David C Randolph MD, PhD, MPHOccupational Medicine/Epidemiology5724 Signal HillMilford, Ohio 45150DOCOCCMED@AOL.COMSeptember 24 2015Beau Rivage, Biloxi MS

EFFECTIVE PAIN MANAGEMENT: A BETTER WAY

Evidence Based Medicine (EBM): Use of scientifically sound evidence to direct medical interventions.

“SYNDROMES”, OBJECTIVE/SUBJECTIVE: Humpty Dumpty Opioids/Opiates: Pharmaceuticals derived from morphine Adjuvants: Medications provided to improve opiate effect, address other

symptoms (i.e. muscle relaxers, antidepressants, anxiolytics, neuroleptics) Chronic benign pain: Pain not due to cancer lasting over 90 days (more on this

later) Drug combinations and drug-drug interaction potential

(mild/moderate/major) Chicken soup

TERM DEFINITIONS

Joe gets hurt Urgent care/ER/Family Doc/Occ health clinic Xrays, MRI, CT PT/Chiro MEDS (NSAIDs, hydrocodone, Oxycodone, muscle relaxers, anti

depressants, Ambien, Xanax, etc.) NO IMPROVEMENT/symptoms worse INJECT, INJECT, INJECT, then inject. Repeat/Increase dose Surgical referral

STANDARD PRACTICES:

“These patients are in pain and I must treat their pain” MR. Smith has an inflamed whozawhatzit and I must inject Mr. Smith has X syndrome. We don’t know what causes it and cannot

prove it, but I know its’ there BECAUSE……. If I don’t inject he will get progressive worse, and I know this

BECAUSE…… Medical science has advanced significantly in pain management and I

can cure him…..

STANDARD RESPONSE TO QUESTIONING COMMENTS:

Disability (The simple act of removing someone from work raises mortality rate 46%)

High costs Poor outcomes Death ….not considered an acceptable outcome……

OUTCOMES

Everything we as physicians do should be safe. How do we know…? Everything we as physicians do should be effective. How do we

know…? (RTW in a BWC scenario is a legitimate outcome) Have narcotics and multiple drugs really helped? Do we know what we are treating? What has happened with the use of narcotics over the past 20 years? What alternatives do we have?

MEDICINE IS SUPPOSED TO HELP….

“Opiate patients are sicker” “Everybody dies” “There aren’t a lot of deaths” “They died because of their injury” Really?.......

DEATH IS NOT CONSIDERED A GOOD OUTCOME

Painkiller Overdoses

National Vital Statistics System, 1999- 2008; Automation of Reports and Consolidated Orders System (ARCOS) of the Drug Enforcement Administration (DEA), 1999-2010; Treatment Episode Data Set, 1999-2009 – [http://www.cdc.gov/vitalsigns/painkilleroverdoses]

1999-2010

Drug Overdose Death Rates by State

[http://www.cdc.gov/vitalsigns/painkilleroverdoses/]

Per 100,000 people (2008)

Reported Deaths from Prescription Opioid Overdose

[www.dshs.state.tx.us/WorkArea/linkit.aspx?LinkIdentifier=id]

1999-2008 By Age

Total Daily Dose Predicts Risk

Arch Intern Med. 2011;171(7):686-691

Dose – Response Relationship

Lumbar fusion study (Spine, Jan. 2011, Nguyen, et. al). Ohio BWC. Studied objective outcomes of lumbar fusions for disc degeneration and/or herniation.

Average age at time of injury 39. Found very poor RTW compared to comparison population associated with daily morphine dose

Current study (in preparation). Ohio BWC (2000-2011) 780,000 claims. Death rates compared among those taking ONLY NSAIDs to those taking short/long acting opiates with Muscle relaxers/antidepressants and those taking SLO+ ASH. Deaths increased 73% SLO+MR/AD, 322% SLO+ASH. Average age at time of entry 40, age of death 50.

Injury of record Strain/sprain. Excluded serious events/co morbidities

What does the literature show?

Daily Morphine Equivalents as Predictor of RTW status

13

Other Factors From Our Research Average age of injured worker at date of injury =

40 years Average age at first opiate prescription = 42 years Average age at time of death = 50 years Average number of meds prescribed = 3 Maximum number of medications prescribed = 20 It appears the medication combinations are

harmful and associated with increase risks of death

WHY ARE WE DOING THIS????????

