hiv pain management: considerations, ideas & suggestions barry eliot cole, md, mpa executive...

HIV Pain Management: Considerations, Ideas & Suggestions

Barry Eliot Cole, MD, MPAExecutive Director, American Society of Pain Educators

Where We Are in 2005

HIV/AIDS pandemic has not ended

In US approx. 1 million are HIV-infected1 in 3 HIV-infected are unaware of diagnosis

Major AIDS era stages: pre- & post-HAART

People being treated for HIV are now healthier, living otherwise normal lives

Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

HIV and Pain OverlapNeuromuscular complications are commonMost common pain problems areMusculoskeletalDistal symmetrical polyneuropathy (DIS)Abdominal painHeadacheOther neurological problemsConsequences of opportunistic infections

Glare PA. Pain in patients with HIV infection: issues for the new millennium. European J Pain 2001; 5 (Suppl A):43-48.

In the Pre-HAART Era

Short life expectancy, so model used was that of cancer patients

Reliance upon the 3-4 step WHO ladder

Expectation for lots of complicationsGlare PA. Pain in patients with HIV infection: issues for the new

millennium. European J Pain 2001; 5 (Suppl A):43-48.

Why Mirror Cancer Pain Therapy?

Was reasonable when large segments of AIDS patients were debilitated and considered to be terminal

Patients surveyed as late as 1998 continued to list pain as being associated with worse perceived health and perceived quality of life

Lorenz KA et al, Ann Intern Med 2001; 134: 854.

Post-HAART

Longer life with more “chronicity”Multiple pains occurNegative impact on QOLMore psychosocial issuesUse of polypharmacy commonUse of “pyramid plus ribbon”

Less efficacy of treatments than cancerGlare PA. Pain in patients with HIV infection: issues for the new

millennium. European J Pain 2001; 5 (Suppl A):43-48.

What About Demanding, Complex Pain Patients?

Drug seekers (addicts and diverters)

Those with special needsMinoritiesSubstance abusersMultiple treatment failures

Personality disordersEntitlement issues

At Risk Groups for Having Poorly Managed Pain

At Risk Groups for Having Poorly Managed Pain

Children

Elderly people

Minorities and people of color

Substance users/abusers

Women

HIV(+)

Pain in the Elderly . . .

Daily pain is prevalent among nursing home residents and is often untreated, particularly among older and minority patients.

Bernabei R, et al. JAMA 1998; 279:1877-82

. . . Pain in Elderly4,003 of 13,625 (38%) patients in 1492 LTCFs

experienced daily pain due to Ca

16% received NSAID or APAP

32% received combo (CIII)

26% received morphine (strong opioid)

26% received nothing at all

Older patients (>85) and minority races were less likely to receive analgesics

Bernabei R, et al. JAMA 1998; 279:1877-82

Underestimation of PainProviders’ concern about dependence.

Underutilization of analgesics occurs; especially for opioids

Important to differentiate between pain from HIV infection or its complications and pain from therapy; other pain syndromes occur as well

Breitbart W et al. Pain 1996; 65: 239.

Larue F, Fontaine A & Colleau S. BMJ 1997; 314: 23.

Pain Prevalence in HIVEstimates of pain prevalence in HIV-infected individuals ranges from 30 to 90%Prevalence of pain increases as disease

progresses30% of ambulatory HIV-infected patients in early stages of HIV disease experience clinically significant pain56% have had episodic painful syndromes of

less clear clinical significanceBreitbart W, Passik SD & Rosenfeld BD (1999). Cancer, mind & spirit.

Bonica’s Textbook of Pain, 4th Ed., 1065-1112.

All Classes of Medications Are Underutilized in AIDS Pain

< 8% of ambulatory AIDS patients reporting pain in the severe range received a strong opioid 18% were prescribed nothing whatsoever 40% were prescribed a non-opioid analgesic 22% were prescribed a weak opioid analgesic

Only 15% received adequate therapy Utilizing the Pain Management Index (PMI) Under medication occurs in only 40% of cancer patients

Adjuvant analgesics were also underutilized < 10% of AIDS patients reporting pain received adjuvants even

though 40% had neuropathic painBreitbart W, Passik SD & Rosenfeld BD (1999). Cancer, mind & spirit.

Bonica’s Textbook of Pain, 4th Ed., 1065-1112.

Headaches

Common complaint from seroconversion to advanced HIV diseaseCauses vary widely

Evaluation may require imaging study & lumbar puncture; plus good PEWith CD4 > 200 little need for CT unless focal

neurological signs, altered MSE or Sz

Must evaluate all “worst headaches of life”Gifford AL & Hecht FM. Headache 2001; 41: 441.Graham CB et al. Am J Neuroradiol 2000; 21: 451.

Chronic Headaches

Common with HIVDue to benign, non-infectious cause when early in HIV infection, before onset of significant immunocompromise

Masci JR (2001). Outpatient Management of HIV Infections, 3rd Ed., CRC Press, Boca Raton, 118.

Causes are muscle tension, vascular, depression, chronic sinusitis, antiretroviral agents (zidovidine) and chronic opioids


Meningitis

Most common cause of AIDS-related meningitis is Cryptococcus neoformans Most infections occur when CD4 < 200 Meningismus may be absent while headache &

fever are commonOther causes of HIV-related meningitis include Strepococcus pneumoniae, Haemophilis influenzae, Neisseria meningitidis, Listeria monocytogenes; HSV/VZV infection; tuberculosis; lymphoma


Brain Lesions

Headaches with focal neurological abnormalities or seizures; think SOL Most common: toxoplasmosisLess common: primary lymphoma, tuberculoma

Many other organisms may cause abscesses of brain with HIV

Other Headache CausesSinusitis is more common in HIV-infected than those without HIV Bacterial, viral and fungal causes

Syphilitic meningitis may occur at any stage of infection with syphilisJC virus infection causes PML After LP there may be post-dural puncture headaches from dural leaks


Oropharyngeal Pain

Candida infections

Gingivitis and periodontitis

Oral ulcers

Neoplasms

Esophageal conditionsPolicar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A

Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

Chest Pain

Fairly common in HIV infectionIf pleuritic consider bacterial pneumoniaThink Tb if patient exposed to Tb

Spontaneous pneumothorax associated with Pneumocystitis carinii (PCP)HAART is associated with insulin resistance & abnormal lipid metabolismCoronary artery disease may occur


Back Pain

Most common painful condition reportedSinger EJ et al. Pain 1993; 54: 15.

