Pain Management and Palliative Care in HIVAIDS Patients

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Pain Management and Palliative Care inHIV/AIDS
Patients

• Timothy L. Sternberg, DMD, MD
• Director, Center for Pain Management
• University of Florida/Shands Jacksonville

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Disclosure of Financial Relationships

• This speaker has no significant financial
  relationships with commercial entities to
  disclose.

This slide set has been peer-reviewed to ensure
that there are no conflicts of interest
represented in the presentation.
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Pain Palliative Care in HIV/AIDSObjectives

• 1. Pain incidence and prevalence
• 2. Barriers to effective pain symptom
  management
• 3. Assessing pain in HIV AIDS
• 4. HIV/AIDS specific painful syndromes
• 5. General pain management guidelines
• 6. Specific treatment strategies

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HIV/AIDS Pain Etiologies

• HIV tissue damage
• Opportunistic Infections
• Malignancies
• Side effect of treatment
• Incidental to HIV disease

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Is pain in HIV/AIDS patients common?

• Not a concern to most patients who just want
  their disease cured.
• Only common in terminal AIDS.
• Only common with high viral loads.
• Common in all stages of the disease.
• No Adequately treated with current available
  care.

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Prevalence of Pain in HIV/AIDS

• 28 asymptomatic HIV seropositive men
• 56 AIDS-related complex
• 80 AIDS
• (Singer, 1993)
• 97 terminal
• (Singh 1992)
• 57-61 hospitalized AIDS patients
• 2nd most common admitting problem
• (Lebovits 1989, 1994)

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Prevalence of Pain in HIV/AIDS

• Average 2.5 different pains
• Severity 5.4 (average) 7.4 (worse) / 10 NRS
• Prevalence correlated
• CDC category
• Number of current HIV related symptoms
• Treatment for HIV related infections
• Absence of antiretroviral therapy
• Intensity correlated
• Females
• Non-Caucasions (Breitbart
  1996)

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Prevalence of Pain in HIV/AIDS

• Pre-HAART 56-80
• Prevalence Post-HAART
• Estimate of 30
• (Newshan, Bennett, Holman, 2000)

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Prevalence of Pain in HIV/AIDS

• Prevalence and Intensity associated with
• Greater impairment functional ability
• Physical symptom distress
• Psychological morbidity

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Barriers to Pain Management

• Pain generally under-treated in HIV/AIDS pts
• Particularly patients with IV drug abuse hx
• Only 15 ambulatory AIDS pts received adequate
  analgesia
• Only 6 with severe pain Rxd opioids
• Under-treatment 85 (cancer 42)
• Women minorities more likely under-treated
• (Brietbart 1994)

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Barriers to Pain Management

• Patient related barriers
• Clinician related barriers
• System related barriers
• HIV specific barriers

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What is the most common barrier to adequate pain
management in HIV/AIDS?

• Fear of addiction
• Poor compliance
• Governmental restrictions
• Poor patient assessment
• Inadequate application of knowledge and
  therapeutic modalities currently available

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Barriers to Pain Management

• Patient related barriers
• Fear of addiction
• Misconceptions about tolerance
• Concern about side effects
• Fear of correlation with disease progression
• Poor compliance with antiviral medications

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Barriers to Pain Management

• Clinician related barriers
• Misconceptions of addiction, dependence, and
  tolerance
• Inadequate training
• Inadequate patient assessment
• Poor pharmacologic knowledge
• Inadequate application of knowledge and
  therapeutic modalities currently available

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Barriers to Pain Management

• System related barriers
• Regulatory issues
• Pharmacy restrictions
• Governmental restrictions
• Economic issues

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HIV/AIDS Specific Barriers

• Many African Americans consider Hospice second
  class care
• Unfamiliarity with medical system
• Inner city prevalence of illicit drug use
• Continued illicit drug use
• Poverty
• Poor access to phones, refrigerators, housing
• Poor compliance with antiviral therapy

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Assessing Pain in HIV AIDS

• Pain history
• Intensity
• Location
• Qualities
• Radiation
• Work-up possible etiologies
• Rule out infections and malignancies
• Consider multiple concurrent etiologies
• Thorough HP
• Eval psychological/emotional/social factors

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Characterizing Pain in HIV/AIDS

• Nociceptive
• Somatic
• w, w/o inflammation
• Visceral
• Neuropathic
• Central
• Peripheral
• Sympathetic

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Assessing Pain in HIV AIDSEtiologies

• HIV related
• tissue damage
• infection
• tumors
• HIV treatment
• Medications
• Chemotherapy, radiation
• Unrelated to HIV

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Which locations are relatively unaffected by HIV
related pain?

