol's CNS depressant properties are primarily mediated by agonist activity at -aminobutyric acid A receptors. Alcohol overdose produces glycogen depletion (hypoglycemia), nausea, vomiting, dehydration, and CNS and respiratory depression. Most fatalities occur at levels greater than 400 mg per dL. Thiamine deficiency is common due to diminished absorption (see Chapter 12 for a detailed overview of the recognition and treatment of alcohol intoxication and withdrawal states).

    • Opioid intoxication is common, with 12,227 cases reported in the United States in 2000. Fatalities related to heroin have recently increased, based on the increased purity of the substance, the lowered cost, and the increasing age of the abusing population. Emergency department visits for complications from or overdoses with oxycodone and hydrocodone have more than doubled in the last several years. The clinical triad of narcotic overdose is characterized by CNS depression, pinpoint pupils, and hypoventilation (see Chapter 10). Response to naloxone during the initial stabilization of any patient presenting with CNS depression may quickly confirm the involvement of opioids. Prescription narcotics used in combination with aspirin, acetaminophen, carisoprodol, caffeine, or other substances may contribute to the clinical presentation.

      • Manifestations. Acute opioid overdosage produces shallow or absent respirations, cyanosis, pupillary miosis, and unresponsiveness. Evidence of a fresh venipuncture wound or tracks due to repeated i.v. injections may be present; however, most heroin abusers insufflate the drug. Massive overdose may be associated with bradycardia or hypotension.

        Heroin pulmonary edema can follow opioid use, even in a conscious person. It is noncardiogenic in nature, and it results from increased pulmonary vascular permeability. Cardiac function is usually normal, and hemodynamic abnormalities are generally absent.

      • Treatment. Assisted ventilation is begun as soon as the patient reaches the treatment area. When naloxone is readily available, tracheal intubation is generally unnecessary. If

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        any delay in administering naloxone occurs, tracheal intubation should be performed.

        Naloxone is a specific narcotic antagonist at CNS receptor sites. It quickly reverses coma and respiratory depression secondary to overdose with oral or i.v. narcotics. The usual dosage requirement is 0.4 to 2 mg for adults and 0.01 mg per kg in children. Continuous infusions of naloxone at two-thirds of the dose required per hour may be given to prompt awakening if resedation occurs. Continuous infusions or repeat boluses are often necessary, because most narcotics have a longer duration of action than naloxone. This is especially true for methadone; its effects may last for days. In general, infusions are titrated to achieve the desired clinical response. Higher doses of naloxone (2 to 10 mg) may be required initially to reverse the CNS depressant effects of pentazocine (Talwin) or the respiratory depression of propoxyphene (Darvon). Emergence from opioid overdosage is characterized by agitation and combativeness. Patients may harm themselves and medical staff. Therefore, if possible, physical restraints should be applied before naloxone is administered (see Chapter 26).

        • Decontamination. For oral opioid ingestions, gastric decontamination as outlined above may be considered (see section V.A.2).

        • Pulmonary edema. This is treated with oxygen and positive-pressure ventilation. Unless evidence of concomitant left ventricular failure or intravascular volume overload is found, the usual approaches to treatment (e.g., diuretics, nitrates, afterload reduction) are of no value, and they should be avoided.

        • Supportive care and disposition. Supportive care is directed toward any residual symptoms that are not reversed by naloxone. Hypotension may require crystalloid infusions. For mixed ingestions, a search for the coingested product may direct the treatment toward more specific supportive measures. In general, once initial stabilization has been achieved, patients should be admitted and observed for the appearance of any recurrence of narcotic overdose symptoms or for the onset of symptoms of narcotic withdrawal. Serious complications from narcotic use include infections (e.g., abscess formation, endocarditis, pneumonia, tetanus), hepatic or GI dysfunction, and neuropathies.

    • Benzodiazepines are among the most widely used drugs in the world, but, when they are taken alone, they rarely produce serious poisoning. The class includes a number of antianxiety, anticonvulsant, and hypnotic agents (see also Chapters 9, 14, and 15).

