Trauma (e.g., crush syndrome, burns, electrical shock)
Muscle ischemia (e.g., thrombosis, embolism, vasculitis, sickle cell disease, pressure necrosis, tourniquet shock)
Drugs: Drug-induced rhabdo can occur through several mechanisms.• Primary, toxin induced (e.g., ethanol, methadone, ethylene glycol, isopropyl alcohol, CO poisoning)
• Long-term intake of drugs associated w/hypokalemia (e.g., thiazides)
• OD of certain drugs (e.g., barbiturates, heroin, cocaine)
• Malignant hyperthermia (usually seen in genetically predisposed individuals, after exposure to halothane, succinylcholine, or pancuronium)
• NMS (associated w/use of phenothiazines, butyrophenones, antipsychotics, cocaine, or diphenhydramine, usually in pts w/dehydration and electrolyte imbalance)
• Use of certain lipid-lowering agents (e.g., combination of statins and gemfibrozil, or erythromycin and simvastatin; and amiodarone; amphetamines, haloperidol)
• Direct myotoxicity (e.g., colchicine, zidovudine, cyclosporine, itraconazole)
Infections• Bacterial (e.g., Streptococcus, Salmonella, Clostridium, Legionella, Leptospira, Shigella)
• Viral (e.g., echo, coxsackie, influenza, CMV, herpes, EBV, hepatitis)
• Parasites (trichinosis)
Excessive muscle stress (e.g., marathon runners, status epilepticus, delirium tremens)
Genetic defects (carnitine deficiency, phosphorylase deficiency, glucosidase deficiency, cytochrome disturbances)
Miscellaneous: brown recluse spider bite, snake bite, hornet sting, polymyositis, dermatomyositis, heat stroke, DKA, hyponatremia, hypophosphatemia, myxedema, thyroid storm, RMSF, hypothermia, CO, cyclic antidepressants, phenylpropanolamine, codeine, phencyclidine (PCP), amphetamines, LSD, Reye’s syndromeDiagnosis
H&P
Variable muscle tenderness. Rhabdo apart from statin use is manifested w/muscle sx only 50% of the time.
Weakness
Muscle rigidity
Fever
Altered consciousness
Muscle swelling
Malaise, fatigue. In statin-induced rhabdo, fatigue (74%) is nearly as common as muscle pain (88%).
Dark urine (secondary to myoglobin in urine, will make dipstick false (+) for RBC’s)Labs
↑↑ CK: Elevations may exceed 100,000 U/L in fulminant rhabdo; the development of renal failure is not directly related to the threshold level of CK; isoenzyme fractionation is useful: if CK-MB >5% of the total CK, involvement of the myocardium is likely.
↑Serum Cr: The etiology of the renal failure is uncertain and probably multifactorial (renal tubular obstruction by precipitated myoglobin, direct myoglobin toxicity, hypotension, dehydration, ↓ GFR, intravascular coagulation).
Serum K+: Preexisting hypokalemia is a contributing factor to rhabdo; fulminant rhabdo can result in life-threatening hyperkalemia secondary to ↑ K+ release from damaged muscle and impaired renal excretion.
Ca2+ and PO4-3: Initially, pts have hyperphosphatemia from muscle necrosis, secondary hypocalcemia from Ca2+ deposition in the injured muscle, and ↓ 1,25-dihydroxycholecalciferol; later (in the diuretic phase of renal failure), hypercalcemia is present as a result of remobilization of the deposited Ca2+ and secondary hyperparathyroidism.
Myoglobin: This is present in the serum and urine; the urine is brownish, has granular casts, and is O-toluidine(+); a quick visual method to separate myoglobinuria from hemoglobinuria is to examine the urine and serum simultaneously: reddish brown urine and pink serum indicate hemoglobinuria, whereas brown urine and clear serum suggest myoglobinuria; ↑ in serum myoglobin precedes the ↑ in CK level and is useful to estimate the risk of renal failure (serum myoglobin levels >2000 μg/L may be associated w/renal insufficiency).Treatment
Vigorous fluid replacement is given to maintain a good urinary output, at least until myoglobin disappears from the urine. Initially NS should be given at a rate of 1.5 L/hr w/close monitoring of cardiac, pulmonary, and electrolyte status. Maintain ↑ rate of IV fluids at least until CPK <1000 U/L. Pts may require >15 L of fluid in the initial 24 hr to achieve urine flow rates of 200 to 300 mL/hr.
Administration of a single dose of mannitol (100 mL of a 25% solution IV during 15 min) remains controversial. Mannitol acts as an osmotic diuretic, renal vasodilator, and intravascular volume expander and may convert oliguric renal failure to nonoliguric.
Alkalinization of the urine w/addition of 44 mEq/L of NaHCO3 is advocated by some experts. The goal is to maintain urine pH >6.5. NaHCO3 may ↑ solubility of uric acid and myoglobulin; however, it may promote Ca deposition.
Hyperkalemia caused by rhabdo is most severe 10 to 40 hr after injury; initial treatment w/sodium polystyrene sulfonate may be indicated; hyperkalemia caused by rhabdo responds poorly to treatment w/glucose and insulin; attempts to correct hyperkalemia and initial hypocalcemia w/Ca infusion may result in metastatic calcifications and severe hypercalcemia in the recovery period; hemodialysis may be necessary in pts w/severe hyperkalemia, volume overload, uremic pericarditis, or uremic encephalopathy.Clinical Pearls
The average length of time on statin Rx before rhabdo is 1 yr. The average time to onset of rhabdo after addition of fibrate to statin Rx is 32 days.