Caused by same musculoskeletal conditions as uninfected people

IVDA may have osteomyelitis of spine with or without epidural abscess

May be due to nephrolithiasis due to indinavir

Policar, M & Arumugam, V (in press). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton.

Abdominal Pain

Many etiologies involved, so workup can be challenging and cause “unexplained” potentiallyCD4 > 200 are unlikely to have opportunistic causes, but with CD4 < 100 disseminated Myocobacterium avium complex (MAC) must be considered; Cytomegalovirus (CMV) infection of the GI tract occurs when CD4 <50

Policar, M & Arumugam, V (in press). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton.

With HAART incidence of opportunistic infections is decreasing (69 to 13% between 1995 and 1998)

Monkemuller KE et al. Am J Gasteroenterol 2000; 95: 457.

Pre-HAART Nonsurgical Causes of Abd Pain

CMV gastritis/enteritis/colitis 20%

Cryptosporidium enteritis 6%

MAC enteritis 9%

Non-Hodgkin’s lymphoma 17%

Pancreatitis 12%

Sclerosing cholangitis 8%

Kaposi’s sarcoma 5%Parente F et al. Scand J Gasterol 1994; 29:511-5.

Causes for Abdominal PainHIV-relatedIatrogenic (medication- or procedure-related)Immune surveillance-related (malignancies)Non-HIV-relatedNonspecific (resolution without specific diagnosis)

Slaven EM et al. Emerg Med Clin North Am 2003; 21: 987.

Non-HIV-RelatedSlaven EM et al. Emerg Med Clin North Am 2003; 21: 987.

Appendicitis

Peptic Ulcer Disease

Diverticulitis

Cholecystitis

Hepatitis

Alcohol-related

Ischemic bowel

Abdominal aortic aneurysm

Immunodeficiency-relatedSlaven EM et al. Emerg Med Clin North Am 2003; 21: 987.

Opportunistic GI infections with MAC, CMV microsporidia

Cholecystitis (CMV)

Abscesses

Sexually transmitted disease-related

Proctitis

Immunosurveillance-relatedSlaven EM et al. Emerg Med Clin North Am 2003; 21: 987.

Lymphomas (GI)

Kaposi’s sarcoma (KS)

Cancer-related obstructions

Other cancers/metastatic disease

Medication-related/iatrogenicSlaven EM et al. Emerg Med Clin North Am 2003; 21: 987.

Perforations secondary to procedures (upper/lower GI tract)

GI upset/reflux/gastritis

Kidney stones (indinavir)

Pancreatitis

Enterocolitis

Most common GI manifestation of HIVMay be acute or chronic, associated with fever and weight lossBacteria, viruses, mycobacteria, parasites and fungi are causesAntimicrobial therapy is indicated; often with antimotility agents for diarrhea


Pancreatitis

35-800 times more likely with HIVHIV meds didanosine, Kaletra and pentamidine; opportunistic infections with CMV, toxoplasmosis, mycobacteria and cryptosporidium; infiltration by lymphoma or KS are causesElimination of offending agent (medication, organism) needed


Appendicitis

Rates of HIV infected similar to non-infectedUsual causes are frequent in HIV, but opportunistic infections may play role AIDS related pathology found in 30% of cases

Whitney TM et al. Am J Surg 1992; 164: 467.

Commonly identified infections associated with appendicitis in HIV are Mycobacterium tuberculosis, MAC and CMV

Slaven EM et al. Emerg Clin North Am 2003; 21: 987.

KS seen in cases of AIDS appendicitisPolicar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A

Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

Cholecystitis

May occur with or without stonesAcalculous twice as common as cholelithiasis

Acalculous associated with infection with Cryptosporidium paarvum, Microsporidium and CMV, plus other pathogens.Antimicrobials are warranted for infection; surgery may be necessary in general


Cholangitis

Usually associated with opportunistic infections, malignancy or immunologic destruction of the biliary epitheliumCryptosporidium and CMV are most common infectionsPresents like cholecystitis with CD4 < 100Stents can relieve obstruction from strictures; sphincterotomy may help treat pain along with celiac plexus neurolysis


Intestinal Perforation

Intestinal perforation in HIV infection is uncommon, but commonly caused by CMV related ulceration

Lymphoma, KS, histoplasmosis, peptic ulcer disease and appendicitis too

Treatment is surgery, with antimicrobials or chemotherapy


Other Abdominal Pain Conditions

Enlarged intra-abdominal lymph nodes MAC, KS or TB

Intestinal obstruction KS or lymphoma

Intussesception Lymphoma, KS or Mycobacterial infection

Toxic megacolonTuberculous peritonitisAbdominal aortic aneurysms


Rheumatologic and Musculoskeletal Pain

Arthritis and arthropathies

Avascular necrosis

Polymyositis (most frequently seen)

Zidovidine myopathyPolicar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management:

A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

Skin

Various skin conditions cause painKSDecubitus ulcersHerpes simplex virus (HSV)


Peripheral Neuropathy

Symptomatic neuropathies occur in 15-50% of patients with HIV; prevalence increases in advanced illness with higher HIV viral load, lower CD4 counts and older age

Martin C et al. Eur J Pain 2003; 7: 23.

Simpson DM et al. AIDS 2002; 16: 407.

Lopez L et al. Eur J Neurol 2004; 11: 97.

Neuropathies Associated with HIV Infection

Distal symmetrical polyneuropathy (DSP)Antiretroviral toxic neuropathies (ATN)Herpes zoster (HZ) and post-herpetic neuralgia (PHN)Mononeuropathy multiplex (MM)Diffuse infiltrative lymphocytosis syndrome (DILS)Lumbrosacral polyradiculopathy (cauda equina syndrome)MononeuropathiesInflammatory demyelinating polyneuropathiesAutonomic neuropathy


Distal Symmetrical Polyneuropathy (DSP)

One of most common HIV neuropathies; presents in middle and late stagesStarts with tingling & numbness in toes, spreads proximally from lower extremitiesPainful dysesthesias or numbness occurDTRs may be decreased or absentMuscle weakness is not prominent


Antiretroviral Toxic Neuropathies (ATN)

Occurs at any stage of HIV infectionIndistinguishable from DSP, except for temporal association with initiation of antiretroviral medicationMore likely than DSP to be painful, have abrupt onset and progress rapidlyNucleoside reverse transcriptase inhibitors (NRTIs) are the class most associated with it “d” drugs: ddl, ddC, d4t Mitochondrial toxicity may be mechanism


Herpes Zoster and PHN

HZ, “shingles” results from VZV reactivationOccurs with age & immunocompromised statusAcute HZ lasts days, healing for weeks; PHN persists > 30 daysPHN pain persists for months to years