      • Epidemiology. In 2000, 49,849 benzodiazepine overdoses were reported to poison centers. Fatal overdose with any benzodiazepine taken alone is quite rare. As with other sedative-hypnotics, the therapeutic concentration ranges are wide, and they reflect individual differences in metabolism, accumulation, and tolerance. Benzodiazepine levels are not useful in the management of an acute overdose.

      • Manifestations. Patients can present with muscle weakness, hypotonia, ataxia, dysarthria, and somnolence. Coma, respiratory depression, hypotension, and hypothermia may occur after very large ingestions or after i.v. administration.

      • Treatment. Measures other than supportive care are sel-dom necessary. Forced diuresis and hemodialysis are not in-dicated. Gastric decontamination as discussed above may be considered.

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        Flumazenil (Romazicon) is a competitive benzodiazepine receptor antagonist that rapidly reverses benzodiazepine effects. Although flumazenil should elicit no effects when taken in the absence of benzodiazepines or related agents, its use in the presence of benzodiazepines can be associated with undesired effects, including agitation, anxiety, nausea, hypotension, dysrhythmias, increased intracranial pressure, and seizures. The incidence of seizures in high-risk overdose patients (i.e., those with jerking movements or abnormal vital signs) is 16%. Flumazenil use should be avoided in chronic benzodiazepine users; patients with a known seizure disorder; and patients who have ingested other drugs, especially TCAs. Flumazenil may be given at a dose of 0.1 mg over 1 minute, up to 1 mg. Because CNS depression related to benzodiazepine overdose is rarely life threatening, most cases can be managed with supportive care only.

    • Barbiturates are still commonly implicated drugs in deliberate self-poisoning.

      • Epidemiology. In 2000, 4,484 cases of barbiturate toxicity were reported to American poison centers. Because of refinements in the principles of supportive care, the case fatality rate in barbiturate poisoning has recently fallen to the range of 1% or less. Short-acting barbiturates, such as secobarbital and pentobarbital, are the most frequently fatal after ingestion. Long-acting barbiturates (e.g., phenobarbital) have a somewhat wider margin of safety, but this varies based on individual tolerance. In general, serum phenobarbital concentrations of 100 to 120 g per mL indicate severe intoxication, even in the tolerant patient. By contrast, the usual therapeutic plasma concentration for phenobarbital ranges from 15 to 40 g per mL.

      • Manifestations. The symptoms of poisoning are similar for all types of barbiturates. Drowsiness, nystagmus, ataxia, dysarthria, and somnolence occur in the early stages of poisoning or in mild cases. The larger the dose, the more profound the level of general CNS depression is. Deep coma, areflexia, muscle hypotonicity, apnea, hypotension, and hypothermia occur in the most serious cases. Barbiturates are known to form concretions when many pills are taken in a short period of time.

      • Treatment. For short-acting barbiturate poisoning, treatment is usually limited to supportive care. Urinary alkalinization is of no value. Secobarbital and pentobarbital are poorly dialyzable.

        Urinary alkalinization significantly enhances the excretion of phenobarbital. Multiple-dose activated charcoal therapy can also be considered. Phenobarbital is removed by hemodialysis, although this is reserved for patients with levels greater than 100 to 120 g per mL, those who are hemodynamically unstable, or those who cannot tolerate a prolonged coma.

    • Glutethimide is no longer marketed in the United States. Nevertheless, 13 poisonings were reported in the United States in 2000. Because it is dangerous and because it may be ingested by persons who have obtained it elsewhere, a discussion of it is included here.

      • Epidemiology and pharmacology. Because glutethimide is lipid soluble and it has a large volume of distribution, the plasma concentrations do not correlate well with the depth of coma. The usual therapeutic plasma concentration for glutethimide ranges from 5 to 15 g per mL. However, nearly all individuals with moderate or severe intoxication have plasma concentrations greater than 20 g per mL. Levels greater

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        than 40 or 50 g per mL are almost always associated with deep coma. Single doses of 10 g or more (10 to 20 times the usual hypnotic dose) generally produce serious poisoning. A hydroxylated polar metabolite of glutethimide may contribute to its CNS depression.

