Case 1: Acetaminophen overdose and cerebral edema
A 37-year-old woman with a history of depression presented after being found by family members with altered mental status. She had been experiencing insomnia and had ingested an estimated 130 tablets of acetaminophen with diphenhydramine (acetaminophen 500 mg/diphenhydramine 25 mg) two weeks prior to admission. She was found to have ingested an additional 142 tablets two days before hospitalization. At presentation she was hemodynamically stable, but concerning examination findings were noted, including lethargy, jaundice, abdominal tenderness, and asterixis. Admission laboratory testing showed an aspartate aminotransferase level of 4,852 U/L (normal range, 10 to 50 U/L), an alanine aminotransferase level of 1,732 U/L (normal range, 10 to 50 U/L), a total bilirubin level of 6.2 mg/dL (normal range, 0.2 to 1.0 mg/dL), an international normalized ratio greater than 8.9 (normal range, 0.8 to 1.2), and an ammonia level of 141 μmol/L (normal range, 11 to 51 μmol/L). She also had an anion gap metabolic acidosis with an anion gap of 25 and a lactate level of 12 mmol/L (normal range, 0.5 to 2.2 mmol/L). She subsequently developed acute kidney injury with presumed hepatorenal syndrome. She was given intravenous fluids, sodium bicarbonate, and N-acetylcysteine.
As her hospitalization progressed, the patient became obtunded and required intubation. An MRI of the brain (Figure 1) revealed cerebral edema, which was treated with hypertonic saline and then mannitol. Intracranial pressure monitoring was deferred due to her coagulopathy. Serial head CTs revealed progressive cerebral edema with uncal herniation, though without any associated derangement in pulse, blood pressure, or respiratory drive. She was not a liver transplant candidate due to an active substance use disorder. Her neurological exam did not improve, she was unable to be weaned from the ventilator, and ultimately met criteria for brain death. The patient's family opted to place a tracheostomy and gastrostomy tube, and she was discharged to a long-term acute care facility.
This patient presented with acute liver failure after acetaminophen overdose, which was complicated by cerebral edema. A recent study in a liver center showed that 20% of patients with acute liver failure developed intracranial hypertension, with mortality exceeding 50%. While the exact mechanisms of the development of cerebral edema in acute liver failure are not well understood, acute elevations in serum ammonia level and oxidative stress are believed to play a role. Increased cerebral edema causes a rise in intracranial pressure that may lead to herniation, which is often fatal. Patients with acetaminophen overdose and/or acute liver failure require close monitoring for the signs of progressive cerebral edema and impending herniation, which are classically clinically known as Cushing's triad: bradycardia, respiratory depression, and hypertension.
Management of cerebral edema focuses on reducing intracranial pressure and maintaining adequate cerebral perfusion. Treatment strategies include intubation with hyperventilation, elevation of the head of the bed to 30 degrees, administration of hyperosmotic agents (hypertonic saline and/or mannitol), induction of hypothermia, and administration of barbiturates. If encephalopathy or cerebral edema worsens, transfer to a liver transplant center should be considered. Liver transplant is often the only definitive treatment; however, uncontrolled intracranial pressure is a contraindication to transplant.
Treatment for acetaminophen overdose depends on the patient's presenting symptoms, severity of laboratory abnormalities, and the time elapsed from acetaminophen ingestion. The Rumack-Matthew nomogram is often used to assist in management decisions, though it is of limited utility when more than 24 hours have elapsed since ingestion. In the event of delayed medical care or severe acetaminophen toxicity, patients may present with acute liver failure. N-acetylcysteine is the gold standard treatment for acetaminophen toxicity; however, it is most efficacious before the onset of liver failure. This patient's acute liver failure at the time of initial presentation suggests a degree of hepatic insult from an initial toxic ingestion two weeks prior to admission.
- Encephalopathy and cerebral edema are complications of acute liver failure that can result from acetaminophen toxicity, for which patients require close monitoring.
- Cerebral edema can preclude emergent transplantation and carries a poor prognosis with increased mortality.
Case 2: Complications of catheter ablation for refractory afib
An 81-year-old woman with a history of paroxysmal atrial fibrillation (AF) presented for elective atrioventricular nodal ablation and permanent pacemaker implantation after medical therapy consisting of anticoagulant, rate-control, and anti-arrhythmic agents had failed. She continued to have episodes of symptomatic AF, with palpitations and light-headedness, and had an unsuccessful elective electrical cardioversion. The implantation of her pacemaker was complicated by a perforation that led to the development of cardiac tamponade, requiring pericardial window and suspension of anticoagulation. Postoperatively, she developed new-onset dysarthria and left-sided weakness. A CT angiogram of the head (Figure 2) showed an acute occlusion of the right middle cerebral artery consistent with cardioembolic stroke, which required emergent mechanical thrombectomy. She was subsequently placed on a heparin infusion. Several days later, she developed swelling, erythema, and pain in her left arm and was found to have an acute deep venous thrombosis of the upper extremity. She concurrently had a marked drop in her platelet count from a peak of 135,000 cells/µL to a nadir of 29,000 cells/µL. Testing for heparin-induced thrombocytopenia (HIT) was positive, via both the HIT antibody and serotonin release assay. Heparin was withdrawn, and she was transitioned to argatroban. The patient did well with minimal residual deficits and was transitioned to a rehabilitation facility for further care.
