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: 10-570%

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 AuthorArticles (Author) Year # of patients Technique (%) Drug (%) System (%) Infection (%) # of complic

Albright et al. 2003 68 11.6 14.9 3.9 1.4 141Albright et al. 2004 100 14.7 0.0 1.0 2.3 54

Smail et al. 2006 64 0.3 0.0 1.5 1.4 13Follett et al. 2000 209 1.7 0.2 4.8 7.0 49

Gilmartin et al. 2000 51 10.2 23.0 4.1 2.3 184Gooch et al. 2004 152 4.1 0.7 9.9 3.8 82

Guillaume et al. 2005 129 3.4 0.2 1.5 1.9 24Ivanhoe et al. 2006 74 3.4 11.2 1.4 2.3 84McCall et al. 2006 48 0.7 0.0 1.7 1.4 15Murphy et al 2002 23 1.4 1.1 1.0 5.2 27Nielsen et al. 2002 79 2.7 0.6 2.9 3.3 35Plassat et al. 2004 40 0.0 6.1 5.3 3.8 72Rawlins et al. 2004 50 5.1 2.6 6.0 0.5 65Sadiq et al. 2006 36 1.0 0.0 3.9 0.0 26

Vender et al. 2006 195 5.8 1.5 9.4 11.3 104Wunderlinch et al. 2006 571 0.0 0.0 0.0 21.1 45

Zahavi et al. 2004 21 5.5 12.9 5.3 0.9 119Hoving et al 2008 17 8.5 9.4 0.5 0.5 80Motta et al. 2007 200 11.6 0.0 3.6 9.4 75

Armstrong et. al. 1997 12 0.3 2.2 1.7 1.4 26Borowski et. al. 2010 174 1.4 5.3 8.2 14.6 112

Heetla et. al. 2009 37 0.0 2.9 1.9 0.9 29Rawicki et. al. 1999 18 0.7 0.6 0.3 0.5 8

Ford et. al. 1996 12 1.0 1.7 0.2 0.0 13Penn et. al. 1995 102 0.0 0.0 11.2 0.0 66

Coffey et. al. 1993 75 1.7 2.2 4.3 0.5 43Teddy et. al. 1992 46 2.7 0.9 4.1 2.3 42Penn et. al. 1989 20 0.3 0.00 0.51 0.00 4

2623 patients 293 technique complications

544 drug complications

587 device complications

213 infections 1637 total complications

Table 1. Technique Complications Defined Complication # of Total Events % of Total % of Surgical

ComplicationsCSF leak (and other CSF-related) 113 6.9 38.6

wound hematoma/seroma 51 3.1 17.4other 23 1.4 7.8

non-serious 22 1.3 7.5pain/discomfort/swelling 16 1.0 5.5

wound dehiscence 14 0.9 4.8spinal headache 14 0.9 4.8surgery related 14 0.9 4.8wound pruritus 4 0.2 1.4wound leakage 4 0.2 1.4moving pump 3 0.2 1.0

skin necrosis/breakdown 3 0.2 1.0suture site inflammation 2 0.1 0.7

incontinence 2 0.1 0.7pocket erosion 2 0.1 0.7

catheter dislodgement during surgery 1 0.1 0.3debridement of granuloma 1 0.1 0.3

incomplete operation 1 0.1 0.3pressure ulcer 1 0.1 0.3

femoral vessel occlusion 1 0.1 0.3skin erosion req. pump removal 1 0.1 0.3

Table 2. Drug Complications

Defined Complication # of Total Events

% of Total % of Drug Complications

headache/nausea/vomiting/dizziness/drowsiness

212 13.0 39.0

hypotonia/hypertonia/muscle weakness/spasms

99 6.0 18.2

epileptic seizures/convulsions/psychiatric

changes/alteration in consciousness

61 3.7 11.2

constipation/urinary or fecal incontinence/drooling or salivation

40 2.4 7.4

drug overdose/withdrawal and drug overinfusion/underinfusion§

28 1.7 5.1

cardiovascular/respiratory system related

20 1.2 3.7

dysarthria/dysphagia/appetite changes/difficulty swallowing

13 0.8 2.4

other 14 0.9 2.6accidental injury 12 0.7 2.2

pain 11 0.7 2.0loss of efficacy/lack of response 8 0.5 1.5

pressure sore 4 0.2 0.7sweating 3 0.2 0.6

auditory hallucinations 2 0.1 0.4

baclofen side effects when oral medication added

2 0.1 0.4

decubitus 2 0.1 0.4

decreased trunk control 2 0.1 0.4significant side effect/drug adverse

effect2 0.1 0.4

dry mouth 2 0.1 0.4

malignant hyperthermia/death* 1 0.1 0.2chemical meningitis 1 0.1 0.2

hair loss 1 0.1 0.2paroxysmal paleness 1 0.1 0.2

urticaria 1 0.1 0.2hypothermia 1 0.1 0.2

coma after baclofen overdose 1 0.1 0.2

Table 3. Device Complications

Defined Complication # of Total Events

# of Total % of Device Complications

catheter kink/break/tear/hole/occlusion

193 11.8 32.9

catheter disconnection/dislodgement/

migration*

137 8.4 23.3

unspecified catheter problems/catheter dysfunction

107 6.5 18.2

pump problems (flip/failure/others)

86 5.3 14.7

catheter problems (drawing out, disconnection, breakage)§

21 1.3 3.6

other 14 0.9 2.4

catheter fibrosis 11 0.7 1.9catheter cut, break, or

disconnection§

6 0.4 1.0

malfunction of unidentified cause

4 0.2 0.7

underinfusion 3 0.2 0.5back pain at catheter site 2 0.1 0.3

inversion 2 0.1 0.3

malfunction of side port 1 0.1 0.2

Table 4. Infection Complications

Defined Complication # of Total Events % of Total % of Infections

Infection (unspecified) 80 4.9 37.6

pump explantation due to infection 50 3.1 23.5

pump/pump pocket infection 46 2.8 21.6

wound infection/dehiscence 10 0.6 4.7

septic/aseptic meningitis 10 0.6 4.7

infection in the back 7 0.4 3.3

urinary tract infection 5 0.3 2.3

lumbar infection 1 0.1 0.5

aspiration pneumonia 1 0.1 0.5

infected hematoma 1 0.1 0.5

infection w/pump salvage after antibiotic therapy

1 0.1 0.5

cystitis 1 0.1 0.5

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