      • Manifestations. Glutethimide produces dose-dependent CNS depression like the barbiturates. Glutethimide has anticholinergic properties, and it frequently produces tachycardia, paralytic ileus, and mydriasis. Cardiovascular depression (hypotension, pulmonary edema) is also common in glutethimide poisoning. Similar to the barbiturates, glutethimide is known to form concretions.

      • Treatment. Management should be supportive in nearly all cases. Treatment of hypotension by intravascular volume expansion should be done cautiously because of the hazard of pulmonary edema.

    • Methaqualone, a drug that has been considered illicit in the United States since 1984, was transiently, but extremely, popular as a drug of abuse and suicide.

      • Epidemiology. Most experience with methaqualone overdose comes from Europe, where a combination hypnotic preparation (Mandrax) containing methaqualone (250 mg) and diphenhydramine (25 mg) in each pill has been available.

      • Manifestations. In Mandrax poisoning, anticholinergic symptoms can be prominent. These include mydriasis, tachycardia, muscular rigidity, twitching, hyperreflexia, and seizures. Overdose with methaqualone alone usually produces barbiturate-like CNS depression. However, excitatory phenomena with a paradoxical increase in muscle tone with hyperreflexia, myoclonus, and seizure-like activity may be seen. Pulmonary edema may occur. Thrombocytopenia and coagulopathy are described in 20% of cases.

      • Treatment. Care is supportive. Gastric decontamination may be considered. Benzodiazepines may be used to control neuromuscular hyperexcitability. Vitamin K or fresh frozen plasma may be indicated to control any overdose emergent bleeding. Hemoperfusion has been used in severe overdoses or in patients whose levels are 100 to 150 g per mL.

    • Ethchlorvynol (Placidyl) can produce serious intoxication. Fortunately, it is no longer manufactured in the United States. It is an uncommon agent of self-poisoning; only 48 cases were reported in 2000.

      • Epidemiology. Single ingestions of 15 g and plasma concentrations greater than 100 g per mL are associated with severe intoxication.

      • Manifestations. Intravenous injection, a common method of abuse, results in noncardiogenic pulmonary edema. Other findings include prolonged coma, hypothermia, hypotension, and respiratory depression. The characteristic odor of ethchlorvynol detected in body fluids of intoxicated patients can be recognized by comparing it with the odor of a freshly opened ethchlorvynol capsule.

      • Treatment. Consider gastric decontamination in oral overdose. Oxygen and positive end-expiratory pressure ventilation may be required for pulmonary edema. Ibuprofen may reduce ethchlorvynol-induced pulmonary toxicity. Activated charcoal hemoperfusion has been used in cases of severe toxicity, but the indications are controversial.

    • Meprobamate (Miltown, Equanil)

      • Epidemiology. In 2000, 140 poisonings were reported. The elderly population is the primary user of this sedative-hypnotic.

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      • Manifestations. Symptoms after overdose resemble barbiturate-like intoxication, with all degrees of CNS depression described. In addition, the drug is maximally concentrated in the myocardium, and it may cause severe hypotension. Meprobamate may also form concretions after an overdose.

      • Treatment. Gastric decontamination, including whole bowel irrigation, may be considered. Care is mostly supportive. Forced diuresis will enhance renal elimination, but it may also predispose the patient to pulmonary edema. The early use of vasopressors and inotropic agents to combat hypotension is advised to avoid fluid overload. Indications for hemoperfusion include cardiovascular instability or levels greater than 100 g per mL.

    • Carisoprodol (Soma)

      • Epidemiology. Carisoprodol is a centrally acting muscle relaxant that is metabolized to meprobamate; it has emerged as a significant drug of abuse. In 2000, 6,125 poisonings were reported. Certain formulations contain added salicylates or codeine. Carisoprodol is commonly abused together with acetaminophen combined with codeine or with propoxyphene or hydrocodone. The latter combination results in a high that is similar to that achieved by heroin abuse.

      • Manifestations. Both CNS stimulation and depression can occur. Fatalities from respiratory depression with aspiration have been described. Tachycardia, hypotension, nystagmus, intermittent agitation, seizures, and prolonged coma have been reported.

      • Treatment. Care is supportive. Gastric decontamination can be considered. Flumazenil should be avoided. Extracorporeal elimination has not been reported. Examination for toxic acetaminophen and salicylate levels is warranted.

