Pain Management

Dr. Lamya Alnaim

Pain is a Very Significant ProblemPain is a Very Significant Problem

Pain has negative effects on sleep, work, enjoyment of activities, sexual function, and personal interactions

Multiple studies show pain of all types is under treated

Pain is a Very Significant Problem

Good medications and treatments are available

Barriers (patient and caregiver) include lack of education, attitudes (myths, cultural differences), and regulatory/legal issues

Definition: Acute Pain An unpleasant sensory and emotional

reaction/sensation secondary to tissue damage Arises from injury, trauma, spasm, or disease

of the skin, muscles, somatic structure or viscera.

Corresponds to the degree of injury Self limiting- limited duration

Definition: Acute Pain Serves a purpose

By inducing an organism to withdraw from or avoid a noxious stimulus.

Responds to conventional therapy. Decreases in intensity as the damaged area

heals and tissue repair takes place.

Definition of Chronic Pain

Any pain that Persists beyond the expected time after a physical

or emotional injurySubjective complaints are magnifiedPain is out of proportion to clinical signsIs accompanied by severe psycho-social issuesResponds poorly to conventional therapy

PAIN

SUFFERING

DEPRESSION

LOSS OF FUNCTION

DRUG ABUSE

FINANCIAL LOSS

DOMESTIC DISRUPTION

Persistent Pain

Who Gets Persistent Pain ? Systemic disease

Diabetes mellitushypothyroidismHIV/AIDSHepatitis CMalignancyNeurological disease….ALS, MSRheumatoid related syndromes

Obesity Psychiatric co-morbidity

ACUTE PAIN Meaningful, linear,

reversible

Well defined, recent onset, clear definable cause

Observable responses

Readily responds to analgesics

Usually nociceptive in origin

CHRONIC PAIN Meaningless, cyclical,

irreversible

Persists over time

Adaptation

Less amenable to analgesics alone

Multiple etiologic componentsnts

Cancer Pain 20-50 % at time of diagnosis

Incidence varies with tumor type

55-95% with advanced disease

50-70% report pain of moderate to severe intensity

30% report excruciating pain

Pain Experience in Ambulatory Cancer Patient Population

Disease Pain Pain due to Disease

Worst Pain > 5

Negative PMI

Breast 71% 83% 60% 43%

GI 61% 91% 58% 41%

GYN 55% 80% 71% 54%

GU 64% 84% 66% 38%

Lymphoma 53% 66% 63% 63%

Lung 74% 85% 63% 34%

Other 74% 85% 64% 42%

Pain Classification Schemes1-Neurophysiologic:

Nociceptive (somatic, visceral) Neuropathic

2-Duration: acute vs. chronic3-Temporal pattern:

continuous intermittent

incident Breakthrough End-of-dose failure

Pain Classification Schemes4-Severity

5-Specific cancer pain syndromes (etiology):

Tumor infiltration of bone, nerve, viscera.

Treatment related.

Types of Persistent Pain Nociceptive

Musculo skeletalJointLigamentousVisceral

NeuropathicCentralSomaticSympathetic

Psychogenic Mixed

Types of Pain: Nociceptive vs. Neuropathic

Nociceptive Mediated by normal nervous system: Inflammatory pain: in response to activation

of peripheral nociceptors by either mechanical pressure, high or low temperature or chemical mediators.

Usually acute

Types of Pain: Nociceptive vs. Neuropathic

Nociceptive Somatic –

arising from skin, bone, joint, muscle, or connective tissue

dull, aching, well-localized. Bone metastasis, invasion of soft tissue

Types of Pain: Nociceptive vs. Neuropathic

Nociceptive Visceral –

vague distribution, referred. Bowel obstruction, carcinomatosis, pleural effusion

arising from internal organs such as the large intestine or pancreas

Types of Pain: Nociceptive vs. NeuropathicNeuropathic mediated by damaged nervous system: Localized to an area of sensory abnormality Pain in response to non-painful stimuli Pain in the absence of ongoing tissue damage Painful peripheral neuropathy, post mastectomy

pain, brachial plexopathy

Mixed TypeCaused by a

combination of both primary injury and secondary effects

Nociceptive vs Neuropathic PainNociceptive

PainCaused by activity in neural pathways in

response to potentially tissue-damaging stimuli

Neuropathic Pain

Initiated or caused by primary lesion or dysfunction in the nervous system

Postoperativepain

Mechanicallow back pain

Sickle cellcrisis

Arthritis

Postherpeticneuralgia

Neuropathic low back pain

CRPS*

Sports/exerciseinjuries

*Complex regional pain syndrome.

