Evidence-based Synthesis Program 

Pain in Patients with Polytrauma:

A Systematic Review

Department of Veterans Affairs

Health Services Research & Development Service

September 2008

Investigators:

Steven K. Dobscha, MD

Principal Investigator

Rose Campbell, MLIS, MS

Research Associate

Benjamin J. Morasco, PhD

Investigator

Michele Freeman, MPH

Research Associate

Mark Helfand, MD, MPH

Director

Prepared for: 

Department of Veterans Affairs

Veterans Health Administration

Health Services Research & Development Service

Washington, DC 20420 

Prepared by:

Portland Veterans Affairs Healthcare System

Oregon Evidence-based Practice Center

Portland, OR
Pain in Patients with Polytrauma

VA-ESP September 2008 ii

PREFACE

VA’s Health Services Research and Development Service (HSR&D) works to improve the 

cost, quality, and outcomes of health care for our nation’s veterans. Collaborating with VA 

leaders, managers, and policy makers, HSR&D focuses on important health care topics that 

are likely to have significant impact on quality improvement efforts. One significant 

collaborative effort is HSR&D’s Evidence-based Synthesis Program (ESP). Through this 

program, HSR&D provides timely and accurate evidence syntheses on targeted health care 

topics. These products will be disseminated broadly throughout VA and will: inform VA 

clinical policy, develop clinical practice guidelines, set directions for future research to 

address gaps in knowledge, identify the evidence to support VA performance measures, 

and rationalize drug formulary decisions. 

HSR&D provided funding for the two Evidence Based Practice Centers (EPCs) supported 

by the Agency for Healthcare Research and Quality (AHRQ) that also had an active and 

publicly acknowledged VA affiliation—Southern California EPC and Portland, OR EPC—

so they could develop evidence syntheses on requested topics for dissemination to VA 

policymakers. A planning committee with representation from HSR&D, Patient Care 

Services, Office of Quality and Performance, and the VISN Clinical Management Officers, 

has been established to identify priority topics and to ensure the quality of final reports. 

Comments on this evidence report are welcome and can be sent to Susan Schiffner, ESP 

Program Manager, at Susan.Schiffner@va.gov. 
Pain in Patients with Polytrauma

EXECUTIVE SUMMARY

BACKGROUND 

Pain resulting from polytraumatic injuries poses numerous challenges during and after 

rehabilitation treatment. The objectives of this report are to systematically review the 

literature to address the assessment and management of pain in patients with 

polytraumatic injuries, to identify patient, clinician and systems factors associated with 

pain-related outcomes in these patients, and to describe current or planned research 

addressing the key questions in this report. 

The key questions were: 

1. Have reliable and valid measures and assessment tools been developed to measure 

pain intensity and pain-related functional interference among patients with 

cognitive deficits due to TBI? Which measures and tools are likely to be most 

useful in assessing pain in polytrauma patients with cognitive deficits due to TBI? 

2. A. Which treatment approaches are most likely to be effective in improving pain 

outcomes (pain intensity and functional interference) in polytrauma patients? 

B. Which pain treatment approaches are most likely to enhance overall 

rehabilitation efforts? 

3. A. Does blast-related headache pain differ in terms of phenomenology and 

treatment from other types of headache pain? 

B.Which treatments are best for persistent blast-related headache pain? 

4. What patient factors are associated with better and worse pain-related clinical 

outcomes among polytrauma patients? Have interventions been developed to 

specifically address these factors? 

5. What are unique provider and system barriers to detecting and treating pain among 

polytrauma patients? Have interventions been developed to effectively address 

these barriers? 

We also sought to identify and describe current or planned research that is addressing or 

will address the key questions. 

METHODS 

Literature Search

Two research librarians independently designed search strategies based on the key 

questions, and conducted searches in Medline of literature published from 1950 through 

July 2008. The results of both searches were combined into a single reference library. 

Three researchers trained in the critical analysis of literature assessed for relevance the 

abstracts of citations identified from these literatures searches. Full-text articles of 

potentially relevant abstracts were retrieved for further review. Reference lists from 

VA-ESP September 2008 iii
Pain in Patients with Polytrauma

articles were reviewed to find additional articles for inclusion. We also searched for inprogress and unpublished trials. Due to a limited number of studies using controls or 

comparators, we included cross-sectional and case report/case series studies in the review 

for some key questions, We systematically rated the quality of cohort and case-control 

design studies. 

Active Research

The PI sent email communications inquiring about active or planned research to a number 

of groups and individuals identified through VA workgroups, personal knowledge of 

investigators, recent publications, and several web-databases which included information 

about funded VA and non-VA projects. Email communications described the evidence 

review project, and asked respondents to describe any relevant projects they were involved 

in or planning as well as to identify other investigators who might be working in these 

areas (snowball approach). Initial email messages were sent at the end of January 2008; 

email messages to newly identified investigators and follow-up communications occurred 

continuously until August 28, 2008. 

RESULTS 

We screened 3252 titles and performed a more detailed review of 578 articles. From these, 

we identified one systematic review, one qualitative research study, and 93 observational 

studies that addressed at least one of the key questions. Studies were excluded for the 

following reasons: 1) the study population did not constitute or include polytrauma 

patients or patients with blast-related headaches; 2) the study addressed perioperative or 

surgical pain management or management of specific orthopedic injuries or only short term 

(less than 3 months post-injury) outcomes; 3) the study outcomes did not include measures 

of pain intensity or pain-related function; 4) the text of the article was non-English. The 

primary findings for each key question are summarized below. Secondary findings are 

presented in further detail within the report. 

KEY QUESTION #1 Have reliable and valid measures and assessment tools been 

developed to measure pain intensity and pain-related functional interference among 

patients with cognitive deficits due to TBI? Which measures and tools are likely to be 

most useful in assessing pain in polytrauma patients with cognitive deficits due to TBI? 

There were no published studies that assessed measures of pain intensity or painrelated functional interference among patients with cognitive deficits due to TBI.

KEY QUESTION #2 A. Which treatment approaches are most likely to be effective in 

improving pain outcomes (pain intensity and functional interference) in polytrauma 

patients? B. Which pain treatment approaches are most likely to enhance overall 

rehabilitation efforts? 

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Pain in Patients with Polytrauma

2A: There were no randomized controlled trials, systematic reviews, prospective 

cohort, case-control, or systematic observational studies that tested the efficacy or 

effectiveness of specific pain treatment approaches among patients with polytrauma. 

2B: One fair-quality retrospective cohort study of patients with trauma-related 

amputation demonstrated that after controlling for demographic factors, injury 

characteristics and other medical morbidity, inpatient rehabilitation was marginally 

associated with increased likelihood of return to work and decreased likelihood of 

reduced hours of work.(GRADE: Very Low) 

KEY QUESTION #3 A. Does blast-related headache pain differ in terms of 

phenomenology and treatment from other types of headache pain? B. Which treatments 

are best for persistent blast-related headache pain? 

There were no randomized controlled trials, cohort studies, case-control studies, or 

other systematic observational studies that compared patients with blast-related 

headache to patients with other types of headache or that specifically addressed 

treatments for blast-related related headache pain. 

KEY QUESTION #4 What patient factors are associated with better and worse clinical 

outcomes among polytrauma patients? Have interventions been developed to specifically 

address these factors? 

There were no randomized controlled trials. One systematic review, 9 cohort, 3 casecontrol, and 13 cross-sectional studies specifically addressed patient factors associated 

with outcomes in TBI patients. Thirty-two cohort, 11 cross-sectional, and 4 case-control 

studies addressed patient factors associated with outcomes in patients with other types of 

polytraumatic injuries. 

Traumatic Brain Injury

One fair-quality systematic review involving 23 studies and 4,206 patients showed that 

overall, 58% of patients with TBI have chronic headache, and that brain injury is 

associated with headache even after adjustment for post-traumatic stress disorder 

(PTSD). This review also found that patients with mild TBI were more likely to have 

headache than patients with moderate or severe TBI. However, our review, which 

included studies not included in the above study, showed mixed findings regarding the 

association between severity of TBI and pain (GRADE: Very Low). 

Psychological factors, including depression and posttraumatic stress disorder (PTSD), 

and insomnia and fatigue are associated with pain in TBI patients. (GRADE: Low) 

Other injuries in polytrauma patients

Characteristics of injuries (location, severity, and whether they are multiple) are 

associated with clinical outcomes including persistent pain and functional status. 

Specific factors associated with worse pain-related outcomes include: multiple injuries, 

VA-ESP September 2008 v
Pain in Patients with Polytrauma

foot injuries or injuries below the knee joint, and concurrent head injury or cognitive 

disability. (GRADE: Low) 

Other factors associated with better outcomes in some studies of patients with 

polytraumatic injuries other than TBI were younger age, higher educational 

achievement, having a white collar job or higher income. (GRADE: Very Low) 

KEY QUESTION #5 What are unique provider and system barriers to detecting and 

treating pain among polytrauma patients? Have interventions been developed to 

effectively address these barriers? 

There were no randomized controlled trials, cohort studies, case-control studies, or 

other systematic observational studies that addressed provider and system barriers to 

detecting and treating pain among polytrauma patients. One qualitative study of 

providers from four VA Polytrauma Rehabilitation Centers (PRCs) addressed potential 

provider and system barriers to treating polytrauma patients. In interviews, providers 

reported that polytrauma patients are very complex to treat, and that the work with this 

population is very challenging and emotionally taxing. The investigators and study 

respondents suggested that increasing use of multidisciplinary and concurrent care and 

consultation from experts may be necessary to provide the care that is needed.

Results—Active Research 

Nineteen relevant active or planned projects were identified and project data were 

collected on 18 of these projects. Fifteen of the studies should generate information 

regarding patient factors that may contribute to pain-related outcomes among polytrauma 

patients (Key Question 4), and 4 studies are testing interventions for pain among 

polytrauma patients (Key Question 2). One active study will test the reliability and validity 

of measures to assess pain in cognitively-impaired TBI patients and another study is using 

primarily qualitative methods to examine the utility of a Computerized Patient Record 

System (CPRS) pain assessment template module to assist clinicians in evaluating pain in 

PRC patients with cognitive impairment (Key Question 1). One study is examining the 

phenomenology and treatment of blast vs. other types of headache (Key Question 3), and 

one study is addressing provider and systems barriers to detecting and treating pain in 

polytrauma patients (Key Question 5).

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Pain in Patients with Polytrauma

TABLE OF CONTENTS

INTRODUCTION

 Background ........................................................................................1 

 

METHODS

 Topic Development .............................................................................2 

 Literature Search Strategy .....................................................................5 

 Study Selection ...............................................................................5 

 Data Abstraction ..........................................................................................6 

 Quality Assessment ....................................................................................6 

 Data Synthesis ...................................................................................7 

 Rating the Body of Evidence ...................................................................7 

 Active Research .......................................................................................8 

 Peer Review ......................................................................................9 

RESULTS

 Literature Flow ................................................................................9 

 Key Question 1 ................................................................................11 

 Key Question 2 ................................................................................12 

 Key Question 3 ..............................................................................15

 Key Question 4 .......................................................................................................18 

Traumatic Brain Injury ......................................................................................19 

Other injuries in polytrauma patients ...............................................................23 

 Key Question 5 ......................................................................................................26 

 Limitations – Literature Review ............................................................27 

 Active Research .....................................................................................................29 

 Limitations – Active Research ...............................................................32 

SUMMARY AND DISCUSSION ............................................................................................33 

CONCLUSIONS .....................................................................................................35 

FUTURE RESEARCH RECOMMENDATIONS .............................................................37

REFERENCES .........................................................................................43 

IN-TEXT FIGURES AND TABLES

 Figure 1. Analytic framework ...................................................................................4 

 Figure 2. Literature flow ............................................................................................10 

 Table 1. Case reports/case series pertaining to Key Question 2 ...............................14 

 Table 2. Summary of active research studies of pain in polytrauma ........................30 

 Table 3. Summary of systematic evidence review by key question ..........................35 

 Table 4. Future research recommendations ...............................................................38 

 Table 5. Potential Research Topics/Designs—Ratings of Priority .................40 

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APPENDIX A. Search strategy 

APPENDIX B. Article screening form 

APPENDIX C. USPSTF quality rating criteria 

APPENDIX D. Reviewer comments and responses 

APPENDIX E. Evidence Tables 

Evidence Table 1. Studies on patient factors associated with polytrauma outcomes 

(Key Question 4) 

Evidence Table 2. Active research projects 
Pain in Patients with Polytrauma

INTRODUCTION 

Polytrauma is defined in the VHA Polytrauma Rehabilitation Centers Directive dated June 

8, 2005 as: “injury to the brain in addition to other body parts or systems resulting in 

physical, cognitive, psychological, or psychosocial impairments and functional disability.” 

The definition of polytrauma has since expanded to include concurrent injury to two or 

more body parts or systems that results in cognitive, physical, psychological or other 

psychosocial impairments. Traumatic Brain Injury (TBI) often occurs in polytrauma and in 

combination with other disabling conditions including amputation, auditory or visual 

impairments, spinal cord injury (SCI), post-traumatic stress disorder (PTSD), and other 

mental health conditions. 

Pain resulting from polytraumatic injuries poses numerous challenges during rehabilitation 

treatment and afterwards. Treatments typically used to reduce pain in these individuals (for 

example, oral opioids) have the potential to interfere with the active rehabilitation needed 

to restore function. 

The objectives of this report are to systematically review the literature to address the 

assessment and management of pain in patients with polytraumatic injuries, to identify 

patient, clinician and systems factors associated with pain-related outcomes in these 

patients, and to describe current or planned research addressing the key questions. 

Background

Major advances in body armor technology and battlefield medicine have improved survival 

from combat injuries that would have been fatal in previous wars.(1) Data from the 

Department of Defense indicate that the lethality of war wounds has decreased from 24% 

in the Vietnam and Persian Gulf Wars to 10% in the current Operation Enduring 

Freedom/Operation Iraqi Freedom (OEF/OIF) conflicts.(2) Survivors of polytraumatic 

injuries among soldiers returning from the current conflicts tend to have more complex 

injuries and emotional trauma than typically seen in the past wars.(3, 4) 

Among 119 casualties admitted to Walter Reed Army Medical Center from OIF during 

March 1 to July 1, 2003, 39% had sustained gunshot wounds, 31% sustained blast and 

shrapnel injuries, and 34% had blunt/motor vehicle collision mechanisms.(5) Among these 

119 patients there were 184 injured areas, and the location of injury was the lower 

extremity for 62% of patients, the upper extremity for 30%, the head and neck for 25%, the 

chest for 25%, and the abdomen for 16%. Among 52 patients with orthopedic injuries 

evacuated during OEF between December 2001 and January 2003, 15 (29%) had suffered 

traumatic amputations, of which 5 (33.3%) were below-knee.(6) All amputations were 

caused by land mines or exploded ordinance. 

Twenty-eight percent of all individuals medically evacuated to the Walter Reed Army 

Medical Center (WRAMC) due to combat injuries during OEF/OIF had a TBI, according 

to a report in 2006.(4) By contrast, 12 to 14% of all combat casualties in the Vietnam War 

had a brain injury.(7) In the current conflicts, Kevlar body armor and helmets have 

VA-ESP September 2008 1
Pain in Patients with Polytrauma

improved overall survival rates and reduced the frequency of penetrating head injuries.(7) 

Because mortality from substantial brain injuries among U.S. combatants in Vietnam was 

75% or greater, soldiers with recognized brain injuries made up only a small fraction of the 

casualties. Between January 2003 and February 2005, 59% of all patients who were 

exposed to a blast and admitted to WRAMC were given a diagnosis of TBI.(7) Closed 

TBI accounted for 88% of all TBI. Moderate to severe TBI accounted for 56% of TBI 

cases. Nineteen percent of TBI patients sustained concomitant amputation. 

