Case 1: Unconscious after fire
A 30-year-old woman is evaluated in the emergency department after she was rescued from her home where her vinyl sofa caught fire. She is intubated and unconscious.
On physical examination, blood pressure is 108/78 mm Hg, pulse rate is 100/min, and respiration rate is 24/min. Oxygen saturation by pulse oximetry is 100% on mechanical ventilation using 50% oxygen. She is unresponsive. She has no visible burns on her skin, and her airway secretions are clear. Brainstem reflexes are all intact.
Serum electrolytes show sodium 140 mEq/L (140 mmol/L), potassium 4.4 mEq/L (4.4 mmol/L), chloride 99 mEq/L (99 mmol/L), and bicarbonate 13.1 mEq/L (13.1 mmol/L). Arterial blood gas studies show pH 7.29, PCO2 28 mm Hg (3.7 kPa), PO2 233 mm Hg (31 kPa). Carboxyhemoglobin is 5%, methemoglobin 2%, and lactate 11 mEq/L (11 mmol/L). The oxygen is increased to 100%.
Which of the following is the most appropriate treatment?
B. Hyperbaric oxygen therapy
C. Methylene blue
D. Sodium nitrite
Case 2: Collapse on a hot day
A 61-year-old man is evaluated in the emergency department after he collapsed on a hot and humid day. He was playing in a marching band and had to stand in the sun for 2 hours while wearing a heavy uniform. No other medical information is available.
On physical examination, temperature is 40 °C (104 °F), blood pressure is 90/45 mm Hg, pulse rate is 110/min, and respiration rate is 20/min. His face is flushed, he is somnolent, and although he is arousable, he is not coherent. There are no signs of trauma.
His clothing is removed.
Which of the following is the most appropriate treatment?
A. Acetaminophen and a cooling blanket
B. Continuous alcohol sponge bath with cooling fans
C. Ice water immersion
D. Intravenous dantrolene
E. Sprayed water and cooling fans
Case 3: Hypothermia
A 19-year-old man is evaluated in the emergency department for cardiac arrest after he fell through the ice of a frozen lake. He was in the water for less than 10 minutes, but when he was pulled out onto the ice he was unresponsive and no pulse could be felt. Bystander CPR was begun immediately and continued for 25 minutes until emergency medical services arrived. At the scene his rectal temperature was 27 °C (80.6 °F). He was intubated and bag ventilated and continued to receive CPR in the ambulance on the way to the emergency department.
On physical examination, temperature is 28 °C (82.4 °F). Oxygen saturation is 97% on mechanical ventilation with 65% oxygen. He is not responsive and shows no spontaneous movement or shivering. His heart rhythm on the monitor is ventricular fibrillation.
Which of the following is the most appropriate management?
A. Continue CPR with active external rewarming
B. Continue CPR with active internal (core) rewarming
C. Continue CPR with passive external rewarming
D. Discontinue CPR
Case 4: Anxiety, fever
A 19-year-old man is brought to the emergency department after he attended a party with friends. He is anxious and tremulous. He has a history of depression. His only medication is fluoxetine.
On physical examination, he is alert and oriented. Temperature is 38.9 °C (102 °F), blood pressure is 136/79 mm Hg, pulse rate is 112/min, and respiration rate is 20/min. Oxygen saturation is 98% breathing ambient air. Physical examination is notable for slow, continuous, horizontal eye movements, tremor of extremities, hyperreflexia, and sustained ankle clonus and spontaneous myoclonus. The physical examination is otherwise normal.
Urine toxicology screening is pending.
Which of the following is the most likely diagnosis?
A. Anticholinergic toxicity
B. Malignant hyperthermia
C. Neuroleptic malignant syndrome
D. Serotonin syndrome
Case 5: Hypertension and nausea
A 60-year-old man is evaluated in the emergency department for headache, nausea, vomiting, and confusion lasting 4 hours. He ran out of his hypertensive medications a few days ago. Current medications are lisinopril, metoprolol succinate, hydrochlorothiazide, and aspirin.
On physical examination, blood pressure is 230/140 mm Hg and pulse rate is 100/min. All other vital signs are normal. He is too uncooperative to perform a mental status examination or funduscopic examination. The cardiovascular examination is positive for an S4 but otherwise normal.
Laboratory studies reveal normal electrolytes; serum creatinine is 1.6 mg/dL (141.4 µmol/L). It was 1.2 mg/dL (106 µmol/L) at his last outpatient appointment.
Electrocardiogram shows left ventricular hypertrophy and sinus tachycardia. Chest radiograph is normal. CT scan of the brain shows no acute findings.
Which of the following is the most appropriate treatment?
