Rhabdomyolysis

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Dr. Kiefer presented a case of rhabdomyolysis today likely multifactorial with a major contribution from drug-drug interactions and increased exertion. It reminded us of the extensive differential for rhabdo and that we need to be on the look out for associated complications.

Rhabodomyolysis is essentially muscle necrosis with the release of intracellular muscle constituents such as creatinine kinase (CK). It can range from asymptomatic elevations in CK to life threatening with severe electrolyte abnormalities and AKI. The classic symptom triad is muscle pain, weakness and dark urine (myoglobinuria).

The causes of rhabdomyolysis can be thought of in three broad categories encompassing an enormous number of etiologies:

  • Traumatic: trauma, crush injuries, surgery, coma, immbolization, electric voltage
  • Nontraumatic, Exertional: extreme exertion (marathon running, cross fit), environmental heat illness, seizures, hyperkinetic states (psychotic agitation, amphetamine OD), metabolic or mitochondrial myopathies, malignant hyperthermia, neuroleptic malignant syndrome
  • Nontraumatic, Nonexertional: alcoholism, drugs (heroin, cocaine, amphetamines, methadone, LSD, statins, colchicine, dietary supplements), toxins (snake or insect venom, mushrooms, fish toxin), infections (influenza A/B, coxsackie, EBV, HSV, parainfluenza, adenovirus, echovirus, HIV, CMV, mycoplasma pneumoniae, bacterial myositis, legionella, tularemia, strep, salmonella, leptospirosis, coxiella burnetti, erclichiosis, malaria), electrolyte abnormalities, endocrinopathies (hyothyroidism, DKA, HHS, pheochromocytoma), inflammatory myopathies, status asthmaticus, capillary leak syndrome, abrupt withdrawl of GABA agonist (ex. intrathecal baclofen)

As you continue to asssess your patient, it is important to monitor for complications and associated symptoms which can include:

  • hypovolemia with third spacing
  • electrolyte derrangements: potassium, phosphate, calcium, uric acid (check and EKG and consider telemetry)
  • metabolic acidosis
  • AKI (monitor UOP and need for dialysis)
  • compartment syndrome
  • DIC (assess for bleeding)

Remember that management is driven by prevention and addressing hte underlying etiology.

  • address hypovolemia and utilize volume to "wash out" obstructing pigment casts in the kidney: 500ml/hr x24 hours and then goal UOP 200-300ml/hr
  • electrolyte managment: assess potassium and monitor for arrythmias

Hypoxia

Today for intern report, Dr. Nelson walked us through a case of an older gentleman with COPD, chronic back pain, and tobacco use who presented with progressive abdominal pain, bloody stools, and unintentional weight loss, found to have rectal adenocarcinoma. His hospital course was c/b hypoxia, which was the focus of our discussion.

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Learning Points:

  1. Hypoxemia has a large ddx including:

    • Hypoventilation (CNS depression, obesity hypoventilation, impaired neural conduction, muscular weakness, poor chest wall elasticity)
    • V/Q mismatch (obstructive lung diseases, pulmonary vascular diseases, interstitial diseases)
    • Right-to-left shunt (anatomic shunts and physiologic shunts)
    • Diffusion limitation
  2. Always evaluate the patient at bedside to assess their vitals (is the pulse ox wave form accurate?), work of breathing/use of accessory muscles, cardiac and lung exams, etc.

  3. Our patient was worked up with an basic labs, ABG, CXR, CT angiography, which were all unrevealing. Ultimately, it was felt that his hypoxia was related to pain with increased splinting in the setting of underlying kyphosis and COPD. His hypoxia improved with pain control.

Stridor/Wheeze

Today, we reviewed an interesting case of an elderly gentleman with a history of metastatic lung adenocarcinoma on palliative nivolumab who presented with acute, progressive, episodic wheeze/stridor in addition to signs and symptoms of hyperglycemia, found to have unilateral vocal cord dysfunction and new autoimmune DM secondary to nivolumab.

Learning Points:

  1. We reviewed the importance of prompt evaluation of the severity of respiratory compromise in the setting of acute wheeze/stridor. We explored the extrathoracic upper airway causes of wheeze/stridor including anaphylaxis, vocal cord edema or paralysis, laryngeal stenosis, goiter, etc. as well as intrathoracic causes including tracheal stenosis, tracheal or bronchial tumors, tracheomalacia, amoung others. Our patient had prompt direct visualization by ENT, which showed unilateral vocal cord paralysis.

