A research synthesis of therapeutic interventions for whiplash-associated disorder ( WAD ) : Part 2 – interventions for acute WAD

1Lawson Health Research Institute; 2Department of Physical Medicine and Rehabilitation, Parkwood Hospital, St Joseph’s Health Care; 3Schulich School of Medicine and Dentistry; 4School of Physical Therapy, Faculty of Health Sciences, University of Western Ontario, London, Ontario Correspondence: Dr Robert W Teasell, Department of Physical Medicine & Rehabilitation, Parkwood Hospital, St Joseph’s Health Care, 801 Commissioners Road East, London, Ontario N6C 5J1. Telephone 519-685-4000 ext 44559, fax 519-685-4023, e-mail robert.teasell@sjhc.london.on.ca The term ‘whiplash-associated disorder’ (WAD) describes the consequences of a whiplash injury, defined as bony and soft tissue injuries of the neck caused by rapid acceleration immediately followed by rapid deceleration of the neck and head (1), almost invariably occurring as a consequence of a motor vehicle collision (MVC). With annual North American incidence rates estimated to be between 70 and 329 per 100,000 people (1,2), whiplash injuries are the most common injury following an MVC (2,3). Although it is widely held that the majority of whiplash patients recover naturally within a few months of their injury, recent research suggests that recovery is often prolonged, with an estimated 50% of patients still complaining of neck pain one year after injury (4). Moreover, WAD is associated with significant economic costs as a result of lost work productivity, medical care, legal services and other disability-related expenses (5,6). Given the scope and cost of WAD, developing effective therapies that prevent chronicity is of obvious importance. revieW

In 1995, the Quebec Task Force (QTF) published its benchmark review (1) of the scientific literature and expert opinion on WAD.One of the primary conclusions of the report was that the majority of therapeutic interventions used in the treatment of WAD had undergone little to no scientific investigation.Accordingly, the QTF emphasized the need for more and higher quality research.More recently, Conlin et al (7,8) conducted a systematic review of the whiplash treatment literature (which included studies published from 1993 to 2003) and noted that despite the QTF's recommendations, "remarkably little quality research" (8) had been published in the area of WAD management.
The objective of the present review was to update and expand on previous work by evaluating the strength of evidence for therapies initiated during the acute (less than two weeks), subacute (two to 12 weeks) and chronic (longer than 12 weeks) stages of WAD.Treatments were grouped according to time from injury to assist clinicians in deciding on an appropriate treatment course because therapies that are effective in the treatment of acute WAD may not necessarily be effective when initiated in the subacute or chronic phase.The present article, the second in a five-part series, evaluates the evidence for interventions initiated during the acute (initial two weeks) phase of WAD.

MeThoD
The following is a brief summary of the methods used for the current review.A more detailed explanation of the methodology is provided in the first article of the present series (9).A multistage screening process was conducted to identify all literature that evaluated therapeutic interventions for WAD published from January 1980 to March 2009, regardless of study design.Multiple databases were searched (including PubMed, CINAHL, EMBASE, PsycINFO, Web of Science and the Cochrane Central Register of Controlled Trials [CENTRAL]) using the following search terms: whiplash AND (therapy OR treatment OR intervention OR rehabilitation OR surgery OR neurotomy).The literature search was limited to clinical studies written in English that examined adult (18 years of age and older) human populations.A study was deemed eligible for review if it met the following criteria established a priori: • The purpose of the study was to evaluate the effects of one or more clearly defined treatment protocols for WAD (eg, 'physiotherapy' without further elaboration was not considered to be a clearly defined protocol).• At least 60% of the participants in the study sample must have experienced a whiplash injury resulting from an MVC; alternatively, the sample must have included a distinct and separately analyzed subgroup of MVC-related whiplash patients.• Evaluation of the treatment effect must have involved measurable outcomes.• The sample included at least three participants with a whiplash injury.In total, the search procedure yielded 969 citations, 387 of which were duplicates.On screening titles and abstracts for relevance, 121 articles were considered for full review and, after applying inclusion criteria, 83 articles were selected for full review.Information abstracted from studies that met inclusion criteria was organized into tables, and studies were grouped according to the type of intervention being investigated.For the current article, only studies that investigated interventions initiated during the acute stage (ie, within the first two weeks) were included.
All of the included randomized controlled trials (RCTs) were evaluated for methodological quality using a standardized rating scale -the Physiotherapy Evidence Database (PEDro) scale.This evaluation tool was designed specifically for assessing physical therapy research and has been validated for the quality assessment of RCTs (10).The PEDro scale consists of 10 equally weighted yes/no questions relating to issues of methodological quality and can be accessed at www.pedro.org.au/english/downloads/pedro-scale/.Two independent raters reviewed each article and discrepancies were resolved through consensus or, when that was not possible, by a third rater.Studies with PEDro scores of 9 to 10 were considered to be of 'excellent' methodological quality, while scores of 6 to 8 were considered 'good' quality and scores of 4 to 5 were considered 'fair' quality.Studies scoring below 4 were judged to be of 'poor' quality and were considered to be methodologically equivalent to non-RCTs for the purpose of formulating conclusions.These descriptive terms of quality assessment were used to simplify the interpretation of results; however, it is important to note that these terms are only intended to provide an indication of a study's rating on the PEDro scale.Non-RCTs were not assigned a PEDro score and were instead given a no score designation.
Due to the limited number of studies investigating each of the specific WAD interventions, it was decided that both meta-analytical and levels-of-evidence approaches would be inappropriate.Therefore, a narrative approach was used to summarize the findings and formulate conclusions.Because studies using a nonexperimental or uncontrolled design are generally considered to be of lower quality, these types of studies were only used to formulate conclusions in the absence of RCTs or when the results of RCTs were conflicting.In addition, when the results of RCTs were conflicting, studies with higher PEDro scores were weighted more heavily.

