Tumor Lysis Syndrome

Today, Dr. Adrian Garcia presented an interesting case of tumor lysis syndrome in a patient with uncontrolled CML

Tumor lysis syndrome is a constellation of lab abnormalities caused my massive tumor cell lysis and is considered an oncologic emergency.  Classically, it presents soon after the initiation of cytotoxic therapy, but spontaneous TLS can also occur (usually in hematologic malignancies including leukemia and lymphoma).

It’s symptoms are nonspecific, but can include constitutional symptoms (anorexia, lethargy, nausea), symptoms of nephrolithiasis (hematuria, flank pain), and consequences of electrolyte abnormalities (heart failure, arrhythmias, seizures, muscle cramps, tetany, syncope, and sudden death). Lab findings include the following:

  • Byproducts of cell-lysis:
    • Hyperphosphatemia
    • Hyperkalemia
    • Hyperuricemia (nucleic acids are broken down into uric acid)
  • Secondary hypocalcemia caused by hyperphosphatemia
  • Acute kidney injury due to nephrolithiasis from uric acid and calcium phosphate stones

The treatment of tumor lysis syndrome includes:

  • High-volume normal saline with a loop diuretic to wash out renal crystals
  • Electrolyte correction:
    • Rasburicase for hyperuricemia
    • Phosphate binders for hyperphosphatemia
    • Hyperkalemia treatment: Kayexalate, insulin/D50, bicarb, albuterol, calcium gluconate if EKG changes
    • Do not treat hypocalcemia unless symptomatic due to increased risk of calcium phosphate precipitation in the renal tubules
  • Indications for hemodialysis:
    • severe oliguria or anuria
    • intractable fluid overload
    • persistent hyperkalemia
    • hyperphosphatemia-induced symptomatic hypocalcemia
    • calcium-phosphate product >= 70

Thanks so much for following along with our interesting cases.

The Octopus’ Trap

Today Dr. Anu Madhavan presented a very interesting case of a middle-aged woman with no cardiac risk factors and no cardiac history who presented with substernal chest pain after experiencing a fire at her workplace. Her troponin was elevated and EKG showed left anterior fascicular block and lateral T wave inversions. She was initially treated with aspirin, high-intensity statin, and heparin drip, but transthoracic echo soon revealed pronounced apical ballooning suggestive of Takotsubo’s cardiomyopathy.

Takotsubo presents very similarly to acute coronary syndrome with substernal chest pain, dyspnea, and rarely syncope in the setting of elevated troponin and ischemic EKG changes (about 44% have ST elevations, some have ST depressions or T wave inversions, and others have additional nonspecific EKG abnormalities). It is often preceded by a stressful (physical or emotional stress), but can present without a trigger as well. Echo typically shows apical ballooning and the wall motion abnormalities extend beyond the typical distribution of any one coronary artery. The name Takotsubo comes from the Japanese word for octopus trap, which is shaped like the LV with apical balloning.

It is diagnosed with the Mayo Clinic criteria, which include transient echo findings (hypokinesis, akinesis, or dyskinesis of the LV mid segments with or without apical involvement that extend beyond a single epicardial vascular distribution), absence of obstructive CAD on angiographic evidence of acute plaque rupture, new EKG abnormalities or modest elevation in cardiac troponin, and absence of pheochromocytoma or myocarditis.

Because our patient did not present with ST elevations and had typical apical ballooning, obstructive CAD was able to be ruled out with coronary CTA instead of cardiac catheterization. The apical ballooning seen on her echo would have required a large, mid or proximal LAD obstructive lesion. Coronary CTA can visualize proximal/mid left sided CAD well, but is very insensitive for distal vessels, RCA, or any pathology when the HR is extremely high.

The treatment of Takotsubo’s cardiomyopathy is not well-supported by randomized clinical trials, but there are suggestions that beta blockers and anticoagulation to prevent LV thrombus should be considered in this population.

Takotsubo’s Illness Script:

Epidemiology: Postmenopausal females most common, psychiatric or neurological disorders may be a risk factor

Pathophysiology: Multiple theories, but likely has something to do with catecholamine excess +/- microvascular spasm

Symptoms/signs: presents like ACS (substernal chest pain +/- dyspnea +/- syncope) with a trigger (emotional or physical stress). However, the trigger is not always present.

Labs: Elevated troponin +/- CK and BNP

EKG: ST elevations most common, ST depressions, other nonspecific findings (QT prolongation, TWI, Q waves)

Echo: Apical ballooning, regional all motion abnormality that extends beyond the territory perfused by a single epicardial coronary artery

Complications: tachyarrhythmias, heart failure, cardiogenic shock, stroke from apical thrombus

Treatment: supportive +/- beta blocker +/- anticoagulation (controversial)

Acute Alcoholic Pancreatitis and ARDS

Our esteemed doctors Madhavan and Garcia presented a fascinating two-part case from Monday and today. Our patient is a young man with a history of heavy alcohol use who presented with diffuse abdominal pain, nausea, and nonbloody nonbilious emesis. 

