MTC 1/14 – Hypoactive Delirium

Thursday morning, Brian Coburn, one of amazing second year Med/Peds residents, presented an interesting case of a 35-year-old patient who presented with hypoactive delirium. The patient’s medical history was significant for epilepsy and opioid use disorder. We started our investigation of possible causes of the patient’s encephalopathy by going through the AEIOUTIPS mnemonic of common causes of altered mental status that can be investigated with basic history, exam, labs, and imaging. Our expert discussants from the Toxicology services provided us a comprehensive overview of the approach to hypoactive toxidromes and judicious interpretation of urine tox screening. After the initial work-up was unrevealing, the team pursued additional investigation with lumbar puncture, EEG, and MRI without contrast that were also negative. The team asked our friends from psychiatry to help elucidate whether the patient’s symptoms may be due to an underlying psychiatric disorder, but the determination was made that a primary medical disease was still the most likely cause.

The patient’s condition continued to progress, and an MRI with contrast ultimately revealed acute, diffuse white matter lesions. Per our radiology colleagues, the differential for these findings included infection/post-infectious causes (viral encephalitis, acute disseminated encephalomyelitis, acute hemorrhagic leukoencephalitis), autoimmune encephalitis, and toxic leukoencephalopathy. Following a repeat LP that was negative for a broad array of infectious, autoimmune, and malignant/paraneoplastic studies, we were left with a diagnosis of opiate-induced toxic leukoencephalopathy. The disease presentation is extremely variable, ranging from minor cognitive impairment, easily confused with psychiatric illnesses, to severe neurological dysfunction. Our toxicologist reminded us that some of these findings can also be seen with potential transient, out-of-hospital anoxic episodes. While there is no proven treatment for toxic leukoencephalopathy, antioxidant therapy with Coenzyme Q10, Vitamin E, and Vitamin C has been used to treat some patients with variable results in the past. The patient received this treatment and spontaneously improved after several days of therapy.

Thank you to Brian, our expert discussants, and our residents for working through the differential of hypoactive delirium and the sequential investigations we needed to get to the bottom of this fascinating case.

Morning Report – Tuesday 12/29 at the VA!

Tuesday morning report at the VA was all about diuretics. We presented a case of a 73-year-old man with history of CHF, CKD and T2DM who presented with progressive dyspnea, bilateral lower extremity swelling, orthopnea, and abdominal distension. Physical exam showed evidence of volume overload with 3+ pitting edema, elevated JVD, and bibasilar pulmonary crackles. We considered various common triggers of heart failure exacerbation before diving into a discussion of diuretics. 

Key points that we highlighted:

  • Decongestion with resolution of symptoms and edema is achieved through “diuresis” = loss of sodium (natriuresis) + loss of water (diuresis). That is why sodium-limited diet is crucial in treatment of fluid overload. 
  • Loop diuretics function as “threshold” drugs that need to achieve a sufficient concentration in order to work. The natriuretic threshold is higher in patients with acute CHF than in healthy persons. That is why hospitalized patients require loop diuretic doses that are higher than stable outpatient doses.
  • Loop diuretics exhibit a “ceiling” effect and doses above the ceiling will not increase the amount of natriuresis. Acute CHF shifts the relation between plasma diuretic concentration and sodium excretion to the right and reduces the “ceiling.” 
  • Patients with chronic diuretic use develop post-diuretic sodium retention and decreased efficacy with each subsequent loop diuretic dose. That is why loop diuretics are dosed multiple times daily and why patients need a net negative sodium balance each day. 
  • Chronic loop diuretic use leads to distal tubular hypertrophy and once maximum loop diuretic effect is reached, auxiliary diuretics are sometimes used (thiazide, aldosterone antagonists, carbonic anhydrase inhibitors). We discussed specific situations you may consider using these agents. 
  • Ethacrynic acid is the loop diuretic of choice in patients with sulfa allergy. 

For further reading, check out this review from the NEJM: 

Ellison DH, Felker GM. Diuretic Treatment in Heart Failure. N Engl J Med. 2017 Nov 16;377(20):1964-1975.

Methemoglobinemia in the Morning

At Hillcrest this morning Janna Raphelson, one of our stellar residents, presented a case of a 75-year-old man with history of steroid-dependent interstitial lung disease, chronic kidney disease, and serious TMP-SMX allergy who presented to the VA with increased dyspnea, fatigue, and headache one month after starting dapsone for Pneumocystis jiroveci pneumonia prophylaxis. He was found to have an acute anemia that was stabilized by transfusion of pRBCs and subsequently characterized as hemolytic. On exam, the patient was cyanotic with an oxygen saturation in the mid-80% that was unresponsive to up titration of supplemental oxygen.

