Systematic Review of the Lite

on Pain in Patients with Poly

i l di nc u ng Traumatic Brain I 

Steven K. Dobscha MD

Portland VA Medical Medical Center

January 21, 2010
Disclosure

• With respect respect to the following following present

present

there has been no relevant (direct or i

financial relationship relationship between between the pre

pre

(and/or spouse/partner) and any for‐p

company which could be considered a 

of interest.
ACKNOWLEDGMENTS

COAUTHORS EXPERTS/REV

• Michael E. Clark PhD

• Robert Kerns Ph

• Benjamin J. Morasco PhD

• Michelle Freeman MPH

• Nina Sayer PhD

• Marti Buffum DN

• Rose Campbell MLIS, MS

• Mark Helfand MH, MPH

• Henry Lew MD, 

, • Nancy Carney Ph

• Ron Gironda PhD• Martin Schreibe• Matthew Bair M• Robyn L. Walker • Drew Helmer M
Sponsors and Funding

• HSR&D Evidence‐Based Synthesis Prog

supported by HSR&D Evidence Based 

Centers & Agency for Healthcare ReseQuality

• Funding supporting investigators part

on the project also included HSR&D R

04129 and NIH K23DA023467‐01A1
Outline

• Background on Pain and Polytrauma• Study Methods• Results*• A ti c ve and F t u ure R h esearch• Limitations• Questions

FULL REPORT AVAILABLE AVAILABLE AT:

http://www.hsrd.research.va.gov/publications/es

Polytrauma‐2008.pdf
Background

• Soldiers Soldiers injured injured and who survive survive in cur

cur

have more complex and multiple injuri

typically seen in previous previous wars

• Orthopedic, soft‐tissue injury, TBI, hea

and emotional injury often co‐occur

• Blast common source of injury

• Pain close to universal among veterans 

polytrauma network sites/centers
Definitions of polytraum

• VHA 2005: “Injury to the brain in addi

other body parts or systems resulting 

physical, cognitive, psychological, or

psychosocial impairments and functio

disability”

• More recently: Inj y ur to 2 or more bo

or systems resulting in cognitive, physpsychological, or other psychosocial psychosocial

impairments
Special challenges challenges in treating treating 

• How best to assess and monitor pain 

veterans with TBI?

• What are benefits and harms of comm

used medications medications to treat pain in this 

• How does blast related (headache) pa

in terms of phenomenology and treatfrom other types of pain?
5 Key Questions:

• KQ1: Have reliable and valid measures and

assessment assessment tools been developed developed to meas

meas

intensity and pain‐related function among 

with cognitive cognitive deficits deficits due to TBI? Which 

and tools are likely to be most useful in as

pain in p y ol trauma patients with cognitive due to TBI?

• KQ2: Which treatment treatment approaches approaches are mo

be effective in improving pain outcomes in

polytrauma patients? patients? Which pain treatme

treatme

approaches are most likely to enhance ove

rehabilitation efforts?
• KQ3: Does blast‐related related headache headache pain 

terms of phenomenology and treatmen

other types of headache pain? Which

treatments are best for persistent blast

headache pain?

• KQ4: What patient patient factors factors are associate

associate

better and worse pain‐related clinical o

among polytrauma pati ? ents Have i 

nte

been developed to specifically address 

factors?
• KQ5: What are the unique provider an

system barriers to detecting and treat

among p y ol trauma patients? Have

interventions been developed to effecaddress these barriers?

• Additional Aim: Identify active researc

addressing addressing Key Questions; Questions; Ask experts experts 

prioritize topics and areas for future r
Methods

• Topic nomination• Key Questions and Scope reviewed and 

with Expert Panel; draft later reviewed reviewed

• Definition of Polytrauma for Review:

– Concurrent Concurrent injury to 2 or more body parts 

resulting in cognitive, physical, psycholog

psychosocial impairments.

– Combat‐related mental conditions co‐occ

injury to at least one other system also co

co

polytrauma.
Scope Includes:

• Assessment and treatment in rehabili

and post‐rehabilitation care settings

• Studies measuring pain‐related outco

specifically specifically pain intensity intensity and pain‐rel

rel

function or interference,

• Measurements 3 or more months from 

date of injury.
Scope Excludes:

• Short‐term (<3 months) outcomes only• B ttl fi ld Battlefield or acute management• Unilateral amputation unless other con

conditions or injuries

• Spinal cord injury unless other concurr

concurr

conditions or injuries
Also did not include:

• Choice of specific surgical strategy or pro

for particular orthopedic injuries

• Perioperative management of traumatic traumatic 

(including burn injuries).

• P t os ‐t ti / t traumatic/post‐concussive hdh ea ac 

unrelated to blast injury, unless sample i

pts. with moderate or greater TBI.