Statin-induced rhabdo is 12× more frequent when statins are combined w/fibrates compared w/statin monoRx.B. Shock
C. Hypothermia
Definition
Rectal temperature <35° C (95.8° F). Accidental hypothermia is unintentionally induced in ↓ core temperature in absence of preoptic anterior hypothalamic conditions.
Diagnosis
H&P
The clinical presentation varies w/the severity of hypothermia; shivering may be absent if body temperature is <33.3° C (92° F) or in pts taking phenothiazines.
Hypothermia may masquerade as CVA, ataxia, or slurred speech, or the pt may appear comatose or clinically dead.
Physiologic stages of hypothermia:• Mild hypothermia (32.2° C-35° C [90° F-95° F]): arrhythmias, ataxia
• Moderate hypothermia (28° C-32.2° C [82.4° F-90° F]): progressive ↓ of level of consciousness, pulse, CO, and respiration; fibrillation, dysrhythmias (susceptibility to VT); elimination of shivering mechanism for thermogenesis
TABLE 13-1
Types of Shock, Physiologic Response, and Basic Treatment
| Type of Shock | HR | Preload | Contractility | SVR | Treatment |
| Hypovolemic | ↑ | ↓↓ | ± | ↑ |
 High-flow oxygen Fluid resuscitation: evaluate perfusion after 60 mL/kg total volume bolused, then consider pressors |
| Septic (early, warm) | ↑ | ↓↓ | ± | ↓ |
 High-flow oxygen Fluid resuscitation Antibiotics Pressors (dopamine, norepinephrine, phenylephrine) |
| Septic (late, cold) | ↑ | ↓↓ | ↓ | ↑ |
 High-flow oxygen Fluid resuscitation Antibiotics Pressors (dopamine, norepinephrine, phenylephrine) |
| Anaphylactic | ↑ | ↓↓ | ↓ | ↓ |
 High-flow oxygen Epinephrine (IM) Fluid resuscitation |
| Neurogenic | ↑ | ↓↓ | ± | ↓↓ |
 Fluid resuscitation Pressors (norepinephrine) |
| Cardiogenic | ↑ | ↑ | ↓↓ | ↑ |
 High-flow oxygen Fluid resuscitation (5-10 mL/kg) CHF management (CPAP/BiPAP, diuretics, ACE inhibitors) Inotropes (milrinone, dobutamine) |
| Obstructive | Cause dependent | Cause dependent | Cause dependent | Cause dependent |
 Therapy directed at primary etiology of shock |
From Tschudy MM, Arcara KM: The Harriet Lane Handbook, 19th ed. Philadelphia, Mosby, 2012.
• Severe hypothermia (<28° C [82.4° F]): absence of reflexes or response to pain, ↓ cerebral blood flow, ↓ CO2, risk of VF or asystole
Labs
Metabolic acidosis and respiratory acidosis are usually present. ↓ K+ initially, then ↑ K+ w/↓ temp; extreme hyperkalemia indicates a poor prognosis; ↓ Hct (caused by hemoconcentration), ↓ leukocytes, ↓ Plt (caused by splenic sequestration), ↑ clotting timeImaging
CXR: generally not helpful; may reveal evidence of aspiration (e.g., intoxicated pt w/aspiration pneumonia)
ECG (Fig. 13-3): ↑ PR, QT, and QRS segments; ↑ ST segments, inverted T waves, AV block; hypothermic J waves (Osborn waves), characterized by notching of the junction of the QRS complex and ST segments, may appear at 25° C to 30° C.Treatment
Secure an airway before warming all unconscious pts; precede ETT w/oxygenation (if possible) to ↓ the risk of arrhythmias during the procedure.
Peripheral vasoconstriction may impede placement of a peripheral IV catheter; consider femoral venous access as an alternative to the jugular or subclavian sites to avoid ventricular stimulation.
A Foley catheter should be inserted, and urinary output should be monitored and maintained >0.5 to 1 mL/kg/hr w/intravascular volume replacement.
Continuous ECG monitoring of pts is recommended; consider ventricular arrhythmia Rx w/bretylium; lidocaine is generally ineffective, and procainamide is associated w/incidence of VF in hypothermic pts.
FIGURE 13-2 General hemodynamic management. DO2, (system) oxygen delivery; PAOP, pulmonary artery occlusion pressure; pHi, intestinal mucosal pH; PPV, pulse pressure variation; SVV, stroke volume variation; VO2, (systemic) oxygen consumption. (From Goldman L, Schafer AI [eds]: Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.)
FIGURE 13-3 Hypothermic J waves. (From Ferri F, Practical Guide to the Care of the Medical Patient, 8th ed, St. Louis, Mosby 2011)
TABLE 13-2
Vasopressor Agents
| Agent | Dose Range | Peripheral Vasculature | Cardiac Effects | Typical Use | |||
| Vasoconstriction | Vasodilation | HR | Contractility | Dysrhythmias | |||
| Dopamine | 1-4 μg/kg/min | 0 | 1+ | 1+ | 1+ | 1+ | “Renal dose” does not improve renal function; may be used with bradycardia and hypotension |
| 5-10 μg/kg/min | 1-2+ | 1+ | 2+ | 2+ | 2+ | ||
| 11-20 μg/kg/min | 2-3+ | 1+ | 2+ | 2+ | 3+ | Vasopressor range | |
| Vasopressin | 0.04-0.1 U/min | 3-4+ | 0 | 0 | 0 | 1+ | Septic shock, post–cardiopulmonary bypass shock state; no outcome benefit in sepsis |
| Phenylephrine | 20-200 μg/min | 4+ | 0 | 0 | 0 | 1+ | Vasodilatory shock; best for supraventricular tachycardia |
| Norepinephrine | 1-20 μg/min | 4+ | 0 | 2+ | 2+ | 2+ | First-line vasopressor for septic shock, vasodilatory shock |
| Epinephrine | 1-20 μg/min | 4+ | 0 | 4+ | 4+ | 4+ | Refractory shock, shock with bradycardia, anaphylactic shock |
| Dobutamine | 1-20 μg/kg/min | 1+ | 2+ | 1-2+ | 3+ | 3+ | Cardiogenic shock, septic shock |
| Milrinone | 37.5-75 μg/kg bolus followed by 0.375-0.75 μg/min | 0 | 2+ | 1+ | 3+ | 2+ | Cardiogenic shock, right heart failure; dilates pulmonary artery; caution in renal failure |
From Goldman L, Schafer AI (eds): Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.
