VA ICU report 6.7.17: Neutropenic fever and subdural hemorrhage.

Case Summary
Thank you to our awesome ICU team and Ivan for presenting a fascinating case of an elderly patient with refractory multiple myeloma who presented with AMS and found to have neutropenic fever and a chronic subdural hematoma!

Top pearls
  • In neutropenic fever, the lack of immune response changes the typical illness script for many infections.
    • Localizing features are often absent and an isolated fever is the most common presentation
    • UTIs may present without pyuria and meningitis without CSF pleocytosis
    • CXR may not show infiltrates; have a low threshold to get a CT chest.
  • Focal neurologic dysfunction is a rare presentation of subdural hematoma, usually a more diffuse process (e.g headache, personality changes) is impaired.
  • A history of trauma is absent in > 50% of cases of chronic subdurals.
    • This is one strong reason to consider a CT in patient with subacute AMS.

Neutropenic Fever
Definition
  •  Neutropenia and fever must be present
    • Fever
      • Defined as temp > 38 for 1 h or one reading > 38.3
    • Neutropenia
      • ANC < 500 or  ANC expected to be < 500 within 48 hours
      • Profound neutropenia defined as ANC < 100
Pathophysiology
  • Febrile neutropenia most commonly develops in patients receiving high dose cytotoxic therapy.
    • Most common in liquid tumors.
    • Of solid tumors sarcomas and germ cell tumors require high dose chemo
  • Risk is proportional to
    • Severity and duration of neutropenia
      • Typically, PMNs nadir 5-10 after chemo and lasts for an average of 5-7 days
    • Coexistent liver or renal insufficiency
    • Pre-existing bone marrow dysfunction (e.g. MDS)
    • Compromise of protective mucosal barriers
      • Mucositis
      • Indwelling lines
Microbiology
  • The vast majority of patients will remain culture negative
  • Bacterial pathogen is isolated in 30% of cases
    • More likely with prolonged and profound neutropenia
    • Historically,  GNR >> GPC, but with more lines, GPC infections are increasing
  • Fungal infections are more likely with prolonged neutropenia and are a common etiology of persistent neutropenic fever
Clinical presentation
  • An isolated fever is the most common presentation with the lack of an immune response accounting for the absence of localizing symptoms.
  • As a result, the physical exam is crucial in the patients, with special attention to
    • Oropharynx
      • Mucositis
      • Periodontal disease
    • Skin exam
      • Closer examination of long-term catheter sites.
    • Peri-rectal exam (peri-rectal abscess)
      • Avoid digital rectal exam
Diagnostics
  • Diagnostics are similarly influenced by a lack of an immune response and thus
    • Pyuria may be absent in UTIs
    • CSF WBCs may be normal in encephalitis/meningitis
    • Radiographic infiltrate may be absent on CXR —> low threshold to get a CT
  • The initial work up is similar to febrile patients without neutropenia (blood culture, UA, CXR, etc)
Treatment
  • Similar to sepsis, early antibiotic therapy is crucial and has a mortality benefit.
  • However, this therapy does not necessarily need to be done as an inpatient.
  • See the treatment algorithm below from a great review in the Mayo Clinic Proceedings Journal.

Subdural Hematoma
Overview
  • Nature of bleeding
    • Venous bleeding from bridging veins account for > 70% of cases
      • Patients at higher risk are those with “longer” bridging veins i.e brain atrophy
    • Arterial bleeds in 20-30%
  • Divided into
    • Traumatic casuses
      • Usually direct head trauma
        • MVA mosts common
    • Non-traumatic
      • Coagulopathy
      • Low-CSF pressure
        • Bridging veins are “tugged” by a shrinking brain.
      • Aneurysm rupture
        • Usually cause SAH, but rarely can cause isolated SDH
      • Dural metastasis
      • AVMs
Clinical Manifestations
The distinction between acute and subacute/chronic SDH (a important masquerader of many conditions) strongly informs the clinical manifestations
Acute subdural
  • Presentation exists along a spectrum ranging from transient LOC to coma.
    • Coma occurs in 50% of cases
Chronic subdural
A history of trauma may be absent in up to 50% of cases. This is one reason to consider a CT in patients with subacute AMS
  • The insidious onset of global deficits/symptoms is most common
    • Insidious headaches
    • Cognitive impairment
    • Apathy
    • Seizures – rare
  • Focal deficits are, again, less common but can be
    • Contralateral
      • Compression of the adjacent cortex
    • Ipsilateral
      • Compression of the contralateral brainstem producing ipsilateral defects
    • Bilateral
      • Bitemporal chronic SDH can lead to intermittent paraparesis – usually proximal
Diagnosis
  • CT is the best initial diagnosis with sensitivity >95%
  • MRI may be needed in rare instances with small subdural
Treatment
  •  Acute SDH
    • The vast majority of acute SDH will require urgent surgical management
  • Chronic SDH
    • The possibly of spontaneous resolution prompts consideration of watchful waiting in some of these patients
      • Consider non-surgical management in patients with minimal symptoms and small hematoma burden
    • Surgical management is indicated in patients with “significant” symptoms
*Reversal of anticoagulation is a critical intervention in all these patients.
Prognosis
  • CT findings that correlate with poor outcome
    • Hematoma thickness and volume
    • Findings of elevated ICP
      • Midline brain shift
      • Reduced patency of basal cisterns
  • Mortality of acute SDH
    • Requiring surgery =  40-60%
    • GCS of 3 on presentation = 93%
    • Age > 50 = 75%
  • Recurrence
    • Acute SDH: rare
    • Chronic SDH: 5-30% of patients
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