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Perioperative pain management in Opioid dependent patient

Amr Zidan, MD, FIPP Chairman, Department of Anesthesia and Pain Management, Tawam Hospital Assistant Professor Johns Hopkins Medicine

Objectives

Pathophysiology Adverse effects of perioperative pain Treatment options Scientific Evidence

Pathophysiology of Postoperative Pain

6 problems: 1. Peripheral sensitization 2. Constant bombardment of the CNS with noxious input 3. Noxious input processed by the CNS 4. Pathophysiological consequences of acute pain 5. Sensitization of the CNS response, called wind-up 6. Induced sensitivity in the nervous system outlasts the stimulus

Pain Pathways:

Tissue damage>>>Algesic substanses release>>>Noxious stimuli>>>A delta and C fibers to the neuraxis>>>Many to anterior and anterolat.Horns>>>Segmental reflex responses , and others via the Spinothalamic and Spinoreticular tracts>>>Supra-segmental, limbic and cortical responses.

1. Peripheral sensitization

2. Constant bombardment of the CNS with noxious input

3. Noxious input processed by the CNS

Adverse spinal reflexes, such as muscle spasm and sympathetic stimulation, are provoked. Supraspinal reflexes incite the mediators of the stress response.

4. Sensitization of the CNS response

Central sensitization refers to enhanced excitability of dorsal horn neurons and is characterized by: 1. increased spontaneous activity 2. Enlarged receptive field area 3. An increase in responses evoked by large and small caliber primary afferent fibers

4. Sensitization of the CNS response

Windup refers to the progressive increase in the magnitude of C-fiber evoked responses of dorsal horn neurons produced by repetitive activation of C-fibers. Triggered by neurotransmitter glutamate and neurokinin peptides (substance P)

Cardiovascular Pulmonary

Gastrointestinal Renal

tachycardia, hypertension, increased SVR, increased cardiac work hypoxia, hypercarbia, atelectasis; decreased cough, VC, FRC; ventilation perfusion mismatch nausea, vomiting, ileus, NPO oliguria, urinary retention

Extremities Endocrine

Central nervous system Immunologic

skeletal muscle pain, limited mobility, thromboembolism vagal inhibition; increased adrenergic activity, metabolism, oxygen consumption anxiety, fear, sedation, Delirium, fatigue impairment

How safe is postoperative pain therapy?

Respiratory and haemodynamic effects of acute postoperative pain management: evidence from published data.

Cashman, J.N. and Dolin, S.J. British Journal of Anaesthesia, 93 (2004) 212-223.

How safe is postoperative pain therapy?

Whereas the incidence of respiratory depression decreased over the period 1980-99, the incidence of hypotension did not
Cashman JN, Dolin SJ. BJA Aug 2004

Effectiveness of acute postoperative pain management


Postoperative pain experience: results from a National Survey suggest postoperative pain continues to be undermanaged
Apfelbaum J L et al Anesth Analg 2003; 97:534-540

Pain - a persistent problem


it remains a common misconception amongst clinicians that acute postoperative pain is a transient condition involving physiological nociceptive stimulation, with a variable affective component, that differs markedly in its pathophysiological basis from chronic pain syndromes.
Cousins MJ, Power I, and Smith G. Regional Analgesia and Pain Medicine, 25 (2000) 6-21

Chronic pain after surgery (%)


Perkins & Kehlet Mastectomy 11-49 Thoracotomy 22-67 Cholecystectomy 3-56 Inguinal hernia 0-37 Vasectomy Amputation Macrae Macintyre 23-49 11-57 5-67 5-65 3-27 3-50 15-63 5-63 0-37 0-37 30-85
Wilson JA, Colvin LA, Power I RCoA Bulletin Sept 2002 IASP January 2011

Pain - a persistent problem

it is now known that clinical pain differs markedly from physiological pain and that acute, chronic and cancer pains share common mechanisms.
Cousins MJ, Power I, and Smith G. Regional Analgesia and Pain Medicine, 25 (2000) 6-21

5. Induced sensitivity in the nervous system outlasts the stimulus


Clinical pain Low-threshold Sensitization following injury Allodynia Hyperethesia hyperpathia

Physiologic pain High-threshold Serve to warn the organism of harm

? Can we avoid total analgesia and block only the clinical pain ? The sophisticated goal of preemptive analgesia to achieve a differential effect on physiologic and clinical pain

Treatment Options
1-Systemic opioids. 2-Patient-controlled analgesia(PCA). 3-Regional anesthetic techniques . a - Intraspinal analgesia. b - Patient-controlled epidural analgesia (PCEA). c - Peripheral nerve and Plexus blocks. 4-intraarticular analgesia. 5-Nonopioid analgesics (NSAIDs, Muscle relaxant, Acetaminophen, neuropathic pain medications,..) 6-Cryoanalgesia. 7-T.E.N.S. 8-Psychologic and other methods.