Correct severe acidosis and electrolyte abnlities.
Hypothyroidism, if present, should be promptly treated (refer to the section on myxedema coma in Chapter 5).
If clinical evidence suggests adrenal insufficiency, administer IV methylprednisolone.
In pts unresponsive to verbal or noxious stimuli or w/ΔMS, 100 mg of thiamine, 0.4 mg of naloxone, and 1 ampule of 50% dextrose may be given.
Warm (104° F-113° F [40° C-45° C]), humidified O2 should also be given if it is available.
Specific treatment:• Mild hypothermia (rectal temperature <32.3° C [90° F]): Passive external rewarming is indicated. Place the pt in a warm room (temperature >21° C [69.8° F]) and cover w/insulating material after gently removing wet clothing; recommended rewarming rates vary between 0.5° C and 20° C/hr but should not exceed 0.55° C/hr in elderly pts.
• Moderate to severe hypothermia: delivery of heat through fluids: Methods include warm GI irrigation (w/saline enemas and by NG tube), IV fluids (usually D5NS w/o K+) warmed to 104° F to 107.6° F (40° C-42° C), peritoneal dialysis w/dialysate heated to 40.5° C to 42.5° C, and inhalation of heated humidified O2. Consider immersion in a bath of warm water (40° C-41° C); active external rewarming may produce shock because of excessive peripheral vasodilation. Ideal candidates are previously healthy, young pts w/acute immersion hypothermia. Extracorporeal blood warming w/cardiopulmonary bypass appears to be an efficacious rewarming technique in young, otherwise healthy pts.
D. Heat Stroke
Definition
Life-threatening heat illness characterized by extreme hyperthermia, dehydration, and neurologic manifestations (core temperature >40° C [104° F])
Diagnosis
H&P
Neurologic manifestations (seizures, tremor, hemiplegia, coma, psychosis, and other bizarre behavior)• Evidence of dehydration (poor skin turgor, sunken eyeballs)
• Tachycardia, hyperventilation
• Hot, red, and flushed skin
• Sweating often (not always) absent, particularly in elderly pts
Labs
↑ BUN, Cr, Hct
Hyponatremia or hypernatremia, hyperkalemia or hypokalemia
↑ LDH, AST, ALT, CPK, bili
Lactic acidosis, respiratory alkalosis (secondary to hyperventilation)
Myoglobinuria, hypofibrinogenemia, fibrinolysis, hypocalcemiaTreatment
Remove the pt’s clothes, and place the pt in a cool and well-ventilated room.
If the pt is unconscious, position the pt on his/her side and clear the airway. Protect the airway and augment oxygenation (e.g., nasal O2 at 4 L/min to keep SaO2 >90%).
Monitor body temperature q5min. Measurement of the pt’s core temperature w/rectal probe is recommended. Goal is to ↓ the body temperature to 39° C (102.2° F) in 30 to 60 min.
Spray the pt w/cool mist, and use fans to enhance airflow over the body (rapid evaporation method).
Immersion of the pt in ice water, stomach lavage w/iced saline solution, IV administration of cooled fluids, and inhalation of cold air are advisable only when the means for rapid evaporation are not available. Immersion in tepid water (15° C [59° F]) is preferred to ice water immersion to minimize risk of shivering.
Use of ice packs on axillae, neck, and groin is controversial because the resulting peripheral vasoconstriction may induce shivering.
Antipyretics are ineffective because the hypothalamic set point during heat stroke is nl despite the body temperature.
Intubate a comatose pt, insert a Foley catheter, and start nasal O2.
Continuous ECG monitoring is recommended.
Insert at least two large-bore IV lines, and begin IV hydration w/NS or lactated Ringer’s solution.
Treat complications as follows:• Hypotension: Administer vigorous hydration w/NS or lactated Ringer’s solution.
• Convulsions: Give diazepam 5 to 10 mg IV (slowly).
• Shivering: Give chlorpromazine 10 to 50 mg IV.
• Acidosis: Use bicarbonate judiciously (only in severe acidosis).
• Observe for evidence of rhabdo, hepatic, renal, or cardiac failure and treat accordingly.
E. Malignant Hyperthermia
Definition
Muscle rigidity and elevated temperature in the setting of recently administered anesthetic agents, most commonly halogenated inhalation agents (halothane) or depolarizing muscle relaxants (succinylcholine)
Etiology
In genetically susceptible individuals, administration of anesthetic agents results in release of Ca2+ from the sarcoplasmic reticulum of skeletal muscles that causes muscle rigidity and hypermetabolism. This leads to significant heat production that overwhelms the body’s normal ability to dissipate heat.
Diagnosis
H&P
Within minutes to hours after anesthetic is given, the pt develops muscle rigidity (especially masseter spasm), hyperthermia (≤45° C), tachycardia that may progress to other dysrhythmias, and hypotension. Skin initially reddens but then becomes cyanotic and mottled. There is also increased CO2 production.
