PAIN CONTROL IN WOUND MANAGEMENT

Dr Wan Azzlan Wan Ismail

Consultant Anaesthetist & Pain Management Specialist, HRPZ II

3.10.2012

Part 1:Physiology of pain

Definition of pain
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
Merskey,1964 International Association for the Study of Pain (IASP)

5th Vital Sign: Doctors training module: Pain Physiology

Spectrum of Pain
ACUTE PAIN
Healing

NO PAIN

Insidious onset

CHRONIC PAIN
post-surgical syndromes / cancer

ACUTE PAIN
5th Vital Sign: Doctors training module: Pain Physiology

CHRONIC PAIN
Courtesy of Prof Ramani Vijayan, MASP

Pain Pathway

Nociceptors (Free nerve endings)

Skin, somatic structures, joints & viscera

A-delta and C nerve fibers Spinal cord

through dorsal horn into substantia gelatinosa through spinothalamic/spinoreticular tract

Brain

Brainstem, Thalamus, Cortex Modulation of perception and response to pain

5th Vital Sign: Doctors training module: Pain Physiology

Pain Pathway
PAG / RAS
Descending inhibitory fibres

PAIN
Sensory cortex
Thalamus

Ascending ST tracts

Free nerve endings Spinal cord

Dorsal horn Afferent nerve ( A / c)
5th Vital Sign: Doctors training module: Pain Physiology
Courtesy of Prof Ramani Vijayan, MASP

Effects of severe unrelieved pain

Physiological
Central Nervous System Endocrine system Cardiovascular System

Respiratory system
Gastrointestinal system Genitourinary system

Psychological Economic
5th Vital Sign: Doctors training module: Pain Physiology

Central Nervous System

sympathetic activity

parasympathetic activity

Hyperalgesia
scarring of pain pathways

Increased risk of developing chronic pain

5th Vital Sign: Doctors training module: Pain Physiology

Endocrine system

Stimulation of stress response Increased cortisol

Increased sympathoadrenal activation Metabolic response to stress

Hyperglycemia Catabolic state

immunosuppression
risk of infection

5th Vital Sign: Doctors training module: Pain Physiology

Cardiovascular System
Increased Heart Rate Increased Blood Pressure
increased myocardial work load myocardial oxygen consumption increased risk of myocardial ischaemia

5th Vital Sign: Doctors training module: Pain Physiology

Respiratory system
Increased abdominal muscle tone + increased diaphragmatic function Inhibition of normal respiration (unable to take deep breaths)
Atelectasis Hypoxia

Inability to cough
Retention of secretions Increased risk of lung infection / pneumonia

5th Vital Sign: Doctors training module: Pain Physiology

Gastrointestinal System
Increased sympathetic and reduced parasympathetic activity
Reduced smooth muscle + sphincter tone Reduced gut motility Ileus, nausea + vomiting Impedes early feeding

5th Vital Sign: Doctors training module: Pain Physiology

Genitourinary System

Increased sympathetic and reduced parasympathetic tone

reduced smooth muscle + sphincter tone urinary retention

5th Vital Sign: Doctors training module: Pain Physiology

Musculoskeletal system
Prevent mobilisation & increased muscle tone

Increased risk of deep vein thrombosis

5th Vital Sign: Doctors training module: Pain Physiology

Psychological
Anxiety Agitation

poor sleep uncooperative patient

5th Vital Sign: Doctors training module: Pain Physiology

Economic

Delayed ambulation and feeding Increased postoperative complications Delayed recovery Prolonged hospital stay Increased cost

5th Vital Sign: Doctors training module: Pain Physiology

Conclusion

Acute pain should be aggressively treated for the following reasons:

Patient comfort Prevent adverse physiological and psychological consequences of unrelieved pain Reduce risk of developing chronic pain

5th Vital Sign: Doctors training module: Pain Physiology

Conclusion

Many drugs and techniques are available for the relief of acute pain, as they are all for short term use, e.g.
epidural analgesia IV opioids NSAIDs/COX2 inhibitors

