การประเมนและจดการอาการปวด

Phichai Chansriwong, MDRamathibodi Hospital, Mahidol University

Objectives

- Incidence– Assessment– Pain management– Management of opioid side effects– Neuropathic pain

Cancer pain

PORTRAITS AND PAIN

Quality of End of Life care in patient’s perspectives: 5 items

• Adequate pain and symptom management• Avoid inappropriate prolongation of dying• Achieving a sense of control• Relieving burden• Strengthening relationships with loved ones

• Quality End-of-Life Care: Patient’s Perspectives, JAMA 1999 281(2) 163-168

Cancer related Pain

• Pain is a very common symptom in cancer patients, and has a great influence on their overall quality of life.

The Battle We Didn’t Choose: Photographing CancerAngelo Merendino

Symptom Prevalence•Pain•Fatigue/Asthenia Constipation•Dyspnea•Nausea•Vomiting•Delirium•Depression/suffering

•80 - 90%•75 - 90%•70%•60%•50 - 60%•30%•30 - 90%•40 - 60%

Incidence

– Ranges:– 33% after curative treatment – 59% on anticancer treatment – 64% with advanced cancer

• Factors associated with development of chronic pain: – CIPN, radiation-induced brachial plexopathy, RT induced chronic pelvic

pain and post surgical pain

• Highest prevalence in pancreatic (44%) and H&N (40%) • Inadequately treated (solid and hematological cancers)

INADEQUATE PAIN ASSESSMENT IS THE GREATEST BARRIER TO OPTIMAL PAIN TREATMENT

PAIN

Missing voice

Assessment

– Assess and re-assess the pain and patient:– Causes, onset, type, site, radiating pain, duration, intensity, relief

and temporal patterns, number of breakthrough pains,– Triggers/relieving factors– Effect of analgesics– Pain description– Physical examination– Investigations– Impact (patient and caregiver)– Alcohol/substance misuse

– Communication with patient and caregiver

The Pain History

Some Questions Particularly Helpful in the Home Setting• What analgesics do they have at home?• How much medication do they have on hand?• Who looks after dispensing the medication?`• What is their nearest hospital phone? Does

the health service deliver? • How do they pay for medication?• How do they renew medications?

Pain Assessment

• Wong - Baker faces pain rating scale ( age> 3 years)

Joint Commission on Accreditation of Health Care Organizations (JCAHO) in 2000. • On a 0 to 10 scale, mild pain can be defined as 0–3, moderate pain as 4–7,

and severe pain as 8–10.• Assessment of a pain complaint is not valid unless a thorough psychosocial

assessment is done

Oncologic emergency

Mechanisms of pain andpathophysiology

• More than two types of pain occur commonly in cancer– Nociceptive Somatic pain– Nociceptive visceral pain– Neuropathic pain

Cancer PainNociceptive Somatic pain: • intermittent to constant• sharp, knife-like, localizede.g. Bone pain• Soft tissue infiltration• Muscle infiltration• Pleural pain• Paraneoplastic syndromes

Nociceptive visceral pain

Nociceptive visceral pain

• Hepatic distension syndrome• Midline retroperitoneal syndrome• Chronic intestinal obstruction• Peritoneal carcinomatosis• Malignant perineal syndrome• Adrenal pain syndrome• Ureteric obstruction syndrome

Neuropathic pain

• Caused by pressure on &/or destruction of• peripheral, autonomic or central nervous• system structures.• Radiation of pain along dermatomal or peripheral

nerve distributions.• Often described as burning and/or deep aching &

associated with dysesthesia or lancinating pain

Neuropathic pain

• Leptomeningeal metastases• Painful cranial neuralgias (e.g., glossopharyngeal neuralgia)

• Painful radiculopathy• Painful peripheral mononeuropathies• Paraneoplastic peripheral neuropathy

Breakthrough pain “Incidental” pain• Breakthrough pain can occur spontaneously or be caused by

activity or end-of-dose failure.• Severe transitory increase in pain on baseline of moderate

intensity or less• Caused by movement, positioning, BM, cough, wound

dressing, etc

Portenoy R, Sem Onc, 24:S16-7-S16-12;1997

movement-related pain

3 categories:1. Volitional incident pain - is precipitated by a voluntary act (e.g. walking).2. Non-volitional incident pain - is precipitated by an involuntary act (e.g. coughing).3. Procedural pain - is related to a therapeutic intervention (e.g. wound dressing).