Central post-stroke pain

Trigeminalneuralgia

Distalpolyneuropathy (eg, diabetic, HIV)

Manifestations of PainAcuteIncreased BP, P,

R.Dilated pupils.Sweating.Focuses on painReports pain Crying, moaning restlessGrimace

ChronicNormalNormalDry skin

Easy distractionNo reportQuiet, sleep, rest Blank or normal

facial expression

Behavio

ral

Physi

olo

gic

Key Principles in Assessment Pain is a multidimensional, subjective, and

uniquely personal experience

Pain is what ever the person says it is, occurring whenever the person says it does

Reliance on observable physiologic and behavioral manifestations in order to verify existence and severity of pain is inadequate

Goals of Assessment Estimate severity of pain (0-10 scale, visual

analog scale)

Form clinical impression regarding etiology

Determine need for additional diagnostic testing

Formulate therapeutic recommendations which take into account the patient’s medical and psychosocial status

Symptom Assessment Site Onset Temporal pattern Quality Relieving/Provoking

factors Associated signs/

symptoms

Impact of function and QOL.

Impact on psychological state.

Response to prior therapy.

Treatment preferences.

Pain Intensity Rating Scales

• Visual Analogue Scale (VAS)

No painNo pain ----------------------------------- ----------------------------------- Worst painWorst pain

• Categorical Scale

None (0) Mild (1 – 4) Moderate (5 – 6) Severe (7 – 10) None (0) Mild (1 – 4) Moderate (5 – 6) Severe (7 – 10)

• Numerical Rating Scale

-------------------------------------------------------------------------------------- 00 No painNo pain

1010Worst pain Worst pain imaginableimaginable

Guidelines in Pain Therapy Assess the pain frequently Pain assessment must be dynamic and not static Use around the clock therapy (ATC) Treat and assess breakthrough pain

aggressively Where possible use oral route Consider age, previous drug usage, hepato-

renal function Monitor for abuse Monitor and treat side effects

Treatment Goals Decrease Intensity and duration of pain Decrease conversion from acute to chronic Decrease suffering and disability Decrease psychological and socioeconomic of

sequel of untreated pain.

Treatment Goals Optimize drug therapy Improve quality of life and optimize ability to

perform activities of daily living Minimize adverse effects of therapy Minimize inappropriate use

Overall Treatment Strategies

Analgesic and adjuvant medications

Physical therapies

Psychological interventions

Anesthetic and neurolytic procedures

WHO Analgesic “Ladder” for Cancer Pain

WHO 3-StepWHO 3-StepAnalgesic Analgesic

LadderLadder

Proposed 4th StepProposed 4th Step

Freedom from Pain

Intrathecal Opioid Delivery

Pain persisting or increasing

Step 3Opioid for moderate to severe pain

± Nonopioid ± Adjuvant

Pain persisting or increasing

Step 2Opioid for mild to moderate pain

± Nonopioid ± Adjuvant

Pain persisting or increasing

Step 1± Nonopioid± Adjuvant

Pain

Algorithm for Medication Selection in Various Pain Syndromes

Cancer

Cancer Pain Cancer: Tumor expansion, nerve compression,

infiltration by tumor, malignant obstruction,

infection of malignant ulcers.