Mononeuropathy Multiplex

MM occurs early or late in HIV infectionIn early stages MM is immune mediated; in advanced AIDS can be caused by infection with CMV, Hepatitis B or C, particularly when associated with cryoglobulinemiaPatients present with numbness, tingling, abnormal sensation, burning pain, dysesthesia or paralysis


Diffuse Infiltrative Lymphocytosis SyndromeDILS characterized by persistent peripheral blood polyclonal CD8+ lymphocyte expansionSee lymphocytic infiltration of parotid glands, lungs, lymph nodes, lacrimal glands, kidneys, muscles and nerves Most common is salivary gland enlargement

Peripheral sensory neuropathy with profound muscle weakness is seen


Lumbosacral polyradiculopathy

Usually associated with CMV infection; also seen with HSV infection, tuberculosis, syphilis or cryptococcal infectionRapidly progressing cauda equina syndrome can occur with AIDSPresents with severe back and leg pain associated with LE weaknessNumbness and tingling can begin in feet or saddle region; progression occurs rapidlyResults in flaccid paralysis with incontinence


Mononeuropathies

Cranial neuropathiesMedian at wristUlnar at elbowPeroneal at fibular headPhrenic at diaphragmPresent with decreased sensation, tingling, burning pain, weakness and paralysis; impairment of taste and hyperacusis


Inflammatory Demyelinating Polyradiculoneuropathy

Two major patterns: Acute inflammatory demyelinating polyneuropathy

(AIDP) aka Guillain Barre syndrome (GBS) Occurs at time of seroconversion (CD4 > 500); evolves

rapidly over days to weeks Chronic inflammatory demyelinating

polyneuropathy (CIDP) Occurs in advanced stages of illness; evolves over

weeks

Motor deficit predominates over mild sensory symptoms


Autonomic Neuropathy

Common in HIV infection76-84% having some abnormalitySeverity of autonomic dysfunction

correlates with progression of HIV diseaseCommon symptoms include nausea,

vomiting, orthostatic hypotension, heat intolerance, diarrhea, constipation, urinary incontinence, bladder dysfunction, impotence, anhidrosis or hyperhydrosis


Diagnosing DSP & ATNLabs unrevealing, but must exclude other

causes of this neuropathy so orderB12 and folate levels, TSH, FBS, LFTs, BUN

and Cr, Serum protein electrophoresis, immunoelectrophoresis, RPR or VDRL

CSF is acellular with slightly higher proteinEMG & NVC show axonal sensory-motor

polyneuropathyNerve biopsy shows axonal degeneration

of long axons in distal regions; density of unmyelinated fibers is reduced

Diagnosing HZ & PHN

Distinctive rash

Direct immunofluorescent assay

Viral culturePolicar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical

Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

Diagnosing MM

Screen for other causes: CBC, lyme Ab titre, hepatitis screen, cryoglobulins, ESR

EMG & NCV show asymmetric sensorimotor axonal polyneuropathy

CD4 <200 suggests CMV infectionPolicar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain

Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

Diagnosing DILS

Peripheral CD8 > 1000/microL; CD8 lymphocytes >60% of peripheral lymphocytesANA, anti-Ro and anti-La Abs absentHLA DR5, DR6 or DR7 found in > 50%; DR2 in 36%Nerve biopsy shows focal loss of myelin fiber

Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542

Diagnosing Lumbosacral Polyradiculopathy

LP with largely PML, elevated protein, glucose normal or reduced

CMV can be cultured in 50%, but us CMV DNA PCR for rapid diagnosis

EMG and NVCs show primary axonal loss in lumbosacral roots with later denervation potentials in leg muscles


Inflammatory Demyelinating Polyradiculopathy

LP done for GBS or CIDPCSP shows elevated protein, lymphocytic pleocytosis of 10-50 cells/mm3, normal glucoseEMG may be helpful for diagnosis of GBS & CIDP; NCV shows slow conduction, delayed latencies & conduction blocks, reduced sensory & motor amplitudes


Diagnosing Autonomic Neuropathy

Dysautonomia assessed by measuringPulse rate variability on standing, rest, deep

breathing, valsalva maneuver, isometric exercise, cold face test and mental stress

Blood pressure is measured during standing, supine, resting and on valsalva


JCAHO Concerns & New Standards Effective 1/1/01Pain in USA is under treatedPain is manageable & must be treatedPatients have right to Pain assessment Adequate amounts of medication Information to make informed choices

Facilities have responsibility to provide information, education, & care continuity

Adverse Physiology of PainIncreased heart rate and blood pressure Altered respiratory function (tachypnea, atelectasis, pneumonia)Lowered paO2 and risk of infectionAltered bowel function (ileus)Risk of DVT with PE (pain limits ambulation)Disuse atrophy and bone demineralizationImpaired immune function

Liebeskind JC. Pain 1991;44:3-4 Akca O et al. The Lancet 1999;354:41-42

AHCPR (1992). Acute Pain Management Guidelines

Pain Management 101Don’t delay management of pain for investigations or disease treatment

Unmanaged pain permanent nervous system changesAmplify pain (“spinal cord wind up”)

Treat underlying cause if possibleRadiation for a neoplasmSurgery for appendicitisAMA (1999). The Project to Educate Physicians on End-of-life Care

Adverse Psychological Effects of Untreated Pain

Anxiety

Frustration

Depression

Desperation

Sleep deprivation

Suicidal ideation

Suffering

Measuring Desire for Death Among Patients with HIV/AIDS

Schedule of Attitudes Toward Hastened Death demonstrated high reliability (195 patients with HIV/AIDS)

The total score significantly correlated with the clinician rating on Desire for Death Rating Scale ratings of depression (Beck Depression Inventory) and

psychological distress (Brief Symptom Inventory)

Schedule of Attitudes Toward Hastened Death significantly correlated with pain intensity physical symptom distress

Rosenfeld B et al. Am J Psychiatry 1999; 156(1): 94-100

JCAHO On Assessment

Pain is a “fifth vital sign”

Pain will be routinely measured

Policies will define points of time when pain assessments are performed

Policies will define actions to be taken if pain intensities reach specified levels

Progress notes must reflect action taken

Measuring Pain

Pain is entirely subjectiveHave to believe what is reportedUse many scales to “measure” painDescriptive analog scaleNumeric analog scaleVisual analog scaleWong-Baker Faces scale

Everyone has to use same scale

Pain Assessment Tools0-10 Numeric Pain Intensity

Scale

0-10 Numeric Pain Intensity Scale

None Moderate Worst Possible

Visual Analog Scale (VAS)

None Pain as bad as itcould possibly be

Simple Descriptive Pain Intensity Scale

None Moderate Very Severe

SevereMild Worst Possible

Faces scale reprinted with permission from Patt RB. Cancer Pain. Philadelphia: JB Lippincott Co.; 1993.Jacox A, et al. Management of Cancer Pain: Clinical Guideline No. 9. March 1994. AHCPR Publication No. 94-0592.