Brain injuries from blasts may go undiagnosed and untreated in patients with polytrauma 

because of the attention focused on more visible injuries. Commonly overlooked painrelated conditions in patients with polytrauma may include soft-tissue damage, PTSD, 

nerve damage, hearing loss and tinnitus, chronic infections, vision changes, lung injury, 

vestibular problems, and undiscovered shrapnel fragments.(8) In addition to the direct 

effects of blasts, injuries can result from the structural collapse and fragmentation of 

buildings and vehicles, and may include crush injuries and compartment syndrome.(9) 

Under a new system established by the VHA in 2005, severely injured soldiers with TBI 

are being referred early in their treatment to one of four VA medical centers in Richmond, 

VA; Tampa, FL; Palo Alto, CA; and Minneapolis, MN) designated as Polytrauma 

Rehabilitation Centers (PRCs). The four PRCs approach treatment of polytrauma patients 

using a mechanism-of-injury approach to provide a comprehensive, efficient, and 

interdisciplinary system of care.(8) Each of the four PRCs has been identifying six to 10 

cases of TBI per month that were missed in military hospitals.(10) 

 

METHODS

Topic Development 

This topic was nominated by Michael Clark, PhD, Clinical Director of the Pain Program, 

James A. Haley VAMC. The scope and key questions for the review were further refined 

in consultation with representatives from the VA HSR&D Service, the VA Evidence 

Synthesis Program, and technical experts in pain, polytrauma, or traumatic brain injury 

(Robert Kerns, PhD; Nina Sayer, PhD; Marti Buffum DNSc, APRN, BC, CS; Michael 

Clark, PhD; Henry Lew, MD, PhD; Nancy Carney, PhD; Ron Gironda, PhD; Martin 

Schreiber, MD). 

1. Have reliable and valid measures and assessment tools been developed to measure 

pain intensity and pain-related functional interference among patients with 

cognitive deficits due to TBI? Which measures and tools are likely to be most 

useful in assessing pain in polytrauma patients with cognitive deficits due to TBI? 

2. A. Which treatment approaches are most likely to be effective in improving pain 

outcomes (pain intensity and functional interference) in polytrauma patients? 

B. Which pain treatment approaches are most likely to enhance overall 

rehabilitation efforts? 

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Pain in Patients with Polytrauma

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3. A. Does blast-related headache pain differ in terms of phenomenology and 

treatment from other types of headache pain? 

B. Which treatments are best for persistent blast-related headache pain? 

4. What patient factors are associated with better and worse pain-related clinical 

outcomes among polytrauma patients? Have interventions been developed to 

specifically address these factors? 

5. What are unique provider and system barriers to detecting and treating pain among 

polytrauma patients? Have interventions been developed to effectively address 

these barriers? 

Polytrauma is defined as concurrent injury to two or more body parts or systems resulting 

in cognitive, physical, psychological or other psychosocial impairments. Combat-related 

mental conditions co-occurring with injury to at least one other system also constitutes 

polytrauma. 

The scope of this review includes the assessment and treatment in rehabilitation and postrehabilitation care settings of persistent pain or exacerbations of pain resulting from 

polytraumatic injuries. We included studies measuring pain-related outcomes, specifically 

pain intensity and pain-related function or interference, 3 months or more from the date of 

injury. 

The scope of this review excludes the following: 

• Short-term (less than 3 months) outcomes following injury. We sought to focus on 

pain persisting into the rehabilitation phase of treatment or longer, and not 

battlefield or acute management of polytraumatic injury. 

• Unilateral amputation without other concurrent conditions or injuries. Bilateral 

amputation was considered polytrauma. 

• Spinal cord injury without other concurrent conditions or injuries 

• Choice of specific surgical strategy or specific procedures for particular orthopedic 

injuries or perioperative management of traumatic injuries. 

• Post-traumatic/post-concussive headache unrelated to blast injury, unless the 

sample includes patients with moderate or greater TBI. 

• Functional outcomes of polytrauma unless pain measures are included as one 

component of the functional outcome measure or in addition to the functional 

outcome measure. 

Figure 1 illustrates the analytic framework that guided our review and synthesis.
Pain in Patients with Polytrauma

Figure 1. Analytic Framework 

Provider and

healthcare

system barriers

KQ = key questio

KQ5

Assessment Treatment

Assessment Treatment

Polytrauma

patients in

rehabilitation

phase or later

Improvements

in pain

intensity and

functional

interference

Pain

intensity and

functional

interference

KQ1 KQ2a KQ2b

Prognostic

KQ4 classification

Polytrauma

patients with ahistory of blast

injury

Improvements in

pain intensity and

functional

interference

Persistent

blast‐related

headache

KQ3b KQ3a

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Pain in Patients with Polytrauma

Literature Search Strategy

Two research librarians (Rose Campbell and Andrew Hamilton) independently designed 

search strategies based on the key questions, and conducted searches in Medline of 

literature published from 1950 through July 2008. Appendix A provides the search 

strategies in detail. The results of both searches were combined into a single reference 

library. Additional articles were identified from reference lists of studies, review articles, 

editorials, and by consulting experts. We also searched for relevant studies in the 

following databases: PsychINFO; the PILOTS Database (the VA PTSD bibliographic 

database); REHABDATA, the bibliographic database of the National Rehabilitation 

Information Center; the DoD Defense Technical Information Center; and the Cochrane 

Database of controlled clinical trials. All citations were imported into an electronic 

database (EndNote X1). We also searched for unpublished and ongoing research studies, 

as described in the section on Active Research to follow. 

Study Selection 

Three researchers (SD, RC, MF) trained in the critical analysis of literature reviewed the 

titles and abstracts identified from the searches. Full-text articles of potentially relevant 

abstracts were retrieved for further review. Each article retrieved was reviewed with a 

brief screening form (see Appendix B) that collected data on the key question to which the 

article applied, as well as key words or emerging themes. Reference lists from pertinent 

articles were reviewed to find additional articles for inclusion. 

Study Inclusion Criteria 

Eligible articles had English-language abstracts and provided primary data relevant to the 

key questions. For a study to be eligible for Key Questions 1, 2, 4 and 5, the sample had to 

have all or a majority of patients with polytrauma, or analyses and findings had to be 

stratified by whether the patients had polytrauma, such that if a minority of the sample had 

polytrauma, readers could discern outcomes for the polytrauma group. For purposes of the 

review, polytrauma was defined as concurrent injury to two or more body parts or systems 

resulting in cognitive, physical, psychological or other psychosocial impairments. TBI of 

moderate or greater severity was also considered polytrauma (head injury itself plus 

associated cognitive sequellae). Combat-related mental conditions co-occurring with injury 

to at least one other system also constituted polytrauma. This definition is consistent with 

the VHA Directive 2005-024 describing the policy for the PRCs. Eligible studies examined 

the assessment and treatment in rehabilitation and post-rehabilitation care settings of 

persistent pain or exacerbations of pain resulting from polytraumatic injuries. 

Eligible study designs included controlled clinical trials, systematic reviews, as well as 

prospective and retrospective cohort studies, case-control design studies, and qualitative 

studies using rigorous qualitative research methods. For these types of study designs, we 

abstracted data as described below. Due to a limited number of studies that included a 

comparator group, we also considered relevant cross-sectional and case report/case series 

VA-ESP September 2008 5
Pain in Patients with Polytrauma

studies for inclusion for some of the key questions. For these study designs, data were not 

formally abstracted nor rated for quality of evidence. 

Study Exclusion Criteria 

Studies examining battlefield/emergency or assessment and care within 3 months of injury 

were not included unless they also examined pain outcomes 3 months or more from the 

date of injury, that is, pain persisting into the rehabilitation phase of treatment or longer. 

We also did not include studies examining choice of specific surgical strategy, the 

perioperative management of traumatic injuries (including burn injuries), or use of 

particular procedures or devices for specific orthopedic injuries. There are numerous case 

reports and case series describing specific surgical interventions for particular types of 

wounds; we felt that their inclusion would not yield generalizable information. We 

excluded studies describing functional outcomes of polytrauma unless a pain measure was 

included and reported as a component of the functional outcome measure or in addition to 

the functional outcome measure. Finally, we excluded studies of post-traumatic/postconcussive headache unless the sample included patients with moderate or more severe 

head injury or included a majority of patients with blast-related head injury. There have 

been a number of narrative reviews of assessment and treatment of post-traumatic 

headache among patients with mild-TBI or post-concussive syndrome; we felt that 

inclusion of these studies was beyond the scope of our key questions. 

Secondary Findings 

For key questions 1, 2, 3, and 4, the investigators included additional information (labeled 

Secondary Findings) from studies that were formally excluded during the search and 

abstraction process, but which contained information that seemed pertinent to the key 

questions and which we felt may be of interest to readers. This additional information does 

not reflect results of a comprehensive, systematic literature search on the specific 

secondary findings topics; rather it reflects information derived from manuscripts 

identified during our main search process. 

Data Abstraction

We abstracted the following data from included studies: study design, setting, objectives, 

eligibility criteria, sample size, intervention or exposure of interest, comparator 

intervention or control group, outcomes measured, timing of outcome assessment, years of 

enrollment/observation, duration of follow-up, demographics, potential confounders 

considered, results, and conclusions. 

Quality Assessment

We assessed the quality of studies when applicable, using criteria developed by the US 

Preventive Services Task Force(11) for rating randomized controlled trials, cohort studies, 

and case control studies (Appendix C). We did not rate the quality of cross-sectional 

studies, case reports, or case series. 

VA-ESP September 2008 6
Pain in Patients with Polytrauma

Data Synthesis 

We constructed evidence tables showing the study characteristics and results for all 

included studies, organized by key question, intervention, or clinical condition, as 

appropriate. We critically analyzed studies to compare their characteristics, methods, and 

findings. We compiled a summary of findings for each key question or clinical topic, and 

drew conclusions based on qualitative synthesis of the findings. 

Rating the body of evidence 

We assessed the overall quality of evidence for outcomes using a method developed by the 

Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) 

Working Group, which classified the grade of evidence across outcomes according to the 

following criteria:(12) 

High = Further research is very unlikely to change our confidence on the estimate of effect. 

Moderate = Further research is likely to have an important impact on our confidence in the 

estimate of effect and may change the estimate. 

Low = Further research is very likely to have an important impact on our confidence in the 

estimate of effect and is likely to change the estimate. 

Very Low = Any estimate of effect is very uncertain. 

The GRADE Working Group also suggests using the following scheme for assigning the 

“grade” or strength of evidence:

VA-ESP September 2008 7
Pain in Patients with Polytrauma

Criteria for assigning GRADE of evidence 

Type of evidence 

Randomized trial = high 

Observational study = low 

Any other evidence = very low 

Decrease GRADE if: 

 Serious (-1) or very serious (-2) limitation to study quality 

 Important inconsistency (-1) 

 Some (-1) or major (-2) uncertainty about directness 

 Imprecise or sparse data (-1) 

 High probability of reporting bias (-1) 

Increase GRADE if: 

 Strong evidence of association-significant relative risk of >2 (<0.5) based on consistent 

evidence from two or more observational studies, with no plausible confounders (+1) 

 Very strong evidence of association-significant relative risk of >5 (<0.2) based on direct 

evidence with no major threats to validity (+2) 

 Evidence of a dose response gradient (+1) 

 All plausible confounders would have reduced the effect (+1)

Active Research

In addition to conducting a formal evidence synthesis, we conducted a survey to identify 

and describe current or planned research that is addressing or will address the key 

questions. Specific objectives were to 1) describe the data that are being collected that will 

help to address the key questions, 2) propose actions needed to address the key questions 

above within a reasonable time frame. 

To identify ongoing or planned research relating to key questions, we began by sending 

email communications inquiring about active or planned research to groups and 

individuals. The groups and individuals sent initial email communications were: 

• Investigators working in the areas of pain, polytrauma or TBI that were known to 

the Evidence Synthesis investigators or, as indicated from recent published 

manuscripts, are currently likely to be conducting studies in these areas. We 

specifically sent initial emails to several DOD researchers thought to be studying 

patients with polytraumatic injuries. 

• Chairs of active VA workgroups, the Assessing pain in TBI workgroup (Buffum), 

VA Polytrauma Centers Workgroup (Clark), and the TBI QUERI Workgroup 

(Sayer). The PI of the current evidence synthesis project is a member of the VHA 

Pain Research Workgroup and sent an email communication directly to all 

VA-ESP September 2008 8
Pain in Patients with Polytrauma

members of this workgroup. We also discussed this evidence synthesis project with 

chairs and members of these workgroups. 

• Investigators of projects on polytrauma and pain identified from queries and handsearches of several VA and non-VA website databases: (National Institutes of 

Health Clinical Trials data base (http:www.clinicaltrials.gov), the Computer 

Retrieval of Information on Scientific Projects (CRISP) database 

(http://crisp.cit.nih.gov/), the Meta-Register of Current Controlled Trials 

(http://www.controlled-trials.com/mrct/), and the VA HSR&D website 

(http://www.hsrd.research.va.gov/research/default.cfm). 

• Each of the five HSR&D VA portfolio managers. 

Email communications described our goals and the task, and asked respondents to also 

identify other investigators who might be working in these areas (snowball approach). 

Initial email messages were sent at the end of January 2008; email messages to newly 

identified investigators and follow-up communications occurred continuously until August 

28, 2008. 

PEER REVIEW 

A draft version of this report was sent to the technical advisory panel and additional peer 

reviewers. Their comments and our responses are shown in Appendix D. 

RESULTS 

Literature Flow 

The combined library contained 3252 citations, of which we reviewed 578 articles at the 

full-text level. From these, we identified systematic reviews and observational studies that 

addressed one or more of the key questions. Figure 2 shows the results of the literature 

search and the organization of themes that emerged for each key question. 

VA-ESP September 2008 9
Pain in Patients with Polytrauma

Figure 2. Management of Pain in Polytrauma Literature Flow 

Abstracts imported from MEDLINE

and PubMed (1950‐July 2008)

Reference mining and personal

communication with investigators

of ongoing studies N = 3093

N = 159

Active research

projects

N=18

Total citations identified for review

N = 3252

Total excluded* articles (N = 467)

Not polytrauma (N=124)

Total articles retrieved   Intervention for surgical/perioperative

N = 578 pain only (N=25)

Outcomes do not include pain measures

(N=62)

Non‐English (N=50)

Does not provide primary data (N=66)

Coded for use in background, methods or

discussion (N=174)

Total articles addressing the key questions

N=95

*Multiple exclusion criteria may apply

KQ3 KQ4 KQ5 KQ1 KQ2

Provider/system

barriers

Blast–related Patient factors

headache

Assessment Treatment

Primary Primary

N=1:

1 cohort

Primary

N=0

Secondary

N=9

Guidelines

and reviews

of studies of

dementia

TBI:

1 SR

11 cohort

2 case control

17 cross‐sect.

Other injuries:

20 cohort

5 case control

2 cross‐sect.

N=1

N=58 qualitative

study

N=0

Secondary Secondary N=6: N=23:

1 cohort   1 SR

1 SR   22 case

reports 4 cross‐sect.  

Note:  Some studies addressed

more than one KQ or subtopic

VA-ESP September 2008 10
Pain in Patients with Polytrauma

Results—Key Question #1: Have reliable and valid measures and assessment tools 

been developed to measure pain intensity and pain-related functional interference among 

patients with cognitive deficits due to traumatic brain injury (TBI)? Which measures and 

tools are likely to be most useful in assessing pain in polytrauma patients with cognitive 

deficits due to TBI?

Summary of findings 

There were no published studies that assessed reliability and validity of measures of pain 

intensity or pain-related function among patients with cognitive deficits due to TBI.

Secondary findings 

• A number of primarily cross-sectional and case-control studies suggest that pain may 

interfere with neurocognitive functioning among TBI patients. Only some of these 

studies adjusted for potential confounders of the relationship between pain and 

neurocognitive performance.

• Several studies suggest that most individuals with cognitive impairment due to 

dementia can understand at least one pain self-assessment measure.

