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To review the literature addressing the assessment and management of pain in patients with polytraumatic injuries including traumatic brain injury (TBI) and blast-related headache, and to identify patient, clinician and systems factors associated with pain-related outcomes.
We conducted searches in MEDLINE of literature published from 1950 through July 2008. Due to a limited number of studies using controls or comparators, we included observational and rigorous qualitative studies. We systematically rated the quality of systematic reviews, cohort, and case-control design studies.
One systematic review, 93 observational studies, and one qualitative research study met inclusion criteria. The literature search yielded no published studies that assessed measures of pain intensity or pain-related functional interference among patients with cognitive deficits due to TBI, that compared patients with blast-related headache with patients with other types of headache, or that assessed treatments for blast-related headache pain. Studies on the association between TBI severity and pain reported mixed findings. There was limited evidence that the following factors are associated with pain among TBI patients: severity, location, and multiplicity of injuries; insomnia; fatigue; depression; and post-traumatic stress disorder.
Very little evidence is currently available to guide pain assessment and treatment approaches in patients with polytrauma. Further research employing systematic observational as well as controlled intervention designs is clearly indicated.
Major advances in body armor technology and battlefield medicine have improved survival from combat injuries that would have been fatal in previous wars . Data from the Department of Defense (DOD) indicate that the lethality of injuries has decreased from 24% among those wounded in the Vietnam War, to 10% among those wounded in the Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) conflicts . Soldiers wounded in our nation's current wars have more multiple and complex injuries and emotional trauma than typically seen in past wars [3,4]. Blast exposure was responsible for 71.5% of traumatic brain injuries and 49.9% of amputations among service members as of August 2008 . Auditory or visual impairments, spinal cord injury (SCI), post-traumatic stress disorder (PTSD), and other mental health conditions are also common.
In 2005, polytrauma was defined by the Veterans Health Administration (VHA) as “injury to the brain in addition to other body parts or systems resulting in physical, cognitive, psychological, or psychosocial impairments and functional disability” . VHA's definition of polytrauma has since expanded to encompass concurrent injury to two or more body parts or systems resulting in cognitive, physical, psychological, or other psychosocial impairments.
Pain resulting from polytraumatic injuries poses numerous challenges during and following rehabilitation. It is unclear how best to assess and monitor pain among patients with cognitive deficits due to traumatic brain injury (TBI). Due to cognitive side effects, commonly used pain treatments (for example, oral opioids) have the potential to interfere with the active rehabilitation needed to restore function in this population. Blast-related headache may differ in terms of phenomenology and treatment from other types of headache.
The objectives of this study were to systematically review the empirical 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 polytrauma patients, and to outline a research agenda to address key questions.
In consultation with a technical advisory panel (clinical or research experts working in the areas of pain, polytrauma or TBI, primarily within the Veterans Affairs (VA) system), we identified five key questions for the review. These questions addressed 1) methods of assessment of pain among patients with cognitive deficits due to TBI; 2) effectiveness of treatment approaches for pain related to polytrauma; 3) the phenomenology and management of blast-related headache; 4) patient factors associated with pain-related outcomes among polytrauma patients; and 5) clinician and systems factors associated with pain-related outcomes among polytrauma patients. The specific key questions are included with the results below.
Polytrauma was defined for this review as concurrent injury to two or more body parts or systems resulting in cognitive, physical, psychological, or other psychosocial impairments. Consistent with VHA's definition, TBI of moderate or greater severity was considered polytrauma (head injury itself plus associated cognitive sequelae). Combat-related mental conditions co-occurring with injury to at least one other system also constituted polytrauma.
The scope of this review included the assessment and treatment in rehabilitation and post-rehabilitation 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. Studies examining battlefield/emergency or assessment and care within 3 months of injury were not included unless they also examined pain outcomes 3 months following injury. We also did not include studies examining choice of specific surgical strategy, perioperative management of traumatic (including burn) injuries, or use of particular procedures or devices for specific orthopedic injuries. We excluded studies describing functional outcomes of polytrauma unless a pain measure was also included. Finally, we excluded studies of post-traumatic/post-concussive headache unless the sample included patients with moderate or 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. Figure 1 illustrates the analytic framework that guided our review.