Rhabdomyolysis, acute renal failure, and DIC may soon follow.Labs
CBC, TSH, electrolytes (especially K+, Ca2+, and phosphorus), PT, PTT , BUN, creat, ALT, AST, and CKTreatment
The most important measures for treatment include stopping the anesthetic agents, starting dantrolene, ensuring physical cooling, and preventing sequelae. Antipyretics are not useful because the hypothalamic set point is not altered by cytokines.
Cool the pt w/an ice bath, ice packs in the groin and axillae, cool spray with fans, or cooling blankets. In severe instances extracorporeal partial bypass or iced peritoneal lavage may be used. Stop cooling when core temperature reaches 38° C to prevent overcooling.
Carefully monitor the pt’s cardiovascular and respiratory status with constant core temperature measurements.
Dantrolene is the mainstay of treatment, starting with a bolus of 5 mg/kg IV, which should be repeated every 5 min until symptoms abate or a maximum of 10 to 20 mg/kg is reached. Then 24 hr of 10 mg/kg/day IV should be given.
β-Blockers or lidocaine may be useful for dysrhythmias, but verapamil should be avoided because its use with dantrolene has been shown to depress cardiac function.
NaHCO3 may be necessary to reverse acidosis.
F. Neuroleptic Malignant Syndrome (NMS)
Disorder characterized by hyperthermia, muscle rigidity, autonomic dysfunction, and depressed/fluctuating levels of arousal that evolve during 24 to 72 hr
Etiology
Neuroleptic drugs have different potencies for inducing NMS:• Typical neuroleptics: high potency, haloperidol; medium potency, chlorpromazine, fluphenazine; low potency, levomepromazine, loxapine
• Atypical neuroleptics: low potency, risperidone, olanzapine, clozapine, quetiapine
Diagnosis
H&P
Muscle rigidity (hypertonia, cogwheeling, or “lead pipe” rigidity)
Hyperthermia (38.6° C-42.3° C, usually <40° C)
Autonomic sx: diaphoresis, sialorrhea, skin pallor, urinary incontinence
Tachycardia, tachypnea
Labile BP (HTN or postural hypotension)
ΔMS (agitation, catatonia, fluctuating consciousness, obtundation)Labs
↑ CPK (>71% of pts, w/mean value of 3700 U/L)
Urinary myoglobin
Leukocytosis, usually 10,000 to 40,000/mm3
Electrolytes and renal function
ABGs
Drug levelsTreatment
Stop all neuroleptic agents, and reinstitute any recently discontinued dopaminergic agents.
Initiate active cooling (cooling blanket and antipyretics).
IV benzos (e.g., diazepam 2-10 mg, w/total daily dose of 10-60 mg) are given to relax muscles and to control agitation.
Bromocriptine 2.5 to 10 mg IV q8h and by 5 mg/day is given until clinical improvement is seen. The drug should be continued for ≥10 days after the syndrome has been controlled and then tapered slowly.
Dantrolene 0.25 mg/kg IV q6-12h is followed by a maintenance dose up to 3 mg/kg/day. After 2 to 3 days, pts may be given the drug PO (25-600 mg/day in divided doses). Oral dantrolene Rx (50-600 mg/day) may be continued for several days afterward.
Electroconvulsive Rx w/neuromuscular blockage is indicated in pharmacologically refractory cases. Succinylcholine should not be used because it may cause hyperkalemia and cardiac arrhythmias in pts w/rhabdo or dysautonomia.G. Anaphylaxis
Sudden-onset, life-threatening event characterized by respiratory, cardiovascular, GI, and cutaneous manifestations, as well as vasodilatory hemodynamic changes in response to a particular allergen
Etiology
Caused by sudden systematic release of histamine and other inflammatory mediators from basophils and mast cells → swelling of the mucous membranes and urticarial rash on the skin. Virtually any substance may induce anaphylaxis.
Foods and food additives: peanuts, tree nuts, eggs, shellfish, fish, cow’s milk, fruits, soy
Medications: antibiotics, especially penicillins, insulin, allergen extracts, opiates, vaccines, NSAIDs, contrast media, streptokinase
Bee or wasp sting, snake venom, fire ant venom
Blood products, plasma, immunoglobulin, cryoprecipitate, whole blood
LatexDiagnosis
H&P
Urticaria, pruritus, skin flushing, angioedema
Nausea, vomiting, diarrhea, difficulty swallowing
Hypotension, tachycardia, weakness, dizziness, malaise, vascular collapseDifferential Diagnosis
Endocrine disorders (carcinoid, pheochromocytoma)
Globus hystericus, anxiety disorder
Systemic mastocytosis
PE, serum sickness, vasovagal reactions
Severe asthma (the key clinical difference is the abrupt onset of symptoms in anaphylaxis versus a history of progressive worsening of symptoms)
Septic shock or other form of vasodilatory shock
Airway foreign bodyLabs
Generally tests are not helpful because anaphylaxis is typically diagnosed clinically.
ABG analysis may be useful to exclude PE, status asthmaticus, and foreign body aspiration.
↑ Serum and urine histamine levels and serum tryptase levels can be useful for dx of anaphylaxis, but these tests are not commonly available in the emergency setting.Imaging
Imaging is generally not helpful.
CXRs for evaluation of foreign body aspiration or pulmonary disease are indicated in pts with acute respiratory compromise.
Consider ECG in all pts with sudden loss of consciousness, chest pain, dyspnea and in any elderly pt. ECG in anaphylaxis usually reveals sinus tachycardia.Treatment
Establish and protect the airway. Provide supplemental O2 if indicated.
IV access should be rapidly established, and IV fluids (i.e., NS) should be administered. The pt should be placed supine or in Trendelenburg’s position if hemodynamically unstable.
Cardiac monitoring is recommended.