Treatment: radiation → mucositis pain

Principles of Analgesia for cancer-Related pain Follow WHO Ladder ATC dosing for continuous pain Rescue dosing for intermittent pain Oral route unless contraindicated No PRN

It is reactive not preventive Requires larger doses to reestablish control which may lead

to side effects

Principles of Analgesia for cancer-Related pain

ATC dosing

Small fixed doses on a schedule to prevent pain

Rescue (Breakthrough) dosing

Fixed doses on a flexible schedule Analgesia is administered in response to pain

or to prevent predictable pain Key to success of pain management Similar to NG in angina Use immediate release opioid or NSAIDs

Calculating Rescue dosing

1. 25-50% of the 4hrly ATC If ATC is 60 mg MS q 4 hrs, rescue can be 15

mg

2. 2-5% of the 24 hr ATC dose

3. Based on response, 50% relief from 2 mg morphine →4 mg should provide ≈ 100% relief

All rescue should be prescribed q 4 hrs

Titrating dosage If 3 or more rescue doses in 24 hr

Calculate ↑ based upon total opioid dose ( ATC+ rescue) taken in the previous 24 hrs.

↑ both the ATC and breakthrough Increase by the following guidelines

Pain > 7 , ↑ dose by 50-100%Pain 4-7, ↑ dose by 25-50%Pain < 4, ↑ dose by 25%

When patient uses < 2 rescue, sustained release opioid should be started

Non Opioid Analgesics

NSAIDS Acetominophen

NSAIDS Mechanism of action

- Inhibition of prostaglandin synthesis

- Synergism with opioid analgesics

Mild to moderate pain

Different side effect profile from opioids

No tolerance or dependence

Ceiling effect

Limited routes

NSAIDS Pain from injury, surgery, trauma, arthritis, or

cancer

Very effective for bone pain

Predominant effect on PNS→synergistic

All are equipotent

Patient response varies

Selective COX-2

Inhibitor

The Arachidonic Acid Cascade and COX-1 and COX-2 Inhibition

X XTraditional NSAID X

Arachidonic acid

COX-1 COX-2

Body Homeostasis• Gastric integrity• Renal function• Platelet function

InflammationPain

The COX 2 Inhibitors

Rofecoxib 25-50 mg daily (Vioxx) →W Celecoxib 100-200mg daily (Celebrex) Valdecoxib 10-20 mg daily (Bextra) →W Etrocoxib Paracoxib (iv use)

The COX 2 Inhibitors

Minimal effect onGastric integrityRenal functionPlatelet function

Potent inhibition of PGI2 →↑ risk if CV events (MI)

Contraindications to COX2 I Previous side effects with COX2 inhibitors Allergy to sulpha drugs History of previous GI bleed pregnancy History of perforated gastric ulcer Esophageal varices Bronchospastic disease Renal dysfunction Coronary artery disease needing aspirin Congestive heart failure

Acetaminophen Same analgesic potency as ASA No neuropsychological and little GI SE Orally, or rectally For musculoskeletal or visceral pain Can be used in 3 ways

1. ATC 1g q 4 hrs as 5 doses in 24 hrs

2. As rescue with ATC opioid 1g q4 PRN

3. As an adjuvant analgesic

Opioids Morphine Sulphate Hydromorphone (Dilaudid) Demerol Fentanyl Methadone Buprenorphine Pentazocine Oxycodone (Roxycodone, Tylox, Percocet) Hydrocodone (vicodin, lortab, Norco) Propxyphene ( Darvon, Darvocet) Codeine

Strong Opioids

Partial agonists

Weak

opioids

Opioids Opioid Agonist: bind w/ opioid receptor site in

PNS & CNS = pain relief

No Ceiling

Titrate to pain relief or side effects

Opioid Antagonist: blocks relief. Naloxone

Opioid Agonist-antagonist: + pain relief. Stadol, Nubain, Talwin (not recommended)

Opioids No rationale for combining two opioids, use

same agent for ATC and rescue pain.

Potent Opiates: Morphine, Hydromorphone. µ-receptors, κ-receptors Treat acute, chronic, sever, or terminal

malignant pain Orally, rectally, IV Infusion, epidural ,

intrathecal Immediate release analgesic effect 4 hrs

Morphine, Hydromorphone. Doses according to

Prior exposurePain severityHepatic, renal functionRoute of administration

Oral: parental, 5:1

Morphine Opioid of choice

Available in multiple routes and formulationsExtensive clinical experience in dosing, route

change and side effects.

