Nestor D. Tomycz M.D., Raj Nangunoori B.S., Joseph Hobbs M.D., Donald M. Whiting M.D., Michael Y. Oh M.D. Department of Neurosurgery, Allegheny General Hospital, Pittsburgh, PA, U.S.A.

 Baclofen: an analogue of γ-aminobutyric acid (GABA)  Oral baclofen  In 1984, Penn and Kroin demonstrated the effectiveness of intrathecal baclofen  Intrathecal baclofen (ITB) has become routine in the management of spasticity and dystonia arising from either spinal or cerebral origin

 Dearth of literature which effectively characterizes complications related to ITB therapy  No coherent system for reporting ITB complications  To better characterize complications related to ITB therapy and to devise a simple, comprehensive, and more patient- centered scheme for complication reporting

 MEDLINE search: January 1985 to May 2010  N≥10 and if complications were reported  Articles were excluded if N<10 and if there were multiple articles by the same author with an overlap in patient populations  310 articles found, 28 met criteria  Reclassified complications into 4 categories: technique, device, drug, and infection

 Technique: due to the operative procedure itself ◦ CSF-related complications (CSF wound leaks, pseudomeningoceles), hematoma/seroma, and wound dehiscence  Drug: subjective complaints and symptoms related to baclofen ◦ Nausea, vomiting, somnolence, hypotonia, hypertonia, gastrointestinal disturbances, respiratory depression, and coma, overdose and withdrawal  Device: problems with the hardware itself ◦ pump (flipping, failure), catheter (kinks, breaks, tears, and migration)  Infections: related to the pump or catheter incision ◦ Wound infection/dehiscence was categorized here due the cause and effect relationship to the two, “wound dehiscence” was otherwise categorized as a complication of surgical technique.

 28 papers met criteria for systematic review and included prospective trials, retrospective studies, and case series  2,623 unique patients, 1,637 complications  Combined complication incidence: 62.4%  Range in total complication incidence: %  Device complications (n=587, 35.5%) were the most frequent followed by drug (n=544, 33.2%) followed by technique (n=293, 17.8%), and infection (n=213, 13.4%)

 Among technique complications, CSF-related complications (n = 113, 6.9%) were the most common followed by hematoma/seroma (n = 14, 0.9%)  Among drug complications, non-postural headache, nausea, vomiting, dizziness, and drowsiness were the most commonly reported (n = 212, 13.0%)  Baclofen overdose/withdrawal: n = 28, 1.7%  Among device complications, catheter-related problems were the most common (n = 193, 11.8%)  8/28 studies (28.6%) reported no drug complications

Table 1. Complications by Author Articles (Author)Year# of patientsTechnique (%)Drug (%)System (%)Infection (%)# of complic Albright et al Albright et al Smail et al Follett et al Gilmartin et al Gooch et al Guillaume et al Ivanhoe et al McCall et al Murphy et al Nielsen et al Plassat et al Rawlins et al Sadiq et al Vender et al Wunderlinch et al Zahavi et al Hoving et al Motta et al Armstrong et. al Borowski et. al Heetla et. al Rawicki et. al Ford et. al Penn et. al Coffey et. al Teddy et. al Penn et. al patients293 technique complications 544 drug complications 587 device complications 213 infections1637 total complications

Table 1. Technique Complications Defined Complication# of Total Events% of Total % of Surgical Complications CSF leak (and other CSF-related) wound hematoma/seroma other non-serious pain/discomfort/swelling wound dehiscence spinal headache surgery related wound pruritus wound leakage moving pump skin necrosis/breakdown suture site inflammation incontinence pocket erosion catheter dislodgement during surgery debridement of granuloma incomplete operation pressure ulcer femoral vessel occlusion skin erosion req. pump removal

Table 2. Drug Complications Defined Complication # of Total Events % of Total % of Drug Complications headache/nausea/vomiting/dizziness/d rowsiness hypotonia/hypertonia/muscle weakness/spasms epileptic seizures/convulsions/psychiatric changes/alteration in consciousness constipation/urinary or fecal incontinence/drooling or salivation drug overdose/withdrawal and drug overinfusion/underinfusion § cardiovascular/respiratory system related dysarthria/dysphagia/appetite changes/difficulty swallowing other accidental injury pain loss of efficacy/lack of response pressure sore sweating auditory hallucinations baclofen side effects when oral medication added decubitus decreased trunk control significant side effect/drug adverse effect dry mouth malignant hyperthermia/death* chemical meningitis hair loss paroxysmal paleness urticaria hypothermia coma after baclofen overdose

Table 3. Device Complications Defined Complication # of Total Events # of Total % of Device Complications catheter kink/break/tear/hole/occlusion catheter disconnection/dislodgement/ migration* unspecified catheter problems/catheter dysfunction pump problems (flip/failure/others) catheter problems (drawing out, disconnection, breakage) § other catheter fibrosis catheter cut, break, or disconnection § malfunction of unidentified cause underinfusion back pain at catheter site inversion malfunction of side port

Table 4. Infection Complications Defined Complication# of Total Events% of Total% of Infections Infection (unspecified) pump explantation due to infection pump/pump pocket infection wound infection/dehiscence septic/aseptic meningitis infection in the back urinary tract infection lumbar infection aspiration pneumonia infected hematoma infection w/pump salvage after antibiotic therapy cystitis

 Our primary objective: report the combined incidence of complications related to ITB therapy and to devise a classification scheme that is more patient-centered  We selected the 4 categories for classification for their simplicity and comprehensiveness  We found a combined complication incidence of 62.4%

 The incidence of complications related to ITB remains high  Much of the reporting on ITB complications has neglected patient- centered complaints (especially drug complications)  Although ITB has been touted as having a lower side effect profile than oral baclofen, drug complications from ITB are not rare  Improvements in ITB may be prompted by better complication reporting  The 4-tiered complication scheme for ITB will help patients better appreciate the risks of ITB