Epinephrine: IM injection at a dose of 0.3 mg of aqueous epinephrine for adults and children >30 kg. Epinephrine 0.15 mg should be given for children <30 kg (1:1000 concentration). IM is preferred because it provides more reliable and quicker rise to effective plasma levels. The dose may be repeated after ≈5 to 15 min if symptoms persist.
Adjunct therapies: These include H1 and H2 receptor antagonists, diphenhydramine 25 to 50 mg IV or IM, or PO in mild cases, and famotidine 20 to 40 mg IV, or PO in mild cases.
Corticosteroids are not useful in the acute episode because of their slow onset of action; however, they should be administered in most cases to prevent prolonged or recurrent anaphylaxis. Commonly used agents are prednisone, methylprednisolone 40 to 250 mg IV in adults (1-2 mg/kg in children), or longer-acting dexamethasone.
Aerosolized β-agonists (e.g., albuterol, 2.5 mg, repeat PRN 20 min) are useful to control bronchospasm.
Vasopressor therapy with epinephrine (1:10,000), or dopamine is indicated in pts with refractory hypotension after crystalloid resuscitation.H. Alcohol Withdrawal
Syndrome that occurs when a person stops ingesting alcohol after prolonged consumption. Sx vary according to the severity of the pt’s alcohol abuse and the time interval from the pt’s previous alcohol ingestion.
Diagnosis
Tremulous state (early alcohol withdrawal, “impending delirium tremens,” “shakes,” “jitters”)• Time interval: usually occurs 6 to 8 hr after the last drink or 12 to 48 hr after reduction of alcohol intake; becomes most pronounced at 24 to 36 hr
• Manifestation: tremors, mild agitation, insomnia, tachycardia; sx relieved by alcohol
Alcoholic hallucinosis: Hallucinations are usually auditory but occasionally are visual, tactile, or olfactory; usually there is no clouding of sensorium as in delirium (clinical presentation may be mistaken for an acute schizophrenic episode). Disordered perceptions become most pronounced after 24 to 36 hr of abstinence.
Withdrawal seizures (“rum fits”)• Time interval: usually occur 7 to 30 hr after cessation of drinking, w/a peak incidence between 13 and 24 hr.
• Manifestations: generalized convulsions w/loss of consciousness. Focal signs are usually absent; consider further investigation w/CT scan of head and EEG if clearly indicated (e.g., presence of focal neurologic deficits, prolonged postictal confusion state). In addition, in a febrile pt who is having a seizure or ΔMS, an LP may be necessary.
Delirium tremens (DTs)• Time interval: variable. It usually occurs within 1 wk after reduction or cessation of heavy alcohol intake and persists for 1 to 3 days. Peak incidence is 72 and 96 hr after the cessation of alcohol consumption.
• Manifestations: profound confusion, tremors, vivid visual and tactile hallucinations, autonomic hyperactivity. This is the most serious clinical presentation of alcohol withdrawal (mortality is ≈15% in untreated pts).
Treatment
Inpatient
Admit to medical ward (private room); monitor VS q4h; institute seizure precautions; maintain adequate sedation.
Labs: serum electrolytes, BUN, Cr, Mg2+, PO4-3, Ca2+ levels, glucose, CPK
Administer oxazepam or lorazepam as follows:• In pts w/DTs, initially lorazepam 2 to 5 mg IM/IV repeated PRN. In stable pts, PO administration may be sufficient: day 1, 2 mg PO q4h while awake and not lethargic; day 2, 1 mg PO q4h while awake and not lethargic; day 3, 0.5 mg PO q4h while awake and not lethargic. Hospital protocols may include oxazepam or chlordiazepoxide (cation if ↑ LFTs) for sedation.
• In pts w/mild to moderate withdrawal and w/o h/o seizures, individualized benzo administration (rather than a fixed-dose regimen) results in lower benzo administration and avoids unnecessary sedation. The Clinical Institute Withdrawal Assessment—Alcohol (CIWA-A) scale can be used to measure the severity of alcohol withdrawal. It consists of the 10 following items: nausea; tremor; autonomic hyperactivity; anxiety; agitation; tactile, visual, and auditory disturbances; headache; and disorientation. The maximum score is 67. When the CIWA-A score is >8, pts are usually given 2 to 4 mg of lorazepam hourly.
• Vitamin replacement: thiamine 100 mg IV or IM for at least 5 days, plus PO multivitamins. The IV administration of glucose can precipitate Wernicke’s encephalopathy in alcoholic pts w/thiamine deficiency; therefore, thiamine administration should precede IV dextrose.
• Hydration PO or IV (high-calorie solution); if IV: glucose w/Na+, K+, Mg2+, and PO4-3 replacement PRN. Hypomagnesemia is very common in alcoholism and can lead to arrhythmias if left untreated.
• Withdrawal seizures can be treated w/diazepam 2.5 mg/min IV until seizures are controlled (check for respiratory depression or hypotension); IV lorazepam 1 to 2 mg q2h can be used in place of diazepam. Generally, withdrawal seizures are self-limited and Rx is not required. The use of phenytoin or other anticonvulsants for short-term Rx of alcohol withdrawal seizures is not recommended.
• β-Blockers: useful for controlling BP and tachyarrhythmias. However, they do not prevent progression to more serious sx of withdrawal and, if used, should not be administered alone but in conjunction w/benzos. β-Blockers should be avoided in pts w/contraindications to their use (e.g., bronchospasm, bradycardia).
Clinical Pearl
Blood ethanol level ↓ by 20 mg/dL/hr in a nl 70-kg person.
I. Acute Poisoning
1. Acetaminophen Poisoning
The amount of acetaminophen necessary for hepatic toxicity varies with the pt’s body size and hepatic function. It is recommended that APAP intake should not exceed 4 g for adults and 90 mg/kg in children within a 24-hr period.
