title: Evaluating the evidence: is phrenic nerve stimulation a safe and effective tool for decreasing ventilator dependence in patients with high cervical spinal cord injuries and central hypoventilation?
abstract: BACKGROUND
  Case reports, case series and case control studies have looked at the use of phrenic nerve stimulators in the setting of high spinal cord injuries and central hypoventilation syndromes dating back to the 1980s. We evaluated the evidence related to this topic by performing a systematic review of the published literature.
  
  
  METHODS
  Search terms "phrenic nerve stimulation," "phrenic nerve and spinal cord injury," and "phrenic nerve and central hypoventilation" were entered into standard search engines in a systematic fashion. Articles were reviewed by two study authors and graded independently for class of evidence according to published guidelines. The published evidence was reviewed, and the overall body of evidence was evaluated using the grading of recommendations, assesment, development and evaluations (GRADE) criteria Balshem et al. (J Clin Epidemiol 64:401-406, 2011).
  
  
  RESULTS
  Our initial search yielded 420 articles. There were no class I, II, or III studies. There were 18 relevant class IV articles. There were no discrepancies among article ratings (i.e., kappa = 1). A meta-analysis could not be performed due to the low quality of the available evidence. The overall quality of the body of evidence was evaluated using GRADE criteria and fell within the "very poor" category.
  
  
  CONCLUSIONS
  The quality of the published literature for phrenic nerve stimulation is poor. Our review of the literature suggests that phrenic nerve stimulation is a safe and effective option for decreasing ventilator dependence in high spinal cord injuries and central hypoventilation; however, we are left with critical questions that provide crucial directions for future studies.
authors.affiliation: Departments of Neurosurgery, Penn State Milton S Hershey Medical Center, Hershey, PA, USA. esieg@hmc.psu.edu.
authors.forename: Emily P
authors.initials: EP
authors.lastname: Sieg
authors.affiliation: Departments of Neurosurgery, Penn State Milton S Hershey Medical Center, Hershey, PA, USA.
authors.forename: Russell A
authors.initials: RA
authors.lastname: Payne
authors.affiliation: Departments of Neurosurgery, Penn State Milton S Hershey Medical Center, Hershey, PA, USA.|Departments of Anesthesia, Penn State Milton S Hershey Medical Center, Hershey, PA, USA.
authors.forename: Sprague
authors.initials: S
authors.lastname: Hazard
authors.affiliation: Departments of Neurosurgery, Penn State Milton S Hershey Medical Center, Hershey, PA, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Rizk
mesh_terms: D002574:Cervical Vertebrae; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D004599:Electric Stimulation Therapy / Q000379:methods*; D006801:Humans; D007040:Hypoventilation / Q000628:therapy*; D010791:Phrenic Nerve / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000628:therapy*
keywords: Central hypoventilation; Diaphragmatic stimulation; High cervical spinal cord injury; Phrenic nerve stimulation; Ventilator weaning