    • Chloral hydrate overdosage is not common at the present time; only 226 cases were reported in 2000. An overdose with chloral hydrate can be severe, and its manifestations may sometimes be confused with opioid overdose.

      • Manifestations. Signs include hypotension, ventricular arrhythmias, respiratory depression, noncardiogenic pulmonary edema, and miosis. Deep coma can develop rapidly (i.e., within 30 minutes).

      • Treatment. Management usually consists of the administration of activated charcoal. For more severe situations, airway support, gastric decontamination, and naloxone (2 mg i.v.) may be necessary. Hypotension is treated with crystalloid therapy. When no response occurs, the administration of norepinephrine is indicated. Other catecholamine vasopressors should be avoided because they may be prodysrhythmic. Premature ventricular contractions, ventricular tachycardia, and torsade de pointes have all been observed. When premature ventricular contractions and ventricular tachycardia are unresponsive to lidocaine (1 mg per kg i.v.), propranolol may be helpful (1 mg i.v., to a total of 5 mg). For torsade de pointes, isoproterenol, atropine, magnesium sulfate, or ventricular pacing may be required. Respiratory complications are treated with supportive measures. Although flumazenil (Romazicon) has been reported to improve chloral hydrate-induced respiratory depression, hypotension, and miosis, its use has also been shown to cause ventricular tachycardia. Flumazenil use for the routine treatment of overdose with chloral hydrate is not recommended at the present time.

C. Identification, Evaluation, and Treatment of Intoxication from Other Agents

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  • Acetaminophen. This agent is responsible for more pharmaceutical-related deaths than is any other substance. In 2000, 108,066 poisonings were reported in the United States.

    • Manifestations. Soon after ingestion, the patient may exhibit mild GI symptoms, or, more commonly, he or she will be asymptomatic. Within 24 hours, subclinical evidence of hepatic injury occurs as transaminase levels become elevated. Untreated patients or those who present beyond 8 hours of ingestion may go on to develop fulminant hepatic or renal failure within 72 to 96 hours.

      Because of the lack of early clinical signs of toxicity, performing an acetaminophen level on all patients with intentional drug overdose is imperative. In the setting of acute ingestion (where the exact time of ingestion is known), this level may be plotted on the Rumack-Matthews nomogram to determine the patient's risk for hepatotoxicity. In other situations, empiric antidotal treatment is indicated.

    • Treatment. N-acetylcysteine (Mucomyst) is a very effective antidote to acetaminophen-induced toxicity. The dose is 140 mg per kg p.o. as a loading dose, followed by 70 mg per kg every 4 hours for 17 additional doses. N-acetylcysteine should be started as soon as possible after acute acetaminophen ingestion, but it should not be withheld in those presenting late. N-acetylcysteine is indicated in those patients who have chronically overused acetaminophen, staggered their ingestion, presented with an unknown time of ingestion, or ingested extended-release formulations or in those who have been nutritionally deprived due to alcohol.

  • Salicylates. Salicylate overdose is common; it accounted for 25,394 reports to poison centers in 2000. Toxicity may be acute or chronic in nature. Neurons are most seriously impacted by the ability of salicylates to uncouple oxidative phosphorylation. Central manifestations of toxicity include hyperpnea, agitation, seizures, lethargy, coma, tinnitus, and hyperpyrexia. Other findings include noncardiogenic pulmonary edema, renal failure, nausea, vomiting, acid-base disturbances, and rarely cardiac dysrhythmias. Irreversible neurologic injury may occur if patients are not aggressively managed.

    • Treatment. Continuous cardiac monitoring and pulse oximetry is indicated. Gastric decontamination, as outlined above in section V.A.2, may be considered. Multidose activated charcoal may be administered. Careful hydration should be instituted, along with glucose supplementation and urinary alkalinization. Alkalinization is generally accomplished by administering sodium bicarbonate, 1 to 2 mEq per kg i.v., followed by an infusion of 100 to 150 mEq sodium bicarbonate per L of D5W at 1.5 times the maintenance fluid rate (see section V.A.3.b) to achieve a target urine pH of 7.5. Potassium supplementation is generally required to accomplish urinary alkalinization. Salicylate level, urine pH, electrolytes, glucose, and arterial blood gas should be monitored every 1 to 2 hours, which generally requires placing the patient in an intensive care unit setting.