• Functional outcomes of p y ol trauma unle

measures included
Literature Search

• 2 librarians independently designed strat• Publications between 1950 and July 2008

• Additional articles from reference lists, re

articles, and experts

• Searched for relevant studies in:

– PsychINFO– VA PILOTS Database– REHABDATA

– DoD Defense Technical Information Center

– C h oc rane D b ata ase of controll de cli i l n ca tri 

a 
Study Selection

• 3 investigators investigators reviewed reviewed titles and abst

abst

select studies for full text review

• Rated quality of RCTs, systematic review

and case‐control control studies studies using criteria criteria 

Preventive Services Task Force

• I ldd nc u ed qualit ti a ve st di u es and case re

case series for some KQs

• Rated overall quality of evidence for KQ

method from GRADE Working Working group
R lt esu

s
Abstracts imported from MEDLINE

and PubMed (1950‐July 2008)

N = 3093

Total citations

identified for review

N = 3252

Active researc

N = 1

Reference mining and personal

communication with investigators

of ongoing studies

N = 159 Total articles

retrieved

Total excluded* ar

Not polytraum

retrieved Surgical/perioperative 

N = 578

Total articles addressing the key questions

Surgical/perioperative 

Outcomes do not include 

Non‐English 

Does not provide prim

Used for contextual p

*Multiple exclusion c

Total articles addressing the key questions

N = 82

KQ1

Assessment

N=0

KQ2

Treatment

N=23:

1 cohort

22 case reports

KQ3

Blast–related

headache

N=0

KQ4

Patient factors

N=58

TBI:

1 SR

Other injuries: 

1 SR

11 cohort

2 case control

17 cross‐sect.

22 cohort

5 case control

2 cross‐sect.

Note: Some studies addressed

more than one KQ or subtopic
Key Question 1—Result

Result

• No published studies that assessed re

and validity validity of measures measures of pain inten

inten

pain‐related function among patients 

cognitive deficits deficits due to TBI.
KQ1—Secondary Finding

• Some cross‐sectional sectional and case‐control control 

suggest that pain may interfere with

neurocognitive functioning among TBI 

• Only a few studies studies adjusted adjusted for confou

confou

• Several studies suggest that most indiv

with cognitive ii t mpa rment due to d 

em

understand at least one pain self‐asses

measure.
Key Question 2

• No randomized controlled trials, system

reviews, prospective cohort, case‐contr

systematic observational studies that te

efficacy or effectiveness of specific paintreatment approaches approaches among patients patients 

polytrauma.
• One fair‐quality retrospective cohort s

patients patients who had undergone undergone amputat

amputat

an urban trauma center

• After controlling for demographic fact

inj y ur characteristics and other medic

morbidity, inpatient rehabilitation wamarginally associated with increased increased

likelihood of return to work and decre

lik lih d likelihood of red d uce hours of work. (

Very Low)
KQ2—Secondary Finding

• 22 manuscripts presented cases or case s

describing pain treatment approaches an

outcomes among patients with p y ol traum

including TBI.

• 5 reports reports: Intrathecal Intrathecal baclofen baclofen may be he

he

spasticity associated with TBI or SCI

• 1 report: Capsaicin helped complex regio

syndrome I

• 1 report: Spinal cord stimulation decrease

opioid use among active duty personnel personnel w

complex regional pain syndrome I
Key Question 3

• No randomized controlled trials, coho

studies, case‐control studies, or other

systematic observational studies thatcompared compared patients patients with blast‐related related 

to patients with other types of headac

that specifically specifically addressed addressed treatments treatments 

related headache pain
KQ3—Secondary Finding

• 1 good q y ualit systematic review of post‐t

headache in TBI

• Blast exposure exposure not specifically specifically identified identified o

as characteristic in any of the studies.

• Most PTH resolves in 6‐12 months, but he

persist beyond 1 year in 18% ‐ 33%

• Many patients with PTH have presentation

to tension tension‐type headache headache or migraine migraine

• Many clinicians treat PTH as they would p

headache.
Key Question 4

• No randomized controlled trials

• 1 systematic review, 11 cohort, 2 case‐con

17 cross‐sectional studies provided informabout patient patient factors factors associated associated with pain

outcomes in TBI patients

• 20 coh t or , 2 cross‐secti l ona , and 5 case‐co

studies provided information about patien

associ d ate wi ht pain‐rel d ate outcomes in 

polytrauma patients
KQ4—TBI

• 1 recent fair‐quality quality systematic systematic review sh

that overall, 58% of patients with TBI hav

hdh ea ac e. B i ra n i j n ury associtd a e with h

even after adjustment for PTSD.

• These findings are consistent with our re

Among patients with TBI, headache pres

one‐third to one‐half of patients up to fivafter injury. (GRADE: (GRADE: Low)
TBI severity and headach

headach

• The recent review also found that pat

with mild TBI more likely to have HA t

patients with moderate or severe TBI.

• However However, our review showed very mix

findings regarding association betwee

severity and pain (GRADE: Very Low)
• 1 fair‐q y ualit retrospective cohort study

quality case‐control study, and 5 cross‐sstudies showed:

– Higher prevalence of HA among pts with m

compared with more severe TBI

– Patients with mild TBI who attend outpati

injury clinics are 2 to 3 times more likely to 

than patients with more severe TBI

• 1 retrospective and 4 prospective cohort s

vary g in q y ualit and 3 cross‐sectional studi

no differences in prevalence of HA accordseverity of head injury. injury.
So why the differences?