We were joined by Dr. Mark Hepokoski from our PCCM division as we unpacked the causes of hypoxemia and why we need to calculate an alveolar-arterial (A-a) gradient. While the patient’s A-a gradient was increased (from baseline IPF and mild interstitial edema), there was a clear discrepancy between his SpO2 (pulse oximeter) and PaO2 (blood gas). This reminded us that impaired oxygen delivery to tissues (hypoxia) has multiple potential etiologies: hypoxemic, anemic, circulatory, histotoxic. The next step in the evaluation of our patient involved obtaining co-oximetry which revealed increased levels of methemoglobin!

The pulse oximeter is only able to distinguish between saturated and unsaturated hemoglobin. If significant levels to methemoglobin build up, the machine interprets this as a saturation of approximately 85%. In addition to causing a functional anemia, methemoglobinemia shifts the hemoglobin-oxygen dissociation curve to the left. This effect causes increased affinity of hemoglobin for oxygen and decreases oxygen unloading in tissues. We compared our patient’s case to the other acquired dyshemoglobinemia that we sometimes encounter, carbon monoxide poisoning. 

Despite the patient’s normal G6PD screen prior to starting dapsone, he still developed known complications of this medication’s oxidative effect: hemolytic anemia and methemoglobinemia. Our patient’s methemoglobinemia was partially treated by blood transfusions and given concern for toxicity in renal failure, he did not receive the standard treatment of methylene blue and vitamin C. The patient slowly recovered following discontinuation of dapsone (switched for inhaled pentamidine for ongoing PJP ppx) and is now back to his baseline. 

Thank you to Dr. Hepokoski for sharing his wisdom and clinical expertise and thank you to all of our applicants for joining us for another great morning report!

Thursday Maputo-VA Conference

This Thursday, we restarted our join teaching conferences with our partners in Maputo, Mozambique! We discussed a case of an 83-year-old man who presented with several months of progressive shortness of breath, dry cough, and weight loss. On exam, he had absence of breath sounds over the right hemithorax with dullness to percussion and absent tactile fremitus. His chest radiograph demonstrated unilateral white out, and we considered two possibilities for this finding: a large pleural effusion or a mainstem bronchial obstruction causing lung collapse. 

Our expert discussant, the legendary VA pulmonologist Dr. Judd Landsberg, guided us through the CXR interpretation and why it was consistent with an effusion: large spacing between ribs and tracheal deviation away from the affected hemithorax.  

A thoracentesis was performed and was consistent with an exudate by Light’s criteria. We formed a differential for exudative effusion and discussed why two possibilities were most likely for this particular patient: malignancy and Tuberculosis. Unfortunately, the patient’s thoracentesis was followed by the discovery of a pneumothorax. We considered the mechanism and management of this complication and how to proceed in case where the pneumothorax is increasing: placement of a chest tube. 

Thank you to Dr. Landsberg for all of his clinical pearls and the Maputo residents for their participation!

Owen Report 11/24: Cough and Dyspnea

This morning we were lucky to be joined by Dr. Darcy Wooten, an amazing HIV Medicine attending and APD of the Infectious Disease Fellowship, to discuss one of her Owen clinic patients.

The 30-year old man with newly diagnosed HIV presented to our hospital with cough, fevers, chills, night sweats, decreased appetite, and recent weight loss. On admission, the patient had a CD4 count of 102 cell/uL and viral load of 185,000 copies/mL. The CXR revealed a diffuse micronodular/miliary pattern and CT showed upper lobe predominant diffuse ground glass opacities. Initially concerning for TB, the patient’s work-up was significant for elevated serum Coccidiodes IgG antibodies, positive cocci complement fixation with a 1:512 titer, and negative bone scan and spine computerized tomography. The patient was diagnosed with severe pulmonary coccidioidomycosis with presumed dissemination (based on the high titer).

The patient was treated with amphotericin B for severe cocci and discharged on fluconazole therapy (along with antiretroviral therapy and Bactrim prophylaxis). He could not tolerate the fluconazole and was switched to Posaconazole. The patient subsequently developed severe hypertension refractive to amlodipine, lisinopril, and hydrochlorothiazide. Work up demonstrated low levels of potassium, renin, and aldosterone. The patient was diagnosed with pseudohyperaldosteronism, taken off Posaconazole, and placed on itraconazole and spironolactone, leading to a resolution side effects. The mechanism behind pseudohyperaldosteronism is similar to that of licorice root extract, where steroid synthesis products directly activate mineralocorticoid receptors. Treatment is focused on cessation of Posaconazole and antagonism of the mineralocorticoid receptor with spironolactone.