0 2 3 4 5 6 7 8 9 101

Changing Philosophy About Pain ManagementPatient actually may know what helps

Locus of control given to patient may provide best level of pain management

Patient can best determine end points

Patient is made part of the team

Opioids play an increasingly important role in long term pain management

Pain Types Responding to Opioid Analgesics

Acute & chronic painCancer & non-cancer painSomatic, visceral and neuropathic pain Doses for neuropathic pain may need to be

greater than those for nociceptive pain

Fibromyalgia? Opioids are the treatment for chronic pain

Bennett, RM. Mayo Clinic Proc 1999; 74:385-398 Bruera E et al. 1999. Opioids in Cancer Pain in Stein, C. (Ed.) Opioids in Pain Control, 309-324.Watson CPN, Babul N. Neurology 1998;50:1837-1841.

We Went to School & Never Learned Opioids!

Most healthcare providers have little real understanding about opioid pharmacology They know doses, names, & structural formulae, Sphincter of Oddi spasm is right answer for exams

What little they know is “folklore” in nature (medicine by mantra or by memorization) Darvocet N100, 1-2 q 4-6 h prn mild-mod pain Demerol 50-75 mg, IM q 4 h prn mod-severe pain

Clinical Concerns Regarding Use of Opioids for Chronic Pain

Cognitive and psychomotor effects

Physical dependency & episodic withdrawal

Tolerance to analgesic effects

Potential changes in pain modulation

Pain reinforcement

Risk of addiction

Use by patients for nonpain purposesSavage SR. Med Clinics of North America 1999;83 (3), 761-786.

Patient Concerns About Taking Opioids

Always lead to addiction

Can’t tolerate the side effects

Once started cannot be stopped

Can’t be treated for pain and the underlying process at the same time

If started too soon won’t work when pain is very bad (no ability to titrate dose)

Questions About Opioids for Long Term Pain Management

If opioids effectively relieve an individual’s chronic pain, what other therapies should be tried before introducing opioids?What level or intensity of chronic pain merits treatment with opioids?Are there specific patients or contexts in which opioids should not be used because of unacceptable risks, despite their ability to relieve pain effectively?How is effectiveness of opioid therapy of pain in individual patients measured?

Savage SR. Med Clinics of North America 1999;83 (3), 761-786.

Opioids and ImmunityBefore HIV/AIDS evidence suggested association of increased pathogenic susceptibility & opioid useFound in epidemiologic and case studies of

heroin addicts with IV drug useConsidered inherent to their lifestyle Infections thought to be due to contaminated

material, metastatic sepsis, or by pathogens transmitted from person to person (sharing)

Alonzo NC & Bayer BB. Infect Disease of North Am 2002; 16(3)

Opioids & Immunity-2

Studies undertaken after recognition of AIDS had new perspective to elucidate effect of opioid use on immune systemBeginning in 1998, incidence of wound

botulism in CA rose nearly 20-fold from historic level (0.5 cases per year between 1951-1997)

Seen in addicts injecting black tar heroinAlonzo NC & Bayer BB. Infect Disease of North Am 2002; 16(3)


Increased prevalence of bacterial, viral and parasitic infections in heroin users suggested immunological impairment Especially cell-mediated immunity

Heroin users have higher rates of lymphadenopathy with extraordinary follicular hyperplasia, leukopenia, lymphocytopenia, drastic increase in CD8+ cells, decrease in CD4+ cells, & suppressed absolute T-lymphocyte counts



Heroin use associated with depressed monocyte adherence and chemotaxis, abnormal lymph node and thymus pathology; elevated serum polyclonal immunoglobulin (primarily IgM & IgG), false positive test for syphilis

Suggest being immunocompromisedAlonzo NC & Bayer BB. Infect Disease of North Am 2002; 16(3)


Opioid immunomodulation (morphine) 90-150 mg oral morphine causes significant

decrease in antibody-dependent cell cytotoxicity and NK-cell cytotoxicity, but no alteration of expression of Fc receptors on effector cells

Yeager MP et al. Clin Immunol Immunopathol 1992;62(3):336-43

Morphine causes prolonged suppression of NK-cell cytotoxicity after 10 mg IM morphine, but not after 100 mg IM tramadol

Sacerdote P et al. Anesth Analg 2000;90:1411-4.


Methadone depresses T-cell function as measured by formation of T-rosettes in response to sheep erythrocytes, decreases granulocyte chemotaxis to fMLP, casein and activated plasmaMethadone-maintained patients have lower CD4 cell % and CD4/CD8 cell ratio & higher CD8 absolute cell count and % of lymphocytes

Carballo-Dieguez A, Sahs J & Goetz R. Am J Drug Alcohol Abuse 1994;20(3):317-29.

Prolonged methadone use reverses heroin use-induced immunosuppressionNovick DM et al. J Pharmacol Exp Ther 1989;250:606-10.

Opioids & Immunity-7Human studies confounded by life style, stress, small numbersAnimal studies suggest opioid induced changes in hypothalamic-pituitary-adrenal (HPA) axis and activation of lymphoid organs innervated by sympathetic nervous system Extensive morphine treatment of mice suppressed

immune parameters by activation of the HPA axis Morphine suppression of T-lymphocyte proliferation not

attenuated by adrenalectomy or RU486 pretreatmentBryant HU, Bernton EW & Holaday JW. J Pharmacol Exp Ther 1988; 245:913-20.Bryant HU et al. Endocrinology 1991;128:3253-8.Flores LR, Hernandez MC & Bayer BM. J Pharmacol Exp Ther 1994;268:1129-34.


Brain and immune system communicate Central application of morphine suppresses immune

cell activities Animals treated with opioids exhibit altered immune

function

Humans exposed to opioids for pain management or maintained on methadone for drug addiction show either no effect or a suppressed immune system, depending on dosage, treatment duration


Milligrams Don’t Matter

We must identify specific outcome(s)Activities of daily livingQuality of lifePain intensity

Patients taking “high” medication doses don’t always have loss of controlMilligrams & blood levels not all of story

Some Patients Need Larger Opioid Doses

There are no standard opioid doses

Patients experience their pain uniquely

Dosages not consistent due to individual variations in pain intensity, mechanisms of action, & other factors

Patients need doses that relieve or modify pain experience without toxicity

Is Acetaminophen Poisonous?