      Hemodialysis effectively enhances the elimination of salicylates, and thus it is indicated for patients with seizures or other neurologic symptoms, renal failure or oliguria, pulmonary edema, intractable acidosis, inability to alkalinize the urine, levels greater than 90 mg per dL in acute overdose and greater than 60 mg per dL with chronic toxicity, or clinical deterioration despite full medical support.

  • Toxic alcohols. Toxic alcohol ingestion is common, with 2,737 methanol, 4,884 ethylene glycol, and 18,870 isopropanol exposures reported in 2000. Even small doses (single swallows) of methanol and ethylene glycol, usually as radiator coolant or antifreeze, may cause toxicity. A latent period before the development of symptoms is characteristic for both ethylene glycol

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    and methanol toxicity, especially when ethanol has been coingested. Because early treatment improves prognosis, therapy should begin immediately based on clinical suspicion of exposure to ethylene glycol or methanol. This should involve the rapid correction of acidosis with sodium bicarbonate, cofactor administration, and alcohol dehydrogenase antagonism with either ethanol or 4-methylpyrazole (see below). Because the presence of acidosis in the setting of exposure to either substance indicates toxic metabolite accumulation, immediate consultation for hemodialysis should be made, even before laboratory confirmation of toxic ethylene glycol or methanol levels.

    • Methanol (wood alcohol) is a common solvent that is oxidatively metabolized by the liver to formic acid. It can cause blindness and irreversible neurologic injury. The presence of methanol and its major toxic metabolite, formic acid, results in a characteristic double-gap (both anion and osmolal gap) acidosis. The so-called blind staggers of methanol intoxication are a characteristic, but late, finding.

      • Manifestations. In addition to visual disturbances, these include CNS depression, tachypnea, abdominal pain, nausea and vomiting, clammy skin, seizures, and metabolic acidosis. Impaired vision ranging from blurred vision to blindness may also be present, as may hyperemia of the optic disk and papilledema.

      • Treatment. Initiate the ABCs and general supportive care, including i.v. administration of 50% dextrose in water, naloxone, and thiamine. Correction of the metabolic acidosis is achieved with sodium bicarbonate (1 mEq per kg). Intravenous alcohol (ethanol) administration, using a loading dose of 10 mL per kg of 10% alcohol and then a continuous drip of 1.5 mL per kg per hour of 10% alcohol, competitively inhibits the production of formic acid because of alcohol's higher affinity for the enzyme alcohol dehydrogenase. An alternative competitive inhibitor is 4-methylpyrazole (Antizol). Folic acid (as leucovorin) may be given at a dose of 1 mg per kg every 4 hours. Hemodialysis should be initiated when the methanol level is greater than 25 mg per dL or when acidosis, visual disturbances, or renal failure is present.

    • Ethylene glycol, which is usually ingested as radiator coolant, antifreeze, or windshield washer fluid, also requires alcohol dehydrogenase for its metabolism. Multiple toxic organic acids, including oxalic acid, glyoxylic acid, and glycolic acid, are formed. Characteristically, these acids may cause renal tubular necrosis and renal failure, but multiple organ systems may be affected.

      • Manifestations. Inebriation is seen within 2 to 12 hours of ingestion, after which cardiopulmonary symptoms such as tachycardia, hypertension, and pulmonary edema develop. Hypocalcemia and myositis are common during this stage. At 24 to 72 hours, renal failure occurs in two-thirds of untreated patients. Delayed cranial neuropathy may be seen.

      • Treatment. Care is similar to that for methanol poisoning. In addition, thiamine, 100 mg, and pyridoxine, 50 mg, are given every 6 hours, theoretically to enhance the formation of nontoxic metabolites.

    • Isopropanol (isopropyl alcohol, rubbing alcohol). Intoxication may be suspected based on apparent inebriation in which the odor of acetone, rather than ethanol, is detected on the breath.