Recall, pain is purely subjective. There is no lab test to prove or disprove pain. No way to measure except by asking. When dealing with addictive meds, the answer may be deceptive. I am NOT saying pain does not exist……

Measure with “Pain scales”, questionnaires……invalid as self reported If a history, exam and appropriate evaluative studies do not provide answer,

Medically unexplained symptoms are present. MUS will explain failure to improve over time. Alternative explanations include psychiatric conditions and addiction Subjective complaints should be evaluated before piling on more drugs Beesdo,J Soc Psych 2010

MEDICALLY UNEXPLAINED SYMPTOMS

SOOO……WHAT ARE WE REALLY TREATING???

Polypharmacy A term directed at describing multiple

medications used simultaneously. The need for same may or may not be justified. The duration of medication use must

continuously be evaluated. As we age, health issues occur which may

require medications to treat Gout Diabetes Hypertension Lipids Heart disease

Polypharmacy All medications and drugs (prescribed or

otherwise) have an effect, but when prescribed together, the effect can be changed Diminished Magnified Altered (based on a toxic combination).

Any ingested substance can interact with the body, and/or any other substance ingested, inhaled or applied.

These responses between medications are termed drug-drug interactions (DDI).

Polypharmacy and Cellular Function All cells have a perfectly balanced fluid which

bathes, feeds, and supports all functions. It is chicken soup for the cell and is perfect in

every way. Any material ingested into our bodies goes into

the chicken soup. If it is beneficial, the cell thrives. If not, the cell has two options - get rid of the

harmful agent(s), or die. Programmed cell death is called apoptosis.

Extra “Ingredients” Can Ruin the Soup!

A Side Effect of Drug-Drug Interaction (DDI)

If one cell dies, the body survives. If the entire organ system is poisoned by a toxin - or a combination of

toxic drugs - the body may die. Common health problems are addressed by various prescribed drugs,

sometimes in combination (e.g., a cough and sore throat gets a Z-Pak and codeinated cough syrup).

Mixing commonly encountered drugs for these common afflictions can impact the delicate balance in the cytosolic soup.

Potentially Fatal Combinations Mixing psychoactive meds like Remeron, Cymbalta, and

Lexapro can lead to an increase in serotonin. This can produce hallucinations, cardiovascular collapse, seizures and death (Serotonin Syndrome).

Azithromycin and Amiodarone or Celexa, Methadone, Norpace (Cardiac instability).

Atenolol (30 major potential DDI) and Verapamil (chest pain, shortness of breath)

Cardizem (66 major potential DDI) and Fentanyl or Tizanidine (dizziness, confusion, respiratory suppression).

Prescription drugs are not alone in DDI. Also see DDI with grapefruit juice, St. John’s Wort, and other over-the-counter preparations.

Polypharmacy “Rationale” “I can’t sleep because of my pain.” “My muscle spasms keep me awake.” “I am depressed/anxious due to my pain.” The response is to provide a prescription for the new

symptoms. Hence, the addition of muscle relaxer, anti-depressant,

anxiolytic, etc. to an already challenged cytosolic soup. There is rarely any attempt to evaluate the additional

complaints. In this population, physical exams are rare, and often boiler

plated. It is not unusual for a Physician’s Assistant or Nurse

Practitioner to be the prescriber (even for Schedule II drugs).

Side Effects Can Become Overwhelming

Mixed medications can lead to respiratory depression, cardiac problems, confusion, somnolence and death .

Cause of death may not always be determined. Published statistics (e.g., CDC) based on REPORTS of drug death. These surface only when autopsy is performed.

Our own research indicated that taking short and long-acting opiates(SLO) together with any combination of muscle relaxers and/or antidepressants increased all cause mortality 73% above those taking only non-steroidal anti-inflammatory drugs (NSAIDs).

SLO opiates with an anxiolytic/sedative/hypnotic increased all cause mortality (ACM) 322% above those taking only NSAIDs.