  2. We reviewed the side effect profile of immune checkpoint inhibitors such as nivolumab including adrenal insufficiency, colitis, encephalitis, hypophysitis, pneumonitis, and type 1 diabetes mellitus.

Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a complication of cirrhosis which signals decompensation. The presentation can be broad. HE is graded on a scale from I- IV which ranges from irritability and incoordination (I) to fatigue and asterixis (II) and somnolence with clonus (III) all the way to stupor and coma (IV). History and exam can often lead to the diagnosis. Checking an Ammonia level can be useful if there is ambiguity. There is no role in trending levels. There is a precipitating factor in 80% of HE cases which include:

  • infection (SBP)
  • GI bleed
  • medications (opiates, benzos)
  • EtOH
  • electrolyte derrangements (hypokalemia, hyponatremia)
  • hypoglycemia
  • hypoxia
  • clot (portal vein or hepatic vein thrombus)
  • HCC
  • s/p TIPS
  • dehydration

Following diagnosis and assesment for trigger, treatment is classicially with Lactulose. The can be administered PO, via a DHT or enema. Lactulose is dosed with the goal of 3 bowel movements per day. If there is no effect in 48 hours or the symptoms severe (HE III, IV), many suggested adding Rifaximin. A potential alternative to Lactulose is poleyethylene glycol. The HELP clinical trial (published in JAMA 2014) noted more rapid improvement in HE with use of 4L bowel prep with PEG compared to standard Lactulose therapy in a small trial of hospitalized patients with acute HE.

Approach to bloating

Thanks Miles for presenting an excellent case on a middle age male coming in with acute-subacute progressive constipation and bloating, new ascites with a diagnosis of peritoneal carcinomatosis of unknown primary.

peritoneal carcinomatosis

Learning points:

  • 1) When a patient comes in with bloating, ask whether alarm symptoms are present eg. anemia, unintential wt loss, progressive, new onset in elderly
  • 2) The differential diagnosis for bloating can be broken down into anatomic, malabsorption, drugs, functional, infection, and neurologic
  • 3) Biomarkers and genetic testing are helpful for diagnosis of carcinoma of unknown primary because it may identify the primary in some cases and can guide treatment. You can set up a free account to access the NCCN guidelines to learn more.

Want more info?

Differential diagnosis for bloating

  • When a patient comes in with bloating, ask about distention, gassiness, and stool quality as well as red flag sx
  • 1) anatomic
    • a) obstruction/ partial obstruction
    • b) gastroparesis
    • c) malignancy - classically ovarian carcinoma
    • d) constipation
  • 2) malabsorption - lactose intolerance, celiac, gluten sensitivity
  • 3) drugs - Ca supplements, consumption of large amts of fiber, any constipating drugs (eg opiates, antihypertensives, anticholinergics, vitD, heavy metals, etc)
  • 4) functional
    • a) functional bloating/ dyspepsia
    • b) aerophagia
    • c) IBS
    • d) dyssinergic defecation -> constipation
  • 5) infection
    • a) giardia, cyclospora
    • b) SIBO
  • 6) neurologic
    • a) dysmotility - connective tissue dz
    • b) Hirschsprung's

Ddx of radiographic "peritoneal carcinomatosis"

  • Malignancy: metastatic dz from bladder, colon, gastric, breast, pancreatic, lung, lymphoma vs
  • Non-malignancy: TB, sarcoidosis, crohn's, endometriosis
  • This NEJM has a nice table of other tumors of the peritoneum that could be considered

Cerebral Amyloid Angiopathy

Today, we discussed an elderly patient with a history of hemorrhagic strokes and vascular dementia presenting with "dizziness", found to have cerebral amyloid angiopathy. A few learning points: 

1) Key differentiating factors for peripheral vs. central vertigo: 

2) Illness script for cerebral amyloid antipathy (CAA): In patients over 60 often with Alzheimer's disease or vascular dementia, deposition of congophilic material in small to medium-sized blood vessels of the brain and leptomeninges weakens the structure of the vessel wall and makes them prone to bleeding, leading to a clinical picture of transient neurologic symptoms and spontaneous lobar hemorrhage.

