Multiple extubation failures following a rhino-enteroviral infection: A unique case report in a pediatric patient.

This case report reviews the hospital course of a 15-month-old girl admitted to the PICU for acute respiratory failure due to enterovirus infection; who subsequently had multiple extubation failures secondary to acute transverse myelitis. This rare presentation highlights the importance of assessing the neurological status in a patient with rhino-enteroviral respiratory infection and of considering acute transverse myelitis as an etiology for difficulty with extubation.

Introduction

Extubation failure in critically ill pediatric patients has been shown to be independently associated with up to a five-fold increased risk of mortality.[1] Although risk factors for extubation failures have been well described, which include young age, prolonged mechanical ventilation, sedative usage, and recently diaphragm atrophy, the etiologies underlying extubation failures are still poorly understood.[2] We describe a case report of a toddler with multiple failed extubation attempts secondary to rare complications of an enterovirus infection, reported in only two other pediatric patients.

Case History

A 15-month-old previously healthy and developmentally normal female presented to an outside hospital emergency department (ED) with 5 days of cough and congestion. While in the ED, she developed hypoxia and significant respiratory distress, requiring intubation and subsequent transfer to our institution's pediatric intensive care unit for further management.

She was intubated with a 4.0 uncuffed ET tube, discovered to be in the right mainstem bronchus and subsequently drawn back to the appropriate location upon admission. A respiratory panel PCR obtained was positive for rhinovirus/enterovirus. The transport team placed the patient on sedation infusions during medical transport, which was continued upon ICU admission. Because the patient was stable on mechanical ventilation with a source for respiratory failure, sedation was not weaned to attempt a thorough neurological examination upon admission. The only neurological examination performed was a pupillary examination revealing adequate sedation. Extubation was attempted on day one of her hospitalization. Prior to this extubation event and each extubation event thereafter, the team ensured improvement in her lung pathology using clinical and radiologic evidence, including an exam that revealed good sounds bilaterally without crackles or wheezes and pre-extubation x-rays that revealed significant improvement in lung pathology including atelectasis, pulmonary edema, and pleural effusions. Additionally, the patient tolerated continuous positive airway pressure (CPAP) trials and was weaned to minimal ventilation support. The first extubation attempt was unsuccessful and she was re-intubated that day with a 3.5 cuffed ET tube situated appropriately. After providing the patient with increased positive end-expiratory pressure (PEEP) and frequency of pulmonary toilet regimen, respiratory status gradually improved with settings able to be weaned. On hospital day seven, the patient underwent a second attempt at extubation that was unsuccessful, and the patient was subsequently re-intubated with a 3.5 cuffed ET tube situated appropriately. Pulmonology was consulted to assist with management and performed a bronchoscopy that was unremarkable and ruled out anatomical defects. On hospital day 16 after continued improvement in respiratory status, the patient underwent a third extubation attempt that was successful. The patient quickly transitioned from bilevel positive airway pressure (BiPAP) to high flow nasal cannula (HFNC).

On hospital day 18, the patient required an increase in respiratory support back to BiPAP and was noted to have movement in her bilateral lower extremities but not in her bilateral upper extremities. All sedation was subsequently held. Neurology was consulted and upon examination noted intact cranial nerves, diffuse hypotonia, 0/5 motor strength in bilateral upper extremities and 3/5 motor strength in bilateral lower extremities, absence of deep tendon reflexes throughout all extremities, and indeterminate sensation in all extremities. An MRI of her brain and spine under sedation was obtained for further workup. MRI showed lesions involving predominantly white matter in the cervical cord from the C2 to T2 levels [see Figure 1], suggestive of a viral myelitis. Repeat MRI with DWI was obtained and ruled out infarction. Infectious disease was consulted and recommended obtaining an LP with CSF and send-out serum autoimmune and demyelinating panels, particularly neuromyelitis optica and lupus. All laboratory tests obtained in this stage of the workup, including infectious and autoimmune conditions, came back normal [Table 1].

Figure 1

Cervical spine magnetic resonance imaging (MRI) with and without contrast showing patchy T2 hyperintensity involving predominantly white matter from second cervical spine to second thoracic spine (C2 to T2) levels on T2 turbo spin echo (TSE) imaging. There is myelomalacia at the third cervical spine to seventh cervical spine (C3 to C7) levels. Repeat imaging showed no definite enhancement or diffusion restriction

Table 1

CSF study results obtained from the first lumbar puncture

CSF parameters	Results
WBC (/mm3)	<1
RBC (/mm3)	3
Glucose (mg/dL)	75
Total protein (mg/dL)	20.8
Meningitis/encephalitis viral panel	Not detected
West Nile IgM Ab	0 (negative)
NMO*/aquaporin-4 IgG Ab	<1:1 (negative)
VDRL†	negative

*NMO=Neuromyelitis optica †VDRL=Venereal Disease Research Laboratory

Due to high index of suspicion for an autoimmune process while waiting for the send-out tests to result, this patient received high dose steroids for 5 days started on hospital day 21, followed by five doses of plasmapheresis in conjunction with hydrocortisone started on hospital day 24, and finally a five-day course of IVIG started on hospital day 36.