He was febrile and tachycardic on exam, but otherwise stable. His abdomen was diffusely tender to palpation and his bowel sounds were hypoactive. His lipase was 563 and a CT of his abdomen and pelvis show fat stranding around his pancreas with a pseudocyst near the pancreatic head.

What are the criteria to diagnose acute pancreatitis?

You must fulfill at least 2 out of the following 3 criteria:

  1. Characteristic pain (acute onset and severe epigastric pain +/- radiation to the back)
  2. Lipase 3x the upper limit of normal or higher
  3. Evidence of pancreatitis on imaging (contrast-enhanced CT abdomen is the modality of choice if the patient can tolerate the contrast load)

Our patient met 2-3 of these. Because his pain was not necessarily characteristic given its diffuse nature, a CT A/P was ordered. If the ER physician had considered him to have pain characteristic of acute pancreatitis, he would not need imaging to make the diagnosis. However, it is wise to get an abdominal ultrasound for patients with their first episode of pancreatitis to rule out gallstone pancreatitis even if there is a history of alcohol use.

Why did this patient get acute pancreatitis?

The most likely etiology in this case was alcohol use, which is the most common cause of acute pancreatitis in the United States. Other possible etiologies include:

Idiopathic

Gallstones

Ethanol

Trauma

Steroids

Mumps/malignancy

Autoimmune

Scorpion stings

Hypertriglyceridemia or hypercalcemia

ERCP

Drugs

What special findings can be seen in the physical exam of a patient with acute pancreatitis?

Physical exam findings of patients with acute pancreatitis should include epigastric tenderness to palpation and may include decreased lung sounds at the lung bases, abdominal distension, decreased bowel sounds. Grey-Turner and Cullen’s signs are ecchymosis at the flanks or umbilicus respectively. These are rare and if present, should prompt consideration of retroperitoneal bleeding from pancreatic erosion into adjactent vascular structures. Panniculitis is an uncommon finding associated with acute pancreatitis that presents as inflamed, erythematous, painful nodules on the lower extremities due to fat necrosis from circulating pancreatic enzymes.

Treatment of acute pancreatitis consists of:

  1. Aggressive fluid resuscitation
  2. Pain control (opting for IV opiates via PCA is justified)
  3. Nutrition: As soon as the patient can tolerate PO, they should be fed even in the setting of ileus. If the patient is unable to take PO, NJ tube should be inserted and nutrition begun within 3-4 days.

What does the pseudocyst on this patient’s CT scan tell you about the course of his disease?

He has most likely had an episode of pancreatitis in the past because pseudocysts to not develop acutely. They are seen 4 weeks after an episode of acute pancreatitis.

What are the complications of acute pancreatitis?

Local complications include fluid collection, walled off necrosis, acute necrotic collections, pseudocyst formation, and hemorrhage from invasion of adjacent vascular structures. These patients can also get ARDS, abdominal compartment syndrome, small bowel obstruction or ileus, pleural effusions, pancreatic ascites, splenic vein thrombosis, and chronic pancreatitis. Pseudoaneurysms can also be formed, which is when a vessel gets eroded and begins to drain blood into a pseudocyst, which becomes a pulsating hematoma.

In the ED, our patient received 3L NS and was placed on an LR infusion at 175 cc/h. Over the following hours, he became acutely hypoxic and required intubation and mechanical ventilation. CXR showed diffuse pulmonary infiltrates with an ABG of 7.42/39/111 on a PEEP of 5 and FiO2 of 100%. His echocardiogram was normal and he didn’t have elevated JVP or peripheral edema.

What are the criteria to diagnose ARDS?

We diagnose ARDS with the Berlin criteria, which have thee components and are as follows:

  1. Timing (within 1 week of known clinical insult or respiratory symptoms)
  2. Imaging with bilateral opacities not completely explained by effusions, lobar/lung collapse, nodules, or cardiogenic pulmonary edema. This requires objective assessment such as TTE to exclude cardiogenic edema.
  3. Hypoxia: We use the PaO2/FiO2 ratio (PF ratio) to evaluate hypoxia (200-300 mild, 100-200 moderate, <100 severe)

What is happening pathophysiologically in ARDS?

Inflammatory cytokines and cells are causing diffuse alveolar damage. This impairs gas exchange, causes alveolar collapse, and decreases surfactant functioning.