Diagnosis
H&P
Clinical presentation varies by dose ingested and time from ingestion.• Phase I (0-24 hr): initial symptoms possibly mild or absent and consisting of anorexia, diaphoresis, malaise, nausea, vomiting and a subclinical rise in transaminase levels
• Phase II (24-72 hr): right upper quadrant pain, vomiting, somnolence, tachycardia, hypotension, and continued increase in transaminases
• Phase III (72-96 hr): hepatic necrosis with abdominal pain, jaundice, hepatic encephalopathy, coagulopathy, hypoglycemia, renal failure fatality from multiorgan failure
• Phase IV (4 days-3 wk): complete resolution of symptoms and complete resolution of organ failure
Labs
Initial labs should include a STAT plasma acetaminophen level with a second level drawn approximately 4 hr after the initial ingestion. Subsequent levels can be obtained every 2 to 4 hr until the levels stabilize or decline. These levels should be plotted on the Rumack-Matthew nomogram (Fig. 13-4) to calculate potential hepatic toxicity. The nomogram cannot be used with pts who present >24 hr after ingestion, extended-release preparations, long-term ingestions, or when the time of ingestion is unknown.
Transaminases (AST, ALT), bilirubin level, INR, BUN, and creat should be initially obtained on all pts.
Serum and urine toxicology screen for other potential toxic substances is also recommended on admission. Screening for infectious hepatitis should also be considered. β-hCG should be obtained in all women of childbearing age.
FIGURE 13-4 Rumack-Matthew nomogram for acetaminophen poisoning. (From Rumack BH, Matthew H: Pediatrics 55:871, 1975. In Rosen P [ed]: Emergency Medicine, 4th ed. St. Louis, Mosby, 1998.)
Treatment
Consultation with a Poison Control Center is recommended for pts who have ingested a large amount of acetaminophen and/or other toxic substances. A single toxic dose of acetaminophen usually exceeds 7 g or 150 mg/kg in the adult.
Hepatotoxicity is defined as any ↑ ALT or AST >1000 IU/L, and hepatic failure is hepatotoxicity with hepatic encephalopathy. For those who cannot be risk stratified using the nomogram, the American College of Emergency Physicians recommends that N-acetylcysteine be administered without delay to those >12 yr and >8 hr after ingestion at presentation.
Administer activated charcoal 1 g/kg PO if the pt is seen within 1 hr of ingestion or the clinician suspects polydrug ingestion that delays gastric emptying.
Determine blood levels 4 hr after ingestion; if in the toxic range, start N-acetylcysteine (NAC) either IV (Acetadote) or PO (Mucomyst). Acetylcysteine IV loading dose is 150 mg/kg ×1 diluted in 200 mL D5W over 15 to 60 min. Maintenance dose is 50 mg/kg diluted in 500 mL D5W over 4 hr, followed by 100 mg/kg diluted in 1000 mL D5W over 16 hr. The dose does not require adjustment for renal or hepatic impairment or for dialysis. Total administration time is 21 hours.
Oral administration is 140 mg/kg PO as a loading dose, followed after 4 hr by 70 mg/kg PO q4h for a total of 17 doses. N-acetylcysteine Rx should be started within 24 hr of acetaminophen overdose. Total administration time is 72 hours.
Advantages of IV administration include more reliable absorption, fewer doses, and shorter duration of treatment.
Monitor acetaminophen level; use a graph to plot possible hepatic toxicity. Repeat AST/ALT and APAP levels after 12 to 14 hr of IV acetylcysteine infusion and continue infusion for >16 hr if transaminases are elevated, if acetaminophen concentration is measurable, or if coagulopathy exists (INR >1.5-2.0).
Provide adequate IV hydration (D5½NS at 150 mL/hr).
In pts on IV N-acetylcysteine who have liver failure, frequent monitoring of VS, O2sat by pulse ox, AST, Cr, hypoglycemia, and infection is essential.
If acetaminophen level is nontoxic, N-acetyl-cysteine Rx may be d/c.2. Amphetamine Overdose
Diagnosis
H&P
Tachycardia, HTN, mydriasis, agitation, seizures, diaphoresis, psychosis, hyperthermiaLabs
Lytes, BUN, Cr, CPKTreatment
Activated charcoal
Gastric lavage for acute large ingestion
Sedation w/benzos (diazepam)
Haloperidol for hallucinations and psychosis
Propranolol or lidocaine for arrhythmiasClinical Pearl
Induction of emesis is contraindicated.
3. Barbiturate Overdose
Diagnosis
H&P
Lethargy, respiratory depression, coma
↓ DTRs, extensor plantar responseLabs
BMP, LFTs, Ca, Mg, PO4
Serum and urine toxicology screen; ethanol, ASA, and acetaminophen levelImaging
CXR, ECGTreatment
IV bolus NaHCO3, 2 mEq/kg IV push, then maintenance infusion begun (132 mEq NaHCO3 in 1 L D5W at 250 mL/hr)
Administration of activated charcoal (0.5-1 g/kg; max: ≤50 g PO) in water or sorbitol by NG tube
Gastric lavage w/early presentation
Clinical Pearl
Avoid inducing emesis.