Details of Studies—Secondary Findings 

Pain may interfere with neuropsychological assessment among TBI patients

We identified several narrative review articles that addressed this topic in depth.(13-15) 

These review articles include a number of primarily cross-sectional and case control 

studies that found negative associations between headache pain and cognitive functioning 

among TBI and non-TBI patients. Most TBI patients in these studies had mild TBI. Most 

of these studies support that acute or chronic pain irrespective of whether a patient has 

TBI, is associated with worse cognitive performance. While cognitive effects associated 

with pain may be quite variable, attention, memory, speed of processing and executive 

control may be most strongly affected.(13) Of note, investigators have identified factors 

other than pain that have the potential to confound or modulate the relationship between 

pain and neurocognitive performance. Such factors include psychological distress, mood, 

or anxiety disorders,(16-18) somatic complaints and concerns,(19) and sleep 

deprivation.(20) Thus, it remains unclear to what extent pain remains negatively associated 

with neurocognitive functioning when potentially confounding factors are considered. 

Assessment of pain in patients with cognitive impairment due to dementia

The recently published VA Evidence Synthesis Report entitled, “Assessment and 

management of acute pain in adult medical inpatients: A systematic review”(21), four 

additional published reviews (22-25), and a guideline for assessing pain in the elderly(26)

have addressed assessment of pain in patients with cognitive impairment due to dementia. 

Together, these reviews indicate that there is limited evidence that most individuals with 

mild to moderate cognitive impairment due to dementia can understand at least one selfassessment pain measure. Among the existing scales of nonverbal behavioral pain 

VA-ESP September 2008 11
Pain in Patients with Polytrauma

indicators, none have been demonstrated to be substantially more reliable or valid than 

others for patients with cognitive impairment due to dementia. However, several of the 

reviews indicate that the Pain Assessment Checklist for Seniors with Limited Ability to 

Communicate (PACSLAC) may be especially promising or useful (27), and that the 

Discomfort Scale may have especially desirable psychometric properties.(28) To date, 

these self-assessment measures have not been specifically tested with TBI patients. 

Guidelines for assessing pain in patients with dementia who cannot understand any of the 

self-assessment measures suggest that multiple assessment methods may be best. Specific 

options include the use of an observational assessment measure, input from family, friends, 

or staff who know the patient well, and empiric pain treatment if the impaired patient has 

diagnoses usually associated with pain.(29-32) 

Key Question #2: A. Which treatment approaches are most likely to be effective in 

improving pain outcomes (pain intensity and functional interference) in polytrauma 

patients? B. Which pain treatment approaches are most likely to enhance overall 

rehabilitation efforts? 

Summary of findings 

2A: There were no randomized controlled trials, systematic reviews, prospective cohort, 

case-control, or systematic observational studies that tested the efficacy or effectiveness of 

specific pain treatment approaches among patients with polytrauma. 

2B: One fair-quality retrospective cohort study of patients who had undergone amputation 

at an urban trauma center demonstrated that after controlling for demographic factors, 

injury characteristics and other medical morbidity, inpatient rehabilitation was marginally 

associated with increased likelihood of return to work and decreased likelihood of reduced 

hours of work. (GRADE: Very Low)

Secondary Findings

• One fair-quality systematic review of primarily case reports on patients with causalgia 

(now known as complex regional pain syndrome II) due to war-related injuries 

suggests that sympathetic blocks and sympathectomy are frequently effective 

treatments. 

• A number of manuscripts presented cases or case series describing pain treatment 

approaches and pain outcomes among patients with polytrauma including TBI. 

Details of Studies—Primary Findings 

One fair-quality retrospective cohort study of patients who underwent amputation at an 

urban trauma center between 1984 and 1994 examined factors that predicted whether a 

patient would receive inpatient rehabilitation and the success of treatment.(33) Seventyeight patients (68% of eligible respondents) who had undergone trauma-related amputation 

at one hospital between 1984 and 1994 were contacted and interviewed an average of 7 

VA-ESP September 2008 12
Pain in Patients with Polytrauma

years after their injuries. The study excluded amputation for non-injury reasons (e.g. 

diabetes), spinal cord injury or TBI. Many patients in the sample had multiple injuries. 

After controlling for demographic factors, injury characteristics and other medical 

morbidity, inpatient rehabilitation was marginally associated with increased likelihood of 

return to work (p=0.09) and decreased likelihood of reduced hours of work (p=0.05). 

Details of Studies—Secondary Findings 

One fair quality systematic review on causalgia (now known as complex regional pain 

syndrome II) was published in 2003.(34) In this review, MEDLINE and Index Medicus 

were searched using the terms, causalgia and neuralgia. All references including new 

cases of causalgia were included. One hundred ten manuscripts describing a total of 1,528 

cases of causalgia were identified. No information about any experimental or longitudinal 

observational studies beyond individual cases or case series was reported. Overall, 57% of 

cases were war-related and 67% of cases were due to high-velocity missiles. It is unclear to 

what extent the overall group had polytrauma, but we infer from the traumatic nature of the 

injuries that polytrauma was likely common. The median nerve and sciatic trunk were the 

nerves most commonly involved and the most prominent clinical manifestations were

burning pain (86%) diaphoresis (73%), paresthesias (96%), and sensitivity to stimuli 

(98%). Response to sympathetic blocks was observed in 88%, and 94% of patients 

undergoing sympathectomy were described as cured. 

A number of manuscripts presented cases or case series describing pain treatment 

approaches and pain outcomes among patients with polytrauma including TBI. This 

information is summarized in Table 1 below. Several case reports support that intrathecal 

baclofen may be helpful for spasticity associated with TBI and related injuries. Despite 

supplemental hand-searches within our reference library for manuscripts on the use of 

opioids in patients with polytrauma including TBI, we found only one case report 

documenting (positive) specific effects of opioids in a TBI patient (included in Table 1) 

VA-ESP September 2008 13
Pain in Patients with Polytrauma

Table 1—Secondary Findings pertaining to Key Question 2: Case Reports/Case Series* 

Study Design/ Study Condition(s) Treatment Approach Results Sample 

(35) Single case Severe TBI with 

brainstem seizures and 

pain 

Mesothalamic electrode 

stimulation 

Attenuated brainstem generated 

seizures and relieved chronic pain 

(36) Single case TBI plus other injuries Acupuncture Decreased pain and anxiety 

(37) 100 consecu-tive 

referrals 

SCI (includes 15 TBI 

patients) 

Botulinum injections and 

physical therapy 

Clinician-reported global 

improvement in 90% of patients 

(38) Single case Complex regional pain 

syndrome I (formerly 

known as Reflex 

sympathetic dystrophy) 

post-amputation 

Topical capsaicin Associated with disappearance of 

pain and autonomic changes 

(39) 4 cases, one with 

TBI 

Spasticity Divalproex sodium (DVS) Marked improvement in pain. One 

patient could not tolerate DVS 

(40) 12 cases, 6 with 

missile head 

injury 

Anxiety and headache Fluphenazine Reductions in headache and 

anxiety 

(41) 2 cases, one with 

TBI 

Central Pain Gabapentin Increased anxiety 

(42) Single case 

(OEF/OIF 

veteran) 

Knee pain due to 

explosion, mild TBI, 

substance use disorder 

and PTSD 

Multidisciplinary care 

including cognitive 

processing therapy 

Decreased knee pain interference 

(43) 7 cases 

(veterans) 

SCI and neuropathic 

pain 

Healing Touch Variable response; overall 

improvement in pain and 

(5 received satisfaction with life 

comparator 

intervention) 

(44) Single case Heterotopic ossification 

in TBI 

Indomethacin and 

Radiation therapy 

No response to indomethacin, but 

decreased pain with radiation 

therapy 

(45) Single Case TBI with heterotopic 

ossification 

Intense physiotherapy 

after surgery 

Improvements in pain and 

behavioral symptoms 

(46) 11 cases (8 with 

TBI) 

Refractory spasticity Intrathecal baclofen Clinican-reported global 

improvement in all cases 

(47) 19 patients (4 

with TBI) 

SCI-related spasticity Intrathecal baclofen Spasticity and pain improved in 14 

pts. 

(48) 9 cases (1 with 

TBI 

Severe spasticity Intrathecal baclofen Most pts. improved, but no change 

in pain in TBI patient 

(49) 14 cases (5 due 

to trauma 

Spastic hypertonia Intrathecal baclofen Decreased pain 

(50) 3 cases with TBI Spasticity Intrathecal baclofen Decreased painful spasms 

(51) Single Case TBI with unilateral 

central pain 

Motor cortex stimulation VAS change from 75-85 to 20-30; 

50%-95% improvement in 

neuropathic symptoms 

(52) Single case Severe TBI Opioid (oxycodone) Increased interaction with others, 

Schizophrenia decreased anxiety 

(53) Single case Multiple medical 

conditions incl. 

polytrauma 

Qigong Therapy Decreased pain, weight loss, 

discontinuance of several 

medications 

VA-ESP September 2008 14
Pain in Patients with Polytrauma

Study Design/ Study Condition(s) Treatment Approach Results Sample 

(54) Single case TBI with severe 

headache 

Sphenopalatine Ganglion 

pulsed radiofrequency 

lesioning 

Long term relief of intractable 

headaches 

(55) 10 consecutive 

cases (7 due to 

trauma) 

Complex regional pain 

syndrome I 

Spinal Cord Stimulation Mean Numeric Rating Scale (NRS) 

pain score decrease of 6.2; 

decreased opioid use 

(56) Single case Blast-related headache Urea and chorionic 

gonadotropin 

Headache free 

*Subjects with TBI had moderate or severe TBI or TBI plus other injuries/complications 

Key Question #3: A. Does blast-related headache pain differ in terms of 

phenomenology and treatment from other types of headache pain? B. Which treatments are 

best for persistent blast-related headache pain? 

Summary of findings 

There were no randomized controlled trials, cohort studies, case-control studies, or other 

systematic observational studies that compared patients with blast-related headache to 

patients with other types of headache or that specifically addressed treatments for blastrelated headache pain. 

Secondary findings 

• Three studies (57-59) addressed the prevalence of headache among patients reporting 

head injuries. In a cross-sectional study of Army infantry soldiers post-deployment to 

Iraq with mild-TBI, most related to blast, 32% of soldiers reporting loss of 

consciousness and 18% of those reporting altered mental status also reported 

headache.(57) In a cross-sectional study of soldiers with injuries from Iraq and 

Afghanistan, two-thirds of whom were exposed to blast, 91% reported postconcussive symptoms, and headache was present in 47% of patients in this group.(58) 

Finally, in a poor-quality cohort study of civilians injured by munitions explosives in 

Yugoslavia, one year after injury, 30% of patients with blast injuries reported a 

constellation of symptoms which included headache, vertigo, and psychological and 

cognitive sequelae.(59) 

• Two cross-sectional studies described blast injuries of the ear including hearing 

deficits, otalgia, and mandibular pain.(60, 61) We include this information because 

these types of problems have the potential to complicate the assessment and treatment 

of blast-related headache. In a study of service members at Walter Reed Army 

Medical Center referred for audiologic testing for follow-up of blast exposure, ageadjusted hearing thresholds were significantly lower than expected, 32% of patients 

had experienced tympanic membrane perforation, 49% reported tinnitus, and 5% 

reported otalgia.(60) In a study of civilians from Iran with war-related blast exposure 

referred to an oral/maxillofacial surgery clinic for evaluation of mandibular problems, 

VA-ESP September 2008 15
Pain in Patients with Polytrauma

pain was a common complaint and levels of pain were associated with distance from 

blasts.(61) 

• We identified one good quality systematic review of post-traumatic headache in 

TBI,(62) but blast exposure was not included as a characteristic in any of the studies, 

nor did the review explore relationships between TBI severity and headache (thus we 

include the results here as secondary findings). The review showed that most 

posttraumatic headache resolves within 6-12 months, but headaches persist beyond 

one year in 18% to 33% of patients. Many patients with posttraumatic headache have 

clinical presentations similar to tension-type headache or migraine. Many clinicians 

treat posttraumatic headache as if they are managing primary headache. 

Details of Studies—Secondary Findings 

In a recent cross-sectional study assessing the prevalence and significance of selfreported history of combat-related mild TBI, soldiers from two US Army combat infantry 

brigades were surveyed three to four months after a yearlong deployment in Iraq in 

2006.(57) Of 4,618 soldiers potentially eligible to participate, 2,714 (59%) completed 

surveys. The authors note that lack of availability to complete questionnaires was mostly 

due to normal transfers to other units, trainings or attendance at military schools. Surveys 

inquired whether soldiers had been injured during their deployments by a blast or 

explosion, a bullet, a fragment or shrapnel, a vehicle accident, or other means, and 

whether the injury involved the head. A soldier was considered to have mild TBI if he or 

she endorsed “losing consciousness,” “being dazed, confused or seeing stars,” or “not 

remembering the injury.” Multivariate logistic regression analyses were used to identify 

correlates of a range of self-reported outcomes including general health, missed 

workdays, medical visits, and somatic and postconcussive symptoms. Of soldiers 

reporting injuries with loss of consciousness or altered mental status, 75% reported being 

exposed to blast or explosion. Five percent reported injury with loss of consciousness, 

10% reported in juries with altered mental status, and 17% reported other injuries during 

deployment. Headache was common, present in 32% of those reporting injury with loss 

of consciousness and 18% of those reporting altered mental status, as compared to 

soldiers who reported other injuries (12%) or no injury (8%) (p<0.001). In models 

adjusted for demographics, mechanism of injury, blast exposure, post-traumatic stress 

disorder (PTSD), depression, combat intensity, and hospitalization, the odds of headache 

remained significantly greater in soldiers reporting loss of consciousness versus other 

injury: 2.38 (1.12-5.07). The odds of headache were not significantly greater in soldiers 

reporting altered mental status vs. other injury: 1.63 (0.92-2.90). Overall, the analyses 

show that, except for in the case of headache when there is loss of consciousness, the 

associations among TBI and physical health problems are no longer significant when 

PTSD and depression are included in models. 

An abstract from a cross-sectional study described the characteristics of soldiers 

returning from Iraq or Afghanistan who were injured in a blast, fall, gun shot wound, or 

motor vehicle accident, and screened for TBI by the Defense and Veterans Brain Injury 

Center (DVBIC) of Walter Reed Army Medicine Center between January 2003 and April 

VA-ESP September 2008 16
Pain in Patients with Polytrauma

2005.(58) The sample included the initial 433 patients seen by the DVIBC. The sample 

was 95% males, modal age 21. Sixty-eight percent reported blast exposure, 79% 

reported loss of consciousness less than one hour, and 43% reported post-traumatic 

amnesia less than 24 hours. Ninety-one percent of patients reported post-concussive 

symptoms. Headache (47%), memory deficits (46%), and irritability/aggression (41%) 

were the most common post-concussive symptoms. 

A poor-quality cohort study of 1,303 civilians who had been injured by munitions 

explosives in Yugoslavia between 1991 and 1994 and admitted to the US Military 

Medical Academy in Belgrade assessed the effects of blast exposure within one year of 

injury.(59) Approximately 30% of patients with 665 blast injuries reported persisting 

symptoms including headache, vertigo, positive Romberg’s sign, retrograde amnesia, 

mental blockage, apathy/lethargy, psychomotor agitation, and anxiety. The study was 

limited by inadequate reporting on rates of follow-up, timing of follow-up assessment, or 

details of the measurement of these symptoms. 