Two research librarians independently designed search strategies based on the key questions, and conducted searches in PubMed and Ovid 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; some of these articles were published prior to 1950. 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; DOD Technical Information Center; and the Cochrane Database of controlled clinical trials. All citations were imported into an electronic database (EndNote X1).
Three investigators (SD, RC, MF) reviewed the titles and abstracts identified from the searches. Full-text articles of potentially relevant abstracts were retrieved for further review. Reference lists from pertinent articles were reviewed to find additional articles for inclusion. 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 readers could discern outcomes for the polytrauma group.
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. Due to a limited number of studies that included a comparator group, we also considered relevant cross-sectional and case report/case series studies for inclusion for some of the key questions. To rate the quality of studies we used criteria developed by the U.S. Preventive Services Task Force for rating randomized controlled trials, cohort studies, and case control studies (Appendix B) . We did not rate the quality of cross-sectional studies, case reports, or case series. 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 (Appendix C) , which classified the grade of evidence across outcomes according to the following criteria: 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. Finally, a draft version of our findings was sent to technical reviewers who provided comments, suggested additional pertinent references, and prioritized future research topics and study designs.
The combined library contained 3,252 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.
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?
We found 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.
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?
We found 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. One study examined the effectiveness of inpatient rehabilitation in helping patients with trauma-related amputation return to work . This study was a fair-quality retrospective cohort study of patients from an urban trauma center between 1984 and 1994. Seventy-eight patients who had undergone trauma-related amputation were contacted and interviewed approximately 7 years after injury. The study excluded amputation for non-injury reasons (e.g., diabetes), SCI or TBI. Many patients 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) (GRADE: Very Low).
We also identified a number of case reports and case series that described pain treatment approaches and pain outcomes among patients with polytrauma including TBI [10–31]. Several case reports supported that intrathecal baclofen may be helpful for spasticity associated with TBI and related injuries [21–25]. In patients with complex regional pain syndrome I, topical capsaicin brought pain relief in a single-case study , and early intervention with spinal cord stimulation was associated with decreases in pain and opioid use in a consecutive-case series of 10 active duty U.S. military personnel, 6 who were injured in OEF/OIF .
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?
We found no randomized controlled trials, cohort studies, case-control studies, or other systematic observational studies that compared patients with blast-related headache with patients with other types of headache or that specifically addressed treatments for blast-related headache pain.
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?
We found no randomized controlled trials. One systematic review, 11 cohort, 2 case-control, and 17 cross-sectional studies specifically addressed patient factors associated with outcomes in TBI patients. Table 1 provides a summary of the data abstracted from the systematic review and cohort studies. One fair-quality systematic review examining relationships between TBI severity and pain was published in 2008 . The review identified 23 studies (15 cross-sectional, 5 prospective observational, and 3 retrospective observational) including 4,206 patients. No randomized clinical trials were identified. Data were pooled across studies utilizing varying samples and designs to obtain overall prevalence rates. The review showed that 58% of patients with TBI have chronic headache. Brain injury was associated with headache even after adjustment for PTSD .
We also identified a number of studies reporting on the prevalence of pain and headache among TBI patients [33–51]. Headache was the most common pain complaint among TBI patients in one prospective cohort and several cross-sectional studies. In the Nampiaparampil 2008 systematic review described previously, the prevalence of chronic pain was 51.5% in patients with mild TBI, compared with 32.1% among patients with moderate or severe TBI . However, our review identified a number of studies not included in the Nampiaparampil 2008 review, and found mixed results on whether the prevalence of headache varies with severity of head injury. While one fair-quality retrospective cohort study , one fair-quality case-control study , and five cross-sectional studies [45,48,49,53,54] reported a higher prevalence of headache among patients with mild TBI as compared with more severe TBI, there were no differences in the prevalence of headache according to severity of head injury in one retrospective  and four prospective cohort studies [33,34,36,55] of varying quality, as well as three cross-sectional studies [44,56,57]. While a more detailed exploration of this topic is beyond the scope of this manuscript, overall we found only limited evidence showing that patients with mild TBI are more likely to have headache or other pain than patients with more severe TBI.