ResULTs
Sixteen RCTs (plus two follow-up studies) and five non-RCTs were identified that evaluated therapeutic interventions initiated during the acute stage of WAD (ie, within two weeks of injury) and met the inclusion criteria.The median PEDro score of the RCTs was 5.5, with scores ranging from 4 to 8 (Table 1).The most common methodological limitations were a failure to blind patients and/or therapists, with only four studies using at least one of these methods.Furthermore, only four of the studies conducted their analyses on an intentionto-treat basis and only six used blinded assessors.Overall, the studies included in our analysis investigated interventions that covered five different treatment categories: educational interventions, exercise programs, mobilization programs, pharmacological interventions and alternative treatments (including pulsed electromagnetic field therapy [PEMT] and laser acupuncture).

educational interventions
Two RCTs of good quality (11,12) and one quasirandomized trial (13) investigated the impact of educational interventions initiated during the acute phase of WAD (Table 2).Two of the studies compared education with advice to act as usual and found conflicting results, with one finding no significant differences between groups (11) and the other finding that patients in the educational group had significantly lower pain ratings six months later (13).Although the study reporting a significant treatment effect was a non-RCT, it is noteworthy that in this study, the educational information was presented in the hospital via a 12 min video, while in the RCT, patients were simply given pamphlets to read at home.Investigating whether the method of delivery affects the impact of educational interventions, Kongsted et al (12) randomly assigned patients to receive either a one-hour information session or an educational pamphlet and reported a nonsignificant trend in favour of those who received the information orally.Evidence regarding the effectiveness of educational interventions is conflicting; however, based on the results of the RCTs, it does not appear that providing educational information during the acute phase provides a significant benefit sufficient to alter outcomes.Nevertheless, further research is needed to determine whether the method of delivery influences the effectiveness of educational interventions.

Conclusions regarding educational interventions in acute WAD:
Based on the existing research, it does not appear that providing educational information during the acute phase provides a significant measurable benefit; however, there is some indication that oral and/or video presentation of educational information may be more effective than the distribution of pamphlets.

exercise programs
Three RCTs and one non-RCT evaluated the effectiveness of exercise programs offered during the acute phase of WAD (Table 3).Two RCTs of good quality (14,15) compared the effect of exercise to immobilization with a soft collar.Both reported exercise was associated with significantly less pain at two and six months, respectively.However, in a follow-up study, McKinney (16) reported that a comparable percentage of patients in both groups had chronic symptoms two years after injury.In an RCT of fair quality, Soderlund (17) compared an exercise routine aimed at mobilization with an exercise routine aimed at improving kinesthetic sensibility and coordination in addition to mobilization.For the purposes of the present review, mobilization programs were differentiated from exercise programs in that exercise programs had specific treatment aims (eg, strength and endurance) whereas mobilization programs were aimed at simply increasing or maintaining mobility.The authors found that, although patients who performed the additional exercises reported a greater 'ability to reduce pain' (a question relating to coping ability), patients in both groups experienced similar levels of recovery at six months after injury.Finally, in a case series that included 45 patients, Baltaci et al (18) found that mobilization and stabilization exercises were associated with significant recovery at 12 weeks, although it is difficult to determine whether this recovery was due to the exercise program or natural recovery because there was no control group.Given the above results, it appears that exercise programs are superior to immobilization, although long-term recovery may be unaffected by either intervention.Supplemental exercise programs, when added to mobilization programs, were no more effective than mobilization programs alone.