An observational study that sought to examine whether blast was related to significant 

hearing changes collected audiologic data on 258 service members.(60) The 

investigators also explored whether polytraumatic injuries were associated with hearing 

loss. Potential subjects were referred for audiologic testing at Walter Reed Army 

Medical Center as part of a standard protocol for soldiers reporting at least one blastrelated exposure. Only 162 out of 258 patients (63%) had hearing test data available for 

review. The mean age was 29 years and 98% were male. Within this group, ageadjusted actual hearing thresholds were significantly lower than expected, and 32% of 

patients had experienced tympanic membrane perforation, 49% reported tinnitus, and 5% 

reported otalgia. There was no association between polytrauma status and other 

characteristics. A cross-sectional study of 495 civilians with blast exposure who were 

referred to an oral/maxillofacial surgery clinic from the Medical Services Centre for War 

Injured Patients in Tehran, Iran between March 1984 and February 1990 reported that 

pain was a common complaint and that levels of pain were associated with distance from 

blasts.(61) In 115 patients, pain was localized in the external acoustic meatus and 15 

patients complained of total facial pain. Forty-nine percent of the sample “responded” to 

limiting jaw movement, adopting a soft-diet, and the use of “pain killers,” and 77% 

responded to a combination of “pain killers” and muscle relaxants. Patient characteristics 

and the timing and methods to measure outcomes were not specified. 

Finally, we identified one good quality systematic review of post-traumatic headache in 

TBI.(62) In this review, the investigators searched MEDLINE for literature on 

posttraumatic headache published between January 1990 and February 2005. Five studies 

specifically describing patient characteristics and types of headache were identified.(63-

67) The total number of subjects in these studies was 423 patients. Blast exposure was 

not included as a characteristic in any of the five studies, and the review did not explore 

relationships between TBI severity and headache. The review showed that posttraumatic 

headache usually resolves within 6-12 months, but that 18% to 33% of the time, 

headaches persist beyond one year. Many (37%) of patients with posttraumatic headache 

had clinical presentations similar to tension-type headache or migraine (29%). Many 

VA-ESP September 2008 17
Pain in Patients with Polytrauma

clinicians treat posttraumatic headache as if they were managing primary headache. The 

authors conclude that there is no universally accepted protocol for treating posttraumatic 

headache, and that randomized controlled trials are needed in this area. 

Key Question #4. What patient factors are associated with better and worse (painrelated) clinical outcomes among polytrauma patients? Have interventions been 

developed to specifically address these factors? 

Summary of Findings 

There were no randomized controlled trials. One systematic review, 11 cohort, 2 casecontrol, and 17 cross-sectional studies specifically addressed patient factors associated 

with outcomes in TBI patients. Twenty cohort, 2 cross-sectional, and 5 case-control 

studies addressed patient factors associated with outcomes in other polytrauma patients. 

Evidence Table 1 in Appendix E shows the data abstracted from these studies. 

Traumatic Brain Injury

• One recent fair-quality systematic review showed that overall, 58% of patients with 

TBI have chronic headache, and that brain injury is associated with headache even after 

adjustment for post-traumatic stress disorder (PTSD).(68) These findings are 

consistent with our review, which included additional manuscripts, which found that 

among patients with TBI, headache is present in one-third to one-half of patients up to 

five years after injury. (GRADE: Low) 

• The recent fair-quality systematic review above also found that patients with mild TBI 

were more likely to have headache than patients with moderate or severe TBI.(68) 

However, our review showed very mixed findings regarding the association between 

severity of TBI and pain (GRADE: Very Low). 

• Psychological factors, including depression and posttraumatic stress disorder (PTSD), 

insomnia and fatigue are associated with pain in TBI patients. (GRADE: Low) 

Other injuries in polytrauma patients

• Characteristics of injuries (location, severity, and whether they are multiple) are 

associated with clinical outcomes including persistent pain and functional status. 

Specific factors associated with worse pain-related outcomes include: multiple injuries, 

foot injuries or injuries below the knee joint, and concurrent head injury or cognitive 

disability. (GRADE: Low) 

• Other factors associated with better outcomes in some studies of patients with 

polytraumatic injuries other than TBI were younger age, higher educational 

achievement, having a white collar job or higher income. (GRADE: Very Low) 

VA-ESP September 2008 18
Pain in Patients with Polytrauma

Details of Studies—Traumatic Brain Injury

Prevalence of pain and headache among TBI patients

One fair-quality systematic review was published in 2008. In this review, 

Ovid/MEDLINE, PubMed, and MD consult databases were searched using the terms brain 

injury, pain, headache, blast injury, combat, combat disorders, war, military medicine, 

wounds and injuries, military personnel, and veterans. The Cochrane Collaboration, 

National Institutes of Health Clinical Trials Database, Meta-register of Current Controlled 

Trials and CRISP database were searched using the term brain injury. Articles were 

included which were published between 1951 and February 2008 (however one article 

from 1939 is also included in the review.(69) The search was not limited by language or 

publication status. Case reports and review articles were cited only if no other data were 

available. Twenty-three studies (15 cross-sectional, 5 prospective observational, and 3 

retrospective observational) including 4,206 patients were identified. No randomized 

clinical trials were identified. Data were pooled across studies to obtain overall prevalence 

rates. The review showed that 58% (95%CI 55.5-60.2%) of patients with TBI have chronic 

headache, and that brain injury is associated with headache even after adjustment for posttraumatic stress disorder (PTSD).(68) 

In our review, we found seven prospective and one retrospective cohort studies that report 

on the prevalence of pain and headache among TBI patients.(70-77) In a good-quality 

prospective cohort study of 146 patients enrolled in acute inpatient rehabilitation for TBI, 

73% reported pain at one year and 55% reported interference from pain.(71) One fairquality prospective cohort study measured prevalence and type of headache among 109 

patients with moderate to severe TBI consecutively admitted to one of four VA Polytrauma 

Rehabilitation Centers (PRCs) over 12 months.(70) On admission, 38% of patients 

reported headache. Sixty-four percent of patients with headache reported no to mild levels 

of incapacitation from headaches. Among patients with headaches at admission, 54% 

reported persistent headache symptoms at six months, and of this group, 96% still had 

headaches at 12 months. Of patients without headache at admission, the majority remained 

headache free over 12 months. In a fair-quality prospective cohort study of 161 patients 

admitted to a brain injury rehabilitation unit, 62% reported some type of pain and 31% 

reported daily pain or continuous pain at six months.(72) Headache was the most 

frequently reported type of pain. In a fair-quality prospective cohort study of 231 patients 

admitted to three trauma centers in France with severe head injuries reassessed five years 

after injury, the prevalence of headache was 44 to 54%, significantly greater than 16% in a 

comparison group with lower limb injury but no TBI.(73) In a poor quality prospective 

cohort study of patients with TBI consecutively admitted to an inpatient urban 

rehabilitation program who completed follow-up assessments, headache prevalence 

increased from 31% 2 years post-injury to 42% 5 years post-injury.(76) In a poor-quality 

prospective cohort study of 132 patients consecutively admitted to an inpatient TBI 

rehabilitation center, 10% of patients had co-existing peripheral nerve injuries, and of these 

patients, 31% reported pain.(77) In a poor-quality retrospective cohort study of 200 

patients admitted to an inpatient accident service, headaches persisted in 17 to 18% of 

cases 6 months after injury.(75) Finally, in another poor-quality retrospective cohort 

VA-ESP September 2008 19
Pain in Patients with Polytrauma

study, 58% of patients admitted to an Australian teaching hospital had headaches 5 years 

after TBI.(74) 

Two fair-quality case-control studies demonstrated that pain is more common or more 

severe in TBI patients than other populations.(78, 79) One of these studies showed that 

overall pain scores were higher in a volunteer community sample of mild to severe TBI 

patients at least 12-months post-injury compared to a group of non-injured controls (17.2 

vs. 10.1, on a scale of 0-78 using the McGill pain questionnaire,p=.013).(78) The other 

study showed that the prevalence of pain complaints was 59% in a sample of patients with 

TBI referred for neuropsychological assessment at a medical center versus 22% of nonTBI patients also referred for neuropsychological assessment (p<.001).(79) 

Several cross-sectional studies also support that pain and headache are common among 

TBI patients.(57, 58, 80-86) In these studies, pain was present in 22% to 90% of patients. 

In one of these studies of young patients admitted to a brain injury rehabilitation ward in 

London an average of 25 weeks after injury, only 12% reported headache.(82) Headache 

was the most common type of pain complaint according to two of these studies.(81, 85) 

Another study found that reflex sympathetic dystrophy (now known as Complex Regional 

Pain Syndrome I) was present in 13 of 100 patients consecutively admitted to an inpatient 

brain injury unit.(84) Notably, in several(81, 85, 86) of the above studies, case status was 

established at the time of outpatient follow-up assessment; thus, patients with persisting 

pain complaints may be overrepresented in these samples. 

Taken together these studies show that pain is common among patients with TBI, present 

in approximately one-third to one-half of patients up to five years after injury. One 

prospective cohort, and several cross-sectional studies suggest that headache is the most 

common pain complaint among TBI patients. 

Relationship between severity of TBI and pain in TBI patients

One fair-quality systematic review was published in 2008. In this review, 

Ovid/MEDLINE, PubMed, and MD consult databases were searched using the terms brain 

injury, pain, headache, blast injury, combat, combat disorders, war, military medicine, 

wounds and injuries, military personnel, and veterans. The Cochrane Collaboration, 

National Institutes of Health Clinical Trials Database, Meta-register of Current Controlled 

Trials and CRISP database were searched using the term brain injury. Articles were 

included which were published between 1951 and February 2008 (however one article 

from 1939 is also included in the review.(69) The search was not limited by language or 

publication status. Case reports and review articles were cited only if no other data were 

available. Twenty-three studies (15 cross-sectional, 5 prospective observational, and 3 

retrospective observational) including 4,206 patients were identified. No randomized 

clinical trials were identified. Data were pooled across studies to obtain overall prevalence 

rates. The review showed that among civilians, the prevalence of chronic pain was 51.5% 

(95%CI 49.8% - 53.2%) among patients with mild TBI, compared with 32.1% (95%CI 

29.3% - 34.9%) among patients with moderate or severe TBI.(68) 

VA-ESP September 2008 20
Pain in Patients with Polytrauma

In our review, which included a number of studies not included in the systematic review 

above, one fair-quality prospective cohort study of 109 patients admitted to one of four VA 

PRCs, no statistically significant relationships were identified between Glasgow Coma 

Scale (GCS) score, Loss of Consciousness (LOC), or duration of post-traumatic amnesia 

(all indicators of head injury severity) and posttraumatic headache prevalence.(70) One 

good-quality prospective cohort study of 146 patients enrolled in a University acute 

inpatient rehabilitation program similarly found that baseline GCS was not associated with 

pain status one year after injury.(71) In another fair-quality prospective cohort study of 

231 patients admitted to French trauma centers with severe head injuries who were 

reassessed five years after injury, headache prevalence was not found to be significantly 

different according to head injury severity.(73) Patients with severe head injury were less 

likely to complete follow-up assessments due to deaths. In an additional prospective cohort 

study of 200 consecutive individuals admitted to an urban hospital with head injuries, 

headache persisting longer than two months was not more prevalent among patients with 

more severe head injuries than patients with milder head injuries.(87) Finally, a poorquality retrospective cohort study of 200 patients admitted to an inpatient accident service 

found no differences in the prevalence of headache when comparing patients with mild 

head injury to those with moderate to severe TBI three and six months after injury.(75) 

In a cross-sectional study of consecutive TBI patients seen in an outpatient brain injury 

clinic, over half of the sample reported chronic pain (primarily headaches), and there were 

similar rates of pain reports when comparing patients with mild TBI to patients with more 

severe TBI.(81) A retrospective review of the records of 200 consecutive cases of head 

injury admitted to the surgical wards of the Edinburgh Royal Infirmary similarly found no 

increase in headache prevalence among patients who had presented with milder head 

injuries.(88) Finally, in a cross-sectional examination of the validity of the SF-36 for 

characterizing outcome after multiple trauma, there were no differences in the SF-36 

bodily pain scale based on severity of head trauma among patients discharged from trauma 

centers who did not have concurrent orthopedic injuries.(89) 

However, one fair-quality retrospective cohort study,(90) one fair-quality case-control 

study (79) and five studies using cross-sectional designs(82, 85, 86, 91, 92) found a higher 

prevalence of headache among patients with mild TBI as compared to more severe TBI. In 

the retrospective cohort study of 228 patients a median of four years after being admitted 

to a university ICU for major trauma, patients with severe head injury were less likely to 

report problems with pain/discomfort (OR 0.31, 95%CI 0.15 - 0.64) after adjusting for 

retrospectively-patient-reported baseline levels of symptoms and functioning. However, 

patients with severe head injury were less likely to participate in the follow-up surveys. In 

five of case-control and cross-sectional studies, study samples were established from 

referrals or attendees of outpatient follow-up clinics for TBI. Generally, patients were seen 

in these follow up clinics between six months and two years after their injuries. In one of 

the studies, the sample consisted of patients admitted to a subacute rehabilitation unit on 

average 25 weeks post-injury,(82) and in the remaining study, it was unclear whether the 

study cohort was established at the time of injury or time of outpatient follow-up.(92) 

Overall, this group of studies found that patients with mild TBI who attend outpatient brain 

injury clinics are two to three times more likely to report headache than patients with 

VA-ESP September 2008 21
Pain in Patients with Polytrauma

moderate or severe TBI. However, the analyses in these studies were not adjusted for 

potential confounding factors, and specific reasons why patients were referred to or sought 

care in these settings were not specified or adjusted for in most of the studies. 

In summary, there is very limited evidence showing that patients with mild TBI are more 

likely to have headache or other pain than patients without TBI. While one retrospective 

cohort, one case-control, and a number of cross-sectional studies suggest that patients with 

mild TBI may be more likely to have headache pain than patients with moderate or severe 

TBI, six prospective cohort studies and additional cross-sectional studies did not find such 

a relationship. In the single systematic review showing a difference in rates of pain across 

levels of TBI severity, data were pooled across studies using different patient samples and 

designs. Most of the studies identified in that review and in our review that found 

associations between milder head injury and headache were done in outpatient settings, up 

to several years post-injury, and did not adjust for potential confounders that may influence 

relationships between TBI severity and pain. On the other hand, most of the samples in the 

identified cohort studies were assembled at the time of admission to a hospital or inpatient 

rehabilitation setting. It is therefore likely that differences in sample composition 

contribute to the differences in findings between the cross-sectional and cohort studies; 

patients with mild TBI may be more likely to be referred to or attend outpatient follow-up 

appointments when they have bothersome or persistent symptoms such as headache. 

Relationships between other patient factors and pain outcomes in patients with TBI

Demographics: There are mixed findings regarding the association between demographic 

factors and pain outcomes in TBI patients. In one good-quality prospective cohort study of 

146 patients enrolled in a university acute inpatient rehabilitation program, pain one year 

after injury was significantly associated with being female and non-white; being non-white 

remained significantly associated with reports of pain at one year in a multivariate 

regression model (taking other factors into account).(71) However, a fair-quality cohort 

study of veterans at VA PRCs(70) and a cross-sectional study of outpatients referred for 

neuropsychological evaluation (93) did not detect significant associations between 

demographic factors and headache frequency. 