In one cross-sectional study , blast exposure was not found to be a significant predictor of pain. Several cohort studies [33,34,58] and one cross-sectional study with TBI patients  identified associations among pain or headache and depression. In another cohort study of TBI patients , frequency of chronic pain was associated with PTSD. Finally, one cohort study , two case-control studies [41,42], and two cross-sectional studies [61,62] identified associations between pain or headache and fatigue or insomnia. There were mixed findings regarding the association between demographic factors and pain outcomes in TBI patients [33,34,63].
In summary, we found that among patients with TBI, headache is present in one-third to one-half of patients up to 5 years after injury (GRADE: Low). Our review showed mixed findings regarding the association between severity of TBI and pain (GRADE: Very Low). Finally, psychological factors, including depression and PTSD, insomnia and fatigue are associated with pain in TBI patients (GRADE: Low).
Twenty-two cohort, two cross-sectional, and five case-control studies addressed patient factors associated with outcomes in patients with polytrauma other than, or in addition to TBI. Table 2 summarizes the findings from the cohort studies. A number of studies support that injury characteristics (in particular, location, severity, and multiplicity) are often associated with pain-related outcomes in patients with amputations or orthopedic injuries. Thirteen cohort studies of varying quality [9,64–76] and one cross-sectional study  found associations between injury severity or multiplicity and subsequent pain and functional outcomes. In contrast, one fair-quality retrospective cohort study  and one poor-quality case-control study  did not find these associations. Some studies that included patients with cognitive disabilities or head injury found associations between head injury or cognitive disability and decreased functional outcome [73–76,80]. In an additional poor-quality case-control study, patients with head injury plus other types of polytrauma were not found to have worse bodily pain at 6 or 12 months compared with patients with TBI alone . Other injury characteristics associated with worse functional and pain outcomes were lower limb injuries [71,75,82–84], open pelvic fracture as compared with closed pelvic fracture , and longer length of hospital stay .
One good-quality  and three fair-quality [9,70,73] cohort studies found associations between younger age and better functional outcomes in polytrauma patients. One good-quality cohort study  and one fair-quality cohort study  found associations between being male and better functional outcomes. In an additional cross-sectional study, phantom pain was more common in women than men . However, in one fair-quality prospective cohort study, there were no significant gender differences in bodily pain scores on the 36-Item Short Form Health Survey (SF-36) at 2 and 8 months post-injury . Finally, in one fair-quality retrospective cohort study, white race was associated with better SF-36 Physical Component and Bodily Pain outcome scores, higher likelihood of return to work, and lower likelihood of reduced work hours . A number of cohort studies found that higher educational achievement [75,76,87] and having a professional/white collar job [70,73,87] were associated with better functional status. Almost no studies reported on relationships between psychosocial factors and pain-related outcomes in patients with polytraumatic injuries other than TBI.
In summary, characteristics of injuries 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).
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 found 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 addressed potential provider and system barriers to treating polytrauma patients . In qualitative interviews, 56 providers reported that polytrauma patients are very complex to treat, and that the work with this population is 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.
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 purpose of this project was to identify and synthesize evidence on the assessment and treatment of pain in polytrauma patients. Overall, the literature provides limited evidence to guide clinicians in this area. Although previous reviews indicate that pain may interfere with neurocognitive performance in TBI patients [88–90], we found no studies on how neurocognitive performance may affect measurement of pain or pain-related interference. The literature also provides limited evidence to guide clinicians in selecting among non-surgical pain treatments in patients with polytrauma. Aside from one study indicating that inpatient rehabilitation may improve outcomes among patients with trauma-related amputation , and a number of case reports/series [10–31], we did not find any rigorous studies of pain intervention studies in this population. Finally, although several studies have suggested that headache is common among blast injury patients [50,51,91], we found no published studies describing how blast-related headache might differ in terms of phenomenology or treatment from other types of headache pain.
