C O C H R A N E :   2 0 1 1 .C A R O L Y N T E J I R I A N , M D M S P G Y - I I I

J O U R N A L C L U BO C T 2 3 , 2 0 1 3

MEDICINAL AND INJECTION THERAPIES FOR MECHANICAL NECK DISORDERS (REVIEW)

BACKGROUND

• Between 26 %and 71% of the population will experience neck pain in their lifetime

• At any one time, 9% of men and 12% of women have a neck complaint.

• The annual incidence in primary care in the UK is 12.1 cases per 1000 person years; in the Netherlands this represents 2% of general practice.

• In a significant minority, pain persists. Up to 15% of patients have associated disability and 5% cite severe disability.

• Neck pain accounts for approximately 15% of hospital physiotherapy and 30% of chiropractic visits.

• Industrial neck-related disorders may cause absenteeism as commonly as low back pain. In Quebec, 7% of compensation claims are neck related

• Motor vehicle crashes leave 24% to 50% of subjects with persistent symptoms at 12 months

• Treatments and their perceived benefits are varied. Medications play an important role, but critical reviews of the evidence base for medicinal therapies are lacking and expert reviews predominate. Are all types of medication equally safe and effective? This is a critical issue for patients, physicians and policy makers.

PATIENT: MS. IMA PAYNE

• 42 yo female PHMx of GERD, HTN, chronic myofacial pain, states that 6 weeks ago she was in a fender-bender. Since then she has had neck pain. Annoying but enough to interfere with sleep. Sometimes radiates to head and causes HA. Takes occasional APAP, which really does not help.

• On physical exam you notice full ROM but painful when turning to right. +TTP along paraspinals, Normal strength in upper extremities.

WHAT TREATMENT OPTIONS TO DO OFFER?

MAKE A L IST

TREATMENT OPTIONS

• NSAIDS• Muscle relaxants• Opiates• Benzos (Xanax will cure it)• Trigger point injections (lidocaine or saline)• Hot or cold compresses• Neck exercises• Acupuncture• Massage• Creams: bengay, capsaicin, diclofenac• Refer for epidural injection• Refer to pain clinic• Anything else?

NUMBER THE LIST IN ORDER OF YOUR PREFERENCE FOR TREATMENT

ONLY THE TOP 5

NUMBER THE LIST IN ORDER OF WHAT YOU NOTICE PATIENTS STATE WORKS

BEST

ONLY THE TOP 5

HOW DOES THIS LIST CHANGE FOR DURATION OF SYMPTOMS?

ACUTE ~ SUB-ACUTE ~ CHRONIC

HOW DOES THE LIST CHANGE WHEN CONSIDERING TREATMENT DURATION?

1DAY & 1D-3MO & 3MO -12 MO & > 1YR

HOW DO YOU KNOW IF YOUR TREATMENT WAS SUCCESSFUL?

MAKE A L IST OF 5 RESPONSES TO TREATMENT

SUCCESS!

• What criteria do you use to consider a treatment successful for your patient?• Pain-free• Decreased pain• Better sleep• Less HA or associated symptoms• Increased QOL• Back to work• Patient satisfaction• Patient does not return to complain about continued pain

WHAT EVIDENCE DO YOU HAVE TO SUPPORT YOUR LIST?

PICOT QUESTIONS

Background: Controversy persists regarding medicinal therapies and injections for treatment of mechanical neck disorders.

• P (patient)• 42 yo patient with chronic myofascial pain, worse in neck

• I (Intervention)• Trigger point injections – because I do so many, people seem to like it, and we are

recently down 2 providers at IHS who offered TPI and now my panel is filling up with these patients.

• C (Comparison)• Muscle relaxants, NSAIDs

• O (Outcome)• Moderate evidence, but there are problems with lack of replication of data and small size

of trials• On trial indicates moderate evidence for IV methylprednisolone given within 8 hours of acute

whiplash, • Lidocaine injection into myofascial trigger points appears effective in two trials. • Moderate evidence that Botulinum toxin A is not superior to saline injection for chronic MND. • Muscle relaxants, analgesics and NSAIDs had limited evidence and unclear benefits.

