Angioedema and hyperkalemia management

Thanks to Audris for presenting the case of a middle-aged man with vasculopathy on ACEi who presented with angioedema requiring intubation!  We discussed the  diagnostic work up and management of angioedema as well as hyperkalemia!


Clinical Pearls

  • First order of business when suspecting angioedema is the ABCs!
  • Treat angioedema in the acute setting with H1 blockers and steroids, even if you are suspicious of a non-histaminergic pathway.
  • Always assess for concurrent anaphylaxis (hypotension or bronchospasm in addition to hives or angioedema).  If anaphylaxis is present, then treatment involves IM 0.3-0.5 mg of 1:1000 dilution epinephrine (1mg/mL), repeat every 20 minutes until symptoms resolve (max 3 doses)
  • If you have access to a functioning kidney, favor loop diuretics over cation exchange binders (i.e. kayexalate) to lower serum potassium!
  • Patiramer is much better tolerated than kayexalate and has a more favorable side effect profile.
  • Calcium gluconate has a role in the treatment of hyperkalemia when EKG changes are present. Give a dose and repeat the EKG.  If no improvement, repeat to a maximum of 3 doses until EKG has normalized.

Angioedema 

  • 3 pathophysiologic subtypes:
    • Mast cell/histamine mediated
      • Etiologies:
        • Allergic reactions: food/insect stings, latex, drugs. Can also be idiopathic. IgE type 1 hypersensitivity
        • Direct mast cell release: drugs (opiates, contrast). IgE is not involved.
        • ASA/NSAIDs: via IgE or direct mast cell release
        • Chronic urticaria w/w/o angioedema
      • S/sx affecting organ systems other than the skin? Suspicious for anaphylaxis ⇒ give epi
      • Treatment: H1 blockers, glucocorticoids. 
    • Bradykinin mediated
      • Inhibition of enzymes involved in the degradation of bradykinin, or deficiency/dysfunction of complement C1 inh
      • More prolonged time course, develops over 24-46 hours and resolves within 2-4 days
      • Relationship between trigger and onset of symptom is not as apparent
      • Not associated with other s/sx. More common to have abdominal pain due to bowel wall involvement.
      • Treatment: bradykinin pathway mediators (ecallantide, icatibant), C1 inhibitor concentrate, or plasma replacement.
    • Unknown mechanism
      • Idiopathic angioedema
      • Infections (in children)
      • CCBs
      • Other drugs: sirolimus, everolimus, amiodarone, metoprolol, risperidone, paroxetine, and etanercept, inhaled cocaine.
      • Herbal meds
      • Urticarial vasculitis
      • Hypereosinophilic syndrome and Gleich syndrome

 

Capture

Hyperkalemia

Agents that reduce serum potassium via transient intracellular shift:

  • Insulin: give with D50 if normoglycemic to avoid hypoglycemia and be sure to check FSG hourly for 4 hours after to ensure no hypoglycemia develops
  • Albuterol (10-20 mg) nebs: this is significantly higher than the dose we give in COPD (2.5 mg) and is equal to ~8 treatments! So make sure to continue the nebs when the patient arrives on the floor from the ER if they are still hyperkalemic.
  • NaHCO3: best for management of chronic hyperkalemia in the outpatient setting.  In the acute management of hyperkalemia, alkalinization of serum with a large bicarb load can lead to a reduction in serum calcium levels.  Lower serum calcium can lead to more cardiac membrane instability and fatal arrhythmias!

Agents that eliminate potassium from the body:

  • Loop diuretics: first choice if a functioning kidney is available!
  • Cation exchange binders: preferred when kidneys are not available
    • Patiramer (available at VMC), much more tolerable than kayexalate and highly effective at lowering serum potassium.  Like kayexalate, it works over hours to days.
    • Sodium zirconium: similar to patiramer but not currently available
    • Kayexalate: not pleasant to take orally. Also carries with it the slight risk of colonic ischemia especially in post renal transplant patients and those with baseline colonic dysfunction (due to infection or inflammation).
  • Dialysis

Indication for using calcium gluconate: when EKG changes are noted.  Repeat doses (maximum 3) until EKG changes have resolved.