Following her initial MRI, the patient returned with an LMA and was re-intubated soon afterwards due to mixed respiratory failure. The patient continued to have no change in symptoms following the intense medication regimen. Due to inability to wean off mechanical ventilation, the patient underwent tracheostomy on hospital day 39 and was eventually transitioned to a trilogy ventilator. The patient was admitted to the inpatient rehabilitation service on hospital day 57. She received a gastrostomy tube on hospital day 74. She was discharged on hospital day 107 with diagnosis of transverse myelitis secondary to enterovirus resulting in tetraplegia, dependence on tracheostomy, ventilator, and gastrostomy tube [Figure 2].

Figure 2

Timeline of patient course throughout hospitalization. CPAP = Continuous Positive Airway Pressure, BiPAP = Bilevel Positive Airway Pressure, MRI = Magnetic Resonance Imaging, ID = Infectious Disease, LP = Lumbar Puncture, PLEX = Plasma Exchange, IVIG = Intravenous Immunoglobulin

Discussion

Our case described here is a unique report of respiratory failure secondary to acute transverse myelitis (ATM) caused by enterovirus in a young child who had multiple extubation failures. Two main types of acute myelitis exist: AFM and ATM.[3] AFM has an incidence of 14 children out of every 1,000,000 and is characterized by lesions primarily restricted to the anterior horn cells resulting in primarily motor weakness. AFM has been shown to be temporally associated with enterovirus D68 and A71, although its causality has yet to be proven.[4] The typical clinical course of AFM involves unilateral paralysis of an extremity that may spread to other extremities. ATM, which our patient was diagnosed with, is less common, with an incidence of two out of 1,000,000 children affected each year. Etiology is thought to be immune mediated, but no identifiable marker has been elicited, and most cases are associated with infectious prodrome.[5] Lesions in both gray and white matter result in sensory, motor, and autonomic dysfunction. Paralysis is typically bilateral and can be rapid. Very few case reports describe enterovirus-associated ATM, and most of these cases have been described in adults.[678910] The only documented case reports of enteroviral-associated ATM in pediatric patients include two patients in a 14 patient case series from Western Australia, in which both patients presented with rapid-onset acute flaccid paralysis and resulted in quadriparesis similar to our patient.[11]

The diagnostic criteria for ATM consist of exclusion of compressive lesions and confirmation of spinal cord inflammation as detected by either: A gadolinium-enhancing lesion in MRI, or CSF evidence of either pleocytosis or elevated immunoglobulin type G (IgG) index. Additionally, exclusion of demyelinating conditions, such as neuromyelitis optica and systemic autoimmune conditions, such as lupus is necessary.[6]

Treatment for ATM includes high dose steroids, intravenous immunoglobulin (IVIG), and plasmapheresis, but no prospective trials have demonstrated efficacy to date. Retrospective analysis has shown improved outcomes with high dose steroids and plasmapheresis in pediatric patients with ATM, and efficacy of IVIG is limited to case reports and series.[1213] Treatment with high dose steroids is preferable as soon as ATM is suspected given that outcomes of patients with mimics of the disease do not worsen with treatment.[13] There is a paucity of literature discussing respiratory dysfunction or the optimal supportive management in acute transverse myelitis. Borrowing from management strategies for acute respiratory failure in neuromuscular disorders, non-invasive ventilation (NIV) is initially used by many institutions although the efficacy of NIV over mechanical ventilation has not been well studied.[14]

In our patient, the respiratory panel PCR being positive for rhino-enteroviral infection and an extubation failure warranted further investigation into underlying etiologies. The patient's young age put her at increased risk of extubation failure but given that she had failed extubation twice within 7 days of hospitalization, prolonged mechanical ventilation, and sedation were not likely risk factors. Successful CPAP trials and pre-extubation dexamethasone prior to the second and third attempt preceded all extubation attempts. Additionally, there were no confounding factors of high-dose steroids, paralytic drug infusions, or drug-induced myopathy prior to diagnosis of ATM.

Declaration of patient consent

The authors certify that appropriate patient consent was obtained.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.