2.1. Patient 1
In early December 2009, a 26-year-old morbidly obese Hispanic female presented with dyspnea and tachypnea. Her medical history was significant for asthma with several previous hospitalizations for flare-ups, and a 20 pack-year history of smoking (). She became confused, cyanotic, and short of breath. Her temperature was 101 °F (38.3 °C) and her oxygen saturation was 65% on room air. A chest radiograph obtained in the emergency ward (EW) demonstrated diffuse bilateral airspace opacities. The patient was admitted for pneumonia. On hospital day 1, she required intubation and mechanical ventilation. Broad spectrum antibiotic coverage was initiated and soon she developed oliguric acute renal failure. A nasal swab reverse transcriptase–polymerase chain reaction (rt–PCR) testing for H1N1 was positive. Over the next 2 days, she became anuric and continuous veno-venous hemofiltration (CVVH) was initiated. Nitric oxide nebulizer treatments were started for difficulty with oxygenation on ARDS ventilator settings. On hospital day 4, the patient had a new fixed (non-reactive) and dilated left pupil, measuring 8 mm. Neurology was emergently consulted for presumed transtentorial brain herniation in the setting of hyponatremia (serum Na, 126 mmol/L) and possible brain edema. Mannitol (100 g) and hypertonic saline (30 mL of 23% sodium chloride) boluses were immediately administered en route to the CT scanner. Imaging revealed diffuse effacement of the cortical sulci, a left uncus tightly abutting the midbrain without frank transtentorial herniation, and subtle loss of gray– white matter differentiation, particularly in the bilateral corticies (left greater than right), indicative of diffuse cerebral edema. An external ventricular drain (EVD) was emergently placed with an opening pressure of 26 cm H2O. Hypertonic saline boluses (23%) and a continuous 3% hypertonic saline infusion with a rate up to 60 mL/hour were administered. In addition, intermittent boluses of mannitol were given and cerebrospinal fluid (CSF) drainage from the EVD (averaging 280 mL of CSF per day) were required over the next 2 days to maintain intracranial pressure (ICP) below 20 cm H2O, and serum Na at a goal of >145 mmol/L (). Her pupils returned to normal size and function 7 hours following the placement of the EVD and initiation of hyperosmolar therapy. CSF culture, chemistries, and cell counts sampled from the EVD catheter remained unremarkable. After 14 days of aggressive therapy without signs of recovery, her family decided to transition her care to comfort measures only, and she died soon thereafter.
Selected characteristics and laboratory, radiologic, and neurodiagnostic results for two patients with acute neurologic complications associated with novel influenza A (H1N1)
Patient 1: graph showing timeline of serum sodium (Na) and intracranial pressure (ICP).
2.2. Patient 2
In mid-August 2009, a 29-year-old, previously healthy man originally from Brazil developed progressive myalgias, dry cough, and headache (), along with chest pain on inspiration. A chest radiograph showed incomplete segmental consolidation of the apical posterior segment of the right upper lobe. Levofloxacin was started for presumed community-acquired pneumonia, and the patient was discharged home. The next day the patient developed nausea, vomiting, and blood-tinged emesis; he returned to his local hospital EW. On presentation, he was afebrile with a respiratory rate of 30/minute and an oxygen saturation of 94% on room air. A chest radiograph obtained in the EW demonstrated multifocal pneumonia. The patient was admitted to the hospital and started on broad-spectrum antibiotics. Later that day the patient was intubated for increasing respiratory distress and hypoxia; then transferred to our hospital.
The neurological exam at the time of transfer was limited secondary to the use of sedation and paralytics necessary for ventilation and oxygenation. Laboratory values revealed a serum sodium of 123 mmol/L (from 136 mmol/L on presentation 1 day earlier) confirming the diagnosis of acute hyponatremia. The patient soon developed oliguric renal failure. On hospital day 3, he was initiated on CVVH. In the early evening on hospital day 4, he was found to have an unreactive 8-mm right pupil. Serum Na was 126 mmol/L. Mannitol (100 g) and hypertonic saline (23%) boluses were immediately administered empirically. Continuous 3% hypertonic saline infusion was initiated. Chemical paralysis continued to be required and the patient was too unstable to undergo a portable CT scan. Given the concern for increased ICP and the inability to obtain routine neurological exams secondary to sedation and paralysis, an ICP monitor was indicated. However, the patient had an iatrogenic coagulopathy (therapeutic heparin infusion necessary to maintain vascular access for CVVH).
By the morning of hospital day 5, the patient’s pupils equalized in size at 4.5 mm. The serum Na was now 148 mmol/L. The patient continued on maximal ventilator settings. On hospital day 6, the patient’s condition stabilized such that a head CT scan could be attained. A non-contrast CT scan of the head demonstrated bilateral effacement of the cortical sulci, tight basal cisterns, and mild loss of gray/white cortical differentiation, consistent with diffuse cerebral edema (). Nasal swab rt–PCR testing for H1N1 was positive. On hospital day 7, the patient’s hemodynamics became increasingly unstable. The patient was unable to lay flat without developing increasing right pupillary diameter (indicating elevated ICP and third nerve compression from the adjacent temporal lobe). On the hospital day 8, the patient became increasingly hypoxic and acidotic. Hemodynamic instability developed into cardiac arrest and the patient expired despite extreme resuscitative efforts.
Patient 2: axial head CT scan showing diffuse cerebral edema.