A. Intravenous hypertensive therapy to lower systolic blood pressure (SBP) to 160 mm
Hg within the first 6 hours
B. Intravenous hypertensive therapy to lower SBP to 120 mm Hg within the first hour
C. Intravenous hypertensive therapy to lower SBP to 160 mm Hg within the first 48 hours
D. Resume usual oral antihypertensive regimen and observe
Case 6: Allergic reaction
An 18-year-old woman is evaluated in the emergency department for lip swelling after eating at a neighborhood picnic. She has a history of peanut and tree nut allergies that have caused lip swelling, but she has never been hospitalized for a reaction. She currently takes no medications.
On physical examination, blood pressure is 100/64 mm Hg, pulse rate is 108/min, and respiration rate is 19/min. Oxygen saturation is 100% breathing ambient air. Bilateral lip swelling is evident that affects the upper lip more than the lower lip. She has no tongue swelling or stridor. Lungs are clear to auscultation. Urticaria is present on the hands and trunk.
Which of the following is the most appropriate immediate treatment?
C. Intravenous fluid bolus
D. Intravenous methylprednisolone
Answers and commentary
Correct answer: A. Hydroxocobalamin.
This patient should be treated with intravenous hydroxocobalamin, which is the preferred antidote for cyanide poisoning. Cyanide toxicity is common in victims of house fires, with up to 90% of rescued victims having elevated cyanide levels and 35% having significantly elevated levels, which is higher than the rate of carbon monoxide poisoning among such victims. Cyanide disrupts oxidative phosphorylation, forcing cells to convert to anaerobic metabolism despite adequate oxygen supply. The result in severe cases is multiorgan failure with coma, seizures, and cardiovascular symptoms, including hypotension, bradycardia, heart block, and ventricular arrhythmias. Early manifestations are nonspecific. Diagnostic clues include lactic acidosis and inappropriately elevated central venous oxyhemoglobin saturation, which manifests as bright red venous blood. Cyanide levels are not readily available and because toxicity is rapidly fatal, prompt empiric treatment is imperative in suspected cases. Hydroxocobalamin avidly binds to cyanide to produce cyanocobalamin, which is soluble, nontoxic, and readily excreted. In addition, ongoing exposure, such as contaminated clothing, should also be eliminated. Hydroxocobalamin can affect accuracy of lab results for methemoglobin, lactate, and other tests, so it is important to obtain blood for these tests before administering the antidote, if possible.
Carbon monoxide is removed by competitive binding of oxygen to hemoglobin. The initial treatment is administration of 100% oxygen, which reduces the half-life of carboxyhemoglobin from 5 hours to 90 minutes. Hyperbaric oxygen therapy yields an even higher alveolar PO2, thereby reducing the half-life to 30 minutes while substantially increasing the amount of oxygen directly dissolved in blood. However, hyperbaric oxygen therapy would not be appropriate because this patient's carboxyhemoglobin level is not high enough to suggest severe carbon monoxide poisoning. Hyperbaric oxygen is usually recommended for levels of 25% to 40% or higher, or for victims with lower levels who are pregnant.
Methylene blue would be recommended for toxic levels of methemoglobin, usually 20% to 30% or higher, but it is not indicated for this patient.
Although sodium nitrite is an antidote for cyanide poisoning, it is contraindicated in victims of smoke inhalation because it works by inducing methemoglobinemia, which would further impair oxygen delivery by additive or synergistic effects on oxygen binding and delivery in cases of carbon monoxide toxicity.
Sodium thiosulfate is also used as an antidote for cyanide toxicity and is safer than sodium nitrite, but has a slower onset of action. It is considered second-line therapy after hydroxocobalamin, but the two agents can be given to the same patient, possibly with synergistic effect. However, they should not be administered simultaneously or through the same intravenous catheter.
- Hydroxocobalamin effectively removes cyanide from the mitochondrial respiration system and is the preferred antidote for cyanide poisoning.
Correct answer: E. Sprayed water and cooling fans.
This patient should be sprayed with water, and fans should be used to lower his body temperature to a safe level (usually 38.5 °C (101 °F) through evaporative cooling. Heat stroke occurs with high ambient temperature and humidity and is defined by the presence of a temperature greater than 40.0 °C (104.0 °F) and encephalopathy. It is often associated with hypotension, gastrointestinal distress, and weakness. Patients with advanced heat stroke exhibit shock, multiorgan failure, rhabdomyolysis, and myocardial ischemia. Exertional heat stroke typically occurs in healthy individuals undergoing vigorous physical activity in warm conditions. In contrast, most patients with nonexertional heat stroke are older than 70 years of age or have chronic medical conditions that impair thermal regulation. Medications and recreational drugs with anticholinergic, sympathomimetic, and diuretic effects, including alcohol, pose added risk. The primary treatment of nonexertional heat stroke is evaporative, external cooling. This involves removing all clothing and spraying the patient with a mist of lukewarm water while continuously blowing fans on the patient. Evaporative and convective cooling techniques are generally the safest and most effective.