Blast exposure: In a cross-sectional study of 188 service members admitted to one of four 

VA PRCs, blast exposure was not found to be a significant predictor of pain.(80) 

Psychological factors: In a fair-quality prospective cohort study of 109 patients admitted to 

one of four VA PRCs, headache density (a measure combining headache-related 

incapacitation and frequency) at six and 12 months was associated with higher depression 

and anxiety levels among patients with persistent headaches, and among patients with 

delayed onset headaches.(70) In another good-quality prospective cohort study of 146 

patients enrolled in a university acute inpatient rehabilitation program, depression one year 

after injury remained significantly associated with reports of pain at one year (taking other 

factors into account).(71) Depression was also found to be a significant factor mediating 

the relationship between pain and community participation. In a fair-quality prospective 

cohort study of 161 patients admitted to a tertiary care center brain injury rehabilitation 

unit, frequency but not severity of chronic pain was associated with PTSD (p<.05).(72) In 

VA-ESP September 2008 22
Pain in Patients with Polytrauma

a multivariate model including psychological factors, only avoidant coping style remained 

significantly associated with pain severity after controlling for PTSD severity. In a fairquality prospective cohort study of 47 patients admitted to a regional trauma center, pain 

was found to be highly correlated with depression (r=.81) in post hoc analyses. Finally, in 

a cross-sectional study of 84 patients from eight outpatient Mid-west rehabilitation centers, 

in a model including perceived stress, impact of events, and litigation status, pain was 

significantly associated with depression (partial R2

 = .07, p=.001).(94) 

Fatigue and Insomnia: In a poor-quality prospective cohort study of 38 TBI patients 

admitted to an inpatient rehabilitation service, there were highly significant correlations 

between levels of fatigue and pain at one and 2 years post-injury (R=.49 and .62, 

respectively, p<.01).(95) Another fair-quality case-control study of community volunteers 

showed that fatigue was correlated with the SF-36 bodily pain scale in TBI patients 

(R=.389, p<.011).(78) In another fair-quality case-control study of patients referred to a 

university outpatient neuropsychology service, pain was highly associated with insomnia 

(p<.001).(79) In an additional cross-sectional study of Canadian community volunteers, 

pain frequency was significantly associated with insomnia in TBI patients; pain remained a 

significant predictor of insomnia in a multivariate model that included depression, severity 

of injury and fatigue.(96) Finally, in another cross-sectional study, pain was significantly 

associated with insomnia in TBI patients admitted to a comprehensive outpatient 

rehabilitation program; however, pain dropped out of a multivariate model in which 

presence of insomnia was the outcome.(97) 

Taken together, this group of studies provides limited evidence that psychological factors, 

including depression and posttraumatic stress disorder (PTSD), insomnia and fatigue are 

associated with pain in TBI patients.

Details of Studies —Other Injuries in Polytrauma Patients 

Injury characteristics—amputations: Studies support that injury factors (location, severity, 

multiplicity) are often associated with pain-related outcomes in patients with amputations. 

In a fair-quality retrospective cohort study of 78 trauma-related amputation patients, many 

of whom had multiple trauma, greater initial severity of injury was associated with 

significantly worse self-reported physical functioning including bodily pain.(33) In another 

fair-quality retrospective cohort study, investigators studied 326 patients from Belgrade 

who experienced missile-caused peripheral nerve lesions, some of whom likely had 

multiple trauma.(98, 99) In multivariate analyses, three factors were significant predictors 

of pain up to five years after injury: type of pain syndrome (e.g., complex regional pain 

syndrome II or deafferentation pain), severity of initial nerve injury, and an absence of pain 

paroxysms. In an additional fair-quality retrospective cohort study examining the longterm results of compartment syndrome, polytrauma patients were compared to those with a 

single injury.(100) The investigators did not find a difference with respect to strength, 

pain, or function and concluded that secondary injuries did not negatively impact the 

outcome of compartment syndrome. A poor-quality retrospective cohort study compared 

functional outcomes of Vietnam Veterans who had isolated transtibial amputations to those 

with amputations and at least one other major injury.(101) The polytrauma group scored 

VA-ESP September 2008 23
Pain in Patients with Polytrauma

significantly lower than the control group on all 8 subscale scores of the SF-36 including 

bodily pain, whereas quality of life scores from the single trauma group did not differ with 

those from the control group. A poor-quality quality case-control study compared 23 

bilateral Vietnam Veteran amputees to age and gender matched controls from a national 

registry. Cases were surveyed an average of 28 years after injury. This study showed that 

while overall physical function was lower in the case group, bodily pain scores were not 

significantly different.(102) Finally, a cross-sectional study provided descriptive data on 

stump pain, phantom sensation, and phantom pain in 40 civilians from Sierra Leone who 

suffered traumatic upper limb amputation in a civil war setting.(103) Interviews were 

conducted 10-48 months post-injury. All amputees (100%) had stump pain in the last 

month and 93% had phantom sensations. Phantom pain was less common among patients 

with bilateral than unilateral amputations (18% versus 38%; no p-value reported). In an 

additional cross-sectional study of civilian amputees, stump and phantom limb pain were 

reported by 73% of multiple level amputees as compared to 63% of upper limb and 74% of 

lower limb amputees (no comparison significance tests reported).(104)

Injury characteristics—orthopedic injuries Studies also suggest that injury factors are 

associated with pain-related outcomes in patients with orthopedic injuries. A good-quality 

retrospective cohort study of 389 patients compared long-term functional outcomes among 

3 groups, based on the site of fracture: above-knee, below knee, or combined fractures 

above and below the knee.(105) A mean of 17 years after injury (minimum 10 years), 

although persistent pain was not significantly more frequent among patients with belowknee fractures compared with above-knee fractures (46% v. 39%, p=0.25), persistent pain 

was significantly more common in patients with combined injuries as compared to 

fractures about the knee joint (58.5% vs. 39.3%, p<.001). Two additional small, fairquality case-control studies compared functional outcomes in small numbers of polytrauma 

patients with and without foot injuries.(106, 107) In both studies, the outcomes of multiply 

injured patients with foot injuries were significantly worse than that of patients without 

foot injuries. Patients with foot injuries had a dramatically lower scores on SF-36 scales of 

physical function, role physical (perception of physical functioning), bodily pain, and 

social function compared to controls.(106, 107) 

In another fair-quality prospective cohort study, 659 patients with multiple orthopedic 

injuries were compared to 165 patients with orthopedic injuries plus other types of 

injuries.(108) Six months post-injury, patients with combined orthopedic and other 

injuries had greater pain intensity and reported more disability than patients with multiple 

orthopedic injuries alone. A fair-quality retrospective cohort study compared pain and 

function in 27 long-term survivors of open pelvic fracture with the experience of 84 

survivors of closed pelvic fracture.(109) Subjects were multiple system blunt trauma 

patients with a pelvic fracture, and associated injuries included head injury, thoracic 

trauma, abdominal injury, extremity fractures, and spinal fractures. Survivors of open 

pelvic fracture had non-significantly lower SF-36 bodily pain scores, and significantly 

lower scores for physical functioning and role physical subscales, indicating worse 

outcomes. Finally, a fair-quality prospective cohort study of orthopedic injuries was 

conducted in 830 polytrauma patients with spine injury.(110) Degree of injury severity was 

VA-ESP September 2008 24
Pain in Patients with Polytrauma

correlated with pain, functional independence, and return to employment one year and two 

years follow-up. 

Injury characteristics—other polytraumatic injuries: A number of additional cohort 

studies examined relationships between various injury characteristics and functional 

outcomes including or in addition to measures of pain.(109, 111-120) Pain intensity was 

not a main outcome in these studies and was often measured using a subscale of a 

functional status measure. In only some of these studies were potentially confounding 

factors adjusted for in analyses involving pain outcomes.(113-115, 119) Most of the 

studies did not have excessive loss to follow-up, and some studies determined that patients 

lost to follow-up were not substantially different from patients represented in the 

study.(112, 113, 115, 116, 120) Almost all of the studies that compared multiply and singly 

injured patients to patients with a single injury, or measured the severity of injury, found 

an association between multiple or severe single injuries and worse functional outcomes 

and pain.(111, 112, 114-118) Some studies that included patients with cognitive 

disabilities or head injuries found associations between head injury or cognitive disability 

and decreased functional outcome.(112-115, 117) In an additional poor-quality case 

control study of 49 patients (setting not specified), patients with head injury plus other 

types of polytrauma were not found to have worse bodily pain at 6 or 12 months after 

injury compared to patients with TBI alone.(121) Finally, other injury characteristics 

associated with worse functional and pain outcomes were lower limb injuries,(114, 116, 

120)longer hospital length of stay,(115) and admission to intensive care unit (ICU) and 

length of ICU stay. 

In summary, many cohort studies as well as several case-control and cross-sectional 

studies found that polytraumatic injury characteristics (principally location, initial severity, 

and multiplicity of injury) are associated with pain and functional outcomes over time. 

Injuries below the knee joint are associated with worse outcomes compared to injuries 

above the knee in polytrauma patients. A number of these studies did not adjust for factors 

that may confound relationships between injury characteristics and pain-related outcomes. 

Demographics: A number of manuscripts reported adjusting for demographic variables 

(mainly age) in multivariate analyses, but did not report whether and to what extent these 

variables were significantly associated with pain outcomes. One good-quality (115) and 

three fair-quality (33, 112, 118) cohort studies found associations between younger age 

and better functional outcomes in polytrauma patients. One good-quality cohort study 

(115) and one fair-quality cohort study (111) found associations between being male and 

better functional outcomes. In an additional cross-sectional study of 40 civilians from 

Sierra Leone who suffered traumatic upper limb amputation, phantom pain was more 

common in women than men (63% versus 25%, p=0.057).(103) However, in one fairquality prospective cohort study of 62 patients injured in traffic accidents, there were no 

significant differences in SF-36 bodily pain scores by gender in bivariate analyses two and 

eight months post-injury.(122) Finally, in one fair-quality retrospective cohort study of 78 

trauma-related amputation patients, being white was associated with better SF-36 PCS and 

bodily pain outcome scores, higher likelihood of return to work, and lower likelihood of 

reduced work hours.(33) 

VA-ESP September 2008 25
Pain in Patients with Polytrauma

Other factors associated with better functional status were higher educational achievement 

(two good-quality (115, 119) and one fair quality (114) cohort studies), having a 

professional/white collar job (one good quality (119) and two fair-quality (112, 118) cohort 

studies) and higher income, job stability, job flexibility and lower physical demands at 

work (one good quality cohort study).(119) The authors of this latter study also found an 

association between receiving worker’s compensation and lower return to work rate. 

Psychosocial Factors: Almost no studies reported on the relationships between 

psychosocial factors and pain-related outcomes in patients with polytraumatic injuries 

other than TBI. In one fair-quality retrospective cohort study of 69 patients admitted to an 

inpatient surgical service, loss of non-work activities was significantly correlated with 

pain.(112) One cross-sectional study provided descriptive data on stump pain, phantom 

sensation, and phantom pain 10-48 months post-injury in 40 civilians from Sierra Leone 

who had suffered traumatic upper limb amputation in a civil war setting.(103) No 

significant relationships were reported between mood and the prevalence of phantom or 

stump pain. 

To summarize, there is very limited evidence regarding the extent to which demographic 

factors are associated with pain-related outcomes in patients with polytraumatic injuries 

other than TBI. Four cohort studies show that younger age is associated with better 

longer-term outcomes in patients with severe multiple injuries, and three cohort studies and 

one cross-sectional study show a relationship between male sex and improved outcomes 

after major trauma. There is almost no information available regarding relationships 

between race and ethnicity and pain-related outcomes. There is almost no information 

available regarding relationships between psychosocial factors and pain-related outcomes 

in patients with polytraumatic injuries other than TBI. 

Key Question #5. What are unique provider and system barriers to detecting and 

treating pain among polytrauma patients? Have interventions been developed to effectively 

address these barriers? 

Summary of findings 

There were no randomized controlled trials, cohort studies, case-control studies, or other 

systematic observational studies that addressed provider and system barriers to detecting 

and treating pain among polytrauma patients. One qualitative study of providers from four 

VA Polytrauma Rehabilitation Centers (PRCs) addressed potential provider and system 

barriers to treating polytrauma patients.(3) In qualitative interviews, providers reported that 

polytrauma patients are very complex to treat, and that the work with this population is 

very challenging and emotionally taxing. Increasing use of multidisciplinary and 

concurrent care, and consultation from experts may be necessary to provide the complex 

care that is needed.

Details of Study 

VA-ESP September 2008 26
Pain in Patients with Polytrauma

This study was a qualitative study of provider perspectives on the rehabilitation of 

patients with polytrauma. This study which used Rapid Assessment Process methodology 

including semi-structured interviews, observation, and field liaison. The purpose of the 

study was to describe, from the perspective of providers working or affiliated with one of 

four VA Polytrauma Rehabilitation Centers (PRCs), 1) patients with combat-related 

polytrauma and their rehabilitation; 2) polytrauma patient family member involvement in 

rehabilitation; and 3) the impact on providers of providing polytrauma rehabilitation. 

Clinicians of various disciplines were selected among the four PRC sites, as well as 

personnel who work closely with the PRCs, including: 1) clinicians who provide regular 

consultation to PRC patients, including pain, PTSD, infectious disease, and low-vision 

specialists; 2) military liaisons who are US Department of Defense (DOD) employees 

housed at the PRC to help active-duty patients navigate across care systems; and 3) the 

VA points of contact who help US Service members obtain needed VA services; specific 

demographics of the clinicians interviewed were not provided. Fifty-six interviews were 

conducted. 

A number of common themes were identified which are pertinent to this key question: 

1. Patients with blast-related injuries including TBI have more injuries and more severe 

injuries than other patient populations. Serious psychiatric disorders, including PTSD 

and injury-related pain are highly prevalent, and complicate rehabilitation for TBI. 

These factors make this patient population quite complex to treat. 

2. Providers find working with this population very challenging and emotionally taxing. 

3. In order to address the level of complexity, providers are increasingly using cotreatment across disciplines, more regular consultation with services outside 

rehabilitation, such as surgery, amputation care, and psychiatry, and more frequent 

consultation with colleagues within and across the PRCs. PRC teams are expanding 

to include experts in areas including pain. 

4. Spouses, parents, siblings, and children have become intensely involved in the 

injured service member's rehabilitation and have their own informational, 

instrumental, and support needs. Providers must respond to family needs and engage 

them as collaborators in the rehabilitation process. 

Limitations—Literature Review

Heterogeneity and Generalizability 

Due to innumerable etiologies and combinations of injuries, there is great heterogeneity 

among polytrauma patients. For example, within the category of blast-related head injury 

alone, there are multiple potential mechanisms of brain injury, and injuries may or may not 

be concurrent with other penetrating head injuries.(123) There is consequent heterogeneity 

among the study samples described in the literature as well as in the methods used to 

describe study samples. Many studies were done at single sites or within specialized types 

of settings. Thus, the conclusions we might draw from a particular study or set of studies 

VA-ESP September 2008 27
Pain in Patients with Polytrauma

may have limited relevance for other polytrauma patients, and comparisons among studies 

may be challenging. 

Scope 

Due in part to the degree of heterogeneity among studies and their descriptions, as well as 

the lack of precision inherent in the term, “polytrauma”, we adopted a fairly stringent 

operational definition for polytrauma (multiple concurrent injuries in two or more systems) 

and focused on identifying studies that clearly included majorities of patients with 

polytrauma in their samples. Thus, for example, some studies of patients with spinal cord 

injuries or amputations were not included unless there was clear indication at the abstract 

or full-text level that multiple injuries were (often) involved. It is therefore likely that some 

manuscripts that might have relevance for the treatment of pain in polytrauma or 

subgroups of polytrauma patients were not identified. Surgical approaches were excluded 

due to the heterogeneity of the conditions being treated with specific techniques. We did 

not feel that information generated from review of specific surgical approaches would be 

very generalizable to the polytrauma patient population as a whole. We note that we did 

search more broadly for studies pertaining to TBI and blast since there is particular 

relevance for a large segment of the OEF/OIF patient population. 

Publication Bias 

Our search strategies were comprehensive and we evaluated a large number of studies for 

possible inclusion in the review. Two librarians independently searched the literature and 

their results were combined to form our reference library. While this process identified 

many manuscripts for potential inclusion in the review, it is possible that our search terms 

did not capture some relevant manuscripts, especially for older studies which might not 

have been indexed in databases as pertaining to polytrauma or multiple injury/trauma. We 

therefore included additional search terms pertaining to blast, TBI, and war, and relied 

extensively on reference lists of studies, review articles, editorials, and consulting experts 

to identify additional manuscripts for review. 

Study quality 

We did not exclude individual studies based on quality rating alone. Thus the strength of 

our conclusions is inherently limited by the quality variation among included studies. We 

did make an effort to note particular methodologic limitations, and each cohort and casecontrol study was closely reviewed for overall quality using a rigorously developed 

approach. Although cross-sectional studies were not formally rated, methodologic 

limitations were often noted. 