Meperidine…….Demerol Used for traumatic and postoperative pain 1/10 potency of morphine Oral or parenteral Short acting Toxic metabolites: nomeperidine

Can accumulate in renal dysfunction and cause CNS stimulation and seizures

Metabolites with long half life >12 hrs High addiction potential Expensive

Methadone Equivalent potency to morphine Orally, IV, rectally, epidurally/intrathecally Long acting adjust dose q 5-7 days Lower addiction and tolerance potential Cheap No active or toxic metabolites 8-12 hour analgesic action ( give Q8-12 hrs)

Longer intervals in hepatic failure

Methadone CNS depression lasts for 36 hrs after overdose

Needs CIVI Naloxone for reversing effect. No renal excretion Dependence on hepatic function (p-450)

Watch for drug-drug interaction

Fentanyl >100 potent than morphine IV, intraspinally as preoperative anesthetic

agent Rapid onset, short duration of action

Transdermal patch: Consistent dosing Oral lollipop

The Fentanyl Patch Indications for use

Severe nausea and vomiting Unable to swallow Children Patients with poor compliance Concern of drug diversion

Beware Opioid naïve Febrile patient Elderly Drug abuser

The Fentanyl Patch disadvantages

Delay in onset of analgesiaResidual activity after the patch is removed

25,50,75,100 mcg Duration 72hrs Steady state requires 24 hrs, use supplemental

short acting to cover initial period.

Weak Opioids Codiene, oxycodone, propoxyphene For mild to moderate pain

Oxycodone Analgesic effect 4 hrs High bioavailability compared to MSO4 No toxic metabolites Less tolerance compared to MSO4 Higher incidence of euphoria Expensive

Tramadol Activity against opioid and serotonergic and

noradrenergeric pathways in CNS. Moderate to sever pain Advantages

Lower abuse liabilityLower risk of respiratory depression

DisadvantagesDizziness, dry mouth, sedation, constipation.

Use lower doses in elderly

3-5.75200130Codeine

4-6200Hydrocodone

2-4430075Meperidine

3-515Oxycodone

3-657.51.5Hydromorphone

4-533010Morphine

DURATIONRATIOPOIVMEDICATION

Equianalgesic Dosing

Dose Conversion

Equianalgesic dose of current opioid

24 hrs dose current opioid

Equianalgesic dose of desired opioid

24 hrs dose current opioid

=

Drug Delivery No evidence that other routes are superior or

have less SE. Choice of route depends on pragmatic

consideration e.g. inability to swallow Can only be done safely with knowledge of

equianalgesic dosing.

OralRoute of choice Simple, noninvasive Reasons for failure: inadequate dose,

parenteral to oral conversion made too quickly, dosing intervals too long

Formulation and dose dependent upon pattern of pain and severity

Long Acting Combined with Short Acting for Chronic Pain

Sublingual, buccal

Simple, noninvasive Unable to tolerate oral dosing, unable to

swallow rapid onset, drug not subject to first-pass effect

fentanyl

Intravenous Most efficient for rapid titration, dose finding,

immediate analgesic effect. Bolus, continuous, PCA. Steady state better maintained with CI. Full effects of increase CI will not be felt until

steady state or approximately 5-6 half-lives. Therefore with IV Morphine 12-18 hours.

Morphine, hydromorphone, fentanyl, methadone

Rectal Morphine, hydromorphone Conversion from oral at 1:1 ratio Sustained release tablets of morphine can be

used by this route.

Subcutaneous Morphine, hydromorphone Equivalent to IV in efficacy and side effects

Conversion to Oral Calculate total daily requirement with PCA Convert to IV morphine Convert to Oral morphine Convert to alternate opioid 75 % as ATC 25% as rescue

Prior to Oral Conversion

Patient able to tolerate oral fluids Oral therapy started prior to removal of PCA Pain control predictable and stabilized IV to oral conversion calculated Side effects under control

Example of Conversion Total morphine for 24 hours on PCA= 60mg

Want to convert to Oxycodone.

60 mgm of MS IV( x 3) = 180 mgm oral.