Acetaminophen and other centrally acting antipyretics are ineffective in the treatment of heat stroke. A cooling blanket could be used as an adjunct, but it is not as effective as evaporative cooling.
Alcohol would evaporate and provide cooling as effective as that from applying water, but it would also be absorbed through the vasodilated skin and could lead to alcohol toxicity similar to that observed in patients who have ingested alcohol and is therefore contraindicated.
Although ice water immersion is sometimes used in younger patients with exertional heat stroke to lower the body temperature rapidly, there is evidence for increased mortality when this method is used in older patients. Also, this patient's core temperature of 40 °C (104 °F) is not so severe that more aggressive measures need to be considered.
The muscle relaxant dantrolene is ineffective in the treatment of heat stroke. It is used for malignant hyperthermia and sometimes for neuroleptic malignant syndrome, although this is an off-label application.
- Patients with nonexertional heat stroke should be treated with evaporative cooling to lower their core temperature to a safe level.
Correct answer: B. Continue CPR with active internal (core) rewarming.
CPR should be continued with active internal (core) rewarming. Conventional treatment of ventricular arrhythmias and asystole is often ineffective until the temperature is raised to greater than 30.0 °C (86.0 °F). Because severe hypothermia may appear clinically similar to death, aggressive rewarming is appropriate in all patients in the absence of obvious irreversible signs of death. A critical first step entails removing wet clothing and covering the patient with insulating material, especially the head and neck. For mildly hypothermic, healthy individuals capable of shivering, this strategy of passive external rewarming alone suffices. Active external rewarming using warm blankets or a forced heated air blanket is commonly used in hemodynamically stable patients with moderate hypothermia. Body cavity lavage with warm fluids is an option for patients with hypothermia that is severe or does not respond to external rewarming. The colon, bladder, and stomach are readily accessible for irrigation but have a small surface area for heat exchange. Rewarming by peritoneal or pleural space irrigation is supported by case reports. Extracorporeal support, including cardiopulmonary bypass, is recommended for patients in cardiac arrest because it maximizes the rewarming rate and can provide hemodynamic support.
Although this man has already received nearly an hour of CPR, there are reports of full recovery in patients with cardiac arrest in the setting of accidental hypothermia, sometimes even after CPR has been performed for many hours. Therefore, continued CPR is indicated until the patient can be rewarmed. Discontinuation of CPR is not appropriate because hypothermia prevents reaching a definite conclusion about the futility or possible effectiveness of continued resuscitation.
- CPR should be continued in patients with accidental hypothermia accompanied by cardiac arrest until the patient can be rewarmed.
Correct answer: D. Serotonin syndrome.
The most likely diagnosis is serotonin syndrome. The features of hyperthermia, tremor, hyperreflexia, ocular clonus (slow, continuous, horizontal eye movements), other clonus (spontaneous or induced), and anxiety are classic features of this syndrome. Hyperreflexia and clonus help distinguish serotonin syndrome from other hyperthermic syndromes and toxic ingestions. This patient's history supports the diagnosis, which usually occurs after coingestion of several serotonergic medications—for example, fluoxetine and methylenedioxymethamphetamine (“ecstasy”). Treatment is mainly supportive, using benzodiazepines as needed to keep the patient calm and to control blood pressure and heart rate. Physical restraint can lead to agitated exertion and worsen hyperthermia. Autonomic instability is common, so close monitoring is recommended. Only in very severe cases of agitation or hyperthermia do patients need to be deeply sedated, intubated, paralyzed, and sometimes treated with cyproheptadine.
Anticholinergic toxicity is unlikely in this patient because he has no signs of mydriasis, dry mucus membranes, or urinary and bowel retention. He does exhibit hyperthermia and agitation, but has clonus and hyperreflexia, which are not associated with anticholinergic toxicity.
Malignant hyperthermia would be very unlikely without a history of inhaled anesthesia agents or neuromuscular blockade. Clinical features of malignant hyperthermia usually include higher fever, muscle rigidity, and, occasionally, hemorrhage but not hyperreflexia or clonus.
Neuroleptic malignant syndrome would be very unlikely without a history of neuroleptic medications, such as haloperidol. It usually develops subacutely during days or weeks, whereas serotonin syndrome typically develops within hours. Rigidity with hyporeflexia is more common, rather than hyperreflexia and myoclonus in serotonin syndrome. Hyperthermia, altered mental status, and rigidity are features of both syndromes. Neuroleptic malignant syndrome usually takes many days to resolve, whereas serotonin syndrome usually resolves within 24 hours.