5th Vital Sign: Doctors training module: Pain Physiology

Part 2: Drugs in Acute Pain Management

Analgesics

Non Opioids
Paracetamol NSAIDS COX-2 inhibitors

Opioids
Weak Strong

Naloxone
5th Vital Sign: Doctors training module: Pain Physiology

Acetaminophen - Paracetamol

Weak inhibitor of both COX1 & COX 2 Analgesic and anti-pyretic but no antiinflammatory activity Orally - peak plasma concentrations in 30-60 minutes Metabolized in the liver Half life 3-4 hours

Acetaminophen - Paracetamol

Commonly used dose (adults) is 1 gram 6 hourly, but can be used up to 4 hourly i.e. maxiumum of 6 grams/day At therapeutic doses - few and uncommon side effects Toxic doses (2-3 X maximum therapeutic dose) - fatal hepatotoxicity

NSAIDS

Effects

Anti-inflammatory Analgesic Anti-pyretic Anti-platelet

Cyclooxygenase Pathways
Arachidonic acid
(-)

Glucocorticoids
(block mRNA expression)

COX-1

(-)

NSAIDs Coxibs

(-)

COX-2

Normal constituent

Inducible

Normal constituent

gastric cytoprotection renal sodium / water balance platelet aggregation

inflammation pain fever

brain kidney endothelium ovary uterus

Diagram based on information in Lipsky PE et al., J Rheumatol, 1998; 24 and Smith WL, Dewitt DL, Adv Immunol, 1996

NSAIDS & COX2 INHIBITORS:

EXAMPLES
NSAIDS

COX 2 INHIBITORS

Diclofenac (Voltaren) Mefenamic Acid (Ponstan) Ibuprofen ( Brufen) Naproxen (Naprosyn, Synflex) Ketoprofen (Orudis, Oruvail) Ketorolac (Toradol) Meloxicam ( Mobic)

Celecoxib (Celebrex) Etoricoxib (Arcoxia) Parecoxib (Dynastat)

NSAIDs /COX 2 Inhibitors

Route of administration

Oral / Parenteral

Effective for mild to moderate pain Opioid-sparing effect when used in combination with strong opioids a lower dosage of opioid is required to achieve comfort Treatment of other associated symptoms i.e. Inflammation and fever

NSAIDS limitations

Ceiling effect to analgesia Adverse effects

Gastric ulceration Reduction in renal blood flow Platelet inhibition Allergic reactions

Bronchospasm Cross allergy is common

NSAIDS limitations

Gastritis and functional thrombocytopenia are common with therapeutic doses Precautions prolonged use can lead to

Renal failure Increased risk of myocardial infarct and stroke

OPIOIDS

Drugs (natural or synthetic ) with morphine-like properties and which act through the opioid receptors.

Commonly used opioids

Weak opioids

Strong opioids

Dihydrocodeine (DF118) Tramadol

Morphine Oxycodone Fentanyl Pethidine

Partial agonist

Nalbuphine

Morphine

Potent analgesic agent: The Gold Standard for all analgesics Acts on mu and kappa opioid receptors in brain and spinal cord Used for moderate to severe pain The first choice of strong opioid for acute pain and for severe cancer pain

Morphine - pharmacokinetics

Bioavailability of oral route is 30% due to first pass metabolism in the liver Converted to morphine-6-glucuronide (active metabolite) and morphine-3glucuronide in liver Excreted through the kidney Elimination half life is 3-4 hours Peak analgesic effect
IM / SC : 30-60 minutes IV : 5 minutes

Morphine adverse effects

Side effects the same as for all opioids:

Nausea and vomiting Respiratory depression Sedation Constipation / Reduced GIT motility Dizziness Pruritus

Reduce dose in renal and hepatic impairment

Morphine clinical use

Aim for analgesia

-

Plasma levels to fall in the analgesic corridor

=> comfortable
-

Below level pain Above level side effects

Difficult to predict => titration of analgesia Using: PCA, Range of doses & dosing intervals

40 35 30 25 20 15 10 5 0
6h r 12 hr 18 hr 24 hr 30 hr 36 hr 0h r 1h r

minimum analgesic level upper safe limit im/sc drug

PHARMACOKINETICS IM or SC MORPHINE
40 35 30 25 20 15 10 5 0
6h r 12 hr 18 hr 24 hr 30 hr 36 hr 0h r 1h r