• Most cross‐sectional studies done in outp

settings, up to several years post‐injury, a

adjust for potential confounders.

• Most samples in the cohort studies assem

the time of admission admission to hospital hospital or inpat

inpat

rehabilitation setting.

• S t ugges s

– Confounders may be important– Patients with mild TBI may be more likely att

outpatient follow‐up visits when they have b

or persistent symptoms such as HA.
KQ4—TBI: Other Factors

• Mixed findings regarding association betw

demographic factors and pain in TBI patie

• 1 cross‐sectional sectional study of service service member

member

PRC, showed blast exposure not a significa

predictor of pain.

• 5 cohort, 2 case‐control and 2 cross‐sectio

studies: Psychological factors (depression, 

and PTSD), insomnia and fatigue are assoc

pain in TBI patients(GRADE: Low)
KQ4 Other injuries in p y ol traum

• Characteristics associated w/ worse outco

– Multiple injuries– Injuries below the knee– Concurrent head injury/cognitive disability(GRADE: Low)

• Characteristics associated w/ better outco

– Younger age, Hi hg er ed ti uca on, Hi hg er inc(GRADE: Very Low)
Key Question 5

• No RCTs, cohort studies, studies, case‐control control st

st

other systematic observational studies 

provider provider and system barriers barriers to detecti

detecti

treating pain in polytrauma patients

• 1 qualitative study of providers from 4 V

Polytrauma Rehabilitation Centers addr

potential provider and system barriers polytrauma patients.
Common Themes

• Patients with blast‐related injuries have m

injuries and more severe injuries injuries

• Psychiatric disorders and pain are prevale

complicate rehabilitation for TBI. These fa

make this population complex to treat.

• Providers find working with this populatio

challenging and emotionally emotionally taxing. taxing.

• Providers increasingly use consultation an

tt t rea ment; teams expanding

• Family members often involved and have 

informational and support needs.
Summary of Literature revie

• Very limited empiric information w/ respe

– Assessment Assessment of pain in patients patients with TBI– Specific treatment approaches in polytrau– U i n que aspect/ h s approaches for bl t as HA– Understanding of provider/system barrier

• Very mixed findings regarding relationship 

TBI severity and persistent pain

• Limited evidence that psychological factor

insomnia and fatigue are associated with 

• Limited evidence that injury characteristic

associated with worse pain outcomes
Active Research—Process

• Emails sent to:

– 73 individuals– 4 VA workgroups (di tl rec y or via Ch i ) a rs– 5 HSR&D portfolio managers,

• Queries and hand searches of database• Responses Responses received received from 47 investigato

investigato

• 19 relevant projects identified. Project 

collected on 18 of these projects.
Active Research—findings

(as of August 2008)

• KQ1: 1 prospective measurement study

• KQ2: 2 clinical clinical trials; trials; 1 cohort; cohort; 1 case se

• KQ3: 1 case series• KQ4: 7 cohort; 5 cross‐sectional studies

• KQ5: 1 qualitative qualitative study
Future Research

• Experts reviewed the report and active 

asked to identify research topics.

• Assign priorities priorities based on:

– degree to which research will address gap

in the review

– quantity and quality of research complete

– feasibility and timeframe necessary– barriers barriers that have prevented prevented research research from 

undertaken before

– pros and cons of research research method
Key

Ques.

Future Research:

Ques. Median priority priority rank = 1 (most import

import

KQ 1 • Quantitative measurement study of reliability an

existing pain assessment tools among patients wi

levels of communicativeness and brain injury.• Examine discriminant validity of tools for distingfrom other forms of distress and impairment (e.g.

PTSD sx)

KQ2 • Ti l r a s of non‐ph lil armacological i i nterventions of va

incl. psychological interventions and telephone‐ba

interventions.• RCTs of integrated treatment approaches includ

comprehensive interdisciplinary rehab., collabora

involving family• Compare individual treatments for common speconditions (e.g., TBI; PTSD; Pain) to integrated trethese overlapping symptoms.
KQ3 • Trials of pharmacologic and non‐pharmacologic t

including patients with blast‐related headache in otrial. Non‐pharmacologic interventions to test inclbehavioral behavioral treatment treatment, hypnosis hypnosis, relaxation relaxation training training

biofeedback.

KQ4 • Prospective cohort study measuring pain outcom

while adjusting adjusting for patient patient and injury characteristi

characteristi

comorbid conditions as well as multiplicity of injur

and location.

KQ5 • Establish treatment guidelines for pain in polytra

expert opinion. Disseminate and measure impact o
Limitations

• Captures literature through July 2008• Heterogeneity and generalizability• Scope

• Publication bias

• Active research

– Email snowb ll a approach; li i d m te f ll o ow‐u

non‐response

– Limited communication with non‐VA resea– Limitations to search algorithms for datab

ongoing trials and studies
QUESTIONS

• Contact: Steven.dobscha@va.gov• http // g /p ://www.hsrd.research.va.gov/pub

/esp/Pain‐in‐Polytrauma‐2008.pdf