Characteristics of BP

• Moderate to severe intensity• Rapid onset (<3 minutes in 43% of patients)• Often unpredictable• Relatively short duration• Frequency: 1-4 episodes per day

Breakthrough Pain• Traditionally, treat with 10–20% of the total

opioid dose in a 24-hour period is given as a breakthrough dose.

• Ideal agent:• Potent, pure opioid agonist• Rapid onset• Early peak effect• Short duration• Easily administered

1/6 dose

Flexible use of oral morphine

• Before predictable BTP• Patient preference

New BP medications

Principles of pain management

Inform and involve patients WHO pain ladder Oral route where possible ‘By the clock’ administration

Rescue medications for breakthrough pain

Choosing the Appropriate Analgesic

• In 1984, the WHO has developed 3-step model

• Comprehensive assessment is vital for good symptom management

Mild pain(0-3)

Moderate pain(4-6)

Severe pain(7-10)

By the mouthBy the clockBy the ladder

Acetaminophen

Codeine

Morphine

WHO pain ladder

WHO approach to drug therapy of cancer pain

• Five essential concepts

1. By the mouth: The oral route is preferred for simplicity in management of nociceptive and neuropathic pain.2. By the clock: in addition to as-needed (prn) doses.3. By the ladder: 4. For the individual: The dose varies from individual to individual.5. With attention to detail: Other factors (e.g., psychosocial distress, spiritual concerns) need to be assessed and dealt with in addition to pharmacotherapy, thereby treating total pain.

WHO ladder

• >85% of patients achieve good pain control using standard oral analgesic regimens

(WHO Analgesic Ladder)

NEW, Recommendation forWHO step II opioids

• Low doses of a step III opioid such as morphine or oxycodone may be used as an alternative step ii opioid instead of codeine or tramadol

• EAPC Guidelines, 2012

Important Issues in the Use of Non-opioid Analgesics

1. Use in full doses for the most part.- caution in patients in renal failure.

2. The non-opioid analgesics that characterize step 1 of the WHO ladder all have a ceiling effect to their analgesia ( a maximum dose past which no further analgesia can be expected).

Analgesic elevator

https://www.iasp-pain.org/PublicationsNews/NewsletterIssue.aspx?ItemNumber=2121

Choices for 1st line therapy

1990• Morphine

2010• Morphine• Oxycodone• Fentanyl• Methadone

Common opioids

MorphineTraditionally, drug of first choice for moderate to severe cancer pain• Familiarity, availability and cost•Absorption –upper small bowel•Liver is major site of morphine metabolism•Kidney is main organ of excretion

Glare P. Morphine In: Opioids in cancer pain. Davis M, Glare P, Hardy J (eds.)2005 Oxford Medical Publications

Morphine

Titration guidelines to start morphine

Opioid naïve:–Start at the lowest available dose and titrate slowly–Increase gradually to analgesia and / or toxicity–Monitor patient pain scores and breakthrough use–Monitor for toxicity features

•Previous opioid use1,2:–Check the conversion ratios

–Dose reduce by 20% - 50% for incomplete cross tolerance

1.Recommended reading: deStoutz ND, Bruera E, Suarez-Almazor M. J Pain Symptom manage 1995 Jul;10(5)378-842.Fine PG, Portenoy RK (2009) Establishing best practices for opioid rotation: conclusions of an expert panel. J Pain SympManage 38:418-425

Opioids and renal impairment

• Mod-severe renal impairment:– Use short acting preparations– Reduce dose and increase dose interval– Considerations for specific opioids, e.g.

alfentanil– Individual considerations (analgesic

need, prognosis, routes, formulations)

Opioids and renal impairment

– Rules of thumb– Avoid codeine and dihydrocodeine– Both morphine and oxycodone have active

metabolites which may accumulate– But inconsistency on the significance of any

accumulation of oxycodone metabolites…..– Alfentanil, fentanyl and methadone

metabolised in liver to inactive metabolites therefore safe!