      • Manifestations. The patient may complain of headache or dizziness and may exhibit neuromuscular incoordination, confusion, and nystagmus. Severe ingestions may result in deep

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        coma that is prolonged compared with that seen with ethanol. Respiratory depression or failure may occur. Isopropanol is a GI irritant; therefore, hematemesis or GI bleeding may be seen. Hypotension portends a poor prognosis.

      • Treatment. Unlike with methanol and ethylene glycol, alcohol dehydrogenase antagonism with ethanol or 4-methylpyrazole is not indicated in treatment of isopropranol. Hypotension should be managed with fluids and vasopressors as needed. When the patient remains hypotensive or has further vital sign deterioration despite these measures, dialysis is indicated. Some authors also recommend dialysis for isopropyl alcohol serum levels greater than 400 mg per dL. Coma itself is not an indication for dialysis, but it may necessitate the use of mechanical ventilation. Care is otherwise supportive, including rewarming, the administration of thiamine, evaluation for hypoglycemia, and monitoring for GI bleeding.

  • Pesticides. Anticholinesterase inhibition is usually caused by the organophosphate insecticides; less frequently, poisonings involve the carbamate insecticides. Poison centers received reports of 11,874 organophosphate and 3,754 carbamate exposures in 2000.

    • Bond formation. Organophosphates form a covalent, spontaneously irreversible bond with acetylcholinesterase, thus producing a cholinergic crisis. This bond, however, is pharmacologically reversible if pralidoxime is given before pesticide binding to acetylcholinesterase becomes irreversible (i.e., usually within 24 to 36 hours). Carbamates also bond to cholinesterase enzymes, but this bonding is spontaneously reversible within 6 to 8 hours.

    • Manifestations. These include stimulation of both muscarinic and nicotinic receptors. Peripheral muscarinic symptoms produce the symptom complex remembered by the mnemonic DUMBBELS as follows: diarrhea, urination, miosis, bradycardia, bronchorrhea, emesis, lacrimation, and salivation. Other effects may include hypotension or hypertension. Nicotinic symptoms include fasciculations, cramps, weakness, paralysis, cyanosis, and respiratory arrest. Tachycardia and hypertension may be seen early, as a result of initial stimulation of the autonomic ganglia.

      ECG findings may show almost any abnormality, from asystole to sinus tachycardia. In general, sinus tachycardia predominates initially as a result of nicotinic autonomic ganglion excitation. Later, parasympathetic tone predominates, causing sinus bradycardia and conduction delays and blocks. QT prolongation may occur.

    • Laboratory findings. These should establish low levels of cholinesterase activity in both the plasma (pseudocholinesterase) and red blood cells (true cholinesterase). Red blood cell cholinesterase is believed to be more accurately and more closely related to the severity of the toxicity, although plasma cholinesterase levels generally are more readily available.

    • Treatment

      • Decontamination should begin with removing all clothing from the patient, and the skin should be scrubbed by personnel wearing protective clothing and gloves to prevent contamination of their own skin. Gastric lavage and activated charcoal are indicated.

      • Supportive measures should focus on airway management and control, because copious secretions, bronchospasm, respiratory muscle paralysis, and vomiting may be present.

      • Cardiac monitoring and i.v. access are mandatory.

      • Atropine competitively antagonizes acetylcholine's actions at the muscarinic receptors, thereby reversing parasympathetic

        P.49


        overstimulation. Initial doses should be 1 to 2 mg i.v. in adults and 0.05 mg per kg in children. Doses may be repeated as needed every 10 to 15 minutes. The therapeutic end point is the drying of pulmonary secretions.

      • Pralidoxime chloride reactivates cholinesterases if it is given within 24 to 36 hours of exposure. This ameliorates toxicity occurring at both muscarinic and nicotinic sites, and it reverses the neuromuscular findings. Patients who require atropine therapy generally also require pralidoxime. A typical regimen for adults consists of an initial dose of 1 to 2 g i.v. over 15 to 30 minutes; subsequent doses are given 1 to 2 hours after the first dose and then every 6 to 8 hours as needed. Some authorities recommend that, to achieve therapeutic concentrations, about 500 mg per h needs to be infused until sustained improvement is noted.