To convert to oxycodone x by 1.5 = 120 mg oxycodone

75% as ATC = 90 mg = 40 mg Q 12 , but factor in 50% less for ICT = 20 mg q 12 hourly

25% as rescue = 30 mg or 5 mg Q 4-6 hourly PRN

One 25 mcg/h transdermal

fentanylpatch/3 days

(72 hours)

Conversion Chart for Starting Dose of Transdermal Fentanyl

Fixed-combination short-acting opioids (6/day):

–Lorcet 5 mg/500 mg–Lortab 5 mg/500 mg–Percocet 5 mg/325 mg–Percodan 5 mg/325 mg–Tylenol + Codeine 30 mg/325 mg–Tylox 5 mg/500 mg–Vicodin 5 mg/500 mg

Long-acting opioids(2/day):– OxyContin 20 mg– MS Contin 30 mg

Multiple patches may be used for doses exceeding 100 mcg/h. Doses up to 6oo mcg/h have been evaluated in clinical trials.

Renal Failure

Methadone Dilaudid Oxycodone Hydrocodone Morphine Fentanyl Demerol

NEUROTOXICITY

SEDATION

TOLERANCE

Liver Failure

Methadone Dilaudid Oxycodone Hydrocodone Morphine Fentanyl Demerol

All pretty much OK, but halve dose

Side effects of opioids Constipation Sedation Mental clouding Respiratory depression Nausea and vomiting Orthostatic hypotension Urinary retention Pruritus Myoclonus

Constipation Decreased gastric,

pancreatic, biliary secretions.

Decrease motility Delayed passage

Tolerance does not develop

Dose dependent Preventative

approach Bulk and stimulant

laxatives

Sedation Common with start,

increase, change drug, pain relief in sleep deprived.

Tolerance to sedative effects 2-7 days.

Other causes: sedatives, sepsis, metabolic imbalances, hypoxia.

Strategies: change dose,

frequency, type of opioid

Stimulants: Caffeine, dextroamphetamines, methylphenidate

Respiratory Depression Direct action on brain Direct action on brain

stem respiration stem respiration receptors; decreased receptors; decreased responsiveness to responsiveness to CO2 levels CO2 levels

Pain is physiologic Pain is physiologic antagonistantagonist

Risk factorsRisk factors

Rapid tolerance Short acting Goal: gradual reversal

without analgesic withdrawal

Naloxone 0.4 mg/10cc; 0.5 cc q 2-3 mins

Nausea - Vomiting Common with start or increase dose

Tolerance within 2-3 days

Rule out other causes

Treatment:

treat constipation, use antiemetics, change opioid

Withdrawal

Physical dependence Causes: abrupt discontinuation, rapid

dose reduction, antagonist, agonist- antagonist

Onset dependent upon elimination half-life

Signs and symptoms 25% of daily dose

Dependence

Physical dependence Psychological dependence Pseudo addiction

Definitions Physical Dependence: involuntary,

adaptation, withdrawal with abrupt reduction or discontinuation

Psychological Dependence (addiction): compulsive use despite harm, for effects other than pain relief

Adjuvant Medications Enhance analgesic

effect of opioids Treat concurrent

symptoms Provide independent

analgesia

Antidepressants Neuroleptics Anticonvulsants Local anesthetics Antispasmodics Muscle relaxants Psychostimulants Corticosteroids NMDA receptor

antagonism Anticholinergics Bisphosphonates

Antidepressant TCA, MAOIs, Clinical effects

Improve moodImprove sleepAnoxiolyticsDecreased pain perception

TCA more easier to use

Antidepressant TCA inhibit reuptake of serotonin and

norepinephrineSerotogergic processes are part of endogenous

pain inhibitory mechanisms TCA have analgesic properties related to

ability to increase pain tolerance Faster onset than antidepressant effect Have local anesthetic properties

Antidepressant Improve sleep disturbances and depression

associated with chronic pain. 1-3 weeks for effect Amitriptyline most commonly used for painful

conditions 50-150 mg/day Anticholinergic side effects

TCA: Adverse EffectsCommonly reported AEs

(generally anticholinergic):blurred visioncognitive changesconstipationdry mouthorthostatic hypotensionsedationsexual dysfunctiontachycardiaurinary retention