• Head and face
• Chest
• Abdomen
• Pelvis
• Musculoskeletal system

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Common Painful HIV/AIDS Syndromes

• Headaches 46
• Oral cavity 53
• Throat pain 20
• Chest pain 41
• Abdominal pain 12-26
• Anorectal pain 34
• Peripheral neuropathy 25 (10-50)
• Musculoskeletal system 72
• Herpes zoster/PHN 5
• Social pain
• Psychological pain

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HIV/AIDS Headache Syndromes

• HIV specific
• Aseptic meningitis with acute infection
• CNS lymphoma
• Metastatic Kaposis sarcoma
• Infections HSV, CMV, Toxoplasmosis, TB, Syphilis
• HIV encephalitis
• HIV treatment
• Zidovudine
• Efavirenz
• Emtricitabine
• Stavudine
• Tenofovir
• Concurrent illness
• Tension-type, Migraines
• Sinus infections

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HIV/AIDS Oral-pharyngeal Syndromes

• Candidiasis 28-75
• Necrotizing gingivitis
• HSV, CMV, HIV, EBV ulcers
• Recurrent aphthous ulcers
• Zalcitabine ulcers
• Kaposis sarcoma
• Dental abscesses

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Oral-pharyngeal Candidiasis
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HIV/AIDS Oral-pharyngeal Syndromes

• Interferes with oral hygiene
• More oral pharyngeal pathology
• Interferes with nutritional intake
• Wasting syndrome

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AIDS/HIV Related Oral Pathology
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HIV/AIDS Chest Pain Syndromes

• Incidence 41
• Pneumocystis carinii pneumonia
• Retrosternal, burning
• Esophagitis (/- dysmotility)
• Candidiasis
• HSV, CMV, HIV ulcerations
• GERD
• Herpes Zoster- Post Herpetic Neuralgia

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Herpes Zoster- Post Herpetic Neuralgia
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HIV/AIDS Abdominal Pain Syndromes

• Nausea
• NRTIs zidovudine, didanosine, emtricitabine,
  lamivudine, tenofovir
• Diarrhea
• Infectious
• NRTIs tenofovir, emtricitabine,
• CMV ileitis, colitis
• Visceromegaly (didanosine)
• Pancreatitis (pentamidine, ddI, ddC, )
• Acalculous cholecystitis
• Schlerosing cholangitis (AIDS cholangitis)
• CMV bowel perforation
• Tumor Kaposis, Lymphoma

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HIV/AIDS Anorectal Pain Syndromes

• Affect 34 AIDS/ARC males
• Infections/STDs
• Trauma
• Fistulae/fissures/abscesses
• Rectal cancers
• KS, NHL, SSC

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HIV/AIDS Anorectal Pain Syndromes
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HIV/AIDS Gynecologic Pain Syndromes

• STDs
• Herpes simplex ulceration
• Human papilloma virus
• Cervical cancer
• Pelvic inflammatory disease

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HIV/AIDS Gynecologic Pain Syndromes
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HIV/AIDS Pain SyndromesPeripheral Neuropathies

• Acute inflammatory demyelinating polyneuropathy
• Chronic inflammatory demyelinating polyneuropathy
• Mononeuritis multiplex
• Radiculitis
• VZV Herpes Zoster post-herpetic neuralgia
• CMV
• HIV
• Distal symmetrical peripheral neuropathy
• HIV (AIDS associated distal sensory neuropathy)
• Toxic (Antiretroviral toxic neuropathy)
• Vitamin deficiencies

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Distal Symmetrical Peripheral Neuropathy