- Classic features of serotonin syndrome include hyperthermia, tremor, hyperreflexia and clonus; treatment is mainly supportive, using benzodiazepines as needed to keep the patient calm and to control blood pressure and heart rate.
Correct answer: A. Intravenous hypertensive therapy to lower systolic blood pressure (SBP) to 160 mm Hg within the first 6 hours.
The appropriate treatment is intravenous hypertensive therapy to lower the systolic blood pressure (SBP) to 160 mm Hg within the first 6 hours. Appropriate intravenous agents could include fenoldopam, nicardipine, or nitroprusside. Hypertensive emergency refers to elevation of SBP greater than 180 mm Hg, diastolic blood pressure (DBP) greater than 120 mm Hg, or both, that is associated with end-organ damage. Patients with hypertensive emergency require rapid, tightly controlled reductions in blood pressure that avoid overcorrection. Management typically occurs in an ICU with continuous arterial blood pressure monitoring and continuous infusion of antihypertensive agents. According to the 2017 American College of Cardiology/American Heart Association hypertension guidelines, for adults with a compelling condition (aortic dissection, severe preeclampsia or eclampsia, or pheochromocytoma crisis), SBP should be reduced to less than 140 mm Hg during the first hour and to less than 120 mm Hg in aortic dissection. For adults without a compelling condition, such as this patient, SBP should be reduced by no more than 25% within the first hour; then, if stable, to 160 mm Hg within the next 2 to 6 hours; and then cautiously to normal during the following 24 to 48 hours.
Because autoregulation of tissue perfusion is disturbed in hypertensive emergencies, reducing blood pressure too rapidly can result in ischemic organ damage. Therefore, targeting a blood pressure of 120/80 mm Hg during the first hour of treatment is inappropriate because it could result in further worsening of kidney injury, encephalopathy, or both.
Conversely, lowering the SBP to 160 mm Hg during 48 hours is likely too slow and not in keeping with current guidelines.
This patient's normal medication combined with observation is not aggressive enough. Eventually he will need a stable outpatient hypertension regimen with education on the importance of adherence to that regimen, but not in this acute setting.
- For adults with a hypertensive emergency and without a compelling condition (such as aortic dissection) systolic blood pressure should be reduced by no more than 25% within the first hour; then, if stable, to 160 mm Hg within the next 2 to 6 hours; and then cautiously to normal during the following 24 to 48 hours.
Correct answer: B. Epinephrine.
This patient should be treated with epinephrine. Anaphylaxis is defined as a severe, potentially life-threatening allergic or hypersensitivity reaction that occurs within seconds to a few hours of allergen exposure, most commonly food, medication, or an insect sting. Classically, anaphylaxis occurs when allergen-specific IgE coating the surface of mast cells and basophils comes in contact with the triggering allergen, thereby precipitating cellular degranulation. The resulting abrupt systemic release of a host of mediators has various effects, including vasoconstriction, vasodilation, increased vascular permeability, and bronchoconstriction. The presentation is variable and findings may include flushing, urticaria, and angioedema (85%); wheeze, stridor, and respiratory distress (70%); and hypotension and tachycardia (less commonly bradycardia) (45%). Initial symptoms and findings may be mild but predicting the ultimate severity of the episode is difficult. The first step in treatment is immediate intramuscular or intravenous administration of epinephrine. There are studies showing increased mortality from anaphylaxis if epinephrine is delayed. The dose may be repeated after 5-15 minutes, or administered continuously as an intravenous solution (although at a lower concentration), until the effects are apparent. Patients can also be given supplemental oxygen and monitored for signs of airway compromise, which may require intubation to maintain airway patency. Following recovery, patients should maintain home access to an epinephrine auto-injector and may benefit from evaluation for anaphylactic triggers.
Diphenhydramine, a histamine1-blocker, is often given because of its effect on itching and urticaria, but it has never been shown to effectively treat distributive shock, airway edema, or outcome in anaphylaxis. It is not a substitute for epinephrine.
Although intravenous fluids are often needed to manage anaphylaxis, they are reserved for use in cases where hypotension persists despite treatment with epinephrine.
Glucocorticoids are often given to reduce the risk of recurrent or persistent symptoms. However, there are no randomized controlled trials that confirm the effectiveness of glucocorticoids in preventing symptom recurrence. More clinically relevant, a study of emergency department patients with anaphylaxis treated with glucocorticoids did not demonstrate a reduction in return visits to the emergency department for recurrent symptoms.
- Epinephrine is the appropriate initial treatment of anaphylaxis.