Desipramine

Nortriptyline

Imipramine

Doxepin

Amitriptyline

FewestAEs

Most AEs

Caveats With the Antidepressants•Start at lowest dose available

•Escalate slowly…every 10 -14 days

•Slow weaning, over a week

•Beware of drug interactions

•Check for

•Glaucoma

•Prostatic obstruction

•Heart block

Drug Interactions With Antidepressants Coumadin Alcohol ( cold medications) Appetite suppressants Quinolone antibiotics Antihistamines Tramadol Anti epileptics Bronchodilators

Neuroleptics Fluphenazine, methotrimeprazine For mild to moderate pain Improve sleep Similar analgesic effects to morphine without

addictive properties or respiratory depression Side effects

High sedative and anticholinergic effectsExtrapyramidal

Anticonvulsants Carbamazapine (Tegretol) Gabapentin (Neurontin) Oxcarbezapine (Trileptal) Topiramate ( Topramax) Zonisamide ( Zonergan) Levetiracetam( Keppra) Lamotragine ( Lamictal) Valproate ( Depakote)

Anticonvulsants

Carbamazapine and valproate for lancinating, burning pain. (neuropathic)

Neural invasion by cancerous tumorSurgical scarringTrigeminal neuralgia

For opioid induced myoclonus dosing start at 100-200mg/d in cancer pain Plasma levels need to be monitored

Anticonvulsants

Carbamazapine and valproate Side effects

Bone marrow suppressionAtaxia, diplopia, Nausea lymphadenopathy, hepatic dysfunction

MonitoringLFTsCBCSerum Drug levels

Gabapentin in Neuropathic Pain Disorders FDA approved for postherpetic neuralgia Neuropathic pain in patients who do not respond to

CBZ and TCA. Neuropathy, multiple sclerosis, migraine Usually well tolerated; serious adverse effects rare

dizziness and sedation can occur No significant drug interactions Peak time: 2 to 3 h; elimination half-life: 5 to 7 h Usual dosage range for neuropathic pain up to 1200-

4800 mg/d

Gabapentin Start as low as possible…..100 mgm q HS Increase slowly by 100 mgm every three days Caution regarding driving ( sedation) Increase to 1200 mgm and assess pain relief If > 50% relief, wait two weeks and reassess Increase to maximum of 3600 mgm Do not exceed 1200 mgm in elderly Elixir in children mgm/kilo

Local anesthetics Lidocaine For neuropatheic pain

Short duration Mexiletine longer acting Doses same as antiarrhythmic dose Side effects

Dizziness, lightheadedness, ataxia, N/VHigh dose lead to tremor and convulsion

Lidocaine available as patches which have lower SE

Local anesthetics Ketamine

At the N-methyl-D-aspartate (NMDA) receptorAnalgesic at subanesthetic dosesFor neuropathetic pain25 mg q 6 hrs , titrate by 25 mg q 24-48hrsSide effects

Psychotomimetic, tachycardia, high BP , ↑ intracranial pressure

Benzodiazepines Diazepam, midazolam Skeletal muscle relaxant and anxiolytic → ↑

pain threshold. Side effects

Sedation, cognitive impairment, depressionAddictiveSerious withdrawal symptoms such as seizures

Corticosteroids Prednisone, Dexamethasone No ceiling effect Opioid sparing effect Dexamethasone

4-16 mg/d in divided dosesOral or IV

Other non-analgesic effectsRelief of nausea and vomitingIncrease energy

Corticosteroids Indications

Bone metastasesVisceral painNeuropathic painNerve compression from tumorSoft tissue or musculoskeletal pain from

inflammatory lesionsHeadache from ↑ intracranial pressurePain from spinal cord compression

Bisphosphonates Analgesic and prevents skeletal complications

of malignancy Treatment of hypercalcemia Indications

Wide spread painful bone metastases at risk of complications

Multiple painful sites of disease at risk of hypercalcemia

Osteolytic bone disease where radiation is CI

Bisphosphonates Pamidronate, zoledronic acid given IV q 4 wks

Nonpharmacologic therapy Surgery Neuroablative blocks and neurolysis Central and peripheral nervous system

stimulation Physical therapy