    • Disposition. Asymptomatic patients may require prolonged observation if they have been exposed to lipid-soluble agents (e.g., chlorfenthion or fenthion) or to those that require conversion to the active pesticide. All symptomatic patients should be admitted to a medical unit, and appropriate antidotes should be administered. Although clinical relapse is rare if the initial treatment is appropriate, months may be required for red blood cell cholinesterase to return to normal levels. Headaches, memory impairment, confusion, depression, and peripheral neuropathies commonly persist for some time in patients with significant exposures.

D. Mixed Drug Overdose

This is almost as common as poisoning with single drugs. Diagnosis, treatment, and prognostication are somewhat more complicated than for a single-drug overdose. Clinicians dealing with psychotropic drug overdose must always consider the possibility that more than one drug is involved. Acetaminophen is the most common coingestant, so serum levels of acetaminophen should be obtained in all patients with intentional overdose. Some of the more common cocktails follow.

  • Alcohol and sedative-hypnotics are a dangerous combination because they cause CNS depression that is at least additive (see Chapters 10 through 12). Evidence suggests that chronic alcohol use can retard the metabolism of other CNS depressants (e.g., chloral hydrate).

  • Phenothiazines and TCAs are coprescribed, and, in other countries, they are sometimes marketed in fixed combinations. Anticholinergic manifestations are prominent in poisoning with these mixtures. The mixtures used dictate the treatment. Because phenothiazines and TCAs often have common unwanted effects (e.g., prolonged cardiac conduction, anticholinergic effects), the toxicities from the combinations are often additive.

E. Withdrawal Toxidromes

The abrupt cessation of many substances can cause a complex group of symptoms that mimics a psychiatric emergency. Alcohol, barbiturates, benzodiazepines, -hydroxybutyrate or its analogues, cocaine, amphetamines, and opioids are but a few. Chapters 9, 10, 12, and 14 should be consulted for further details on the withdrawal syndromes associated with alcohol, opioids, and sedative-hypnotics. The manifestations of withdrawal are varied, including diarrhea, hypertension, mydriasis, tachycardia, insomnia, hyperthermia, lacrimation, hallucination, cramps, yawning, piloerection, depression, anxiety, and seizures. The agent involved largely dictates the treatment, but supportive measures include i.v. access, cardiac monitoring, hyperthermia control, and hypertension control. Seizures may generally be treated with i.v. lorazepam (usually 1 mg, but up to 4 mg may be required). Observation with close medical follow-up may be all that is needed for patients who present with mild withdrawal symptoms. For patients with dysrhythmias, hallucinations, hyperthermia, seizures, or

P.50


symptomatic hypertension, hospitalization in a medical unit is generally required.

F. Clinical Relapse

Although not a toxidrome per se, clinical relapse refers to a phenomenon in the course of overdose treatment in which clinical worsening follows a period of improvement. It has been reported with almost every psychotropic drug. Glutethimide, meprobamate, lithium, and TCAs are the most commonly implicated drugs. Glutethimide and meprobamate use has significantly decreased, as noted above, in the last several decades.

  • Etiology. The etiology of the clinical relapse phenomenon is not clear. At least three mechanisms are theoretically possible.

    • The parent drug and its active metabolites are initially tied up in the enterohepatic circulation, but they are subsequently released into the systemic circulation.

    • A portion of the ingested agent is initially unabsorbed from the GI tract due to poor splanchnic circulation, and concretions are formed. When hypotension is treated and splanchnic blood flow is restored, the remaining quantity is rapidly absorbed.

    • Highly lipid-soluble drugs (e.g., glutethimide, short-acting barbiturates) are initially distributed into lipid storage sites other than the brain. At a later time, after adequate cardiac output is restored and blood flow to these sites increases, the drug reappears in the systemic circulation.

  • Manifestations. The signs and symptoms of relapse include worsening of neurologic, hemodynamic, and respiratory status. Serum concentrations of the drug may rise. Deterioration usually follows a period of clinical improvement ranging from a few hours to a few days after drug ingestion.

  • Treatment. Management consists of continued supportive care. The possibility of relapse underscores the need for continued close monitoring after clinical improvement occurs.