Does patient drink alcohol beverages? If so, daily APAP max. tolerance is 2-3 g If not, daily APAP max. tolerance is 4 g

Perhaps APAP is nephrotoxic? 500,000 mg (1000 tabs of Darvocet, Vicodin, etc.) in lifetime

doubles ESRD risk 2,500,000 mg in lifetime triples ESRD risk APAP + NSAIDs worse than APAP alone!Perneger TV, Whelton PK, Klag MJ. NEJM 1994;331(25):1675-1679

Perhaps APAP is not nephrotoxic? Moderate APAP use does not increase risk of renal dysfunction

Rexrode KM et al. JAMA 2001;286:315-321

Non-Steroidal Anti-Inflammatory Meds

Toxicities: GI, renal, hepatic & platelets

GI bleeds annually harm US arthritics 107,000 hospitalized 16,500 dead

Are COX-2 inhibitors less toxic? Not free of renal toxicity, CHF, MI, HTN, CVA risks No 20 year long term studiesSingh G et al. Arch Intern Med 1996;156:1530

Singh G. Am J Med 1998;105(1B):31S-38S

Adjunctive Therapy for Pain Control

Medications that supplement primary analgesics so utilized in pain management may themselves be primary analgesics use at any step of WHO ladder

Rarely discussed in osteoarthritis, common in fibromyalgia and other pain statesCo-analgesics should be utilized in conjunction with NSAIDs (COX-2 NSAIDs)Alter neurotransmitters: DA, NE, 5-HTAlter receptor function: GABA, NMDA

Adjuvant Medications

Anxiolytics (GABA)

Anticonvulsants (GABA, NMDA-receptors, Sodium channels)

Antidepressants (5-HT, NE)

Antipsychotics (DA blocking)

Psychostimulants (DA enhancing)

Let’s Use Psychopharmacology!

We have tried every class availableAntidepressants, anticonvulsants,

antipsychotics, anxiolytics & stimulants

These are potent & potentially toxic agents with increasing age & illnessConfusion, delirium, dry mouth, etc.Cardiovascular effects leading to falls,

fractures, lacerations & subdurals

CYP2D6, Codeine & Codeine-like Opioids

Codeine must be converted to morphine & hydrocodone to hydromorphone for analgesia Without CYP2D6 there is no conversion to morphine and no analgesia Congenitally absent in 7-10% of US whites, 3% blacks

& 1% asians

Many common medications inhibit CYP2D6 Amiodarone, fluoxetine, haloperidol, paroxetine,

propafenone, propoxyphene, qunidine, ritonavir, terbinafine, thioridazine

Supernaw RB. Am J Pain Management 2001;11: 30-31.

Randomized Trial of Amitriptyline and Mexiletine for Painful HIV Neuropathy

Randomized, double-blind, 10-week trial of 145 patients assigned equally to amitriptyline, mexiletine, or placeboPrimary outcome measure was change in pain intensity between baseline and final visitImprovement in amitriptyline group (0.31+/-0.31 units [mean+/-SD]) and mexiletine group (0.23+/-0.41) was not significantly different from placebo (0.20+/-0.30)Neither amitriptyline nor mexiletine provided significant pain relief in patients with HIV-associated painful sensory neuropathy.

Kieburtz K et al. Neurology 1998 Dec; 51(6): 1682-8

Acupuncture & Amitriptyline for HIV-related Peripheral Neuropathy-1

Randomized, placebo-controlled, 10 city trial Each site enrolled patients into 1 option

modified double-blind 2 x 2 factorial design of standardized acupuncture regimen (SAR), amitriptyline, or combination compared with placebo

modified double-blind design of an SAR vs. control points double-blind design of amitriptyline vs. placebo.

250 with HIV-peripheral neuropathy 239 Pts were in the acupuncture comparison

125 in the factorial option 114 in the SAR option vs. control points option

136 patients were in amitriptyline comparison 125 in the factorial option 11 in amitriptyline option vs. placebo option

Shlay JC et al. JAMA 1998 Nov 11; 280(18): 1590-5

Acupuncture & Amitriptyline for HIV-

related Peripheral Neuropathy-2 Treatments given for 14 weeks SAR vs. control points Amitriptyline (75 mg/d) vs. placebo Both therapies

Measured changes in mean pain scores at 6 & 14 weeks using pain scale from no pain to extremely intense(outcome)

Patients in all 4 groups showed reduction in mean pain scores at 6 and 14 weeks compared with baseline values

Neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy


Acupuncture & Amitriptyline for HIV-related Peripheral Neuropathy-3

For both the acupuncture and amitriptyline comparisons, changes in pain score were not significantly different between the groups At 6 weeks, the estimated difference in pain reduction for patients

in the SAR group compared with those in the control points group (a negative value indicates a greater reduction for the "active" treatment) was 0.01 (95% confidence interval [CI], -0.11 to 0.12; P=.88) and for patients in the amitriptyline group vs. those in the placebo group was -0.07 (95% CI, -0.22 to 0.08; P=.38)

At 14 weeks, the difference for those in the SAR group compared with those in the control points group was -0.08 (95% CI, -0.21 to 0.06; P=.26) and for amitriptyline compared with placebo was 0.00 (95% CI, -0.18 to 0.19; P=.99)


LamotrigineRDBPCT of patients with HIV-associated DSP received lamotrigine or placebo during a 7-week dose escalation phase followed by a 4-week maintenance phase92 were randomized in stratum receiving neurotoxic ART and 135 in stratum not receiving neurotoxic ARTMean change from baseline in Gracely Pain Scale for average pain was different between groups at end of maintenance phase in either stratum, but slope of change in score for average pain reflected greater improvement with lamotrigine than with placebo in stratum receiving neurotoxic ART (p = 0.004); as did mean change from baseline scores on VAS and McGill Pain Assessment Scale

Simpson DM et al. Neurology 2003;60(9)

Intrathecal Ziconotide

Ziconotide is a selective N-type calcium channel blocker inhibiting neurotransmitter release108 patients with refractory pain despite use of systemic or intrathecal opioids in the titration phase, mean VAS scores improved more in ziconotide group (51%) than placebo group (18%); serious adverse effects were more common in ziconotide group (31%) than placebo group (10%)48 patients receiving ziconotide proceeding to maintenance phase had benefit of ziconotide continued

Doggrell AS. Expert Opin Investing Drugs 2004;13(7):875-7

Intrathecal Ziconotide-2DBPCRT with 32 sites and 111 patients; ziconotide was titrated over 5-6 days, followed by 5-day maintenance phase for responders and crossover of nonresponders to opposite treatment group67 of 68 patients receiving ziconotide & 38 of 40 patients receiving placebo were taking opioids at baseline 36 had used intrathecal morphine

VASPI scores were 73.6 mm in ziconotide group and 77.9 mm in placebo groupMean VASPI scores improved 53.1% in ziconotide group and 18.1% in placebo group (P<.001)Pain relief was moderate to complete in 52.9% on ziconotide, 17.5% in placebo group (P<.001)5 on ziconotide had complete pain relief, 17.5% on placebo

Staats PS et al. JAMA 2004;29(1):63-70.