• Most common HIV/AIDS neuropathy
• Usually late complication
• Sensory predominantly small fiber
• Pain, paresthesias soles of feet
• Signs large fiber
• Reduced Achilles DTR/vibration sense
• Etiology HIV infection or treatment
• AIDS Associated Distal Sensory Neuropathy
• Antiretroviral toxic neuropathy (NRTIs)
• Risk Factors
• age, high viral load, low CD4 count, cumulative
  NRTI dose

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Common Painful HIV/AIDS Syndromes
Musculoskeletal system

• Arthropathies
• Reactive arthritis
• Reiters syndrome
• Non-specific arthralgias
• Psoriatic arthritis
• HIV arthritis
• Septic arthritis

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Common Painful HIV/AIDS Syndromes
Musculoskeletal system

• Myopathies
• Inflammatory polymyositis
• Subacute proximal weakness and myalgia
• HIV and other virus, infection vs. inflammation
• Zidovudine
• Necrotizing non-inflammatory myopathy
• Zidovudine
• Infectious Myositis
• Toxoplasmosis
• Microsporidiosis mysositis

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HIV/AIDS Social Pain

• Young
• Family estrangement
• Social stigma
• STD's
• Drug use
• HIV
• Homosexual
• Poor coping mechanisms
• Limited support

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Unos Cuantos Piquetitos(A Few More
Sticks)Frida Kahlo
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Pain Palliative Care in HIV/AIDS Management
Options

• Cognitive-behavioral interventions
• Systemic pharmacotherapy
• General pain management medications
• HIV/AIDS specific pain medications
• Interventional techniques
• Surgical techniques
• Physical Modalities
• Electro-stimulation therapy

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General Pain Management Principles

• Thorough assessment
• Somatic nociceptive vs. neuropathic pain
• Intensity, quality, timing
• Exacerbating and relieving factors
• Treatment history
• Pharmacologic history
• Psychosocial modifiers

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Systemic Pharmacotherapy General Management
Principles

• By the patient
• By the syndrome
• By the clock
• By the analgesic ladder
• Consider drug interactions

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General Pharmacotherapeutic Principles WHO
Analgesic Ladder in HIV/AIDS
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Nociceptive Neuropathic Analgesic Ladder
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Optimal Use of AnalgesicsWorld Health
Organization Step Ladder

• Begin with non-opiate, nonsteroidal
  anti-inflammatory agents (NSAIDS)
• Add a weak opiate, such as codeine or
  hydrocodone (with or without an adjuvant)
• Move to a stronger opiate, such as oxycodone,
  morphine (with or without an adjuvant)
• Complementary, non-pharmacologic strategies
• Interventional strategies

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WHO Analgesic Ladder in HIV/AIDS

• Non-opioid analgesic
• Acetaminophen
• Tramadol
• NSAID
• Weak opioids
• Propoxyphene
• Hydrocodone
• Strong opioids
• Oxycodone
• Morphine
• Hydromorphone (Dilaudid)
• Fentanyl (Duragesic)

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Non-Opioid Analgesics
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NSAIDs Side Effects

• Gastric irritation/ulceration
• Prolong bleeding time, esp. ASA
• CNS stimulation
• Hepatic dysfunction
• Renal dysfunction
• Elevated BP
• Edema
• Allergic Rxn's

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Opioid Analgesics
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Opioid Analgesics
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Opioid Side Effects

• Respiratory System
• -depresses ventilation
• GI System
• - N/V
• - Constipation
• Biliary muscle spasm
• GU System
• -urinary retention
• -urinary urgency
• Cutaneous System
• -vasodilation
• -flushing
• -pruritis

CNS -euphoria -dysphoria -confusion -sedation -mi
osis
CV System -Orthostatic hypotension
-Venodilation -Bradycardia
(tachycardia with meperidine)
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Analgesic Ladder for Neuropathic Pain
Opioid analgesic Topical capsaicin,
lidocaine TCA/SRRI, anticonvulsant, topical
agent
Anti-arrhythmic Topical capsaicin,
lidocaine TCA/SRRI, anticonvulsant analgesic
I certainly
Anti-epileptics TCA/SNRI /- analgesic
Tricyclic Antidepressant Serotonin/NE Reuptake
Inhibitor /- analgesic
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Anti-neuropathic Pain MedicationsFirst Line
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Anti-neuropathic Pain MedicationsSecond Line
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Antineuropathic Medications Efficacy