Morning Report 10/27–Thrombocytopenia

Today we discussed a case of thrombocytopenia with our expert discussant hematologist oncologist Dr. Tanaka. We discussed a case in which a patient with CLL developed severe thrombocytopenia. We discussed ruling out pseudothrombocytopenia when evaluating thrombocytopenia. This is caused by the anticoagulant EDTA in the blood collection tube and can be fixed by using a tube with citrate or heparin. We then broke down thrombocytopenia causes into three main buckets underproduction, splenic sequestration and peripheral destruction. The final diagnosis for our patient was immune mediated platelet destruction secondary to CLL.

Morning Teaching Conference – Mon 10/26

On Tuesday morning we discussed a case of a 77-year old man who presented with epigastric abdominal pain and was found to have gallstone pancreatitis. The patient went on to develop a prolonged ileus and an extended hospital stay. Two weeks later, the patient developed a new leukocytosis and tachycardia and was found to have pancreatic necrosis. We brainstormed the early and late complications of pancreatitis. We additionally discussed the standard recovery timeline from pancreatitis. The development of walled-off necrosis is a key distinction in the evaluation of post-pancreatitis complications.  Our teams also came up with the antibiotic choices they would consider when treating the patient. Finally, we discussed the procedural considerations to treatment of necrotic collections. The initial approach often involves placement of percutaneous or transluminal drain (or stent). Serious cases may also need to be treated with necrosectomy  – either surgical using video-assisted retroperitoneal debridement (VARD) or endoscopic. A special thank you to our discussant, Dr. Phil Fejleh, the advanced endoscopy GI fellow, for sharing all of his expertise!

Morning Report 10/13: Inpatient Fever

This morning one of our stellar resident, Dr. Mandy Mohindra, presented a patient who developed a fever six days into a hospitalization for volume overload. The patient reported a history of worsening chills with rigors, loss of appetite, nausea and vomiting, and fatigue. He had an infiltrated IV with right upper extremity swelling on exam. The patient’s history was significant for liver transplantation three years before (on tacrolimus), diabetes, and severe aortic stenosis. We discussed the decision to start empiric antibiotics, and the workup eventually revealed MRSA bacteremia. The most likely source was the infiltrated peripheral IV.

We were lucky to have our Infectious Disease expert extraordinaire, Dr. Annie Cowell, to lead us through the management of Staph Aureus bacteremia as we discussed the need to evaluate for potential sites of metastatic MRSA infection.  A wrinkle in our patient’s case was that his blood cultures were persistently positive for MRSA. This prompted a change of antibiotics from vancomycin to ceftaroline and daptomycin and a search for endocarditis. A transthoracic echocardiogram did not reveal valvular vegetations, but a subsequent ECG revealed a new 1st degree heart block. The patient underwent a transesophageal echocardiogram which ultimately demonstrated a paravalvular abscess for which cardiothoracic surgery was consulted. Thank you to all of our resident teams for participating in the discussion. And thank you to Dr. Cowell for adding context to our patient’s clinical course! 

Morning Report 9/17: Sickle Cell VOC

September is Sickle Cell Awareness Month and this morning Alex Sykes, one of our awesome R2s, presented a case of a 26-year old man with homozygous sickle cell disease who presented with acute hip pain. We were lucky to have the patient’s hematologist, UCSD’s Dr. Srila Gopal, join us as an expert discussant. We covered the various genetic variants of sickle cell spectrum as we reviewed the patient’s electrophoresis (note that the reason he has any Hb A is due to prior transfusions!) and discussed environmental triggers of vaso-occlusive crises (VOCs). We then covered the why behind the use of hydroxyurea in patient with sickle cell disease and learned about exciting new therapies that are being implemented and researched. Finally, we covered the pathophysiology of vaso-occlusive crisis before learning that our patient’s pain was due to an infarct of the right acetabulum. Many thanks to Dr. Gopal for sharing her vast wisdom with us. 

Morning Report Tue 8/25: Evidence-based medicine

On Tuesday, we heard evidence-based medicine presentations from three of our residents, Mitch Biermann, Ambika Munaganuru, and Janna Raphelson. Thank you to Dr. Ben Hulley, one of our VA hospitalists, for leading our three R2s through a structured process of evaluating the available evidence. The key parts of the process involve specific and narrow question generation followed by increasingly refined searches though public medical databases. The team used the PICO method to determine their clinical question. Iterative processes of refining a clinical question is necessary to reach a relevant and answerable question. 

Mitch explored the use of Everolimus and Panobinostat for treatment-refractory metastatic pancreatic cancer, Ambika looked into the evidence behind use of acupuncture for low back pain, and Janna analyzed the initiation of naltrexone during inpatient admissions for alcohol withdrawal. Thank you all for educating us on the latest evidence around these topics!