VA-ESP September 2008 28
Pain in Patients with Polytrauma

RESULTS—ACTIVE RESEARCH

Summary of findings 

Nineteen relevant active or planned projects were identified and project data were collected 

on 18 of these projects. Pain measures constitute main outcomes in 8 of the studies, and 

will be collected as secondary outcomes in 10 of the studies. Fifteen of the studies should 

generate information regarding patient factors that may contribute to pain-related outcomes 

among polytrauma patients (Key Question 4), and 4 studies are testing interventions for 

pain among polytrauma patients (Key Question 2). One study will test the reliability and 

validity of measures to assess pain in cognitively-impaired TBI patients and another study 

is using primarily qualitative methods to examine the utility of a CPRS pain assessment 

template module to assist clinicians in evaluating pain in PRC patients with cognitive 

impairment (Key Question 1). One study is examining the phenomenology and treatment 

of blast vs. other types of headache (Key Question 3), and one study is addressing provider 

and systems barriers to detecting and treating pain in polytrauma patients (Key Question 

5). 

Details of findings 

Email communications were sent to a total of 73 individuals, 4 VA workgroups (via their 

chairs), and 5 HSR&D portfolio managers, inquiring about possible projects the addressing 

key questions and inquiring about identifying others who might be doing or planning 

research relevant to the key questions. Individual email recipients included 41 VA 

investigators, 5 Department of Defense (DOD) investigators, and 27 non-VA, non-DOD 

investigators. Responses were received from 47 investigators. Nineteen relevant projects 

were identified and project data were collected on 18 of these projects. Table 2 on the 

following pages lists the ongoing studies for which data were available. The 

characteristics of these studies are described in further detail in Appendix E, Evidence 

Table 2. 

VA-ESP September 2008 29
Pain in Patients with Polytrauma

Table 2. Summary of active research studies of pain in polytrauma 

Pain-related 

variable(s) 

main or 

secondary 

outcome? 

Title of Project Main objective(s) of project Study characteristics KQ 

Concurrent Validity of 4 

Pain Intensity Scales in 

persons with Polytrauma 

and Cognitive 

Impairment(124) 

Examine the concurrent validity of four pain 

intensity scales in the traumatic brain injury 

(TBI) inpatient rehabilitation population 

Main Study design: 

prospective randomized 

measurement study 

Sample: 15 TBI patients 

1 

Pain Assessment in 

Polytrauma 

Rehabilitation Centers 

(PRCs)(125) 

Evaluate utility of CPRS pain assessment 

templates, modify education materials; 

develop pain reports for clinicians and pain 

assessment database; identify best practices 

for pain care 

Main Study design: Qualitative

Sample: Providers and 

nursing staff in two PRCs 

1,5 

Evaluation of Stepped 

Care for Chronic Pain 

(ESCAPE)(126)

Compare a stepped care intervention vs. 

usual care in OIF/OEF veterans with chronic 

and disabling musculoskeletal pain 

Main Study design: RCT 

Sample: 300 OIF/OEF 

veterans 

2,4 

The ViRTICo Trial: 2,4 

Virtual Reality Therapy 

& Imaging in Combat 

Veterans(127) 

Compare effects of Virtual Reality Exposure 

Therapy & Imaging compared with 

Prolonged Exposure (current first-line 

therapy) 

Secondary Study design: controlled 

clinical trial 

Sample: OEF/OIF 

veterans with PTSD and 

TBI combined; PTSD 

alone; TBI alone; neither 

PTSD or TBI. 

Regional Anesthesia 

Military Battlefield Pain 

Outcomes Study(128) 

Determine short-term and long-term painrelated outcomes in OEF/OIF veterans with 

traumatic extremity injuries; evaluate efficacy 

of early aggressive advanced regional 

anesthetic interventional techniques 2-yrs 

post-injury

Main Study design: 

prospective cohort 

2,4 

Sample: OEF/OIF 

soldiers with one or more 

maligned or amputated 

limbs 

Chronic Headache 

among OEF/OIF 

Veterans Exposed to 

Blasts(129) 

Evaluate initial characteristics and treatment 

of blast-TBI in OEF/OIF veterans; assess 

feasibility and effectiveness of brief cognitivebehavioral headache management treatment 

(BCBHMT) 

Main Study design: case 

series 

Sample: OEF/OIF 

veterans 

2,3 

To determine the relationship between Post- 4 

Traumatic Stress Disorder (PTSD), TBI, selfreport of headaches, and combat-related 

injury in Operation Enduring Freedom (OEF) 

and Operation Iraqi Freedom (OIF) veterans 

Main Study design: Crosssectional 

Sample: 343 male and 

female veterans 

registering for care 

Headaches in veterans 

returning from 

Iraq/Afghanistan: 

relation to trauma and 

combat-related 

injury(130) 

Long-term Outcomes in 

Burned OEF/OIF 

Veterans (LOBO)(131) 

Assess long term outcomes in OEF/OIF 

veterans with combat burn injury, combat 

nonburn injury, and in civilian burn patients 

Secondary Study design: 

Prospective cohort 

Sample: OEF/OIF 

veterans 

4 

Women Veterans Cohort 

Study(132) 

Assess health care utilization, costs, stress, 

and satisfaction in OEF/OIF veterans

Secondary Study design: 

Prospective cohort 

4 

Sample: OEF/OIF 

veterans 

VA-ESP September 2008 30
Pain in Patients with Polytrauma

Pain-related 

variable(s) 

main or 

secondary 

outcome? 

Title of Project Main objective(s) of project Study characteristics KQ 

Pain and Emotional 

Disorders in Veterans 

with and without 

Polytrauma(133) 

Describe the prevalence, types, and course of 

pain and psychiatric disorders, as well as 

functional outcomes, among OEF/OIF vets 

with and without polytraumatic injuries

Main Study design: 

Prospective cohort 

Sample: 150-200 

polytrauma and 300-400 

non-polytrauma OEF/OIF 

veterans 

4 

Multidiscipline 

Assessment of Blast 

Victims for Cognitive 

Rehabilitation(134) 

Determine whether blast exposure is 

associated with neuropsychological deficits 

and/or psychiatric disorder and identify 

contributors to blast-related post-concussive 

syndrome 

Secondary Study design: 

Prospective cohort 

Sample: OEF/OIF 

veterans 

4 

Telerehabilitation of 

OEF/OIF combat 

wounded with TBI(135) 

Provide care coordination and monitor 

functional and cognitive outcomes of 45 

veterans discharged from a VA PRC with TBI; 

monitor for adverse effects of pain medication 

Secondary Study design: Prospective 

cohort 

4 

Sample: OEF/OIF 

veterans with TBI 

Predicting Rehabilitation 

Costs for VA Patients 

with Traumatic Brain 

Injury(136) 

Compare cost for rehabilitation for veterans 

with combat TBI to veterans with non-combat 

TBI; compare utility of measures in predicting 

costs; examine affect of PTSD on 

outcomes/costs 

Secondary Study design: 

Retrospective cohort 

Sample: OEF/OIF 

patients with TBI 

4 

Characterization and 

Care Coordination of 

Polytrauma 

Patients(137) 

Study & describe characteristics of 

polytrauma patients, including cognitive, 

emotional, physical and overall functional 

impairment 

Secondary Study design: Crosssectional 

Population: OIF/OEF 

patients 

4 

Pain, mental health, and 

daily function in 

OIF/OEF veterans(138) 

Describe the pain concerns of OIF/OEF 

veterans, examine association between pain, 

comorbid mental health concerns, and daily 

functioning 

Main Study design: Crosssectional 

Sample: 233 OIF/OEF 

veterans 

4 

Clinical Characteristics 

of Patients with 

Polytrauma and BlastRelated Injuries(139) 

Describe clinical characteristics, interventions 

and outcomes for inpatients with polytrauma 

and blast-related injuries 

Main Study design: Crosssectional 4 

Sample: Veteran 

(Assessment and treatment = primary) inpatients at 4 PRCs 

Evaluation of 

Polytrauma Pain(140) 

Retrospectively examine pain experiences of 

soldiers and veterans with polytraumatic 

injuries incurred during OIF/OEF 

Primary Study design: Crosssectional 4 

Sample: OIF/OEF 

veterans 

Secondary Study design: 4 

Measurement study 

Sample: 60 persons with 

SCI and chronic 

neuropathic pain, 25 

persons with SCI without 

neuropathic pain, and 25 

healthy controls 

Determine the validity and reliability of 

Magnetic Resonance Spectroscopy (MRS) as 

a diagnostic and outcome measure for clinical 

trials of SCI chronic pain populations; to 

improve the management of chronic 

neuropathic pain following SCI 

Validity and reliability of 

proton magnetic 

resonance spectroscopy 

as a diagnostic and 

outcome measure in 

clinical trials involving 

people with SCI(141) 

One study is addressing assessment of pain in cognitively impaired patients due to TBI 

(Key Question 1) using a prospective randomized measurement study of four pain intensity 

scales in persons with polytrauma and cognitive impairment.(124) Another study will 

evaluate the usability and utility of CPRS pain assessment templates in two PRC sites; a 

VA-ESP September 2008 31
Pain in Patients with Polytrauma

template contains a module designed to assist clinicians in evaluating pain in patients with 

cognitive impairment.(125) 

Four studies are testing interventions in patients with polytrauma (Key Question 2): Bair is 

using an RCT design to test a stepped care intervention for OEF/OIF veterans with chronic 

and disabling musculoskeletal pain.(126) It is expected that some enrollees will meet 

criteria for polytrauma. Gallagher’s prospective cohort study will evaluate the efficacy of 

early advanced regional anesthetic techniques on pain and mental health outcomes two 

years post-injury.(128) Using a pre-post evaluation design, Gironda is piloting a brief 

cognitive headache management intervention for OEF/OIF veterans suffering from 

persistent blast-related headache.(129) In a controlled clinical trial, Roy is testing whether 

the Virtual Reality Exposure Therapy and Imaging intervention improves measures of 

functional health and disability compared to prolonged exposure therapy among veterans 

with PTSD and TBI.(127) 

One study is examining clinical characteristics of headache conditions among OEF/OIF 

veterans referred to a VA Blast Injury Clinic (Key Question 3).(129) 

Thirteen studies will provide information about patient factors associated with outcomes in 

polytrauma patients (Kew Question 4). Six studies utilizing prospective cohort designs 

(128, 131-135) and one study using a retrospective cohort design (136) will follow samples 

of OEF/OIF soldiers or OEF/OIF veterans over time; outcomes include measures of pain, 

functional status, or adverse effects of pain treatments. Two clinical trials (126, 127) and 5 

cross-sectional studies (130, 137-140) will also generate information regarding the 

relationship of patient factors to pain outcomes in polytrauma patients. An additional study 

is likely to include polytrauma patients and will examine the validity and reliability of 

Magnetic Resonance Spectroscopy as a diagnostic tool for clinical trials involving SCI 

patients with chronic pain.(141) A study objective is to determine pathophysiological and 

psychosocial contributors to pain after SCI. 

Finally, in an ongoing study using qualitative and quantitative methods to evaluate the 

utility of CPRS pain assessment tools, information will be generated regarding provider or 

system barriers to treating pain among polytrauma patients (Key Question 5).(125) 

Limitations—Active Research 

Although we made efforts to identify VA and non-VA investigators who are conducting or 

planning projects that address key questions, it is very likely that potentially relevant 

projects were not found. Our primary means of surveying was using email; many 

investigators did not respond to our queries, and we presume that in many of these cases, 

these investigators were not doing research relevant to the key questions. A snowball 

approach was used to identify relevant research projects; this approach identified several of 

the projects included in this review. We note that we communicated with several 

military/DOD and a number of non-VA, non-DOD investigators during the process. In 

addition, we searched a number of web-databases to identify funded VA and non-VA 

projects.

VA-ESP September 2008 32
Pain in Patients with Polytrauma

SUMMARY AND DISCUSSION 

Pain from polytraumatic injuries poses numerous challenges during and after 

rehabilitation treatment. Pain assessment and intervention efforts are further complicated 

when the injuries include TBI. The overall purpose of this project was to identify and 

synthesize evidence on the assessment and treatment of pain in polytrauma patients. 

Overall, the literature provides very limited evidence to guide clinicians in this area. 

Although some previous investigations indicate that pain may interfere with 

neurocognitive performance in TBI patients, there have been no published studies 

examining approaches to assessing pain among patients with moderate to severe TBI. 

Studies that have been done with patients with cognitive impairment due to dementia 

indicate that most cognitively impaired individuals can understand at least one selfassessment measure. Guidelines suggest that for patients with dementia who cannot 

understand any of several self-assessment measures available, an observational assessment 

measure or input from family, friends, or staff who know patients well, or empiric pain 

treatment if the patient has diagnoses usually associated with pain, may be helpful. How 

well these findings and guidelines might apply to younger patients with cognitive 

impairment due to TBI is currently unknown. One ongoing VA research study is 

examining the validity and reliability of 4 pain intensity scales in persons with polytrauma 

and cognitive impairment, and an additional VA study is examining the utility of a CPRS 

pain assessment template module to assist clinicians in evaluating pain in patients with 

cognitive impairment in PRCs. 

The literature also provides very limited evidence to guide clinicians in selecting among 

non-surgical pain treatments in patients with polytrauma. Aside from one good quality 

retrospective cohort study indicating that rehabilitation may improve outcomes among 

patients with trauma related amputation, no systematic pain intervention studies have been 

done in the polytrauma population. A number of case reports suggest possible approaches 

to treating pain in polytrauma patients, ranging from intrathecal baclofen pumps for pain 

associated with spasticity to alternative therapies including healing touch. These potential 

treatment modalities have not been rigorously tested with polytrauma patients. Despite 

potential concerns about adverse effects, we found only a single case report regarding the 

use of opioids for pain other than for acute care among TBI patients. Several ongoing 

research projects are testing interventions in patients with polytrauma. These interventions 

include stepped care for chronic musculoskeletal pain, advanced regional anesthetic 

techniques, brief cognitive headache management therapy for persistent blast-related 

headache, and Virtual Reality Exposure Therapy and Imaging for veterans with PTSD and 

TBI. 

Although several studies show that headache (as well as auditory deficits and otalgia) is 

common among blast injury patients, there are no published studies describing how blastrelated headache might differ in terms of phenomenology or treatment from other types of 

headache pain. One VA study is currently examining clinical characteristics of headache 

conditions among OEF/OIF veterans referred to a VA Blast Injury Clinic. 

VA-ESP September 2008 33
Pain in Patients with Polytrauma

VA-ESP September 2008 34

From a number of cohort studies, there is moderate evidence showing that injury factors 

(including location, severity, and the number of different injuries) are associated with pain 

and functional status over time. TBI itself is associated with worse outcomes when 

compared to polytrauma patients without TBI, and there is some evidence that pain is 

common among TBI patients, present in one-third to one-half of patients up to five years 

post-injury. However, contrary to what is often reported in the literature and reported in a 

recent systematic review, we found very limited evidence to support that patients with mild 

TBI are more likely to have headache or other pain than patients without TBI. While 

predominantly cross-sectional studies suggest that patients with mild TBI may be more 

likely to have headache pain than patients with moderate or severe TBI, six prospective 

cohort studies and several additional cross-sectional studies did not find a relationship 

between TBI severity and headache prevalence. Most of the cross-sectional studies were 

done in outpatient settings up to several years post-injury, and did not adjust for potential 

confounders that may influence relationships between TBI severity and pain. In these 

studies, cases were identified based on who was referred or attended outpatient follow-up 

visits. It is thus likely that differences in sample composition contribute to the differences 

in findings between the cross-sectional and cohort studies, in that patients with mild TBI 

may be more likely to be referred to or attend outpatient follow-up appointments when 

they have bothersome or persistent symptoms such as headache. 