1) Standardize treatment based on scientifically guidelines(e.g. ESI, fusions, daily narcotic doses,etc)

HISTORY AND PHYSICAL EXAM (SHERLOCK HOLMES) 2) Ongoing evaluation of patients taking opiates (UDT, state monitoring

for abusive behavior, limits of narcotic doses, etc) Utilization review by appropriately trained medical professionals SAFE AND EFFECTIVE

SOLUTIONS

Epidural steroid “series of three” Fusion surgery CRPS Pain level Narcotics and side effects ADDICTION

EXAMPLES OF EVIDENCE

42 yo wm, Date of injury 2002, injured right ankle descending from a ladder. Off work since. Diagnosed with “RSD” or “CRPS I”. Developed DVT with PE, vague GI complaints, BS elevation 200, “adrenal insufficiency, sleep apnea, hypogonadism, decreased testosterone, HTN, symptoms “spread” to all 4 extremities. He has lost all his teeth. He uses a motorized WC and crutches.

Treatment involved multiple injections including sympathetic blocks, facet blocks, ESI, RFA all without benefit despite multiple repeats. Attempts at SCS unsuccessful.

Meds include over 700 MED with Exalgos, actiq suckers (1600mcg 6x/day), clonidine, 3 different testosterone preparations, multiple anti depressants including atypical antipsychotics

CASE FOR CONSIDERATION

Review of polypharmacy include 12 major (potentially lethal) DDI Despite all interventions, he reports increasing symptoms During course of exam lasting over 2 hours, he used 2 Actiq suckers SSDI granted in 2003 Extensive lab/procedural requests were discussed. He discussed these

with his attorney and refused. He continues to see his POR, travelling 2 hours for office visits and refills monthly.

Diagnostic possibilities include RA, Lupus, Buergers dis, addiction, somatoform disorder, anxiety, depressive disorder

CRPS I ?????

Sprained ankle and CRPS I ?????

No pathologic explanation No confirmatory lab studies No “true positives” No scientific explanation No attempt at a differential diagnosis Medicine by Hubris Safety/health risks due to failure to diagnose, Treatment clearly unsafe and ineffective.

CRPS I is a “Default condition” ONLY!!!

NOT CRPS !!!...no evidence of a differential diagnosis anywhere. Painful extremities with evidence of vascular compromise and dysautonomia

(Subject for another discussion) Autoimmune condition heads the list Evidence of addiction/substance use disorder Urgent need to detox and discontinue harmful drug combinations Early demise of patient is predictable. Rules of the system provide very few

options, but enforced continuation of harmful medications and combinations is lunacy.

INSANITY IS DEFINED AS REPEATING THE SAME ACTION AND EXPECTING A DIFFERENT RESULT.

WHAT IS THE DIAGNOSIS/PROGNOSIS?

As clinicians and clinical researchers, we have grave concerns regarding the article discussion of incidence, pathophysiology, diagnosis and treatment of CRPS.

Our concerns include a clinical diagnosis of CRPS reported with “sensitivity of 0.99 and specificity of 0.68”. The original study

“Validation of propose diagnostic criteria (the “Budapest criteria”) for Complex Regional Pain Syndrome” published in 2010 includes 113 CRPS Type I and 47 non-CRPS neuropathic pain patients. It appears that CRPS Type I patients are analyzed with the small proportion of CRPS Type II (13%) patients. This is inaccurate as CRPS Type I and CRPS Type II patients are different clinically.1

There is no gold standard test to confirm the true positive patient with CRPS. Therefore, it is not possible to calculate sensitivity.

Additionally, no raw data was provided to reproduce the reported sensitivity and specificity. The analysis assumed 70% and 50% CRPS prevalence. The assumption for this high prevalence of CRPS to calculate positive and negative predictive value is not supported.2, 3

Differential diagnoses and testing are not discussed even when diagnostic criteria are “based solely on clinical signs and

symptoms…objective tests are not needed for diagnosis and is directly related to the lack of definitive pathophysiological mechanisms”. The differential diagnosis for painful limb or painful peripheral neuropathy is lengthy and should be addressed. Since CRPS is a diagnosis of exclusion, a differential diagnostic process would seem mandated. The absence of such a discussion raises concerns regarding validity of a diagnostic conclusion, especially given the common nature of those conditions which should be considered.