Choosing the Right Dose

• Starting Doses of Potent Opioid in Opioid Naïve Patients:

• 5-15 mg IR morphine/ MSS q4h

Fentanyl

Fentanyl

•Synthetic opioid, mu receptor agonist•Lipophilic, low molecular weight molecule•More potent than morphine (75:1 – 150:1)•Transdermal application

–Depot in skin and subcutaneous tissues–Delay of 17 – 48 hours before maximal steady state plasma

concentrations–Slow titration process

- This limits its use in emergency situations, though, since it takes up to 18 -24 hours to reach peak

National institute for Health and Care Excellence (NICE) Opioids in palliative care Evidence Update 58, May 2014

• Transdermal fentanyl may be considered for patients in whom:

–oral opioids are not suitable• AND

–analgesic requirements are stable

Oxycodone

•Semi-synthetic derivative of thebaine•Clinical use since 1917•Half-life of 2 – 3 hours•Clinical duration of effect is 4 – 5 hours•High oral bioavailability•Cancer and non-cancer pain•Cornerstone of pain management in a wide variety of settings 1

1. Riley J, Eisenberg E, Muller-Schwefe Get al. Oxycodone: a review of its use in the management of pain. Curr Med Res Opin 2008 ;24:175-192

Oxycodone

•Action at the mu and kappa receptors•In-vitro binding studies, suggest lower affinity for the mu opioid receptor•Hepatic metabolism, renal excretion•High oral bioavailability (up to 87%)•Bioavailability increased in elderly by 15%Dose conversion = 2/3 of morphine

Nielsen et al. Pain 2007. Dec 5; 132(3):289-300. Ordonez Gallego A et al. Clin Trans Oncol 2007 May; 9(5):298-307

Is oxycodone a superior drug to morphine?

• Higher oral bioavailability• Morphine 22%-48% vs Oxycodone 42% - 87%• The oral availability of morphine is 20 - 40% which

means that for every 10mg of morphine given orally 2 to 4mg reaches the systemic circulation.

• oxycodone is approximately 80%, which means that for every 10mg of oxycodone given orally approximately 8mg reaches the systemic circulation.

Is oxycodone a superior drug to morphine?

• More predictable pharmacokinetics• Greater potency • Largely inactive metabolites• Adverse effects of oxycodone are similar to

those of morphine.

Methadone

• low cost and well-understood pharmacological properties, methadone is now accepted as a second-line opioid for the treatment of cancer-related pain.

• Methadone is tightly bound to A-1-acid-glycoprotein, shows high lipid solubility, and given its significant tissue distribution, sustains a steady level in plasma during chronic treatment. No active metabolites are currently known.

Methadone

• Metabolism by the cytochrome P450.• methadone, there are two phases identified:

– a rapid and extensive distribution phase (half-life of 2–3 hours) followed by a slow elimination phase (half-life of 15–60 hours).

• This extended elimination phase is of particular clinical importance since it can result in accumulation and toxicity.

• It is also considered to be an NMDA receptor antagonist and may have a role in the management of opioid-resistant and neuropathic pain.

• Adverse effects include sedation, nausea, and respiratory depression.

Methadone : indications in palliative care

methadone has many advantages in palliative care. It can be administered orally, rectally, and intravenously and inexpensive.(1) treatment of patients with opioid resistance and

neuropathic pain (2) as a second-line agent in opioid rotation.

Treat for opioid addiction. It was termed a “killer drug” by the New York Times.

Oral to IV opioids

• ผสมยา Morphine NSS ในสดสวน 1 mg/1 cc เพอใหคดงาย

(Morphine 1 amp = 10 mg/1ml)

Dose conversion : Morphine VS fentanyl

Beribart’s method

คานวณ Fentanyl 1 µg/hr ตอ

Morphine oral 2 mg/24 hrs

ตวอยางเชน ผปวยตองการ 360

mg/24hrs = Fentanyl patch 180 µg/hr

หรอใช Fentanyl 50 µg/hr จานวน 3

แผนรวมกบ Fentanyl 25 µg/hr อก1

แผน

Patients usually benefit from rotations from a previous opioid to methadone over 3 days,

Meperidine: not recommend

• It is predominantly a mu opioid receptor agonist, available in oral and IV formulations.

• It undergoes hepatic metabolism to normeperidine and is excreted renally.

• With the potential for increased central nervous system excitability and convulsions, it should be used with extreme caution in renal impaired and elderly patients.