SEARCH STRATEGY

• Required several days of searching. Google scholar, Pubmed, Cochrane• Search term: “Injection therapies” worked best• Eventually chose this Cochrane review because of

relevance to practice.

Peloso PMJ, Gross A, Haines T, Trinh K, Goldsmith CH, Burnie SJ, Cervical Overview Group. Medicinal and injection therapies for mechanical neck disorders. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD000319. DOI:

10.1002/14651858.CD000319.pub4.

ABSTRACT

• Objectives: To determine the effects of medication and injections on primary outcomes (e.g. pain) for adults with mechanical neck disorders and whiplash.

• Search methods: We searched CENTRAL, MANTIS, CINAHL from their start to May 2006; MEDLINE and EMBASE to December 2006. We scrutinized reference lists for other trials.

• Selection criteria: We included RCTs with adults with neck disorders, +/- headache or radicular findings. We considered medicinal and injection therapies, regardless of route of administration.

• Data collection and analysis: Two authors independently selected articles, abstracted data and assessed methodological quality.• 36 trials examined the effects of oral NSAIDs, psychotropic agents, steroid injections,

and anesthetic agents. Trials had a mean of 3.1 on the Jadad Scale for methodological quality; 70% were high quality.

• Jadad scale: Was the study randomized, blinded, description of w/d & dropouts? 3 pts

ABSTRACT CONCLUSIONS

Main results• Acute whiplash: IV methylprednisolone within 8 hours of injury reduced pain at 1 week and

sick leave but not pain at 6 months compared to placebo in one trial. • Chronic neck disorders at short-term follow-up: IM injection of lidocaine was superior

to placebo, and dry needling, but similar to ultrasound in one trial each. • Chronic neck disorders with radicular findings: epidural methylprednisolone and

lidocaine reduced neck pain and improved function more when given by intramuscular route at one-year follow-up, in one trial.

• Subacute and chronic neck d/o: muscle relaxants, analgesics and NSAIDs had limited evidence and unclear benefits.

• Chronic neck disorders +/- radicular findings or headache: moderate evidence from 5 high quality trials that Botulinum toxin A IM injections had similar effects to saline in improving pain, disability or global perceived effect.

Authors’ conclusions• Moderate evidence, but there are problems with lack of replication of data and small size of

trials• On trial indicates moderate evidence for IV methylprednisolone given within 8 hours of acute whiplash, • Lidocaine injection into myofascial trigger points appears effective in two trials. • Moderate evidence that Botulinum toxin A is not superior to saline injection for chronic MND. • Muscle relaxants, analgesics and NSAIDs had limited evidence and unclear benefits.

STUDY: OBJECTIVES

Objectives:• To determine what medication are effective in adults with

mechanical neck disorders (MND), whether these medication were delivered by oral, IV, IM or intra-articular routes.

• Outcomes evaluated were pain, measures of performance (i.e.

function, ADLs, disability), employment status, ROM, patient satisfaction, and patient global perceived effects.

• Factors that influenced the magnitude of treatment effects, particularly methodological quality, patient characteristics (i.e. symptom duration), nature and mechanisms of neck pain (i.e. disorder subtype), type of medication used (i.e. analgesic, etc.) and the route of delivery (i.e. oral, injection, etc).