Conclusions regarding exercise programs in acute WAD:
Although long-term recovery may be unaffected by either exercise or immobilization in a soft collar during the acute phase of WAD, it appears that exercise programs are significantly more effective in reducing pain intensity over both the short and medium term.Conversely, supplemental exercise programs added to mobilization programs may not be any more beneficial than mobilization programs alone.

Mobilization programs
In total, seven RCTs and three quasirandomized trials assessed the relative effectiveness of active mobilization, advice to 'act Pettersson and Toolanen (30), 1998 Foley-Nolan et al (31), 1992 Vassiliou et al (15), 2006 Kongsted et al (12), 2008 McKinney et al (14), 1989 Kongsted et al (23), 2007 Mealy et al (22), 1986 Dehner et al (28), 2006 Schnabel et al (19), 2004 Aigner et al (33), 2006 Borchgrevink et al (26), 1998 Rosenfeld et al (20) as usual' and immobilization initiated during the acute phase of WAD (Table 4).As mentioned previously in the present review, mobilization programs were differentiated from exercise programs in that exercise programs had specific treatment aims whereas mobilization programs were aimed at simply increasing or maintaining mobility.Four of the RCTs (two of good quality and two of fair quality) and two of the non-RCTs compared the use of mobilization exercises with immobilization using a soft collar, with three of the RCTs reporting that mobilization was associated with significantly greater reductions in pain at the time of follow-up, ranging from eight weeks to three years (19)(20)(21)(22).Furthermore, Mealy et al ( 22) also reported that mobilization was associated with improved cervical range of motion (ROM) at eight weeks after injury.In contrast, in an RCT of good quality, Kongsted et al (23) reported that patients who performed mobilization exercises and patients immobilized with a soft collar had similar outcomes in terms of pain, disability and work capability at one year after injury.It should be noted, however, that a large proportion of patients in the soft collar group reported poor compliance with the study protocol.A subsequent analysis showed that patients who actually wore the collars as frequently as was stipulated had a significantly higher risk of being disabled and/or having altered work ability compared with patients in the mobilization group.Similarly, neither of the non-RCTs found significant differences between mobilization and immobilization with a soft collar in terms of pain or cervical ROM (24,25).
In addition to comparing active mobilization with immobilization, Kongsted et al (23) included a third trial condition in which patients were advised to act as usual (ie, remain active but within the limits of pain).Although the authors found that all three groups experienced similar levels of recovery, almost onehalf of the patients in the act-as-usual group sought other interventions.In fact, a large percentage of patients in all three treatment groups used cointerventions, making it difficult to isolate and determine the effect of each individual treatment.Two other RCTs of fair quality also investigated the effectiveness of advising patients to act as usual.Comparing advice to act as usual versus immobilization with a soft collar, Borchgrevink et al (26) found that advice to remain active was associated with significantly better recovery in terms of a wide range of outcomes, including neck pain, headache, memory and concentration.Dehner et al ( 27) compared advice to act as usual to active (joint mobilization, soft tissue and trigger point treatments) and passive (heat, massage and electrotherapy) physical therapy and found that both types of therapy were associated with lower median periods of disability.However, it should be noted that 65% of the participants in the act-as-usual group used other neck interventions during the study period or were lost to follow-up.In terms of reducing pain at two months after injury, active therapy was significantly more effective than passive therapy (27).
Finally, two studies investigated issues related to length of or type of immobilization.In an RCT of fair quality, Dehner et al (28) compared patients who were immobilized with a soft collar for either two or 10 days and reported no significant

Conclusions regarding mobilization in acute WAD:
Although there is some conflicting evidence, it appears that immobilization with a soft collar is less effective than active mobilization and no more effective than advice to act as usual.In contrast, there is strong evidence that active mobilization is associated with reduced pain intensity and limited evidence that mobilization may also improve ROM, although it is not clear whether active mobilization is any more effective than advice to act as usual.

Pharmacological interventions
A single study was identified that investigated a pharmacological intervention initiated during the acute phase of WAD (Table 5).In an RCT of good quality, Pettersson and Toolanen (30) examined the use of methylprednisolone, a drug with both neuroprotective and anti-inflammatory effects.The authors reported that treatment with methylprednisolone was associated with a significant reduction in disabling symptoms, total number of sick days and sick leave profile at six months after injury.However, on review of the study's results, it appears that these differences were largely accounted for by a small number of outliers.Thus, although the results from this study suggest that methylprednisolone is effective in the treatment of WAD, further study using a larger sample size is needed before any definitive conclusions can be drawn regarding the clinical significance of this intervention.