4. Cocaine Overdose
Diagnosis
H&P
Phase I• CNS: euphoria, agitation, headache, vertigo, twitching, bruxism, nonintentional tremor
• N/V, fever, HTN, tachycardia
Phase II• CNS: lethargy, hyperreactive DTRs, seizures (status epilepticus)
• Sympathetic overdrive: tachycardia, HTN, hyperthermia
• Incontinence
Phase III• CNS: flaccid paralysis, coma, fixed dilated pupils, loss of reflexes
• Pulmonary edema
• Cardiopulmonary arrest
Psychological dependence manifested w/habituation, paranoia, hallucinations (cocaine “bugs”)
CNS: cerebral ischemia and infarction, cerebral arterial spasm, cerebral vasculitis, cerebral vascular thrombosis, subarachnoid hemorrhage, intraparenchymal hemorrhage, seizures, cerebral atrophy, movement disorders
Cardiac: acute myocardial ischemia and infarction, arrhythmias and sudden death, dilated cardiomyopathy and myocarditis, infective endocarditis, aortic rupture
Pulmonary (secondary to smoking crack cocaine)• Inhalation injuries: cartilage and nasal septal perforation, oropharyngeal ulcers
• Immunologically mediated diseases: hypersensitivity pneumonitis, bronchiolitis obliterans; pulmonary vascular lesions and hemorrhage, pulmonary infarction, pulmonary edema secondary to LV failure, pneumomediastinum, and pneumothorax
GI: gastroduodenal ulceration and perforation; intestinal infarction or perforation, colitis
Renal: AKI secondary to rhabdo and myoglobinuria; renal infarction; focal segmental glomerulosclerosis
Obstetric: placental abruption, low infant weight, prematurity, microcephaly
Psychiatric: anxiety, depression, paranoia, delirium, psychosis, suicideLabs
Toxicology screen (urine): Cocaine is metabolized within 2 hr by the liver to major metabolites, benzoylecgonine and ecgonine methyl ester, that are excreted in the urine. Metabolites can be identified in urine within 5 min of IV use and ≤48 hr after PO ingestion.
Blood: CBC, lytes, glucose, BUN, Cr, Ca
ABGs
Serum CK and troponinsTreatment
Inhalation: Wash nasal passages.
Agitation:• Check STAT glucose.
• Diazepam 15 to 20 mg PO or 2 to 10 mg IM or IV for severe agitation
Hyperthermia:• Check rectal temperature, CK, electrolytes.
• Monitor w/continuous rectal probe; bring temperature down to 101° F within 30 to 45 min.
Rhabdo:• Vigorous hydration w/urine output ≥2 mL/kg
• Mannitol or bicarbonate for rhabdo resistant to hydration
Seizure management (status epilepticus):• Diazepam 5 to 10 mg IV over 2 to 3 min; may be repeated every 10 to 15 min PRN
• Lorazepam 2 to 3 mg IV over 2 to 3 min can be used instead of diazepam.
• Phenytoin loading dose 15 to 18 mg/kg IV at a rate not to exceed 25 to 50 mg/min under cardiac monitoring
• Phenobarbital loading dose 10 to 15 mg/kg IV at a rate of 25 mg/min. An additional 5 mg/kg may be given in 30 to 45 min if seizures are not controlled.
• Refractory seizures, consider:
• Pancuronium 0.1 mg/kg IV
• Halothane general anesthesia
• Both require EEG monitoring to determine brain seizure activity.
HTN:• Cocaine-induced HTN usually responds to benzos. If this fails:
• Consider A-line for continuous BP monitoring.
• Avoid the use of CCBs (may potentiate the incidence of seizures and death, especially in body packers).
• The use of β-blockers may exacerbate cocaine-induced vasoconstriction.
• Phentolamine (unopposed adrenergic effects) or NTG may be required.
• If diastolic pressure >120 mm Hg: hydralazine hydrochloride 25 mg IM or IV; may repeat q1h
• If HTN uncontrolled or hypertensive encephalopathy is present: sodium nitroprusside initially at 0.5 μg/kg/min not to exceed 10 μg/kg/min
Chest pain:• CXR, ECG, cardiac enzymes
• Benzos for agitation
• ASA and NTG for ischemic pain
• Percutaneous transluminal coronary angioplasty may be preferred over thrombolysis for cocaine-associated MI.
• The use of β-adrenergic blockers remains controversial because of the unopposed α-adrenergic effects of cocaine. Thus consider using β-blockers w/alpha blocking properties (eg. Labetalol).
• The combination of nitroprusside and a β-adrenergic blocking agent or phentolamine alone or in addition to a β-adrenergic blocking agent may successfully treat myocardial ischemia and HTN.
Ventricular arrhythmias:• Antiarrhythmia agents should be used w/caution during the early period after cocaine exposure as a result of their proarrhythmic and proconvulsant effects.
• Propranolol 1 mg/min IV for up to 6 mg is given (may result in unopposed α-adrenergic effects).
• Lidocaine 1.5 mg/kg IV bolus is followed by IV infusion (controversial: may be proarrhythmic and proconvulsant).
• Termination of ventricular arrhythmias may be resistant to lidocaine and even cardioversion.
5. Ethanol Poisoning
Diagnosis
H&P
Alcohol inhibits the conversion of lactate to glucose in the liver. Alcoholic ketoacidosis usually follows binge drinking.
Abd pain, vomiting, starvation, volume depletionLabs
AG metabolic acidosis
↑ Osmolal gap (difference between the measured and calculated serum osmolality)
N/↓ blood glucose
↑ BUN, Cr, hypophosphatemia, hypokalemia, hypomagnesemiaTreatment
Volume repletion, thiamine and glucose administration
Correction of hypophosphatemia, hypokalemia, and hypomagnesemia if presentClinical Pearl
Metabolic acidosis is also associated w/ingestion of ethylene glycol and methanol in addition to ethanol. Direct measurement of these substances should be performed whenever possible.