Subcutaneous route

Drug Conversions: Subcutaneous morphine

Watson M., Lucas C., Hoy A., Back I (2005) Oxford Handbook of Palliative Care Oxford University Press Oxford.

Subcutaneous morphine is 2 times the potency of oral morphine.

Route of administration SC cannula insertion sites

Acceptable Not proper

• Anterior aspect of the upper arms or anterior abdominal wall

• Anterior aspect of the thigh• The scapula if the patient is

distressed and/or agitated• Anterior chest wall

• Skin folds• Directly over a

tumor site• Lymphoedematous

limb• The abdominal wall

if ascites present• Bony prominences

– little SC tissue, absorption reduced

• Previously irradiated skin

• Sites near a joint• broken or bruised

skin

Watson M., Lucas C., Hoy A., Back I (2005) Oxford Handbook of Palliative Care Oxford University Press Oxford.

Drugs must not be given by the SC route

they may cause tissue necrosis:• Antibiotics.• Diazepam.• Chlorpromazine.• Prochlorperazine (stemetil®).

Watson M., Lucas C., Hoy A., Back I (2005) Oxford Handbook of Palliative CareOxford University Press Oxford.

Naloxone

• เปน competitive inhibitor แยงจบท opiate receptor แตการ

จบของ naloxone กบ receptor ไมมฤทธลดอาการปวดและไมกดการ

หายใจทศนยควบคมการหายใจ

• naloxone จะแสดงฤทธตอตานฤทธของสารจาพวกฝนภายใน 1-2 นาท หลง

ฉดเขาเสนและมฤทธอยได 1-4 ชวโมง โดยม half-life ในเลอดประมาณ 60นาท

ขอบงใช

• แกการกดการหายใจจากการไดรบสารเสพตด หรอ opiates เกนขนาด

• ทดสอบเพอวนจฉยแยกโรคผ ปวย coma วามสาเหตจากยาเสพตด หรอยาแก

ปวด opiates อนๆ

Naloxone

ขนาดและวธใช

• ไมควรIM เนองจากการดดซมไมสมบรณและไมแนนอน

• ผ ปวย coma จากสาร opioid– ฉดขนาด 0.4-2 mg IV และซาทก 2-3 นาท ถาผ ปวยยงไมรสกตวหลงใหยา

ไปแลวรวม 10 mg แสดงวาอาจไมใชภาวะเปนพษจาก opioid– กรณ opioid ทม half-life ยาว เชน methadone,

propoxyphene การแกฤทธตองใหซาทก 1-4 ชวโมง

• Infusion กรณตองการใหยาตอเนองควรให 0.4-0.8 mg/hr ผสม

ใน 5% dextrose ปรบขนาดยาตามอาการแสดงของผ ปวย

Naloxone

• รปแบบของยา

• Naloxone HCI (Narcan) 0.02 mg/ml (2 ml/amp) สาหรบ ฉดหรอ 0.4 mg/ml (1 ml/amp) สาหรบฉด

Wermeling DP. Review of naloxone safety for opioid overdose : practical considerations for new technology and expanded public access. 2015.

http://med.mahidol.ac.th/poisoncenter/sites/default/files/public/pdf/books/Antidote_book5-04_Naloxone.pdf

Opioids and respiratory function

• Respiratory depression is one of most feared opioid effects

• Parenteral opioid titration in cancer pain is:– Not associated with respiratory depression– No significant changes in ET CO2– No significant changes in oxygen saturation

• Titration of parenteral opioids for moderate to severe cancer pain is not associated with respiratory depression

– Estfan B, Mahmoud F, Shaheen P, Davis MP et al Palliat Med 2007 21:81-86

Constipation

• Constipation is easier to prevent than treat

Opioid induced bowel dysfunctionOpioids bind to mu receptors in GI tract resulting in:

–Reduced motility throughout GI tract–Reduced pancreatic and biliary secretions–Increased fluid reabsorption–Reduced forward propulsion

•Uncoordinated peristaltic movements•Increased sphincter tone

Nondrug treatments: increasing fluid and dietary fiber intake, increasing physical activity, and establishing a toileting routine.

Constipation• There are no studies showing superiority of

one laxative over another. • senna with or without a stool softener.• If patients do not have an adequate response,

a trial of an osmotic agent (e.g., sorbitol), Bulk forming laxatives, enema may be used.