Oral agents TCAs (2.64) opioids (2.67)
gabapentin (4.29) tramadol (4.76) pregabalin
(4.93) Topical agents aspirin/diethyl ether
(1.83) lidocaine patch (2) capsaicin
(3.26) (Numbers needed to treat) e.g., PHN
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Systemic Pharmacotherapy Antiretroviral-Analgesic
Interactions

• Fentanyl Clearance decreased by ritonavir
• Methadone Withdrawal reported with nevirapine,
  efavirenz
• Phenytoin, Carbamazepine reduced levels/efficacy
  of NNRTIs/protease inhibitors
• TCAs/trazadone inhibited metabolism by
  ritonavir
• Benzodiazepines Enhanced sedation with
  ritonavir, protease inhibitors

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Are treatment with opioids in a patient with a
past history of addiction contra-indicated?

• Yes
• No

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Opioid Treatment with Chemical Addiction

• Diagnose pain syndrome and pathway
• Differentiate dependence, tolerance, addiction,
  and pseudo-addiction
• Maximize non-opioid medications
• One clinic - one doctor - one pharmacy - one
  month
• Written agreements
• Long-acting or controlled release formulations

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My Nurse and I Frida Kahlo
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Specific TreatmentHeadache Syndromes

• Primary headaches
• - Abortive acetaminophen, NSAID's
• Migraines triptans (5HTS antagonists)
• - Prophylactic TCA's, b-blockers, Ca
  channel blockers
• Zizovudine/NRTI associated HA
• - Resolves with discontinuance
• Cerebral toxoplasmosis
• - sulfadiazine 1-4 gm/d
• with pyrimethamine (Daraprim) 50-75 mg/d
• Cryptococcal meningitis
• - fluconozole (Diflucan) 12 mg/kg/d, then 6
  mg/kg/d
• Cerebral lymphoma
• - steroids/radiation

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Specific Treatment Oral-pharyngeal Syndromes
Candidiasis

• Nystatin
• (Mycostatin) 100,000 u/ml, 5 ml qid swish and
  swallow
• Vaginal suppositories, Dissolve in mouth qid
• Clotrimazole
• (Mycelex) troches 10 mg, Dissolve in mouth 5x/d
• Ketoconazole
• (Nizoral) 200 mg, 1 qd, Maintenance
• Hepatoxicity
• Fluconozole
• (Diflucan) 100 mg, 2 stat, then 1 qd
• Less toxic, expensive
• Itraconazole (Sporanox)
• Soln 10mg/ml, 10 ml bid swish and swallow
• 100 mg tabs bid
• Hepatoxicity

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Specific Treatment Oral-pharyngeal Syndromes

• Aphthous ulcer stomatitis
• Nonsteroidal aphthasol (Amlexanox) 5 qid
• Non steroidal Orabase qid
• Triamcinolone (Kenalog in Orabase) 0.1 qid
• Dexamethasone (Decadron) elixir 0.5mg/5ml rinse
  and expectorate qid
• Diphenhydramine/AlOH,MgOH (Benadryl/Maalox) 30/60
  ml 5 mg swish and swallow tid before meals
• Diphenhydramine/sucrulfate (Benadryl/Carafate)
  30/60 ml 5 mg swish and swallow tid before meals
• Periodontal/periapical abscesses
• Dental treatment
• Pen VK 250-500 mg qid
• Erythromycin 250 mg qid
• Cephalexin (Keflex) 250-500 mg qid

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Specific Treatment Oral-pharyngeal Syndromes

• Primary (acute) herpetic (HSV) gingivostomatitis
• acyclovir (Zorivax) 200 mg tabs, 2 tid x 7days
• Recurrent herpes simplex
• penciclovir (Denavir) cream 1 q2h x 4d
• docosanol (Abreva) cream (OTC) 5x/d x 4d
• Shingles (HVV) acute herpes zoster
• acyclovir (Zorivax) 800 mg caps, 1 5x/d x 7days
• valacyclovir (Valtrex) caps 500 mg 2 tid x 7 d
• Sympathetic plexus (stellate ganglion) blocks

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Stellate Ganglion Block
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Specific TreatmentChest Pain Syndromes

