A 55-year-old woman undergoes elective ventral hernia repair. Past medical history is significant for hypertension and asthma. She had uneventful induction of anesthesia. Five minutes after cefazolin was started for perioperative prophylaxis, the patient becomes hypotensive and progressively hypoxic with high peak airway pressures. Diphenhydramine, steroids, a H2-blocker, bronchodilators, and epinephrine are administered, with clinical improvement. A decision is made to postpone surgery, and she is transferred to the intensive care unit (ICU) for further management.
Which of the following laboratory levels can help determine whether the episode was related to anaphylaxis as compared to asthma exacerbation?
Correct Answer: B
Mast cells have preformed mediators, including tryptase, which can be used to measure systemic mast cell activation. Concentrations of α-tryptase correlate with mast cell number, whereas β-tryptase concentrations are associated with acute mast cell activation. Total serum tryptase can be used to confirm a diagnosis of anaphylaxis, although samples need to be collected within 4 hours of a suspected anaphylactic reaction. β-tryptase levels are thought to peak 30 to 60 minutes after a reaction, with a half-life of 2 hours. Normal total tryptase ranges from 1 to 10 ng/mL. If baseline tryptase is >20 ng/mL in a patient without acute symptoms of anaphylaxis, indolent systemic mastocytosis should be suspected and further evaluation sought. Histamine elevation is short-lived after an anaphylactic episode; however, metabolites, such as N-methyl histamine and prostaglandins, can be measured in the urine for 24 hours after an anaphylactic event and may be useful for diagnosis. Other potentially useful biomarkers are being studied, including platelet-activating factor, bradykinin, chymase, and others. Amylase, lipase, and pseudocholinesterase are not mast cell mediators, so not related to the diagnosis of anaphylaxis.
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A 33-year-old woman is admitted to ICU s/p motor vehicle accident with traumatic brain injury, and CT scan of the head showed subdural hematoma without midline shift and bilateral frontal contusions. On day 2 of admission, she starts having seizures. She is given 1000 mg phenytoin and started on a maintenance dose. She remains in the ICU due to waxing and waning mental status. On day 5 as you are examining the patient, red-purple macules and papules are noticed on chest and abdomen, as well as on the bilateral upper and lower extremities. Similar lesions are also seen in mouth and genital area.
Which of the following will help to differentiate Stevens-Johnson syndrome (SJS) from toxic epidermal necrolysis (TEN)?
Correct Answer: C
This patient’s presentation is consistent with SJS and TEN. SJS and TEN are severe acute inflammatory exfoliative skin reactions with unclear etiology usually triggered by medications or, less frequently, by upper respiratory infections. SJS and TEN are believed to be variants of same condition; Nikolsky sign is almost always present in both. Both TEN and SJS occur 1 to 3 weeks after exposure to inciting agent. The difference between the two is related to the percentage of BSA affected: SJS affects less than 10% and TEN affects greater than 30%, while a range of 10% to 30% is referred to as SJS/TEN overlap.
Pharmacologic triggers can be divided into drugs administered for shorter durations (eg, antibiotics such as trimethoprim/sulfamethoxazole, sulfonamides, cephalosporins, quinolones, and aminopenicillins) and medications administered chronically (eg, carbamazepine, oxicam nonsteroidal anti-inflammatory drugs, phenytoin, phenobarbital, allopurinol, and valproic acid).
Treatment consists of immediate discontinuation of the triggering agent and early transfer to a burn unit, which significantly reduces morbidity and mortality. Recent trials of immunosuppressive therapy, steroids, and immunoglobulins have not shown improvement in outcome. Application of silver nitrate may lead to cross-reactivity with antibiotics and is not recommended. Diagnosis is usually clinical and biopsy of affected areas is not required.
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A 48-year-old woman with a history of poorly controlled hypertension, coronary artery disease, and chronic renal failure is admitted to ICU after presenting to emergency room (ER) with hypertensive emergency. Her blood pressure was controlled with sodium nitroprusside. After 32 hours of treatment, the patient develops agitation, confusion, and metabolic acidosis.
Which of the following is used for the prevention/treatment of this adverse effect of nitroprusside?
The signs and symptoms of the patient are consistent with cyanide toxicity from nitroprusside. Nitroprusside causes toxicity through release of cyanide and accumulation of thiocyanate. Most common symptoms of cyanide toxicity are changes in mental status, including convulsions, encephalopathy, coma, and even unexplained cardiac arrest. Metabolic acidosis can be present, though this may be a late event. Cyanide reacts in high affinity with metals such as ferric iron (Fe 3+ ) and cobalt and also binds to numerous critical enzyme systems in the body. Cyanide inhibits oxidative phosphorylation and thereby causes central nervous system and cardiovascular dysfunction due to cellular hypoxia. It does this by primarily binding to and inactivating the enzyme cytochrome oxidase (cytochrome a3).
Risk of cyanide toxicity can be decreased by utilizing nitroprusside at recommended doses for short period of time. Thiosulfate is a specific antidote for cyanide toxicity associated with nitroprusside infusion. Sodium thiosulfate removes cyanide from the blood through the action of the enzyme rhodanese. It has also been recommended that thiosulfate infusions be used for patients receiving high doses of nitroprusside. Cyanocobalamin is not effective as an antidote and is not capable of preventing cyanide toxicity. Hydroxocobalamin, a precursor of vitamin B12, may also be used to treat cyanide toxicity. It contains a cobalt moiety that binds intracellular cyanide forming cyanocobalamin.