Gradenigo Syndrome

Thanks to Amit for presenting the fascinating case of a middle-aged woman with history of DM2 who presented with subacute onset of unilateral periorbital pain, L CN 6 palsy, and L otorrhea, with MRI findings of petrous apicitis consistent with the super rare Gradenigo syndrome!


Clinical Pearls

  • Gradenigo syndrome is a rare and life threatening complication of otitis media and involves inflammation of the medial aspect of the temporal bone, specifically the apex of the petrous bone (a pyramid shaped bone jutting medially from the temporal bone)
  • Gradenigo is clinically characterized by a triad of otorrhea, diplopia (due to CN6 palsy), and hemifacial pain (CN5 palsy).
  • This is a very rare complication since most cases of otitis media are treated with antibiotics early on.
  • Remember that a common cause of an isolated CN 6 palsy in a diabetic patient is diabetic neuropathy/ophthalmoplegia.  A patient who has more cranial nerves affected than CN6 alone, you should be concerned about cavernous sinus thrombosis.

Gradenigo syndrome:

  • First described in 1904 by Guiseppe Gradenigo.

    Petrous pyramid
    Source: AO Surgery Reference
  • A rare and potentially life threatening complication of otitis media involving the inflammation of the apex of petrous pyramid (medial aspect of temporal bone). Occurs any time between 1 week to 3 months after acute otitis media (AOM) and up to 3 years after chronic suppurative otitis media (CSOM).
    • Should suspect this syndrome any time there is CN 6 palsy in the setting of otitis media, whether acute or chronic
  • Clinically, Gradenigo syndrome is characterized by triad of ear discharge, diplopia, and hemifacial pain
    • Suppurative otitis media (ear discharge and pain)
    • Trigeminal neuralgia involvement causes pain in the distribution of the nerve manifested as hemicranial headache and hemi-facial pain
    • Abducens nerve involvement causes ipsilateral lateral rectus palsy and lateral gaze palsy
  • Infection spread from suppurative otitis media to the petrous apex may be via pneumatized air cell tracts, through vascular channels, or as a result of direct extension through fascial planes
  • Organisms are not well studied but the most common one appears to be pseudomonas.  Staph, strep, pneumococcus, and TB have also been reported.
  • If left untreated, it can result in serious complications such as meningitis, intra-cranial abscess, sinus thrombosis
  • Treatment
    • Broad spectrum antibiotics IV for up to 6 weeks (to treat a presumed temporal bone osteomyelitis)
    • Fluoroquinolone ear drops
    • Tight glucose control
  • Differential diagnoses to consider:
    • Cavernous sinus thrombosis
      • Headache
      • cavernous sinus thrombosis
        Source: UpToDate

        Papilledema

      • CN palsies (see picture of what runs through cavernous sinus)
    • Ophthalmoplegic migraine:
      • Rare condition, often manifests in children and young adults
      • Diagnosis of exclusion
      • Most commonly affects CN3 (but can go to CN4 and CN6 as well)
      • Can sometimes precede the headache
      • Review article here
    • Diabetic ophthalmoplegia
      • Common cause of isolated CN6 palsy
    • Neoplasms
      • Nasopharyngeal cancer
      • Plasmacytoma
      • Pituitary adenoma
      • CN6 neuroma
      • Skull base tumors
      • Sohenoid sinus tumors
      • Squamous cell
    • Stroke
    • Demyelinating diseases
    • Vasculitis
    • Idiopathic intracranial hypertension

Complications of acute otitis media

  • Intratemporal
    • Tympanic membrane rupture (leads to hearing loss and pain relief!)
    • Labrynthitis (nausea, vomiting, tinnitus, vertigo)
    • Mastoiditis
    • CN palsies (including Gradenigo syndrome)
  • Extratemporal
    • Epidural, subdural, and brain abscesses
    • Skull base osteo
    • Otitic hydrocephalus (without meningitis or brain abscess)
    • Otitic meningitis
    • Lateral sinus thrombosis