Analgesic corridor

Onset 30 min (slow) Duration of action 3-4 h => same for IM & SC

minimum analgesic level upper safe limit im/sc drug

5th Vital Sign: Doctors training module: Pharmacology

PHARMACOKINETICS IV MORPHINE
50 40 30 20 10 0
6h r 12 hr 18 hr 24 hr 30 hr 36 hr 0h r 1h r

Analgesic corridor

minimum analgesic level upper safe limit IV morphine Infusion

5th Vital Sign: Doctors training module: Pharmacology

Onset faster (3-5 mins); higher peak plasma levels Duration of action same as IM, i.e. 3-4 hours Bolus required before starting infusion; if not, adequate plasma levels not achieved for many hours

PHARMACOKINETICS PCA / small frequent boluses

35 30 25 20 15 10 5 0

Analgesic corridor

minum analgesic level upper safe limit iv drug

Good quality analgesia Well within the analgesic corridor less risk of toxicity

5th Vital Sign: Doctors training module: Pharmacology

When the level of morphine is below the analgesic corridor (especially if the dosing interval is too long)
=> patient experiences pain

If a higher dose is given to prolong the duration above the analgesic corridor
=> more side effects or complications CONCLUSION: The best way is to give smaller doses of morphine more frequently

Morphine Pain Protocol

Used for rapid control of severe pain Route: IV Morphine dilution: 10 mg in 10 mls (1mg/ml) Monitoring (every 5 minutes)

Pain score Sedation score Respiratory rate Pulse rate Blood pressure

Morphine Pain Protocol

Adapted from the Acute Pain Service, Royal Adelaide Hospital , South Australia

Morphine and other opioids: Tolerance and Addiction?

Tolerance is a physiological phenomenon where increasing doses of a drug are required to produce the same pharmacological effect, or where the same dose produces less effect.

Addiction is associated with a psychological dependence on the drug, craving for the drug when it is not available, and drug-seeking behaviour including cheating, lying and stealing to obtain the drug.

Morphine and other opioids: Tolerance and Addiction?

Addiction does NOT occur if morphine is used for the relief of pain (acute pain or cancer pain)

Patient on PCA will reduce the dose of morphine once the wound heals and pain decreases In patients with cancer pain who are on morphine, requirement for higher doses is usually due to disease progression

Tolerance is usually not a problem when used in the short term for the management of acute pain

Morphine and other opioids: Withdrawal

However, patients who are on long term opioids, even when taken for pain, will experience withdrawal symptoms (e.g. increased pain, abdominal cramps, sweating, diarrhoea, agitation)

Dihydrocodeine (DF118)

Natural opioid Side effects Only oral form is available in Constipation Malaysia: 30 mg tab Worst constipating effect Converted to morphine in the compared to other liver opioids Used for mild to moderate pain Dose: Tab 30mg-60mg 6hrly (max 360mg/day) Onset: 15 to 30 min (peak 1h) Duration: 4-6hr

Pethidine

Dose: 1-2mg/kg (usually 50 100 mg 4 H) Route: iv /im /sc

Peak analgesic effect :

IM : 20-30 minutes IV : 5 -10 minute

Side Effects are the same as for all opioids

Nausea/vomiting Sedation Respiratory depression Constipation / Ileus

Metabolised in liver to Norpethidine which has a hallucinogenic and convulsant effect Elimination half life is 2.4-7 hours Norpethidine has a long half life (12 hours) and hallucinogenic effects outlast the analgesic effects of pethidine

NOT recommended for use in chronic or cancer pain management

Fentanyl

Highly selective mu agonist 50-80 times more potent than morphine (10 mg morphine = 100 mcg fentanyl) Cardiovascularly stable but may cause bradycardia of vagal origin Potent respiratory depressant For acute pain, the IV form is used (not transdermal) Indicated when rapid pain relief is required for short periods of time, e.g. burns dressing

Pharmacokinetics :

Metabolized rapidly in liver to norfentanyl Elimination half life is 1.5-6 hours Short duration of action is due to redistribution rather than metabolism Peak analgesic effect : IV : 3 minutes Duration of action : IV : 30-60 minutes

Available in transdermal patches but these are NOT suitable for management of acute pain