Conclusions regarding pharmacological interventions in acute WAD:
While there is some evidence that methylprednisolone infusion is effective in improving recovery from WAD, further research using larger sample sizes is needed before firm conclusions can be drawn regarding the clinical benefit of this intervention.

Alternative treatments
PeMT: The effectiveness of PEMT was examined in two RCTs, although only one specified that therapy was initiated during the acute phase (Table 6).In an RCT of good quality, Foley-Nolan et al (31) randomly assigned patients to wear soft collars fitted with either an active or inactive PEMT device.Patients in the active PEMT group reported less pain at two and four weeks, and greater cervical ROM at 12 weeks; however, the groups were no longer significantly different in terms of pain intensity at 12 weeks after treatment.Similarly, Thiule and Walzl (32) reported a significantly greater reduction in pain and improvement in cervical ROM among patients who received PEMT compared with those who received medication alone.Unfortunately, because Thiule and Walzl (32) failed to report the duration of follow-up or the time from injury to the initiation of therapy, their results could not be used in formulating conclusions about the effectiveness of PEMT for acute WAD.

Conclusions regarding PEMT in acute WAD:
Although there is some evidence that PEMT decreases pain intensity and increases cervical ROM over the short term, the evidence is insufficient to support the use of this treatment with confidence.
Laser acupuncture: One RCT of fair quality investigated the use of laser acupuncture as a treatment for acute WAD (Table 7).Aigner et al (33) compared treatment with laser acupuncture combined with cervical collar use versus treatment with a collar and placebo laser and found no significant short-or long-term differences between the two treatment groups.Although there were some technical variables associated with the use of laser  acupuncture that may not be fully accounted for (eg, strength of the laser and duration of irradiation), it does not appear that this intervention is beneficial for patients with acute WAD.

Conclusions regarding laser acupuncture in acute WAD:
Laser acupuncture does not appear to be any more effective than placebo in the treatment of acute WAD.