Are Opioids Addictive for Everybody?

No! Watch out for cherry syrup addicts!

Opioid addicts should not get opioids without consideration of the facts

“Odds” of non-addict addiction from prescribed medications is 1/800 to <1/10,000

CIIIs not encoded for less problems Result in “conditioning” to use CIIIs “denatured” to limit amount of opioid taken

Do All Opioid Medication Users Get Into Trouble?

Low back pain study for 12 months

Osteoarthritis study for 18 months

Methadone maintenance for a lifetime

Multi-gram doses in hospice patients

EPEC curriculum and end-of-life care

We have no predictive tools yet

Long Term Opioid Administration: Stable Doses & Pain Control, & Reduction

in Side Effects106 patients enrolled (76% = women, 42% > 64 yrs)Baseline median dose = 20 mg/d & baseline median pain intensity = 2 (moderate)Median daily dose increased until week 16, where it stabilized at 40 mg/d No further increases for one year Increases in dose were accompanied by reduction in pain

Median pain intensity fell to stable level within 2 weeks and remained slight to moderate for > 1 yrSide effects lessened between 8th & 40th weeks Especially for “sleepiness” and “sick to stomach”

Roth, S. et al. 1998 APS Poster Board 168.

ATC CR Oxycodone for Osteoarthritis Pain

133 pts were randomized to placebo, 10 mg or 20 mg q 12 h for 14 days

106 pts enrolled in open-label study for 6 months; then Tx for optional 12 months

During long-term Tx mean dose remained stable at 40m mg/d

58 pts completed 6 mos, 41 completed 12 mos, 15 completed 18 mos

Roth SH et al. Arch Internal Med 2000;160:853-860.

US Trends in Medical Use & Abuse of Opioids (1990-96)

Joranson DE et al. JAMA 2000;283(13):1710-1714

Increased use Hydromorph = 19% Fentanyl = 1168% Morphine = 59% Oxycodone = 23%

Decreased use Meperidine = 35%

Changes in abuse Down 15% Down 59% Up 3% Down 29%

Down 39%

Estimated # of Opioid ED Drug EpisodesYear-End 2002 ED DAWN Data, SAMHSA

Drug 1994 1995 1996 1997 1998 1999 2000 2001 2002

codeine 9439 8732 7594 7869 6620 4974 5295 3720 4961

fentanyl 28 22 34 203 286 337 576 710 1506

hydrocod 9320 9686 11419 11570 13611 15252 20098 21567 25197

meper 925 1045 876 864 730 882 1085 665 722

methad 3252 4247 4129 3832 4810 5426 7819 10725 11709

morph 1099 1283 864 1300 1955 2217 2483 3402 2775

oxycod 4069 3393 3190 5012 5211 6429 10825 18409 22397

propoxy 6731 6294 5889 6502 5826 5632 5485 5361 4676

What Defines Addicts?

Fusion of anxiety and denial

Constantly anxious about availability of drug & always trying to obtain more of it

No insight into toxicity of drug on their health, life, relationships, etc

No awareness that control has been lost

Intend to quit when a “little bit sicker”

Response Styles Specific to Substance Abuse

Disacknowledgment

Misappraisal

Denial

ExaggerationRogers R, Kelly KS 1997. Denial and misreporting of substance abuse. In R Rogers (Ed.)

Clinical Assessment of Malingering and Deception. New York, NY: Guilford Press.

Suggestive Signs of Addiction during Opioid Therapy of Pain-1

Loss of control Compulsive overuse, unable to take

medications as prescribed Frequently runs out of medication early

despite dose agreement Frequently reports lost or stolen prescriptions Solicits multiple prescribers Uses multiple pharmacies to fill prescriptions

Savage SR. Med Clinics of North America 1999;83(3), 761-786.


Preoccupation with drug use Noncompliant with other treatment

recommendations Misses other appointments, always arrives for opioid

prescriptions Uses street drugs, involved with street culture Preference for short-acting or bolus dose

medications Reports no relief with other medications or

treatments Reports allergies to all other medicationsSavage SR. Med Clinics of North America 1999;83(3), 761-786.


Adverse consequences of opioid useDeclining function despite apparent analgesiaObserved to be frequently intoxicated or highPersistently over sedated

Savage SR. Med Clinics of North America 1999;83(3), 761-786.

Pain & Addiction DifferencesSchnoll SH, Finch J. J Law Med Ethics 1994; 22:252-256

Pain patients:Not out of control with medicationsMeds improve QOLAware of SEsConcerned about medical problemsFollow the Tx planHave meds left over

Addicted patients:Out of control with medicationsMeds decrease QOLUnconcerned by SEsDenial about medical problemWon’t follow Tx planNever have meds left

Opioids Getting Patients Into Trouble . . .

Meperidine (Nor-meperidine)> 400 mg/d causes confusion, delirium,

myoclonus, seizures with renal disease

Mixed agonist-antagonistsDelirium, hallucinations, psychosis with

continued use (8-12 Talwin /d, 1 bottle Stadol nasal spray/d)

. . . Opioids Getting Patients Into Trouble

Propoxyphene (nor-propoxyphene)Confusion, delirium and other bad outcomes

Fentanyl transdermalHeat increases the delivered dose (overdose)Cachexia makes absorption erratic (wt < 110 lbs)

Addicts chew, smoke or shoot the fentanyl

JCAHO & Meperidine

It’s pharmacist’s responsibility to limit access to meperidine in LTC facilities (JCAHO) Use ordering as an “educational opportunity”

Limit duration of use APS: stop meperidine after two consecutive days

Limit overall daily dosage APS limit (1999): 600 mg/d But if pt >60 yrs, try to limit to <400 mg/d

APS (1999). Principles of Analgesic Use in the Treatment of Acute Pain and Chronic Cancer Pain: A Concise Guide to Medical Practice, Fourth Edition.