Overall, we found limited evidence regarding other patient characteristics that are 

associated with pain-related outcomes in polytrauma patients. Factors found to be 

associated with worse outcomes across at least several studies were: multiplicity of injury, 

head injury or cognitive disability, and lower limb injuries. Factors associated with better 

outcomes in a few studies were: younger age, higher educational achievement, and having 

a white collar job. Among TBI patients, factors found to be associated with pain and painrelated function in several studies included depression, PTSD, insomnia, and fatigue. 

Fifteen ongoing research studies will provide additional information about patient factors 

associated with outcomes in polytrauma patients. Seven studies utilizing cohort designs 

will follow samples of OEF/OIF soldiers or OEF/OIF veterans over time, and should help 

to identify important correlates of pain-related outcomes among polytrauma patients. 

Finally, there is almost no evidence that addresses provider and system barriers to 

treatment of pain among polytrauma patients. In one rigorously conducted qualitative 

study, providers reported that polytrauma patients are very complex to treat, and that the 

work with this population is very challenging and emotionally taxing. In order to provide 

high quality care to this complex patient population, clinicians have increased their use of 

multidisciplinary and concurrent care, and consultation from experts. One active study, 

which is using qualitative and quantitative methods to evaluate the utility of CPRS pain 

assessment tools, is likely to generate information regarding provider or system barriers to 

treating pain among polytrauma patients. 
Pain in Patients with Polytrauma

CONCLUSIONS Table 3. Summary of Systematic Evidence Review by Key Question 

Quality 

(GRADE) of 

Evidence* 

Key Question Type of Evidence Comments 

1. Are pain assessment tools reliable and Very Low*valid in patients with cognitive deficits due to TBI? 

No direct evidence on pain assessment tools in TBI 

 No particular assessment tool or strategy is known to 

pain intensity or pain-related function in patients with c

 Most patients with mild cognitive impairment due to de

least one pain self-assessment measure. 

 Pain may interfere with neurocognitive functioning in T There is no evidence that pain assessment tools for d

applied to persons with cognitive impairment related to 

2a. Which treatment approaches are most effective in improving pain outcomes in polytrauma patients? 

No direct evidence on effective pain treatment approaches for polytrauma 

Very Low  No rigorous studies have been done assessing potent

in patients with polytrauma. 

2b. Which pain treatment approaches enhance overall rehabilitation efforts? 

1 retrospective cohort study 

Very Low  Inpatient rehabilitation may be associated with increas

work and decreased likelihood of reduced hours of wo

3a. Does blast-related headache pain differ from other types of headache pain? 

No evidence comparing blastrelated headache to other types of headache 

Very Low  It is not known how blast-related headache differs from 

terms of phenomenology or outcome. 

 Headache and auditory deficits are common among p

3b. Which treatments are best for persistent blast-related headache pain? 

No evidence on treatment of blastrelated headache 

---  Specific treatments for blast-related related headache 

VA-ESP September 2008 
Pain in Patients with Polytrauma

VA-ESP September 2008 Table 3. Summary of Systematic Evidence Review by Key Question, continued Key Question Type of Evidence 

Quality 

(GRADE) of 

Evidence 

Comments 

Very Low  There are mixed findings regarding the association betw

pain. 

Patients with TBI: 1 

systematic review, 10 

cohort, 3 case-control, 

and 11 cross-sectional 

studies 

Low†  Psychological factors, including depression and posttra

(PTSD), and insomnia and fatigue are associated with 

Low  Specific factors associated with worse pain-related outc

injuries, foot injuries or injuries below the knee joint, ancognitive disability. 

4. What patient factors are associated with better and worse clinical outcomes among polytrauma patients? Have interventions been developed to address these factors? 

Other patients: 

32 cohort studies, 

3 cross-sectional 

studies 

Very Low  Factors associated with better outcomes are younger a

achievement, having a white collar job or higher income

5. What are unique provider and system barriers to detecting and treating pain among polytrauma patients? Have interventions been developed to address these barriers? 

1 qualitative study of 

interviews with 

providers 

Very Low  In qualitative interviews, providers reported that polytra

complex to treat, and that the work with this population emotionally taxing. Increasing use of multidisciplinary consultation from experts may be necessary to provide 

* GRADE: Very low = any estimate of effect is very uncertain.† GRADE: Low = research is very likely to have an important impact on our confidence in the estimate of effect and may change the e
Pain in Patients with Polytrauma 

FUTURE RESEARCH RECOMMENDATIONS 

In order to highlight gaps between the key questions and information available from the 

literature and information to become available based on current research, Table 4 depicts 

the results of the literature review of studies that have been published to date, the types of 

studies necessary to address the key questions, and the research we identified that is 

currently being done to address the key questions. 

Table 5 lists potential study topics and designs as suggested by the investigators and expert 

reviewers based on the above identified information gaps, and includes their cumulative 

ratings of the priority of conducting particular studies. Raters were asked to review the 

research topics and assign them high, medium or low priority, the most important criterion 

being to achieve the highest possible impact on patient care in the VHA. In rating the 

suggestions for future research, raters were also asked to consider: 1) the degree to which 

the proposed research will address information gaps identified in the systematic review, 2) 

the quantity and quality of the research completed so far including systematic reviews; 3) 

research currently planned or in progress; 4) the feasibility and timeframe that would be 

necessary to complete the proposed research; 5) existing barriers that have prevented this 

research from being undertaken before, and 6) the pros and cons of different research 

methods that might be appropriate for each research question. Table 5 presents the mean 

priority ranking for each research topic, based on input from 11 reviewers. Because these 

are preliminary rankings, a panel or other mechanism to achieve consensus is needed to 

refine and finalize the recommendations for future research. 

We also note the following considerations for conducting and funding research in this 

area: 

• Substantial heterogeneity in the causes and types of polytraumatic injuries, as well as 

the dynamic nature of recovery from injuries, create challenges for defining and 

comparing distinct patient populations in research studies, as well as for developing 

and testing generalizable interventions. In future research it is critical that 

investigators comprehensively describe polytrauma study samples, settings, 

recruitment methods, and measurements. 

• Due to the level of heterogeneity in the causes and types of polytraumatic injuries, 

interventions that have the potential to apply, and that are able to be tested among 

patients with a wide-spectrum of injury patterns may be especially desirable. 

• Pilot studies of interventions may be especially helpful to determine feasibility of 

treatment approaches in the polytrauma patient population before proceeding to 

larger-scale randomized clinical trials. Enhancement of funding mechanisms that 

facilitate such pilot work is desirable. 

• Battlefield, acute-phase, or early rehabilitation pain interventions may have an 

important impact on subsequent pain-related outcomes. The DOD may obtain followup survey data that could be used or augmented to conduct pain outcome research. 

Mechanisms that foster improved DOD/VA collaborations including additional data 

collection may highly desirable. Establishment of a joint DOD-VA pain workgroup 

might facilitate such collaboration.

VA-ESP September 2008 37
Pain in Patients with Polytrauma 

Table 4. Summary of Literature Review Findings and Identified Ongoing Research 

Results of Literature 

Review Key Question or Subquestion Types of studies needed to answer question Identified ong

Qualitative research in rehabilitation patients with polytrauma 

 Qualitative/quantitative study o

regarding pain education & as

1. Are pain assessment tools reliable and valid in patients with cognitive deficits due to TBI? 

No direct evidence on pain assessment tools in TBI or polytrauma. 

Prospective observational study of reliability and validity of instruments in rehabilitation patients with polytrauma 

 Prospective randomized study 

scales in TBI patients(124) 

Exploratory research: feasibility of treatment modalities in case series 

 Case series pilot of cognitive b

headache(129) 

 Clinical trial of Virtual reality th

outcome)(127) 

Case series and case 

reports of various pain treatments. 

2a. Which treatments improve pain outcomes in polytrauma patients? 

 Little to no information 

on use of opioids or integrated care approaches 

2b. Which pain treatment approaches enhance overall rehabilitation efforts? Effectiveness research: Controlled comparisons 

of different treatment strategies in patients with polytrauma before or at inception of rehabilitation 

RCT of stepped care in OIF/O

musculoskeletal pain(126) 

 Prospective cohort study of ou

anesthesia(128) 

3a. Does blast-related headache pain differ from other types of headache pain? 

None. Prospective, observational studies to determine 

whether features of injuries, including exposure to blasts, are associated with a different clinical course and outcome. 

 Case series pilot of cognitive b

Headache and headache(129) 

auditory deficits are common in patients exposed to blast 

Exploratory research: feasibility of treatment modalities in case series 

 Case series on brief cognitive

management treatment (BCBH

3b. Which treatments are best for persistent blast-related headache pain? 

None. 

Effectiveness research: Controlled comparisons of different treatment strategies in patients with blast-related headache 

 No identified studies using this 

VA-ESP September 2008 
Pain in Patients with Polytrauma 

Results of Literature 

Review Key Question or Subquestion Types of studies needed to answer question Identified ong

Prospective observational study of factors associated with pain-related outcomes among polytrauma patients. 

 6 prospective cohort studies e

pain-related) outcomes).(128, 

 1 retrospective cohort study(1

studies.(130, 137-140) 

4a. What patient factors are associated with better and worse (pain-related) clinical outcomes among polytrauma patients? 

Cohort, case control, 

and cross-sectional studies. 

 Injury characteristics, 

insomnia, fatigue, and psychosocial factors are associated with pain-related outcomes (Grade: Low) 

Effectiveness research: Controlled comparisons of different treatment strategies in patients with and without certain characteristics 

 Clinical trial of Virtual reality th

secondary outcome)(127) 

 RCT of stepped care in OIF/O

musculoskeletal pain(126) 

Exploratory research: feasibility of treatment No identified studies using this modalities in case series 

4b. Have interventions been developed to specifically address these factors? 

None. 

Effectiveness research: Controlled comparisons No identified studies using this of treatment strategies in patients with comorbid conditions 

Qualitative research in rehabilitation patients with polytrauma 

Qualitative/quantitative study o

regarding pain education & as

5a. What are unique provider and system barriers to detecting and treating pain among polytrauma patients? 

One qualitative study of interviews with providers. Prospective observational study of provider and No identified studies using this 

systems factors associated with pain-related outcomes in polytrauma patients. 

Exploratory research: feasibility of treatment No identified studies using this modalities in case series 

5b. Have interventions been developed to effectively address these barriers? 

None. 

Effectiveness research: Controlled No identified studies using this comparisons of treatment strategies in patients with polytrauma 

VA-ESP September 2008 
Pain in Patients with Polytrauma 

Table 5: Future Research Topics/Designs – Ratings of Priority 

M

Key Question or 

Subquestion 

Results of Literature 

Review Future Research Topic Suggestions 

Quantitative measurement study of reliability and validity of existing pain assessment tools among patients with varying levels of communicativeness and brain injury. Examine the discriminant validity of tools for distinguishing pain from other forms of distress and impairment (e.g., restlessness, PTSD symptoms) 

1. Are pain assessment tools reliable and valid in patients with cognitive deficits due to TBI? 

No direct evidence on pain assessment tools in TBI or polytrauma. 

Examine the validity of assessment tools in the context of a clinical trial of an intervention for a specific pain condition. For example, in trial of opioids for patients with multiple orthopedic injuries and TBI, use tool to measure changes in pain over time. 

 Examine utility, reliability and validity of CPRS Pain assessment modules being used in VA PRCs for assessment of non-communicative patients with pain. Qualitative study to identify pain behaviors in different cognitively impaired TBI states. From this information, develop and test new tool or modify existing tools to match severity and type of cognitive impairment. 

Qualitative/quantitative research using partnership with family (and staff) to identify key pain behaviors. Develop or modify tool to incorporate information from patient, caregivers, and empiric trials of analgesics (i.e., guideline recommended approaches). 

Trials of non-pharmacological interventions of varying treatment intensity, including psychological interventions and telephone-based interventions. RCTs of integrated treatment approaches including comprehensive interdisciplinary rehab., collaborative care, and treatment involving family members. 

 Primarily case 

series and case reports of various pain treatments. 

2a. Which treatments improve pain outcomes in polytrauma pts? 

Compare treatments for common specific core conditions (e.g., TBI; PTSD; Pain) to integrated treatment of these core overlapping symptoms. 

 Little to no 

information on use of opioids or integrated care approaches. 

2b. Which pain treatment approaches enhance overall rehab. efforts? 

Systematic prospective observation methods and single case experimental designs with replication to study the relationship between pain control and rehabilitation outcomes. 

VA-ESP September 2008 
Pain in Patients with Polytrauma 

M

Key Question or 

Subquestion 

Results of Literature 

Review Future Research Topic Suggestions 

Cross sectional study describing and comparing characteristics of veterans with headache presumed to be blast-related to veterans with headache not known to be blast-related. Prospective observational cohort study comparing outcomes of veterans with blastrelated headache to those without blast-related headache 

3a. Does blast-related headache pain differ from other types of headache pain? 

 None.  Headache and 

auditory deficits are common in patients exposed to blast. 

Study associations between comorbid psychiatric conditions and headache among patients with blast-headache; compare to patients with non-blast-headache 

Perform routine imaging on soldiers exposed to blast to assess for structural abnormalities and correlate with headache symptoms 

3b. Which treatments are best for persistent blastrelated headache pain? 

 None. Trials of pharmacologic and non-pharmacologic treatments, including patients with 

blast-related headache in one arm of the trial. Non-pharmacologic interventions to test include cognitive behavioral treatment, hypnosis, relaxation training, and biofeedback. 

Prospective cohort study measuring pain outcomes over time. Measuring contributions of patient characteristics and comorbid conditions, while adjusting for injury characteristics including multiplicity of injury, pain type, and location. Prospective cohort study examining relationships between pain, PTSD, and TBI, and pain-related outcomes 

Some evidence that injury characteristics, insomnia, fatigue, and psychosocial factors are associated with pain-related outcomes 

Collaborate with DOD to collect or obtain existing pre-deployment DOD survey data to adjust for baseline characteristics prior to injuries in prospective or retrospective 

cohort studies. 

4a. What patient factors are associated with pain-related outcomes in polytrauma patients? Have interventions been developed to specifically address these factors? (see 2. above) 

Use data obtained in collaboration with DOD and/or from Landsthuhl Regional 

Medical Center to identify long-term effects of battlefield, acute-phase, or early rehab. treatment. 

Evaluate contribution of partnership with family and other social variables to painrelated outcomes in polytrauma patients. 

VA-ESP September 2008 
Pain in Patients with Polytrauma 

VA-ESP September 2008 

Key Question or 

Subquestion 

Results of Literature 

Review Future Research Topic Suggestions 

M

Establish treatment guidelines for pain in polytrauma based on expert opinion. Disseminate and measure impact of guidelines on care. Evaluate patient perceptions of provider and systems barriers, and the impact of efforts to mitigate those barriers. Evaluate implementation of CPRS pain assessment tools in PRCs. Refine tools and reevaluate. Couple evaluation of site-specific organizational factors with multi-site prospective observational study of patient pain-related outcomes. Identify associations between organizational factors and patient outcomes. Identify adaptations PRCs are making to accommodate diversity among polytrauma patients with pain. Measure the impact of polytrauma pain education on provider behavior. 

5a. What are unique provider and system barriers to detecting and treating pain among polytrauma patients? Have interventions been developed to effectively address these barriers? 

One qualitative study of interviews with providers. 

Formative evaluation of implementation of guidelines and education and impact on treatment processes in PRCs. 
Pain in Patients with Polytrauma 

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86. Yamaguchi M. Incidence of headache and severity of head injury. Headache 

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94. Bay E, Donders J. Risk factors for depressive symptoms after mild-to-moderate 

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96. Ouellet M-C, Beaulieu-Bonneau S, Morin CM. Insomnia in patients with traumatic 

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100. Frink M, Klaus A-K, Kuther G, Probst C, Gosling T, Kobbe P, et al. Long term 

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101. Dougherty PJ. Transtibial amputees from the Vietnam War. Twenty-eight-year 

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103. Lacoux PA, Crombie IK, Macrae WA. Pain in traumatic upper limb amputees in 

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Pain in Patients with Polytrauma 

105. Zelle BA, Brown SR, Panzica M, Lohse R, Sittaro NA, Krettek C, et al. The impact 

of injuries below the knee joint on the long-term functional outcome following polytrauma. 