We did find moderate evidence showing that injury factors (including location, severity, and the number of different injuries) are associated with pain and functional status over time. 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 pain-related function in several studies included depression, PTSD, insomnia, and fatigue.
TBI itself is associated with worse outcomes when compared with 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 5 years post-injury. Contrary to conventional wisdom and what was documented 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 with more severe 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. We note that most of the cross-sectional studies were done in outpatient settings of patients who had been injured years previously, and did not adjust for potential confounders that may influence relationships between TBI severity and pain. In contrast, most of the patients in the prospective studies were identified in inpatient or rehabilitation settings closer to the time of injury. It is likely that differences in sample composition contribute to the differences in findings between the cross-sectional and cohort studies, such 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.
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 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.
Due to innumerable etiologies and combinations of injuries, there is great heterogeneity among polytrauma patients, and resulting substantial variability among the study samples described in the literature. In addition, samples were drawn from a variety of settings over a wide range of time following injuries. Thus, the conclusions drawn from a particular study or set of studies may have limited relevance for other polytrauma patients or other settings; comparisons must be made cautiously. Because of 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 and focused on identifying studies that included majorities of patients with polytrauma in their samples. Consequently, one potential limitation of this review is that some manuscripts were not identified that might have relevance for the treatment of pain in polytrauma patients. We note that we did search more broadly for studies pertaining to TBI and blast as there is particular relevance for a large segment of the OEF/OIF patient population. In addition, we did not exclude individual studies based on quality rating alone. Thus, the strength of our conclusions is inherently limited by quality variation among included studies. We did review each cohort and case-control study for overall quality using a rigorously developed approach. Finally, we did not attempt to distinguish studies that reported on patients injured in combat or who were exposed to blast vs studies of patients injured in other settings. It is possible that combat-related trauma is associated with different polytrauma characteristics as well as different pain-related outcomes.
We asked our technical advisory panel and other experts to review the results of our literature review, suggest potential study topics and designs, and assign priorities to the research topics and designs (Table 3). Priority scores were based on potential to achieve the highest possible impact on patient care in the VA. 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. Raters gave high priority to a variety of different research designs including randomized trials, prospective observational studies and in some cases, cross-sectional studies. Because these are preliminary rankings, a panel or other mechanism to achieve consensus is needed to refine and finalize the recommendations for future research.
Overall, there is very little evidence to guide clinicians in assessing pain among patients with cognitive deficits due to TBI, treating pain related to polytrauma, and managing blast-related headache. Some evidence suggests that injury characteristics are associated with pain-related outcomes, and that psychological factors including depression and PTSD, and insomnia and fatigue are associated with pain among TBI patients. Future research is clearly indicated using varying designs to improve our knowledge of pain assessment and treatment in the polytrauma patient population.
The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Project RCD 04129 (Dobscha), National Institutes of Health K23DA023467-01A1 (Morasco) and Evidence-based Practice Center funding which is supported by the Agency for Healthcare Research and Quality. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs.
We gratefully acknowledge the assistance of research librarian Andrew Hamilton, MS, MLS, and the participation of Robert Kerns, PhD; Nina Sayer, PhD; Marti Buffum DNSc, APRN, BC, CS; Drew Helmer, MD; Henry Lew, MD, PhD; Nancy Carney, PhD; Ron Gironda, PhD; Martin Schreiber, MD; Matthew J. Bair, MD, MS; Valerie A. Lawrence, MD, MSc; John D. Otis, PhD; Daniel M. Storzbach, PhD; and Robyn L. Walker, PhD in helping us identify and refine key questions, critically reviewing drafts of the findings, and prioritizing research topics.
Two librarians independently designed search strategies based on the key questions. The results of both searches were combined into a single reference library.
Database: Ovid MEDLINE(R) 1950 to January Week 5 2008
This search was saved in PubMed to provide automatic weekly updates:
|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.|
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:
Randomized trial = high
Observational study = low
Any other evidence = very low
Disclosures: None for any author.