The patient had refractory symptomatic AF despite maximal medical therapy and attempted cardioversion. Patients with symptomatic AF that persists despite medical management and electrical cardioversion are candidates for invasive therapies. Options include catheter ablation with pulmonary vein isolation to permanently remove the ectopic arrhythmic foci (76% success rate), atrioventricular nodal ablation with pacemaker placement (initial atrioventricular node ablation successful in 92%, with second attempt needed in 8%), or cardiac surgery involving the MAZE technique to mechanically obliterate the pathologic electrical pathways (90.4% success rate at three years after surgery). Due to the risk of cardioembolic stroke, guidelines recommend anticoagulation prior to AF ablation and for at least three months following, irrespective of the patient's baseline stroke risk. The decision to continue anticoagulation long term depends on the success of the procedure and the patient's baseline risk of stroke as assessed by common decision aids (e.g., CHA2DS2-VASc).
There are important, although uncommon, potential complications of AF ablation procedures, including stroke (occurs in 1.4% of patients with a CHA2DS2-VASc score ≥2 and 0.3% of those with a CHA2DS2-VASc score of 0 or 1), induced cardiac arrhythmia (20% to 40% of patients require repeat ablation), venous thromboembolism (deep venous thrombosis in 0.33% and pulmonary embolism in 0.29%), valvular damage (mitral valve injury in 0.1%), pulmonary vein stenosis (0.01 to 0.1%), esophageal perforation (0.2% prevalence of an atrioesophageal fistula), pericardial perforation (1.1% to 1.3% tamponade), and major bleeding. This case was further complicated by HIT, which is very rare in post-catheter ablation patients, with only two case reports in circulation describing this phenomenon.
- Although uncommon, complications from catheter ablation procedures for AF can be severe and life-threatening.
- Stroke is one of the most disabling complications from catheter ablation of AF, hence the importance of continuing anticoagulation for at least three months after ablation, barring contraindications.
Case 3: Critical aortic stenosis and coronary artery disease
A 74-year-old man with a history of multiple cerebral vascular accidents and chronic kidney disease presented with several days of generalized weakness, chest pain, and multiple syncopal episodes. Upon presentation, he was found to be tachycardic. His physical examination was notable for bibasilar rales. An electrocardiogram revealed T-wave inversions in the inferior leads. Labs were notable for a troponin level of 1.65 ng/mL (normal range, 0.000 to 0.034 ng/mL) and pro-B-type natriuretic peptide level of 35,446 pg/mL (normal range, <125 pg/mL). Chest X-ray showed bilateral pleural effusions. Transthoracic echocardiogram showed a bicuspid aortic valve with fusion of two leaflets, a cross-sectional area of 0.67 cm2 (normal value >2.5 cm2), a peak velocity of 3.5 m/s (normal value <2.6 m/s), and a mean gradient of 32 mm Hg (normal value <10 mm Hg).
The patient underwent left- and right-heart catheterizations that revealed triple-vessel coronary artery disease (CAD) with 90% stenosis of the left main artery, elevated left ventricular end diastolic pressure (30 mm Hg), normal cardiac index (2.3 L/min/m2), and reduced left ventricular ejection fraction (35% to 40%). During hospitalization, he underwent careful diuresis. He was not a candidate for surgical aortic valve replacement or coronary artery bypass grafting (CABG) because he did not want to receive blood products due to his religious beliefs. Ultimately, he had a drug-eluting stent placed in the left main artery and a transcatheter aortic valve replacement (TAVR), which were done with no complications. The patient was discharged from the hospital in stable condition.
The patient presented with non-ST-elevation myocardial infarction (NSTEMI) in the setting of critical aortic stenosis, with the classic triad of angina, heart failure, and syncope. CAD is common in patients with critical aortic stenosis, with an estimated incidence of 60% to 65% in patients undergoing aortic valve replacement. In patients with CAD, the decline in cardiac output and coronary flow resulting from critical aortic stenosis can lead to ischemia and myocardial infarction.
Definitive treatment for aortic stenosis is valve replacement. Aortic valve replacement is indicated in the following situations: 1) symptomatic patients with severe aortic stenosis noted by cross-sectional area of the valve less than 1 cm2, 2) asymptomatic patients with severe aortic stenosis undergoing surgery for coronary artery bypass or on the aorta, and 3) asymptomatic patients with severe aortic stenosis and left ventricular systolic dysfunction with ejection fraction less than 50%. Once valve replacement is indicated, patients are typically evaluated for surgical valve replacement or TAVR.
For patients with concomitant CAD and aortic stenosis, surgical valve repair with CABG is considered the preferred treatment. This patient would have been an excellent candidate for CABG with open surgical valve replacement if he had been willing to receive blood transfusions. However, given the risks of open surgery without blood product support, TAVR was the preferred approach in this case. For patients who are not surgical candidates or who are awaiting valve replacement, medical therapy includes optimization of loading conditions through careful management of hypertension and volume status. In critically ill patients who are not surgical candidates, palliative percutaneous balloon valvuloplasty may improve symptoms; however, the procedure is associated with a high morbidity rate and does not provide a durable result.
- Critical aortic stenosis may present as NSTEMI, particularly in patients with concurrent CAD.
- Concomitant critical aortic stenosis and CAD are common and are typically managed with surgical valve replacement and CABG; however, in high-risk surgical patients, percutaneous coronary intervention with stenting can be considered prior to TAVR.