Injury 2005;36(1):169-77. 

106. Tran T, Thordarson D. Functional outcome of multiply injured patients with 

associated foot injury. Foot & Ankle International 2002;23(4):340-3. 

107. Turchin DC, Schemitsch EH, McKee MD, Waddell JP. Do foot injuries 

significantly affect the functional outcome of multiply injured patients? Journal of 

Orthopaedic Trauma 1999;13(1):1-4. 

108. Urquhart DM, Williamson OD, Gabbe BJ, Cicuttini FM, Cameron PA, Richardson 

MD, et al. Outcomes of patients with orthopaedic trauma admitted to level 1 trauma 

centres. ANZ Journal of Surgery 2006;76(7):600-6. 

109. Brenneman FD, Katyal D, Boulanger BR, Tile M, Redelmeier DA. Long-term 

outcomes in open pelvic fractures. Journal of Trauma-Injury Infection & Critical Care 

1997;42(5):773-7. 

110. Hebert JS, Burnham RS. The effect of polytrauma in persons with traumatic spine 

injury. A prospective database of spine fractures. Spine 2000;25(1):55-60. 

111. Vles WJ, Steyerberg EW, Essink-Bot ML, van Beeck EF, Meeuwis JD, Leenen LP. 

Prevalence and determinants of disabilities and return to work after major trauma. J 

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112. Anke AG, Stanghelle JK, Finset A, Roaldsen KS, Pillgram-Larsen J, Fugl-Meyer 

AR. Long-term prevalence of impairments and disabilities after multiple trauma. Journal of 

Trauma-Injury Infection & Critical Care 1997;42(1):54-61. 

113. Soberg HL, Bautz-Holter E, Roise O, Finset A. Long-term multidimensional 

functional consequences of severe multiple injuries two years after trauma: a prospective 

longitudinal cohort study. Journal of Trauma-Injury Infection & Critical Care 

2007;62(2):461-70. 

114. Holtslag HR, van Beeck EF, Lindeman E, Leenen LPH. Determinants of long-term 

functional consequences after major trauma. Journal of Trauma-Injury Infection & Critical 

Care 2007;62(4):919-27. 

115. Meerding WJ, Looman CW, Essink-Bot ML, Toet H, Mulder S, van Beeck EF. 

Distribution and determinants of health and work status in a comprehensive population of 

injury patients. J Trauma 2004;56(1):150-61. 

116. Mkandawire NC, Boot DA, Braithwaite IJ, Patterson M. Musculoskeletal recovery 

5 years after severe injury: long term problems are common. Injury 2002;33(2):111-5. 

117. Dimopoulou I, Anthi A, Mastora Z, Theodorakopoulou M, Konstandinidis A, 

Evangelou E, et al. Health-related quality of life and disability in survivors of multiple 

trauma one year after intensive care unit discharge. American Journal of Physical Medicine 

& Rehabilitation 2004;83(3):171-6. 

118. Brenneman FD, Redelmeier DA, Boulanger BR, McLellan BA, Culhane JP. Longterm outcomes in blunt trauma: who goes back to work? J Trauma 1997;42(5):778-81. 

119. MacKenzie EJ, Morris JA, Jr., Jurkovich GJ, Yasui Y, Cushing BM, Burgess AR, 

et al. Return to work following injury: the role of economic, social, and job-related factors. 

Am J Public Health 1998;88(11):1630-7. 

120. Stalp M, Koch C, Ruchholtz S, Regel G, Panzica M, Krettek C, et al. Standardized 

outcome evaluation after blunt multiple injuries by scoring systems: a clinical follow-up 

VA-ESP September 2008 49
Pain in Patients with Polytrauma 

investigation 2 years after injury. Journal of Trauma-Injury Infection & Critical Care 

2002;52(6):1160-8. 

121. Lippert-Gruner M, Maegele M, Haverkamp H, Klug N, Wedekind C. Healthrelated quality of life during the first year after severe brain trauma with and without 

polytrauma. Brain Inj 2007;21(5):451-5. 

122. Fitzharris M, Fildes B, Charlton J, Kossmann T. General health status and 

functional disability following injury in traffic crashes. Traffic Injury Prevention 

2007;8(3):309-20. 

123. Taber KH, Warden DL, Hurley RA. Blast-related traumatic brain injury: what is 

known? Journal of Neuropsychiatry & Clinical Neurosciences 2006;18(2):141-5. 

124. Walker W. Concurrent Validity of Four Pain Intensity Scales in persons with 

Polytrauma and Cognitive Impairment. A research study in progress. Richmond VAMC. 

125. Kerns R. Pain Assessment in Polytrauma Rehabilitation Centers (PRCs). A 

research study in progress. HSR&D QUERI Program RRP07-288. VA Connecticut 

Healthcare System. 

126. Bair M. Evaluation of Stepped CAre for Chronic Pain (ESCAPE). A research study 

in progress. VA Rehabilitative Research and Development F44371. Indianapolis VAMC. 

127. Roy MJ. The ViRTICo Trial: Virtual Reality Therapy & Imaging in Combat 

Veterans. A research study in progress. Uniformed Services University, Bethesda MD. 

128. Gallagher RM. Regional Anesthesia Military Battlefield Pain Outcomes Study. A 

research study in progress. RR&D Service 951. Philadelphia VAMC. 

129. Gironda RJ. Chronic Headache among OEF/OIF Veterans Exposed to Blasts. A 

research study in progress. Tampa VAMC. 

130. Afari N. Headaches in veterans returning from Iraq/Afghanistan: relation to trauma 

and combat-related injury. A research study in progress. San Diego VAMC. 

131. Lawrence VA. Long-term Outcomes in Burned OEF/OIF Veterans (LOBO). A 

research study in progress. VA HSR&D SDR 07-042. San Antonio VAMC. 

132. Brandt C, Haskell S. Women Veterans Cohort Study. A research study in progress. 

HSR&D DHI 07-065-2. VA Connecticut Healthcare System. 

133. Clark ME. Pain and Emotional Disorders in Veterans with and without Polytrauma. 

A research study in progress. HSR&D SDR-07-047. Tampa VAMC. 

134. Storzbach D. Multidiscipline Assessment of Blast Victims for Cognitive 

Rehabilitation. A research study in progress. VHA RR&D B5060R. Portland VAMC. 

135. Siddharthan K. Telerehabilitation of OEF/OIF combat wounded with TBI. A 

research study in progress. Tampa VAMC. 

136. Lew H. Predicting Rehabilitation Costs for VA Patients with Traumatic Brain 

Injury. A research study in progress. VA Boston HealthCare System. 

137. Lew H. Characterization and Care Coordination of Polytrauma Patients. A research 

study in progress. VA Boston HealthCare System. 

138. Helmer D. Pain, mental health, and daily function in OIF/OEF veterans. A research 

study in progress. Houston VAMC. 

139. Lew H. Clinical Characteristics of Patients with Polytrauma and Blast-Related 

Injuries. A research study in progress. VA Boston HealthCare System. 

140. Walker RL. Evaluation of Polytrauma Pain. A research study in progress. Tampa 

VAMC. 

VA-ESP September 2008 50
Pain in Patients with Polytrauma 

141. Widerstrom-Noga E. Validity and reliability of proton magnetic resonance 

spectroscopy as a diagnostic and outcome measure in clinical pain trials involving people 

with spinal cord injury. A research study in progress. Miami VA HCS. 

142. Goel A, Phalke U, Cacciola F, Muzumdar D. Atlantoaxial instability and 

retroodontoid mass--two case reports. Neurologia Medico-Chirurgica 2004;44(11):603-6. 

VA-ESP September 2008 51
Pain in Patients with Polytrauma 

APPENDIX A. SEARCH STRATEGY 

Two librarians (AH and RC) independently designed search strategies based on the key questions.  The

results of both searches were combined into a single reference library.   

Below is the search strategy designed by AH:  

Database: Ovid MEDLINE(R) <1950 to January Week 5 2008>

Search Strategy:

‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ 

1     polytraum$.mp. (2115)

2     exp Multiple Trauma/ (7404)

3     (multiple adj3 (wound$ or injur$ or traum$ or casualt$)).mp. (12171)

4     1 or 2 or 3 (13048)

5     exp Blast Injuries/ (1862)

6     exp Brain Injuries/ (34104)

7     ((head or crani$ or cereb$ or brain$ or explosi$ or explod$ or blast$) adj3 (traum$ or wound$ or injur$

or damag$)).mp. (88531)

8     5 or 6 or 7 (90818)

9     exp pain/ (218224)

10     exp pain measurement/ (33373)

11     exp nociceptors/ (8377)

12     (pain$ or agony or agoniz$ or nocicept$).mp. [mp=title, original title, abstract, name of substance

word, subject heading word] (334241)

13     9 or 10 or 11 or 12 (392032)

14     9 or 10 (230078)

15     4 and 14 (175)

16     5 and 14 (12)

17     exp War/ (25443)

18     exp Military Personnel/ (15657)

19     exp Military Medicine/ (21662)

20     exp Veterans/ (5122)

21     exp Veterans Disability Claims/ (209)

22     Hospitals, Veterans/ (4480)

23     exp "United States Department of Veterans Affairs"/ (3021)

24     (desert storm or gulf war or enduring freedom or iraqi freedom).mp. (1606)

25     exp Iraq War, 2003 ‐/ or exp Iraq/ (2569)

26     (iraq or soldier$ or veteran$ or combat$ or militar$ or battle$).mp. (77729)

27     17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 (94873)

28     exp "wounds and injuries"/ or in.fs. (580168)

29     27 and 28 (9834)

30     8 and 13 (1988)

31     limit 30 to humans (1836)

32     limit 31 to english language (1402)

33     limit 31 to abstracts (1447)

34     32 or 33 (1681)

35     4 and 13 (500)

36     limit 35 to humans (491)

37     limit 36 to english language (359)

38     limit 36 to abstracts (465)

39     37 or 38 (483)

40     13 and 29 (449)

VA-ESP September 2008 52
Pain in Patients with Polytrauma 

VA-ESP September 2008 53

41     limit 40 to humans (441)

42     limit 41 to english language (383)

43     limit 41 to abstracts (375)

44     42 or 43 (424)

45     34 or 39 or 44 (2480)

46     limit 45 to yr="2000 ‐ 2008" (1163)

47     limit 45 to yr="1902 ‐ 1999" (1317)

48     from 47 keep 1 (1)

Below is the search strategy designed by RC.  This search was saved in PubMed to provide automatic

weekly updates:

"Brain Injuries"(142)  

OR "Multiple Trauma"(142)  

OR "Blast Injuries"(142)  

OR TBI[All Fields]  

OR "traumatic brain injury"[All Fields]  

OR "traumatic brain injuries"[All Fields]  

OR polytrauma[All Fields]  

OR multitrauma[All Fields]  

OR "multi trauma"[All Fields]  

OR "poly trauma"[All Fields]  

OR (("Wounds and Injuries"(142) OR "injuries "[Subheading]) AND ("War"(142) OR "Iraq War, 2003 ‐"(142)

OR "Gulf War"(142)))  

AND ("pain"[MeSH Terms] OR pain[Text Word])
Pain in Patients with Polytrauma 

APPENDIX B. ARTICLE SCREENING FORM 

Author, Year______________________ Title ________________________________________ 

Key words or categories: 1. Does the study population constitute or include: 

a. Polytrauma patients in or after rehab phase ......................

b. Patients with blast-related headaches ............................

c. Neither a) nor b) ...............................................STOP 

2. Does the study intervention strictly address: 

a. Perioperative or surgical pain management ................STOP 

b. Treatment for burn injuries only ............................STOP 

3. Do the study outcomes include measures of pain (pain intensity 

 and/or pain-related function)? 

c. No ...............................................................STOP 

 d. Yes .................................................................... Notes: 

4. Is the text of the article in English? 

a. No ...............................................................STOP 

b. Yes ...................................................................

5. Does the article provide primary data? 

a. No (letter/commentary/non-systematic review) ............STOP 

b. Yes ...................................................................

6. If this article meets no other criterion, should it be saved 

for background? 

a. No ................................................................STOP 

b. Yes ...................................................................

Circle the Key Question(s) to which this article applies: 

6. Have reliable and valid measures and assessment tools been developed to measure pain intensity and 

pain-related functional interference among patients with cognitive deficits due to TBI? Which measures 

and tools are likely to be most useful in assessing pain in polytrauma patients with cognitive deficits due 

to TBI? 

7. Which treatment approaches are most likely to be effective in improving pain outcomes (pain intensity 

and functional interference) in polytrauma patients? Which pain treatment approaches are most likely to 

enhance overall rehabilitation efforts? 

8. Does blast-related headache pain differ in terms of phenomenology and treatment from other types of 

headache pain? Which treatments are best for persistent blast-related headache pain? 

9. What factors are associated with better and worse clinical outcomes among polytrauma patients? Have 

interventions been developed to specifically address these factors? 

10.What are unique provider and system barriers to detecting and treating pain among polytrauma patients? 

Have interventions been developed to effectively address these barriers? 

For reference: Definition of Polytrauma: Concurrent injury to two or more body parts or systems that results in cognitive, 

physical, psychological or other psychosocial impairments. Combat-related mental conditions co-occurring with injury to at 

least one other system also constitutes polytrauma. Scope of Review: The scope includes the assessment and treatment in 

rehabilitation and post-rehabilitation care settings of persistent pain or exacerbations of pain resulting from polytraumatic 

injuries. The scope of this review excludes the following: battlefield/emergency assessment and care; treatment of burn 

injuries; choice of surgical strategy, and perioperative management of injuries suffered in trauma. The scope also excludes 

post-traumatic/post-concussive headache unrelated to blast injury, unless the sample includes patients with moderate or greater

cognitive deficit. 

VA-ESP September 2008 54
Pain in Patients with Polytrauma 

VA-ESP September 2008 55

APPENDIX C. USPSTF QUALITY RATING CRITERIA

Randomized Controlled Trials (RCTs) and Cohort Studies 

Criteria

• Initial assembly of comparable groups: RCTs—adequate randomization, including concealment 

and whether potential confounders were distributed equally among groups; cohort studies—

consideration of potential confounders with either restriction or measurement for adjustment in the 

analysis; consideration of inception cohorts 

• Maintenance of comparable groups (includes attrition, cross-overs, adherence, contamination) 

• Important differential loss to follow-up or overall high loss to follow-up 

• Measurements: equal, reliable, and valid (includes masking of outcome assessment) 

• Clear definition of interventions 

• Important outcomes considered 

• Analysis: adjustment for potential confounders for cohort studies, or intention-to-treat analysis for 

RCTs (i.e. analysis in which all participants in a trial are analyzed according to the intervention to 

which they were allocated, regardless of whether or not they completed the intervention) 

Definition of ratings based on above criteria

Good: Meets all criteria: Comparable groups are assembled initially and maintained throughout the study 

(follow-up at least 80 percent); reliable and valid measurement instruments are used and applied 

equally to the groups; interventions are spelled out clearly; important outcomes are considered; 

and appropriate attention to confounders in analysis. 

Fair: Studies will be graded “fair” if any or all of the following problems occur, without the important 

limitations noted in the “poor” category below: Generally comparable groups are assembled 

initially but some question remains whether some (although not major) differences occurred in 

follow-up; measurement instruments are acceptable (although not the best) and generally applied 

equally; some but not all important outcomes are considered; and some but not all potential 

confounders are accounted for. 

Poor: Studies will be graded “poor” if any of the following major limitations exists: Groups assembled 

initially are not close to being comparable or maintained throughout the study; unreliable or 

invalid measurement instruments are used or not applied at all equally among groups (including 

not masking outcome assessment); and key confounders are given little or no attention.