STUDY: METHODS

Types of trials: RCT and quasi RCT (randomization based on date, MRN, SSN…)

Type of Participants:Included adults (>18yo) with acute, sub-acute, or chronic neck disorders categorized as:• Mechanical neck d/o (MND), including whiplash associated disorders described as myofascial neck pain, and

degenerative changes• Neck disorder with headache or radicular findingsWe excluded studies if they investigated neck disorders with:• Definite or possible long tract signs (e.g. myelopathies);• Neck pain caused by other pathological / neurological entities (e.g. RA, ankylosing spondylitis, spasmodic torticollis, fx

and dislocations• HA not of cervical origin, co-existing headache when either neck pain was not dominant or the headache was not

provoked by neck movements or sustained neck postures, or ’mixed’ headache

Types of interventions: • Medications with known MOA delivered by any route. • Controls were either placebo, active, inactive, or no treatment

Types of outcomes: • pain reports: improvement - subjective, tenderness, threshold (examiner measured)• performance: ADLs, disability related to neck pain, work status• quality of life• patient global perceived effect• patient satisfaction• ROM of c-spine

STUDY: METHODS

Search Methods• These computerized bibliographic databases were searched without language

restrictions, by a research librarian, for medical, chiropractic, and allied health literature

• Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Manual Alternative and Natural Therapy Cumulative Index to Nursing and Allied Health Literature (CINAHL), Index to Chiropractic Literature

• Unpublished studies from specific conference proceedings.

Study selection• Pairs of authors with expertise in medicine, physiotherapy, chiropractic, massage

therapy, statistics, and clinical epidemiology independently identified citations and selected studies and reached consensus.

• A third author resolved disagreements. • Included 36 studies out of 1011 indentified

• 23 mechanical neck d/o• 4 whiplash d/o, acute & chronic• 8 degenerative changes• 8 with headaches• 15 with radicular signs

RISK OF BIAS IN INCLUDED STUDIES

• Assessed methodologic quality using 2 different authors and a consensus process. Studies were graded on two different sets of criteria• Jadad score (5 pt total, high quality =3)• Mean 3.1 (70% scored > 3)

• Cochrane grading of allocation concealment

• All but one study was randomized• 29/36 studies failed to describe allocation concelment• 19/36 studies failed to describe appropriateness of

double blinding• 8/36 lacked a adequate description of withdrawals

and dropouts

B L A H , B L A H , B L A H … . C U T T O T H E C H A S E A L R E A D Y !

RESULTS

EFFECTS OF INTERVENTIONINCONSISTENT OR CONTRADICTORY RESULTS IN MULTIPLE RANDOMIZED TRIALS

Divided up into the following categories:• Strong evidence - denotes consistent findings in multiple high

quality randomized controlled trials

• Moderate evidence - denotes findings in a single, high quality randomized controlled trial or consistent findings in multiple low quality trials

• Limited evidence - indicates a single low quality randomized trial

• Unclear evidence - denotes inconsistent or contradictory results in multiple randomized trials

• No evidence - means no studies were identified.

GUESS THE NUMBER OF HIGH QUALITY STUDIES

STRONG EVIDENCE OF BENEFIT

• NONE

• No high quality, RCT, that were replicated

• Therefore they did not calculate a NNT• Not able to do sensitivity analysis on for symptom

duration and neck disorder subtypes

HOW MUCH EVIDENCE DO YOU THINK THERE IS BEHIND TRIGGER POINT

INJECTIONS?

C O M PA R E D RY N E E D L I N G T O L I D O C A I N E T O BO T U L I N U M T OX I N

MODERATE EVIDENCE OF BENEFITMULTIPLE LOW QUALITY STUDIES

Intramuscular injections of local anesthetics (3 trials, 195 ppl)

• Single session lidocaine superior to dry needling

• Pain improvement at 2 (SMD - 3.46 (95% CI -4.46 to -2.46)) & 4 weeks (SMD -1.27 (95% CI -2.25 to -0.29)for chronic myofascial pain. (2 different trials)

• No difference when compared to botox (SMD-0.49 (95%CI -1.41 to 0.42).

• IM lidocaine + neck stretches, better than neck stretches alone, although not superior to US + neck stretches. NNT 3. (SMD -1.36 (95% CI -1.93 to -0.80)

• Too much heterogeneity between the 3 trials to perform a meta-analysis.

WHAT DO YOU TELL YOUR PATIENT WITH LESS THAN 8 HOURS OF WHIPLASH?