Morphine May Not Be the “Gold Standard” Any Longer

Consider other “gold standards” we don’t use that much today

Chlorpromazine (Thorazine) for psychosisAmitriptyline (Elavil) for depression

Trend to use semi-synthetic opioidsFentanylOxycodoneHydromorphone

Morphine MetabolitesMorphine MetabolitesMetabolites are eliminated renally

• Unmetabolized morphine: 2-8 %• Glucuronide metabolites: 50-80% (W>M)

Morphine-3-glucuronide Devoid of analgesic activity Antagonist to morphine analgesic activity

peripheral site of antagonism (NMDA-receptors) May induce allodynia and hyperalgesia CNS excitation leads to agitation, confusion, delirium and seizure;

thought to be responsible for myoclonus Morphine-6-glucuronide

Same affinity for mu-1 receptor (analgesic activity) as morphine

• Others metabolites pathways: Demethylation (Normorphine) Conjugation, diglucuronidation, sulfonation

Hydrocodone Combinations

All are CIIIs & immediate release in USA Stable blood levels only with 4-6 hour use

All contain some APAP or NSAID Is hydrocodone really strong enough by itself? Are liver & kidney damage possible with use?

Many states are tracking hydrocodone Most abused drug in NV (42 M doses in 2000)Las Vegas Sun September 9, 2001:E1.

Las Vegas Sun October 7, 2001:E1.

Is Oxycodone Enough?It is a pure opioid agonist Semi-synthetic derivative of morphine

Many assumed that oxycodone was not very strong, because it was “denatured” (APAP) No established ceiling dose for oxycodone Record dose is 9600 mg / day base with 1200 mg

q h for breakthrough pain (ovarian Ca patient)

Metabolites not linked to CNS excitation

Role of HydromorphoneSemi-synthetic derivative of morphineMore potent than morphineLess CNS toxicity than morphine

more than oxycodone & fentanyl

Available as oral & injectable formsOral:

Short-acting: 2 mg, 4 mg, 8 mg Long-acting controlled release approved (Palladone )

Injectable: up to 10 mg/ml (Dilaudid HP) Record dose is 60-600 mg IV/h for pain of pelvic sarcoma…

equivalent to 900-9000 8 mg po tabs/d

Fentanyl

Fentanyl transdermal (Duragesic)peak effect after application 24 hourspatch lasts 48–72 hoursmust ensure adherence to skin, thermal and pain

stability, & patients weigh > 110 lbsAlternative for patients who cannot tolerate oral,

parenteral or rectal routes (very few) or are allergic to other opioids (fentanyl is synthetic)

Oral (Actiq)25-50% bioavailability (25% from buccal absorption,

25% from absorption of fentanyl in swallowed saliva after 1st pass effect)

Short- vs. Long-acting

It does make a difference We have to pharmacologically choose

We want to maintain stable blood levels for most conditions Hypertension Diabetes Infection Seizures Pain

Long-acting OpioidsFentanyl (Duragesic transdermal patches)

Hydromorphone (Palladone)

MorphineMS Contin, Oramorph, Kadian, Avinza

Oxycodone (OxyContin)

Oxymorphone (in development)

Tramadol (in development)

Are Controlled Release Meds Only for Cancer Pain?

No, they are for pain necessitating more than a few doses of medication for relief!

Immediate release medications are best for single dose administration or breakthrough

What medication used for any length of time shouldn’t be given as CR? Insulin = NPH, Lente, etc. Cardiovascular = CR, XL, etc.

Are Controlled Release Meds Only for “Chronic” Pain

No, for painful conditions requiring more than a few doses of medication! When don’t we want pain well controlled?

Why not use CR medications for post-op pain or rehabilitation? When doesn’t the patient want pain relief? Can we shorten the length of rehabilitation?

Why not achieve best pain control with least medication by using CR medications?

Reuben SS et al. Anesthes & Analgesia 1999;88:1286-1291Cheville A et al. J Bone & Joint Surgery 2001;83-A(4):572-576

What Is So Bad About Single Entity Opioid Analgesics?

CIIs are not less addictive that CIII-VsAddiction is a state of mind, not physiology

CIIs require careful record keepingHave to at least write out the prescription

CII prescriptions alone do not trigger more investigations than CIIIs

Are CIIIs Really Easier to Use?

Can be telephoned to the pharmacyDid physician obtain a proper history?Did physician do a good faith examination?Did physician write a progress note for Rx?Did physician arrange for follow-up care?

Don’t have to write out the prescriptionWhy practice with less than all options?

Are “Narcs” After Opioid Prescribers in General?

S. CA: 0.5 of 90 FTEs in the S. CA Bureau of Narcotic Enforcement for prescribing Review rate of triplicate prescriptions

8% since 1940 but only 1.7% recently

NV: prescribe to non-patients (yourself, family

members, lovers), phone in 1200 CIIIs/mo but see no one or advertise RX price to get in trouble AZ & UT examine number of pills/prescription Pills have intrinsic street value Opioid schedule not the issue

What About Opioids for Known Substance Abusers

Opioids for HIV pain control in patients with substance abuse history raises issues How to treat pain in people who have a high tolerance to

narcotic analgesics How to mitigate this population’s drug-seeking and

potentially manipulative behavior How to deal with patients who may offer unreliable

medical histories or who may not comply with treatment recommendations

How to counter the risk of patients spreading HIV while high and disinhibited

Breitbart W, Passik SD & Rosenfeld BD (1999). Cancer, mind & spirit. Textbook of Pain, 4th Ed., 1065-1112.

Approach to Pain Management for Substance Abusers-1

Substance abusers deserve pain control; we have an obligation to treat pain & suffering for all our patientsAccept and respect the report of painBe careful about the label of “substance abuse;” distinguish between tolerance, physical dependence, and addiction (psychological dependence)Not all substance abusers are the same; distinguish between active users, those in methadone maintenance and those in recovery

Breitbart, W (2001). Pain in HIV disease. Bonica’s Management of Pain, 3rd Edition, 739-753.

Approach to Pain Management in Substance Abusers-2

Individualize pain treatment plan of careUse the principles of pain management (APS, 1999)Set clear goals and conditions for opioid therapy; set limits, recognize abuse behavior, make consequences clear; use written contracts; & establish a single practitioner for prescribingUse a multidimensional approach; pharmacologic and nonpharmacologic interventions, attention to psychosocial issues, team approach

Breitbart, W. (2001). Pain in HIV disease. Bonica’s Management of Pain, 3rd Edition, 739-753.APS (1999). Principles of Analgesic Use in the Treatment of Acute Pain and Chronic Cancer

Pain: A Concise Guide to Medical Practice, 4th Edition.