Nalbuphine

Partial Agonist: therefore, has a ceiling effect 10 mg nalbuphine = 10 mg morphine Route of administration: IV or IM Onset: 2-3 min Duration: 3-6hr Indication: moderate pain Commonly used in Emergency Department

Side effects are the same as for all opioids Thought to be safer because of lower risk of respiratory depression due to ceiling effect Will act as an opioid ANTAGONIST in the presence of a full agonist like morphine

Do not use on patients who are already on strong opioids (morphine or fentanyl)

Oxycodone

Synthetic opioid Sustained release form is Oxycontin Indicated for the relief of moderate to severe pain Dose: 10 - 20mg 12 hrly Onset: 30 min Duration of action: 12 hours Immediate release: Oxynorm 5mg tablets 4 hrly prn

Side effects are the same as for all opioids Dose adjustment required in renal and hepatic Insufficiency Used as an alternative to morphine in Opioid rotation

5th Vital Sign: Doctors training module: Pharmacology

Tramadol

Synthetic weak opioid Also increases the levels of noradrenaline (NA) and serotonin (5HT) in the CNS Used for the relief of moderate to moderately severe pain Dose: 50-100mg 6-8hrly (max 400 mg/day) Most common use is oral but also available in injection (IV/SC/IM) IV should be given as slow bolus Onset: 30 min to 1h (peak 2-3h) Duration: 4-6hr

Dose adjustment required in renal and hepatic Insufficiency Side effect same as for all opioids Also has effects on CVS due to NA/5HT May interact with drugs like Amitriptyline, Carbamazepine, Digoxin, MAOI, SSRI, Warfarin Available combined with paracetamol (ULTRACET) which has Acetaminophen 325mg and Tramadol 37.5mg

NALOXONE

Pure opioid antagonist Used in diagnosis and treatment of opioid overdose Give IV (diluted) or IM Half-life 45 60 minutes

Part 3: MANAGEMENT OF SIDE- EFFECTS of OPIOIDS

NAUSEA AND VOMITING

Nausea and vomiting is a common side effect, but should not be a reason for withholding opioids in patients with severe pain

Drugs used to treat nausea and vomiting:

Metoclopramide 10-20 mg stat and 6 hourly Ondansetron 8 mg IV stat and 8H if necessary Granisetron 2 mg IV stat and 8H if necessary Haloperidol 1 mg BD IV or 1.5 mg BD oral Dexamethasone 4 mg IV stat

RESPIRATORY DEPRESSION

May occur with overdose of opioids. Very uncommon Always associated with sedation ! Risk of respiratory depression is minimal if strong opioids are titrated to effect and are only used to relieve pain (i.e. not to help patients to sleep or to calm down agitated patients). Risk of respiratory depression is also minimal in patients on chronic opioid use (e.g. patients on morphine for cancer pain).

RESPIRATORY DEPRESSION Management

1. Confirm Diagnosis: Respiratory Rate <8/minute AND Sedation Score = 2 (difficult to arouse) OR Sedation Score = 3 (unarousable) Pin-point pupils
0 = none (patient is alert) 1 = mild (patient is sometimes drowsy) 2 = moderate (patient is often drowsy but easily arousable) 3 = unarousable S = patient is asleep, easily arousable

RESPIRATORY DEPRESSION Management

2. Administer oxygen face mask or nasal prongs 3. Stimulate the patient tell him/her to breathe 4. Dilute Naloxone 0.4 mg in 4 mls
give 0.1 mg (1 ml) every 1-2 minutes until the patient wakes up or Respiratory Rate > 10

5. Monitor RR, Sed Score Hrly X 4 hrs.

Give another dose of naloxone if resp dep recurs and refer the patient to the ICU / HDU for close monitoring (patient may require a naloxone infusion)

Key points:
For Pain as the 5th Vital Sign to have an impact in improving pain management in our hospitals, doctors & staff should understand all the analgesic medications available and know how and when to use them Important points to note on the pharmacology of drugs are

Onset and duration of action (so you know how often to prescribe the drug) Side effects (so you can anticipate and treat SE)

Key points:

During and after administration of analgesic medication, we must monitor: Pain score

Sedation score, Respiratory rate

** Aim is to achieve reasonable pain relief without unacceptable side effects

Thank You

Have a Nice Day!