MODERATE EVIDENCE OF BENEFITSINGLE HIGH QUALITY STUDY

IV Glucocorticoid for whiplash (1 trial, 40 ppl)

• Acute whiplash of less than 8 hours duration. IV methylprednisolone 30mg/kg as s single bolus followed by a 5.3/kg infusion over 23 hours

• Led to reduced pain at 1 week and reduced sick leave. No change in pain at 6 months.

• SMD-0.90 (95%CI -1.57 to -0.24)NNT not able to calculate

LIMITED EVIDENCE OF BENEFITSINGLE LOW QUALITY RCT

Epidural injections (1 trial 50 ppl)

• Epidural with methylprednisolone + lidocaine was superior to IM methylprednisolone + lidocaine for chronic neck d/o with radiation.

• Improved pain at 4 weeks and 6 months. pain:

SMD -1.46 (95% CI -2.16 to - 0.76

UNCLEAR EVIDENCE

• Oral psychotropic agents (8 trials, 578 ppl): • Cyclobenzaprine (flexeril) no superior to placebo at 14 days• Diazepam (valium) not superior to placebo• Cyclobenzaprine + lysine cloniximate (NSAID derived from nicotinic acid)

better than lysine alone• Tetrazepam (another benzo) superior at 1 week to APAP• Phenobarbital not better than placebo• Fluoxetine, not better than amitriptyline for pain at 6 weeks

• Oral anti-inflammatory and oral analgesics (5 trials, 270 ppl)• Compare tenoxicam + ranitidine to acupuncture . No difference at 4 weeks• Ibuprofen + manipulation to manipulation alone. No difference at 4 weeks

• Nerve block injections (2 trials, 48 ppl)• Occipital nerve block using prilocaine was better than saline for treating HA.

Similar results when using bupivicaine

MODERATE EVIDENCE OF NO BENEFIT

• Botulinum A toxin (6 trials, 285 ppl): no benefit over saline IM,. No difference to lidocaine or dry needling. No difference if dose in increased

• Intra-cutaneous injections: (1 trial 20 ppl): sterile water vs saline. No difference

• SQ injections of CO2 (1 trial, 57 ppl): IV CO2 (vasodiltor) + PT, no difference than PT alone.

• • Melatonin (1 trial, 81 ppl): no benefit for sleep or general health at

4 weeks

• IM injections of multivitamins (1 trial, 60 ppl): no change in chronic pain

LIMITED EVIDENCE OF NO BENEFIT

Morphine added to epidural injection of triamcinolone and lidocaine (1 trial, 24 ppl): • Chronic neck pain with radicular findings. • No benefit.

SIDE EFFECTS & COSTS

• No serious side effects reported in any study• However most studies were small with short term follow-

up only

• Only two studies described cost of treatment• Epidurals described as “low cost”• Botox cost $335 USD for 100U, need 100-200U for neck

H O W W I L L T H I S C H A N G E YO U R P RAC T I C E ?

DISCUSSION

WILL THIS DATA CHANGE YOUR PRACTICE?

• Steroids for whiplash?• Use of trigger point injections? (lidocaine, saline,

botox)• Occipital nerve blocks?• Use of psychotropics: amytriptalline? Flexeril?• Use of NSAIDs?• Melatonin?

WHAT TO THE AUTHORS THINK?

• “Disappointing” results

• High quality positive trials have not been replicated

• Some moderate evidence exists, but not a lot. • Oral psychotropics give a mixed picture, as do NSAIDs. No evidence for Tylenol.

• Oral medications are used in clinics every day, however there are no high quality studies to ensure more good than harm is being done for patients with neck pain.

• NSAIDs, muscle relaxants and TCAs have good data for beneficial use for LBP, but have not

been studied for neck pain. Yet there is no research that indicates different spinal areas respond similarly to treatments.

• No high quality, replicated trials, this limits ability to meta analyze results and calculate NNT

• Need studies that compare drugs and injections to PT and manual therapy, and whether synergistic effects occur.

QUESTIONS?