Oxycodone-with-naloxone controlled-release tablets (Targin) for chronic severe pain

• Practical: The naloxone component reduces, but does not eliminate,

opioid-induced constipation

• In key trials, the prevalence of constipation with oxycodone-with-

naloxone CR compared with oxycodone CR was about 25% lower

among people with a history of constipation, and 7% lower in an

unselected group.

• The available strengths are oxycodone/naloxone: 5 mg/2.5 mg, 10

mg/5 mg, 20 mg/10 mg and 40 mg/20 mg.

• (Fixed dose ratio of 2:1)

TREATMENTS OF OIN

• if neurotoxicity is “mild” can reduce the dose of opioid----without rotating it

• Moderate to severe---rotate the opioid and reduce the dose 20-30%

• reduce opioid dose and add an adjuvant• Naloxone not recommended for neurotoxicity

Opioid Rotation• Metabolites cause OIN• Change to another opioid analgesic• 25 - 50% dose reduction• Morphine/oxycodone• Second line agentsfentanylmethadone

Other treatment

• Surgical: med failure or intolerated– Post herpetic neuralgia

• Dorsal root entry zone (DREZ) dressing, Spinal cord stimulation

– Trigeminal neuralgia • Microvascular decompression, Radiofrequency thermoregulation ,

Motor cortex stimulation , Gamma knife

• PM&R• Alternative treatments

– ฝงเขม / นวด

Tricyclic antidepressants

– Blocks the presynaptic re-uptake of serotonin and noradrenaline in the CNS, enhancing the action of the descending inhibitory pathways2 classes:– Tertiary amines (amitriptyline, imipramine, doxepin, clomipramine)– Secondary amines (nortriptyline, desipramine)– Amitriptyline: start low dose at night and titrate accordingly– If intolerable adverse effects/no benefit in one week then consider stopping the drug

Anticonvulsants

– Chemical analogue of GABA (but not GABA receptor agonist) – Reduces calcium influx in hyper-excited neurones – No good evidence that more effective than TCAs– No direct comparator studies – Caution in renal impairment– Common side effects: gastric intolerance (nausea and vomiting), sedation, ataxia, dizziness and confusion

– Gabapentin: 300 - 1200 mg tds – Pregabalin: 75mg - 300mg bd

Intractable Severe Pain Syndromes

• Rarely a patient will have pain that is totally intractable to good control.

• This type of suffering is difficult for patient, family and care providers to observe.

• Counseling services must be available.• Consultation with pain management experts must be

sought.• Terminal sedation may be the only option close to

death.

Patient-controlled analgesia (PCA)

Indicated in refractory pain syndromes with acute exacerbations of pain. PCAs are available for use on an outpatient basis with appropriate supervision. In the outpatient or home setting, the SC route may be considered because of its convenience and ease of use.

Miscellaneous

In refractory pain situations, drugs include:• psychotropic drugs• Benzodiazepines• Bisphosphonates• Steroids• Lidocaine• Ketamine• Capsaicin• radiopharmaceuticals (strontium-89, samarium-153),

Nerve blockade

– Peripheral nerve blocks rarely principle pain management – Neurolytic blocks: 3-6 mths relief – Eg. Superior hypogastric plexus (pelvic/perineal); celiac plexus (pancreatic)

Alternative Therapies• Acupuncture • Cognitive-behavioral therapy (CBT)• Meditation/relaxation• Guided imagery• Herbal preparations• Magnets• Therapeutic massage

Psycho-Social-Spiritual

Codeine

- Codeine , it can be one of the most constipating of all drugs - half-life of 2–3 hours- metabolized by the liver- Approximately 10% of the Caucasian population has mutations in the hepatic enzyme CYP2D6 and therefore cannot convert codeine to morphine, resulting in poor analgesic efficacy.

End of life

• – Consider alternative route of administration – Maybe accompanied by other symptoms: dyspnoea, agitation, delirium and anxiety

• – May require sedation • – Multidisciplinary team approach

Conclusion

• Opioids are essential medications for symptom management in cancer care.

• MST, Fentanyl, Oxycodone are the treatment of choice in cancer pain.

• Thailand stills be an inadequate morphine consumption nation group and need improvement in cooperation of health professional for cancer pain treatment