What should be your overall ventilation strategy for this patient?

Low tidal volume, which necessitates a high respiratory rate to maintain minute volume.

Higher PEEP to stabilize alveoli and increase recruitment.

Although a higher FiO2 is required to oxygenate these patients, minimizing FiO2 as much as possible to prevent oxidative damage is important.

How should you calculate the patient’s initial tidal volume?

First, you will need their predicted body weight, which can be calculated via formulas or MD calc or looked up based on their height. Keep in mind that there are different formulas and tables for men and women.

Men: 50 + 2.3[(height in inches)-60]

Women: 45.5 + 2.3 [(height in inches) -60]

Tidal volumes for ARDS patients should be low, start at 6mL/kg. 

How should you set their initial respiratory rate?

Your goal is to maintain the patient’s baseline minute ventilation despite having to use a decreased tidal volume to protect their damaged lungs.

Minute ventilation = tidal volume x respiratory rate

Your respiratory rate should never go above 35 and you should watch to make sure your patient is not breath stacking/auto-PEEP.

How do you set your PEEP and FiO2?

Start with a PEEP of 5 and an FiO2 of 100%. Over the next hour, you should wean FiO2 to as low as possible while adjusting PEEP using the ARDS Network guidelines, which includes a chart of appropriate PEEP levels per FiO2. Always start at the lowest PEEP included if there is a range. You want the lowest FiO2 possible to maintain an oxygen saturation by pulse oximeter of 88-95% OR PaO2 on ABG 55-80mmHg.

How do you make sure your pulmonary pressures are not too high?

Monitor plateau pressure Q4 hours and every time you make adjustments to ventilator settings. Plateau pressures should be maintained below 30 for ARDS patients. If your plateau pressure is too high, you have three main options:

  1. Decrease your tidal volume (this will require increasing your respiratory rate to maintain minute ventilation)
  2. Decrease your PEEP (this may decrease recruitment and cause hypoxia)
  3. If present, treat any ventilator dyssynchrony with neuromuscular blockade

What about the pCO2?

The main problem in ARDS is hypoxia, but when we are using a low tidal volume ventilator strategy, it is easy to make our patients hypecapneic. Some patients are so difficult to ventilate due to their low lung compliance that it is impossible to maintain normal oxygen and carbon dioxide without exceeding your plateau pressure limit of 30. For this reason, a strategy of permissive hypercapnea is employed in ARDS.

A pH 7.25-7.5 is tolerated in these patients without an increase in mortality.

 

A rare case of Adult Still’s Disease

Our wonderful medical student Tae presented a very interesting case today: a middle-aged male with no past medical history who presented with acute left knee pain and effusion, fevers, and leukocytosis. 

With any monoarticular, painful joint effusion without a history of trauma, arthrocentesis should be performed to rule out septic arthritis and look for crystalline arthropathies (gout and pseudogout). This patient’s synovial fluid showed 10 thousand WBCs with >75% neutrophils.

Interpretation of synovial fluid studies: When interpreting synovial fluid studies, many factors should be taken into consideration. The general cutoffs for WBC count in the fluid are guidelines, but there is significant overlap between categories.

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When differentiating between noninfectious inflammatory arthritides and septic arthritis, the distinction is not clear cut. The more WBCs you see in the joint fluid, the more likely it is to be a septic joint (>50,000 WBC is typical), but immunocompromise can decrease the WBC count and early in the course of septic arthritis, counts may be lower. Noninfectious inflammatory arthritis can have WBC counts >50,000 as well so history and other clinical data must be taken into account.

In this patient’s case, the WBC count of only 10 thousand falls in the classical non-infectious, inflammatory arthritis range. Gram stain did not show any organisms, but cultures grew rare growth Strep viridans and Actinomyces after more than 3 days in the micro lab. Outside of hematogenous spread of polymicrobial bacteremia and direct penetrating trauma to the joint, polymicrobial septic arthritis is exceedingly rare. Although all of this cast doubt on the diagnosis of septic arthritis, the patient was treated with Vancomycin and Zosyn initially, then narrowed to Zosyn alone. However, fevers continued, WBC count rose from 21 to 31, and procalcitonin increased from 0.83 to over 5.  A second arthrocentesis was performed, which showed a WBC count of only 30 thousand and no organisms on gram stain with a negative culture. He was subsequently taken to the operating room for arthroscopic drainage and debridement, which did not yield any pus. The orthopedic surgery team deemed the knee to not be a septic joint and did not think bacterial joint infectious could be responsible for his worsening condition.