Management of Hospitalized Substance Abusers-1

Patients are admitted early enough to allow for stabilization of drug regimen & avoid withdrawalPatients are admitted to private rooms near the nursing station for monitoringPatients possessions are thoroughly searched; any drugs & alcohol beverages are removedPatients are restricted to their rooms or floors until danger of withdrawal or illicit drug use has been diminishedPatients wear hospital gowns/pajamas

Breitbart, W et al. (1999). Cancer, mind & spirit. Textbook of Pain, 4th Ed., 1065-1112.

Management of Hospitalized Substance Abusers-2

Patients visitors are restricted to family & friends who are known to be drug freePackages brought to hospital are searched for contraband by security service Patients provide daily urine sample for drug testingPatients are assessed several times daily for adequacy of pain relief providedMedications are prescribed to take into account patients pre-existing tolerance (opioid requirements)Medications are given around-the-clock

Breitbart, W et al. (1999). Cancer, mind & spirit. In Textbook of Pain, 4th Ed., 1065-1112.

Ten Tips for Prescribing Opioids

Cole BE. The Pain Practitioner 1998;8(4):4 and 2002;12(3):5-8.

Obtain the Proper Data

Always perform a thorough history and physical exam on pain patientsDo not lump diagnoses together, try to determine what is really wrongScreen all patients for substance abuse and forms of psychological dependencyPathological gamblingSmoking

Chart All of It

Chart what you hear, see, think and feel

Leave nothing for a future reader’s imagination

Make chart entries sufficiently detailed to stand alone if separate from rest of chart

Explain What you are going Alternatives considered How you intend to follow the patient over time

Obtain Informed Consent

Be certain your patient understands what is being proposedBe certain your patient understands the risks and the benefits of opioidsGet patient to agree to use only you for controlled substance prescriptionsDiscourage patients from visiting ER for current pain or “doctor shopping”

Use One Pharmacy

Patient should select one pharmacy to use

Call the pharmacist and explain diagnosis, prognosis, reason for plan to use opioids Ask pharmacist what meds are available Determine concerns the pharmacist may have Ask pharmacist to share concerns with you and to

please keep you informed about any bothersome behaviors in future

Share the Blame

If you are a primary care physician use consultants to back up care plan

Consultants may bePain Management specialistsDisease specialistsOrgan system specialists

Use Long-Acting Medication

Give controlled-release medication When pain is expected to last for an extended

period of time and the patient requires continuous around-the-clock analgesia

Prescribe medications time contingentlyBack up sustained action meds with immediate release medications Break through medications

Address need for larger “base” of controlled-release when PRNs > 3/24 hours

See Patients on Opioids

See patients receiving medication on a regular basisWhen new prescriptions are issued

Always document why there is a need for opioid analgesicsDo not give open ended prescriptions Vicodin, #500, refill x5

Avoid telephone prescribing of any controlled substances

Determine Minimum Dose Required

What is the minimum dose that manages pain, improves function and is toxicity free?

Try to decrease the opioid dose by 25-35 %Over a weekendMonitor “up” time becoming “down” time

Have patient participate in decision for trials and times for the trials to occur

Drug Screens for Everyone

Order tox screens on patientsKnow the limitations of methodologies used

Look for prescribed meds being in the urineBe certain that the screening technique utilized

has the ability to identify the prescribed opioid

Check to see if there are illicit substances

Do urine studies on 2 consecutive visitsNo one expects that!

Quinolones & False-Positive EMIT Opioid Urine ScreeningSeveral quinolones cross-react with opioids: Levofloxacin (Abbott AxSYM, CEDIA, EMIT II) Ofloxacin (Abbott AxSYM, CEDIA, EMIT II) Pefloxacin (CEDIA, EMIT II, Roche OnLine Assay) Enoxacin (CEDIA, EMIT II) Gatifloxacin (EMIT II) Lomefloxacin (Roche OnLine Assay) Moxifloxacin (Roche OnLine Assay) Ciprofloxacin (Roche OnLine Assay) Norfloxacin (Roche OnLine Assay)Baden LR, Horowitz G, Jacoby H, Eliopoulos GM. JAMA 2001;286:3115-3119

Continue to Receive Pain Related Education

Regulations, rules & standards are continuously evolvingNew trends involve legislation, litigation & regulationThere are still controversies about opioidsRegulators have their needs too, don’t just assume they will go awayListen to their issues & get to know them

The World With Lawyers

“Pain management…a new and potentially lucrative area of malpractice law.”Milligan DB, NEJM 1998;339(10):705 & 707

“Be prepared for civil negligence litigation or medical disciplinary action…to promote increased attention by physicians who are providing care to patients in pain.”Tucker KL, NEJM 1998; 339(10):707

New Legal Theory

Failing to treat elderly dying patient with pain is a form of elder abuse not malpracticeBergman v Chin (Alameda County, CA)

Chin owes Bergman’s family $250K (jury awarded $1.5 million)

Rather than prosecute for elder abuse (criminal code) just file civil suitNo tort caps on awards for civil suits!

This is out on appeal now

Where’s The Risk Now?< 5% of disciplinary actions taken for over prescribing by state medical boards in any year directly concern the treatment of pain.

“Compassion in Dying has put medical boards and the public on notice that it was willing to assist chronic pain patients and their families make complaints and/or in filing suits against practitioners who fail to provide adequate pain relief by under prescribing.” Martino A. J Law, Medicine & Ethics 1998;26:332-349

Patients have Rights

Right to necessary information

Right to necessary treatmentsAnalgesiaSedation

Right to be free of burdensome TxRefuse unwanted treatment

Consideration for time limited trials

Practitioners have Rights

Can’t be forced to prescribe medicationWill be scrutinized for “doing nothing”

May refer to colleague if unwilling to treat according to patient demands

Must balance advocacy with changing philosophy about painChanging legal environment

Summary

HIV-related pain has evolved over the past 20 years from disease to treatment-relatedProblems with opioids are not always problems we think (i.e. addiction vs. immune suppression)Molecules don’t just “hook” patientsPatients with psychopathology take drugs to get

high and many got HIV from addictive behaviors

All patients can be helped with their pain

Keep in touch

Barry Eliot Cole, MD, MPA

Executive Director, American Society of Pain Educators

[email protected]

hiv pain management: considerations, ideas & suggestions barry eliot cole, md, mpa executive...

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