Reply to BMJ- 08/25/15

Treatments are being promulgated even when there is “little support from high quality RCTs for many of the most common treatment approaches to CRPS”. Multidisciplinary care has no randomized controlled trials. Sympathetic ganglion blockade has been shown to be “ineffective”. Most importantly, most of these studies did not explain how the diagnosis of CRPS was established.

Various interventions including opioids, antidepressants, anti-convulsants, sympathetic blocks “have no supporting

evidence” secondary to lack of RCTs or negative trials. The current recommendations state treatment of “CRPS must be guided by the collective experience of other clinicians”. The author correctly stated “it should be emphasized that clinical acceptance as part of the standard care does not necessarily imply efficacy”.

In summary, physicians are treating patients with a diagnosis which cannot be confirmed, incidence is estimated,

pathophysiology is speculative, treatments are ineffective, experimental, lack supporting evidence for efficacy, absence of sufficient high quality evidence, and at best has “some evidence for efficacy”.

Painful peripheral neuropathy with dysautonomia is pathophysiologically explainable, is scientifically based, and responds to

appropriate intervention once the diagnosis is objectively established. “No human investigation can claim to be scientific if it does not pass the test of mathematical proof”. Leonardo da Vinci

Reply to BMJ- 08/25/15

Differential Diagnosis of the Painful Limb or Painful Peripheral Neuropathy: Commonly Encountered Diagnoses

Congenital Causes

Hereditary sensory/autonomic neuropathies

Fabry’s disease Amyloidosis Porphyria

Toxic causes

Heavy Metals (lead, arsenic, thallium, mercury)

Organic Solvents (glue) Nitrous oxide Organophosphate insecticides Ciguatera toxicity Chronic alcoholism

Pharmacologic

Chemotherapeutic agents (e.g. Cisplatin, Vinca alkaloids)

Cardiovascular (Amiodarone, Perhexilene)

Antibiotics (e.g., Isoniazid, Metronidazole, Dapsone)

Phenytoin Etanercept Allopurinol Triazole (fungicides) Chronic steroid use

Trauma

Systemic Conditions Chronic Renal failure Hepatic failure Peripheral vascular disease Raynaud’s disease Vasculitis Connective tissue disorders (Rheumatoid arthritis, Lupus, Sjögren’s syndrome) Cancer (paraneoplastic

syndromes, direct neural tissue metastasis, CNS involvement)

Systemic amyloidosis Sarcoidosis (SFN)

Infectious

Hepatitis B Hepatitis C HIV Epstein - Barr virus Herpes Varicella-Zoster Herpes Simplex Cytomegalovirus Lyme disease Diphtheria Leprosy Borreliosis Syphilis

Endocrine Hypothyroidism Diabetes79, 80 Impaired glucose tolerance Hyperparathyroidism

Inflammatory

Acute inflammatory demyelinating neuropathy (Guillain-Barre syndrome)

Chronic inflammatory demyelinating polyneuropathy

Inflammatory Bowel Disease (Crohn’s Disease, Ulcerative Colitis, Celiac Disease)

Nutritional/Metabolic Disorders

Vitamin B1, B6, B12 Vitamin D (chronic pain

syndromes) Vitamin E Trace Mineral Deficiency

(Copper, Zinc, Selenium) Hyperlipidemia79,80

Other

Small Fiber Neuropathy (SFN) 79, 80 Secondary localized spasm Thrombosis Entrapment neuropathy Cellulitis

THERE IS NO SCIENCE BEHIND CONTINUED USE OF THE DRUGS FOR THE LIFE OF THE CLAIMANT, UNLESS THE GOAL IS TO SHORTEN THAT LIFE.

MEDICAL REVIEW OF THESE CLAIMS AND THE ASSOCIATED POLYPHARMCY SHOULD BE MANDATED BEFORE FINALIZATION

THIS REVIEW SHOULD BE PERFORMED BY A MEDICALLY TRAINED PHYSICIAN WITH BACKROUND IN PHARMACOLOGY/PHARMACOEPIDEMIOLOGY TO AVOID FAULTY OR FLAWED CONCLUSIONS.

APPLICATION TO EXISTING SETTLEMENT POLICIES

Answers maybe…….

Questions???