• Pneumocytis carinii pneumonia
• - TMP/SMX
• Candidiasis
• Ketoconazole (Nizoral) 200 mg qd maintenance
• Fluconozole (Diflucan) 100 mg, 2 stat, then 1 qd
• less toxic, expensive
• Herpes simplex esophagitis
• - Acyclovir (Zorivax) 200 mg tabs, 2 tid x 7days
• Herpes zoster/PHN - Acyclovir, TCA's,
  Gabapentin
• Epidural steroid injections
• Sympthetic (stellate ganglion) blocks

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Specific Treatment Esophagitis

• Underlying cause
• CMV esophagitis- Ganciclovir (Cytovene) 1000 mg
  tid
• Topical lidocaine
• Proton pump inhibitors
• Pro-kinetic agents
• metoclopramide (Reglan) 10 mg tid
• Coating agents
• sucralfate (Carafate) 1 gm b.i.d.

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Specific Treatment H. Zoster/PHNEpidural
Steroid Injection
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Specific Treatment Abdominal Pain Syndromes

• Infectious diarrhea
• Ciprofaxin 500 mg bid x 5d, TMP/SMX DS bid x 5d,
  or Metronidazole 500 mg tid x 10 d
• Fluids
• Loperamide (Imodium) 2 mg p each stool
• Antispasmotics
• Cholangitis/cholecystis
• Cefuroxime /or piperacillin /or mexolcillin
• Endoscopic sphincterotomy? (sclerosing
  cholangitis)
• CMV iliitis/colitis
• Ganciclovir (Cytovene), 1000 mg tid
• Antispasmotics
• Drug induced pancreatitis and visceromegaly
• pentamidine, didanosine, deoxycytidine
  associatedresolve with discontinuance
• Celiac plexus block

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Specific Treatment Anorectal Syndromes

• Clindamycin aminoglycoside
• Sitz baths
• ID, surgery
• Topical lidocaine (2-5 gel)
• Glycerin/petrolatum/shark liver oil (Preparation
  H)
• Hydrocortisone 1
• Witch Hazel (50) (Tucks pads)

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Specific TreatmentPeripheral Neuropathies

• Acute or Chronic Inflammatory Demyelinating
  Polyneuropathy
• Plasmapheresis
• Steroids
• Zidovudine
• Distal Symmetrical Polyneuropathy
• TCA's (amitriptyline, nortriptyline,
  desipramine), SNRI's
• Anticonvulsants (gabapentin, carbamazepine)
• Tramadol
• Opioids
• Vitamin B E supplementation
• Topical capsaicin or lidocaine (Lidoderm)
• Sympathetic neurolysis

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What medications are not effective in treating
neuropathic pain?

• TCAs (e.g., amitriptyline, nortriptyline, etc)
• SSRI antidepressants (e.g. Prozac, Paxil, etc.)
• SNRIs (e.g., Cymbalta, Effexor)
• Opioids
• Anti-epileptic medications (e.g. gabapentin)
• 6. Topical lidocaine and capsaicin

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Treatment Peripheral NeuropathiesEfficacy
Antineuropathic Medications

Oral agents TCAs (2.64) opioids (2.67)
gabapentin (4.29) tramadol (4.76) pregabalin
(4.93) Topical agents aspirin/diethyl ether
(1.83) lidocaine patch (2) capsaicin
(3.26) (Numbers needed to treat) e.g., PHN
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Specific Treatment Musculoskeletal system

• Non-specific arthralgias
• NSAIDs
• Non-opioid analgesic
• Reactive arthritis
• Methotrexate (Rheumatrex) 2.5-10 mg/wk
• Intra-articular steroid injections
• Myopathies
• NSAIDs
• Non-opioid analgesic
• AZT
• Steroids
• Zidovudine myositis discontinue if possible

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Specific Treatment ArthriditesHip and SIJ
Intra-articular Injections
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SummaryPain Palliative Care in HIV/AIDS

• Recognition
• Prevalence
• Barriers
• Common HIV painful syndrome
• Thorough assessment
• Nociceptive vs. neuropathic
• Dx specific process
• Systemic pharmacotherapy
• NSAIDs, opioids, anti-neuropathic medications
• Syndrome specific therapy
• Reassessment, adjustment, and empathy

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The End