The lobar location helps distinguish CAA-related ICH from hypertensive ICH that more commonly arises in the putamen, thalamus, and pons. However, CAA is the 2nd leading cause of hemorrhagic stroke after HTN. Check out this nice review of CAA in the BMJ. 

3) Treatment of CAA: Acute management of CAA-related ICH is similar to that as for other spontaneous ICH, including BP management

And, because anticoagulant and antiplatelet agents increase the frequency and severity of ICH, these should be avoided in individuals who have probable CAA. 

The important MRI correlates of CAA include: Cerebral micro bleeds, White matter changes (leukoaraiosis), Convexity subarachnoid hemorrhage, Cortical superficial siderosis, and Silent acute ischaemic lesions

The important MRI correlates of CAA include: Cerebral micro bleeds, White matter changes (leukoaraiosis), Convexity subarachnoid hemorrhage, Cortical superficial siderosis, and Silent acute ischaemic lesions

SJS-TEN

Today we discussed a case of Stevens-Johnson Syndrome in a young man who was initially hospitalized for sepsis secondary to spontaneous bacterial peritonitis who developed progressive oral ulcers, groin desquamation, and severe oral swelling and hemoptysis requiring intubation a few days after starting pip/tazo. Some learning points: 

1) Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS and TEN) are considered variants of a disease continuum and are distinguished primarily by severity, based upon the percentage of body surface involved with blisters and erosions. 

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2) The most common trigger of SJS/TEN is drugs, usually started in the last 8 weeks (average 14 days). The most common causes for adults are: allopurinol, anticonvulsants (lamotrigene, phenobarbital, carbamazepine), sulfa antibiotics, NSAIDs, and nevirapine.

Infection with Mycoplasma pneumoniae is the next most common trigger. Other rare causes include vaccinations, contrast, herbal medicines, and radiation (particularly if on a common trigger drug).

A careful history is the key to finding the trigger and preventing future episodes--and the ALDEN criteria can help. 

3) The diagnosis is clinical and is suggested by a prodrome of fever and malaise and a painful rash with erythematous macules/targetoid lesions (or in some cases vesicles and bullae with a positive Nikolsky sign, associated with oral, ocular, and/or genital mucositis with painful mucosal erosions. Biopsy is can help confirm and exclude other causes. 

4) The SCORTEN score can assist in assessing the severity and includes a point for each of: age, malignancy, BSA, tachycardia >120, urea, glucose, bicarb. Scores >2 should be treated in the ICU.

5) Management includes discontinuation of the offending medication--and supportive care (wounds, fluids/electrolytes, nutrition, pain control, monitoring for superinfections).  The use of systemic corticosteroids and IVIG is controversial.

Fluids or Diurese?

Today we discussed a core internist-struggle: To give fluids or not to give fluids, that is the question!  We discussed a case where the differential came down to pneumonia/sepsis vs decompensated heart failure, and the question: treat with IV fluid resuscitation or diurese?

Faculty, I want to make it known that our interns are ready to be senior residents!  They did a fantastic job at identifying key history, physical exam, radiographic, and serologic findings to aid in their decision making and treatment plan.

Some learning points identified were the following:

1. There is a value of a PA and lateral chest xray instead of a single-view portable to evaluate for pneumonia vs pulmonary edema.  This helped the team identify Kerley lines, evaluate a possible retro-cardiac consolidation, and determine the presence of small effusions.

2. The physical exam, especially the presence of a 3rd heart sound and elevated JVP, are imperative in this evaluation.  Here is a nice table of the likelihood ratios for dyspnea due to heart failure.

3. Captopril dosing and conversion between it and lisinopril is about 5:1 in total daily dosing.  Here is a review by New Zealand's Pharmaceutical Management Agency on how to convert the two doses.

4. Broad DDx of shock/hypotension:
        Distributive: Septic, anaphylactic, neurogenic, adrenal insufficiency, cirrhosis
        Cardiogenic: MI, HF
        Obstructive: PE, tamponade, pneumothorax, abdominal compartment syndrome
        Hypovolemic: blood loss, overdiuresis, significantly low PO intake

Since you are probably curious... the patient was diuresed and clinically improved.