DisCUssion
In total, 23 articles that evaluated interventions initiated within the first two weeks following a whiplash injury were identified.The results of the current review support both the consensus recommendations of the QTF (1) and the evidencebased recommendations of Conlin et al (7,8) -activationbased therapies initiated during the acute phase appear to be the most effective means of reducing the duration and severity of whiplash-associated neck pain, ROM deficits and disability.
Despite substantial evidence that activation-based therapies are the most efficacious treatment options for patients with acute WAD, the relative effectiveness of exercise programs, active mobilization and advice to act as usual remains unclear.There are several reasons for this.First, the majority of activation-based therapies have been compared with immobilization and not other activation-based interventions.Second, exercise is often investigated as one aspect of a broader treatment regimen; for example, some exercise programs incorporate multiple forms of exercise (eg, stretching and gradual resistance) and/or therapeutic elements (such as heat application and reassurance that whiplash injury is usually of relatively short duration).Finally, given the degree of recovery that occurs naturally following a whiplash injury, it can be difficult to determine whether an observed improvement is due to the intervention or to natural recovery, which is especially true regarding advice to act as usual, in which the intervention may function more by allowing natural recovery to take place.Conversely, one trial did compare mobilization and advice with a physiotherapy program and, although no significant differences were found at either one or two months after treatment, a significantly greater percentage of patients in the mobilization group reported being symptom free two years after injury (14,16).This suggests that simple mobilization exercises and advice to remain active may produce better long-term results than more formal physiotherapy exercise programs, although the latter are superior to no treatment.Furthermore, it may be that certain exercises, such as strengthening exercises, only serve to slow recovery when compared with simple mobilization exercises, suggesting that remaining active is critical but attention is needed to ensure exercise programs are not too aggressive because more aggressive programs may reaggravate healing tissues.Immobilization of the neck using a soft cervical collar has repeatedly been shown to be ineffective at best.At worst, this technique may impede natural recovery by promoting prolonged neck stiffness through inhibiting movement and discouraging patients from taking an active role in their own recovery.While the ineffectiveness of soft collars has long been recognized clinically, researchers often use cervical collars as a control condition.In light of the substantial evidence demonstrating the ineffectiveness of soft collars for the treatment of acute WAD, the ethics of immobilizing patients with a soft collar as a control treatment warrants serious reconsideration.Not only is knowingly providing inefficacious treatment ethically questionable, but comparing experimental treatments with a therapy that may be harmful offers little scientific value.Alternatively, directly comparing active treatments with one another avoids the ethical dilemma of prescribing a cervical collar and offers an opportunity to explore which particular neck exercise regimens are most effective in treating acute WAD.
In addition to activation-based treatments, there is also some evidence suggesting that both PEMT and methylprednisolone infusion may improve recovery over the short term; however, the literature supporting both of these interventions was limited.In contrast, it has been demonstrated that laser acupuncture and educational interventions are ineffective in improving recovery from acute WAD.It should be noted, however, that some evidence suggests that verbal and/or video presentation of educational information may be more effective than the distribution of pamphlets.Further complicating this issue, several of the studies that were described as providing advice to act as usual also contained aspects of educational intervention.Clearly, further research is needed to clarify whether providing patients with educational information, either alone or in conjunction with other interventions, is beneficial during the acute stage of WAD.
The present review was limited by several methodological concerns.First, because of the small number of studies in the whiplash literature, the criteria for inclusion were quite broad.All studies were included regardless of study design as long as 60% of the sample experienced a WAD and they included a sample of at least three participants with a whiplash injury.This may have resulted in the inclusion of some studies of lower scientific merit; however, such studies were only used to formulate conclusions in the absence of superior RCTs, and these limitations were noted in the conclusions themselves as well as in the discussion.Second, there are limitations with the quality assessment process used in the current review to evaluate the methodological quality of RCTs.For example, it is possible that an RCT with significant between-group differences at baseline that did not blind patients, therapists or assessors could still have a PEDro score of 6 and be considered a study of good methodological quality despite these significant limitations.Again, these issues were noted in relevant conclusions and study descriptions.Nevertheless, these measures do not negate the need for readers to be 'critical consumers' of the material presented.
According to Dufton et al (34), the longer the delay between injury and the commencement of therapy, the greater the risk that patients will go on to develop chronic symptoms.Moreover, interventions initiated during the subacute phase do not appear to be effective in reducing whiplash-related symptoms (see part 3 in this series [35]).Given this evidence, it seems to be very important that patients begin therapy as soon as possible after sustaining their injury.Nevertheless, a large percentage of patients with whiplash-related injuries recover naturally over a relatively short period of time.This highlights the need for research of a controlled design that allows one to make a clear distinction between treatment-related improvement and natural recovery, particularly for interventions initiated during the acute phase.Based on the results of the current review, activation-based therapy appears to be the most efficacious approach when managing acute WAD (Table 8).However, further research is needed to determine the optimum protocol (eg, duration and intensity) for activation-based treatments as well as which form of activation-based therapy offers the greatest benefit for patients with acute WAD.

Educational
Based on the existing research, it does not appear that providing educational information during the acute phase provides a significant measurable benefit; however, there is some indication that oral and/or video presentation of educational information may be more effective than the distribution of pamphlets

Exercise programs
Although there is some conflicting evidence, it appears that immobilization with a soft collar is less effective than active mobilization and no more effective than advice to act as usual.In contrast, there is strong evidence that active mobilization is associated with reduced pain intensity and limited evidence that mobilization may also improve range of motion, although it is not clear whether active mobilization is any more effective than advice to act as usual Mobilization There appears to be strong evidence that immobilization with a soft collar is less effective than active mobilization and no more effective than advice to act as usual.In contrast, active mobilization appears to be associated with reduced pain intensity, although it is not clear whether active mobilization is any more effective than advice to act as usual Pharmacological While there is some evidence that methylprednisolone infusion is effective in improving recovery from WAD, further research using larger sample sizes is needed before firm conclusions can be drawn regarding the clinical benefit of this intervention

Pulsed electromagnetic field therapy
Although there is some evidence that pulsed electromagnetic field therapy decreases pain intensity and increases cervical range of motion over the short term, the evidence is insufficient to support the use of this treatment with confidence Laser acupuncture Laser acupuncture does not appear to be any more effective than placebo in the treatment of acute WAD

TAble 4 -continued Summary of studies evaluating simple mobilization exercises for acute whiplash-associated disorder (WAD) Reference, year, country, score Population and methods Outcome measures Results
ns No score; NSAID Nonsteroidal anti-inflammatory drug; PEDro Physiotherapy Evidence Database; ROM Range of motion; VAS Visual analogue scale

TAble 6 Summary of studies evaluating pulsed electromagnetic field therapy (PeMT) for acute whiplash-associated disorder (WAD) Reference, year, country, score Population and methods Outcome measures Results
NSAID Nonsteroidal anti-inflammatory drug; PEDro Physiotherapy Evidence Database; ROM Range of motion; VAS Visual analogue scale