6. Ethylene Glycol, Isopropyl Alcohol, and Methanol Poisoning
Diagnosis
H&P
Ethylene glycol is a component of antifreeze and industrial solvents. It has a sweet taste and may be ingested accidentally or in suicide attempts. Methanol is a component of wood alcohol (moonshine liquor), copy machines, embalming fluid, paint removers, and windshield wiper fluid. Isopropyl alcohol is found in rubbing alcohol.
CNS sx (lethargy, seizures, coma), renal failure, pulmonary, cardiac failure
Dehydration
Optic papillitis leading to blindness from metabolism of methanol to formaldehyde and formic acidLabs
AG acidosis in ethylene glycol and methanol poisoning. Isopropyl alcohol does not cause ↑ AG or ketoacidosis because the metabolite is acetone, but test results are (+) for ketones.
↑ Osmolal gap (difference between the measured and calculated serum osmolality)
Ca oxalate crystals in the urine in ethylene glycol poisoning
Toxicology screen and quantificationTreatment∗
Competitive inhibition of alcohol dehydrogenase w/fomepizole (preferred) or ethanol (when fomepizole is not available) and hemodialysis (in all cases when ethanol is used as Rx and in fomepizole Rx and profound acidemia and signs of optic or renal injury)
Criteria for initiation of Rx: ethylene glycol plasma concentration ≥20 mg/dL (3.2 mmol/L) or methanol plasma concentration >20 mg/dL (6.2 mmol/L); suspected ethylene glycol or methanol ingestion and two or more of the following criteria: arterial pH <7.3, Osmo gap >10 mOsm/L, serum CO2 level <20 mmol/L
Dosing of fomepizole:• Pts not undergoing hemodialysis: Loading dose is 15 mg/kg BW, followed by 10 mg/kg q12h; after 48 hr, 15 mg/kg q12h.
• Pts undergoing hemodialysis use the same dose except the drug is given 6 hr after the first dose and q4h thereafter.
• Continue fomepizole Rx until the plasma ethylene glycol or methanol concentration is <20 mg/dL.
IV rehydration is indicated in all pts, with NaHCO3 administration in pts w/pH <7.3.
In methanol poisoning, administer folinic acid (leucovorin) 1 mg/kg BW IV (≤50 mg) or stereospecific levoleucovorin at one-half dose of leucovorin. The administration of folate is beneficial because formic acid is catabolized to CO2 and water by tetrahydrofolate synthetase (enzyme dependent on stored folate).
Pyridoxine may be beneficial in ethylene glycol poisoning (pyridoxine is a cofactor in metabolism of glycolic acid to glycine).Clinical Pearls
The CNS dysfunction is primarily the result of the keto aldehyde metabolites.
Intratubular obstruction and ARF may be caused by oxalate crystals in ethylene glycol poisoning.7. Carbon Monoxide Poisoning
Etiology
Exposure to smoke from fires; motor vehicle exhaust; or the burning of wood, charcoal, or natural gas for cooking or heating in poorly ventilated areas. CO is a colorless, odorless, tasteless, nonirritating gas. When inhaled, it produces toxicity by causing cellular hypoxia.Diagnosis
H&P
Mild to moderately severe poisoning may manifest w/headache, fatigue, dizziness, nausea, dyspnea, confusion, or blurry vision.
Severe poisoning may manifest w/arrhythmias, myocardial ischemia, pulmonary edema, lethargy, ataxia, syncope, seizure, coma, or cherry-red skin.Labs
↑ Carboxyhemoglobin (COHgb) level. Note: COHgb level >5% in nonsmokers confirms exposure. Heavy smokers may have levels of 10%.
Direct measurement of SaO2. Note: Pulse oximetry and ABG may be falsely nl because neither measures SaO2 directly. Pulse oximetry is inaccurate because of the similar absorption characteristics of oxyhemoglobin and COHgb. ABG is inaccurate because it measures O2 dissolved in plasma (which is not affected by CO) and then calculates SaO2.
Lytes, glucose, BUN, Cr, CPK, ABG (because lactic acidosis and rhabdo may develop)
Pregnancy test in women of childbearing age (fetus at high risk)
Treatment
Removal from site of CO exposure
Ensuring of adequate airway
Continuous ECG monitoring
Fetal monitoring if pregnant
100% O2 by tight-fitting nonrebreather mask or ETT for 6 to 12 hr (↓ half-life of COHgb from 4-6 hr to 60-90 min)
Hyperbaric O2 (2.5-3 atm)
Half-life of COHgb to 20 to 30 min, amount of O2 dissolved in plasma
Questionable whether there is any beneficial effect over normobaric O2
May prevent the delayed neurologic sequelae of CO poisoning by ↓ cellular hypoxia and toxicity
Consider for individuals with:• Severe intoxication (COHgb >25%, h/o loss of consciousness, neurologic sx or signs, CV compromise, severe metabolic acidosis)
• Persistent sx after 2 to 4 hr of normobaric O2
• Pregnant women w/COHgb >15% or signs of fetal distress: CO elimination slower in fetus than in mother; fetal Hgb has greater affinity for CO than does adult Hgb
• Should be instituted quickly if deemed necessary
• Consider concomitant poisoning w/other toxic/irritant gases that may be present in smoke (e.g., cyanide) or thermal injury to airway. Toxic effects of CO and cyanide are synergistic.
• Identify source of exposure and determine whether the poisoning was accidental.
Clinical Pearls
Survivors of severe poisoning are at 14% to 40% risk for neurologic sequelae ranging from parkinsonism to neuropsychiatric sx (personality and memory disorders). Neurologic deficits are usually apparent within 3 wk of poisoning (but may manifest months later). Brain MRI may show changes in the white matter and basal ganglia.
Sx of toxicity and prognosis do not correlate well w/COHgb levels.∗ Data from Brent J: N Engl J Med 360:21, 2009.