On review of systems, the patient also endorsed some mild left elbow pain and joint swelling over the past two weeks that had now resolved. A mild transaminitis was also observed on admission labs with extremely elevated CRP and ESR. During the admission, his right knee began to hurt and XR revealed another small effusion. He subsequently developed a diffuse, maculopapular rash, which was thought to be a drug rash. He was switched from Zosyn to Ceftriaxone and then again to Clindamycin, but the rash, fevers, and leukocytosis persisted. Tests for gonorrhea, chlamydia, HIV, syphilis, and viral hepatitis were all negative. Fungal and anaerobic cultures of synovial fluid were negative.  Blood cultures did not show any growth and echocardiogram did not show any abnormalities or vegetation. ANA and anti-CCP were negative, and rheumatoid factor was only very weakly positive (only mildly above the upper limit of normal).

Finally, his ferritin came back at >17,000 and the diagnosis of Still’s disease was made. Still’s is a rare rheumatologic condition akin to juvenile rheumatoid arthritis. It is an out of control immune reaction that typically presents with daily or twice daily fevers, an evanescent salmon-colored maculopapular rash, and polyarticular arthritis. It can also cause severe nonsuppurative pharyngitis, liver dysfunction, pleural effusions, pericarditis, lymphadenopathy, and splenomegaly. The Yamaguchi criteria can be used to diagnose it after infectious, malignant, and other rheumatologic causes are ruled out. It is treated with high dose steroids and sometimes IL-1 or IL-6 inhibitors.

After this patient begun high dose steroids, his fevers and rash resolved, transaminitis slowly improved, and his arthritis became less severe, confirming the diagnosis of Still’s disease.

The Dutch Physician with a Calm Disposition

Today we reviewed a case of Boerhaave Syndrome, named after Dr. Hans Boerhaave who was the first physician to have written about a patient with an esophageal rupture after severe retching.

  • Suspect it in any patient with severe chest discomfort followed by vomiting or retching, [though it can happen without a history of retching]. The presence of subcutaneous emphysema on examination (crepitus) in conjunction with the aforementioned two makes Mackler’s Triad, which is seen in only 14% of patients.
  • The diagnosis is made by contrast esophagram (avoid Barium and chose Gastrografin instead) or by CT scan
  • Treatment is to make the patient strictly NPO, IV antibiotics and surgical consultation
  • Contrast this with a Mallory Weiss tear in which there is a partial thickness, longitudinal laceration of the esophagus or stomach that may present with chest pain, vomiting and hematemesis

We also reviewed the anatomically based framework to abdominal pain, and considered our differential for epigastric pain as well as severe, diffuse abdominal pain.

For epigastric pain, we considered the following:

  • Acute MI
  • Acute pancreatitis
  • Chronic pancreatitis
  • PUD
  • GERD
  • Gastritis
  • Gastroparesis
  • Functional Dyspepsia

For severe diffuse pain

  • obstruction (i.e SBO or hepatobiliary obstruction)
  • perforation (esophageal, gastric, or intestinal)
  • ischemia (ie mesenteric)
  • inflammatory/infectious

 

A Lung Mass… But what kind??

Our visiting Stanford resident, Dr. Tiffany Guo, presented a very interesting case of an elderly female with a heavy smoking history who presented with a subacute dry cough and progressive dyspnea on exertion with new unilateral shoulder pain.

An initial differential for any heavy smoker with a dry cough and dyspnea should be broad, but include the following tobacco-related diagnoses: COPD, lung cancer, pulmonary HTN, postobstructive pneumonia, and smoking-related ILD including Langerhans cell histiocytosis, respiratory-bronchiolitis associated ILD, desquamative interstitial pneumonia, and sometimes, IPF, acute eosinophilic pneumonia, and pulmonary alveolar proteinosis. The smoking-related ILDs are a heterogeneous group, but in general, they tend to be asymptomatic or present with dry cough and dyspnea, occasionally with systemic symptoms like weight loss and fever. Physical exam may show rales or clubbing and PFTs show a restrictive lung defect. The diagnosis becomes more clear with specific findings on HRCT scan. Although these disorders are rare, they are important considerations because some have treatments and patients may be eligible for lung transplantation.

With this patient’s new onset shoulder pain, we also discussed Pancoast syndrome as a possible diagnosis. Pancoast syndrome consists of shoulder pain (most common initial symptom), Horner syndrome (ipsilateral ptosis, miosis/pupilary constriction, and anhidrosis/loss of sweating on the face), and weakness of the muscles of then hand due to a superior pulmonary sulcus tumors. This was not the diagnosis in our particular patient, but is an important diagnostic thought.

Our patient’s chest X-ray revealed a right hilar mass in the lung. While waiting for biopsy and counseling your patient on your initial concerns for malignancy, it is helpful to have a basic knowledge of the main types of lung cancer and their treatments.

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