ADDITIONAL READING

American Academy of Clinical Toxicology, European Association of Poison Control Centers. Position statements: ipecac syrup, gastric lavage, single-dose activated charcoal, whole bowel irrigation, cathartics. Clin Toxicol 1997;35:699 762.

American Academy of Clinical Toxicology, European Association of Poison Control Centers. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. Clin Toxicol 1999;37:731 751.

American College of Emergency Physicians. Policy statement: management of elder abuse and neglect. Ann Emerg Med 1998;31:149 150.

American Heart Association. BLS for healthcare providers. Dallas: American Heart Association, 2001.

American Medical Association. Diagnostic and treatment guidelines on domestic violence. Chicago: American Medical Association, 1992.

Berkowitz CA. Child abuse and neglect. In: Tintinalli J, Kelen G, Stapczynski S, eds. Emergency medicine, a comprehensive study guide, 5th ed. New York: McGraw-Hill, 2000:1949 1952.

Canto JG, Shlipak MG, Rogers WJ. Prevalence, clinical characteristics, and mortality among patients with myocardial infarction presenting without chest pain. JAMA 2000;283:3223 3229.

Centers for Disease Control and Prevention. Influenza activity, United States, 2000 2001 season. MMWR Morb Mortal Wkly Rep 2000;49:1085 1087.

Centers for Disease Control and Prevention. Recommendations and reports, prevention and control of influenza. MMWR Morb Mortal Wkly Rep 2000;49(RR-03):1 46. Available at http://www.cdc.gov/mmwr/pdf/rr/rr4903/pdf. Accessed November, 2002.

Eisenberg MS, Mengert T. Cardiac resuscitation. N Engl J Med 2001;344:1304 1313.

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Feldhaus KA. Female and male sexual assault. In: Tintinalli J, Kelen G, Stapczynski S, eds. Emergency medicine, a comprehensive study guide, 5th ed. New York: McGraw-Hill, 2000:1953 1955.

Gallagher J. Acute abdominal pain. In: Tintinalli J, Kelen G, Stapczynski S, eds. Emergency medicine, a comprehensive study guide, 5th ed. New York: McGraw-Hill, 2000:497 515.

Litovitz TL, Klein-Schwartz W, White SR, et al. 2000 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 2001;19:337 395.

Mills KC. Tricyclic antidepressants, newer antidepressants and serotonin syndrome, monoamine oxidase inhibitors. In: Tintinalli J, Kelen G, Stapczynski S, eds. Emergency medicine, a comprehensive study guide, 5th ed. New York: McGraw-Hill, 2000:1063 1085.

Muelleman RA, Lenaghan PA, Pakisser PA. Battered women: injury location and types. Ann Emerg Med 1996;28:486 492.

Olshaker JS, Browne B, Jerrard DA, et al. Medical clearance and screening of psychiatric patients in the emergency department. Acad Emerg Med 1997;4:124 128.

Olson KR. Poisoning & drug overdose, 3rd ed. Stamford, CT: Appleton & Lange, 1999.

Salber P, Taliaferro EH. Domestic violence. In: Tintinalli J, Kelen G, Stapczynski S, eds. Emergency medicine, a comprehensive study guide, 5th ed. New York: McGraw-Hill, 2000:1956 1960.

Taliaferro EH, Salber PR. Abuse in the elderly and impaired. In: Tintinalli J, Kelen G, Stapczynski S, eds. Emergency medicine, a comprehensive study guide, 5th ed. New York: McGraw-Hill, 2000:1960 1962.

Valenzuela TD, Nichol G, Clark LL, et al. Outcomes of rapid defibrillation by security officers after cardiac arrest in casinos. N Engl J Med 2000;343:1206 1209.

White SR. Nonbenzodiazepine sedative-hypnotics. In: Tintinalli JE, Ruiz E, Krome RL, eds. Emergency medicine, a comprehensive study guide, 4th ed. New York: McGraw-Hill, 1994:761 764.

1Toxic serotonin syndrome is now the preferred term.



Manual of Psychiatric Therapeutics Paperback
Manual of Psychiatric Therapeutics: Practical Psychopharmacology and Psychiatry (Little, Browns Paperback Book Series)
ISBN: 0316782203
EAN: 2147483647
Year: 2002
Pages: 37

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