Nitroprusside can cause a dose-dependent conversion of hemoglobin to methemoglobin. Methylene blue is used for treating methemoglobinemia, and not cyanide toxicity.
A 28-year-old woman presents to the emergency department with sudden onset of generalized fatigue, fever, chills, and blurry vision. She was recently diagnosed with urinary tract infection and started on Bactrim 2 days ago. On physical examination, her skin is mildly jaundiced. She has multiple purpura over her extremities. Laboratory tests reveal: Hemoglobin 8.0 g/dL, platelet count 57/mm3 , and creatinine of 2.8 mg/dL. Of note, renal function was normal 4 days ago. On peripheral smear, multiple schistocytes are present (∼2%). She is admitted to ICU due to metabolic disarray and for additional workup. She reports no history of illicit drug use, recent diarrhea, or no other significant past medical history. Vitals are:
Serum lactate dehydrogenase (LDH) is elevated. Serum ADAMTS13 level was send from emergency department, showed a mild reduction.
Based on these findings what is most probable diagnosis?
Thrombotic microangiopathy is characterized by platelet microthrombi in small vessels leading to thrombocytopenia and microangiopathic hemolytic anemia. Microthrombi may also lead to systemic effects like acute kidney injury, neurologic abnormalities, and cardiac ischemia. In this patient, the presence of schistocytes (>1%) with hemolytic anemia (anemia, jaundice, elevated LDH) is suggestive of microangiopathic hemolytic anemia. This, in addition to thrombocytopenia and the systemic symptoms, supports a diagnosis of thrombotic microangiopathy.
Schistocytes are not typical of disseminated intravascular coagulation and even, if present, are usually <0.5%. A higher percentage of schistocytes (>1%) suggests thrombotic microangiopathy.
Important causes of thrombotic microangiopathy include thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, complementmediated thrombotic microangiopathy, and DITMA. Thrombotic thrombocytopenic purpura is associated with a lesser degree of renal involvement (or no renal involvement), and the levels of ADAMTS13 (when available) are very low (<10%). Hemolytic uremic syndrome is usually accompanied by marked abdominal signs and symptoms (diarrhea, abdominal pain, nausea). Immune thrombocytopenic purpura is caused by immune-mediated destruction of platelets and not associated with microangiopathic hemolytic anemia.
This patient most likely has DITMA. DITMA is caused by either immune-mediated or toxin-mediated mechanisms. Various drugs have been implicated. Drugs known to cause immune-mediated DITMA include quinine, trimethoprim-sulfamethoxazole (Bactrim), and quetiapine. Common culprits in toxin-mediated DITMA are cancer chemotherapeutic agents, immunosuppressants (calcineurin inhibitors), and recreational drugs of abuse. The diagnosis of DITMA is made clinically, based on the findings of thrombotic microangiopathy with the appropriate history of exposure to a culprit drug. Immune-mediated DITMA is not dose dependent and occurs within 2 weeks of drug exposure, with a longer duration of exposure making the diagnosis less likely. ADAMTS13 activity is normal or only mildly decreased. ADAMTS13 activity <10% strongly supports a diagnosis of thrombotic thrombocytopenic purpura.
Management of DITMA involves discontinuation of culprit drug and supportive care. DITMA (caused by either immune- or toxin-mediated mechanisms) requires the presence of the drug to cause cellular damage. Thus, once the drug is cleared from the circulation, no further organ injury occurs.
A 58-year-old woman is admitted to hospital with fever, productive cough, and shortness of breath. Chest x-ray is consistent with right lower lobe consolidation. She was treated as an outpatient for community-acquired pneumonia with oral ciprofloxacin, without improvement in symptoms. Medical history is significant for hypertension, gastroesophageal reflux disease (GERD), bipolar disorder, and depression. Her medications include carvedilol, omeprazole, aripiprazole, and amitriptyline. An ECG at time of admission shows normal sinus rhythm with prolonged QT interval.
Which of the following medications should be discontinued FIRST based on patient’s ECG findings?
Correct Answer: D
Amitriptyline should be discontinued as the ECG demonstrates QT prolongation. Many medications prolong QT interval, including amitriptyline and ciprofloxacin; QT prolongation may be markedly increased in patients taking more than one medication with this effect. Other drugs that have been implicated include antiarrhythmic agents, antibiotics (including macrolides and fluoroquinolones), antipsychotics, and antidepressants. A corrected QT (QTc) interval greater than 500 ms is associated with increased risk of torsades de pointes (TdP). In cases of prolonged QT interval, all QT prolonging agents should be discontinued. Beta-blockers (carvedilol) do not prolong QTc. An exception is sotalol, also a class III antiarrhythmic, which causes QT prolongation. Although rare, proton pump inhibitors (omeprazole) can cause prolonged QTc after chronic use (occurs due to hypomagnesemia). Aripiprazole is a quinolinone antipsychotic which unlike atypical antipsychotics may cause a decrease in QTc interval.
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