Multimodal Analgesia

Applying What We Know to Postoperative Pain Management


1. Prevent sensitization or stimulation of peripheral receptors

Antihistamines NSAIDs Local anesthetics

Applying What We Know to Postoperative Pain Management


2. Diminish or eliminate the bombardment of the CNS with nociceptive input

Regional anesthesia and Peripheral nerve blocks Intrathecal or epidural analgesia Systemic opioids Small-dose IV ketamine

Applying What We Know to Postoperative Pain Management

3. Continue treatment until the inflammatory reaction that fuels the nociceptive input is minimized NSAIDS Sustained release opioids Consultation with a pain psychologist

Opioid Dependent patients


Acute Chronic, cancer-related Chronic, non cancer-related

What We Already Know about This Topic


Acute pain management of patients with chronic pain who are opioid-tolerant is often difficult. Few interventions have reduced postoperative opioid requirements or pain scores in this patient population.

Consensus definitions

Tolerance:
a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug's effects over time.

Physical Dependence:
a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.

Savage, et al 2003

Consensus definitions

Addiction:

A primary, chronic, neurobiological disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving.

At variance with WHO & DSM-IV definitions

Savage, et al 2003

Perioperative Management in Opioid-Tolerant Patients


Opioid dependence lowers pain threshold and raises pain sensitivity Constant opioid receptor activity may produce hyperalgesia Chronic opioid users tend to underreport their opioid use. Psychiatric comorbidities are common. Cross-addiction to cannabis, cocaine, alcohol, etc. At risk of under and over treatment Chronic opioid users have higher postop pain scores, yet more frequent incidence of sedation and respiratory depression

1. Rapp et al. Pain 1995; 61:195201. 2. Compton et al. J Pain Symptom Manage 2000; 20:237 245. 3. Breivik et al. Eur J Pain 2005; 9:127130. 4. Rosenblatt et al. Practice 2005; 5:210.

Opioid Dose-effect Relationship

Tolerance

OIH

What Should I do?

From: Kuehn BM. Scientists Probe Ways to Curb Opioid Abuse Without Hindering Pain Treatment. JAMA. 2007;297(18):19 65-1967.

Pre-operative

Identify chronic opioid user (whose responsibility?) Precise opioid use (doses, opioid type, etc.) Potential for increased postoperative pain Patients fears and expectations related to pain management Effective management strategies after previous procedures Postoperative management options/ appropriate regional techniques for complementing opioid analgesia Post discharge pain management plan Continuation of preoperative opioid regimen on day of surgery (prevent withdrawal, falling behind on opioid requirement) VERY IMPORTANT
Rapp. Pain 1995; 61:195201.

Immediate Preoperative Period


Conversion of oral to IV route Consider the bioavailability of oral opioid (Methadone and Oxycontin higher than morphine) Consider chronic opioid users are at high risk for gastric aspiration QT prolongation associated with ventricular arrhythmias in patients on oral methadone >200 mg (consider preoperative EKG)
1. 2. 3. 4. Brill S. Acute Pain 2003; 5:4550. Wallden J. Anesth Analg 2004; 99:429434. Kurz A. Drugs 2003; 63:649671. Walker. Pain 2003; 103:321324.

Intraoperative

Administration of opioids to meet the following requirements:


Chronic need ( daily dose ) Intraoperative surgical pain Anticipated postoperative pain

Avoid muscle relaxant if possible or reverse paralysis early Titration of opioid to respiratory rate 14 to 16 if possible in spontaneously ventilating patient

Intraoperative

Administration of adjuvant medications:


Ketamine 0.5 mg/kg IV bolus followed by 4 g/kg/min infusion Ketorolac 30 mg IV (if NSAID or COX-2 not started preoperatively) Acetaminophen 1,000 mg if not started preoperatively

Institution of appropriate regional technique:

Continuous techniques preferable

Local infiltration with local anesthetic if other technique not possible

Fentanyl patch & Long Acting Opioids

Continue for minor procedures To provide background analgesia Do not apply a warming blanket directly over the patch Convert to IV for major procedures Alterations in body temperature Alterations in intravascular fluid volume Set a Basal Rate that is equivalent to their preop. daily requirement Additional demand doses for post op. pain
1. Rose. Anesth Analg 1997; 84:764772. 2. Frolich. Anesth Analg 2001; 93:647648.

Use of Adjuvant Systemic Analgesics

NMDA Antagonists : Ketamine, Dextrometorphan NSAIDs Acetaminophen Gabapentin, Lyrica, Duloxetine, TCAs, SSRI Alpha 2 Agonist Dexmedetomidine, Clonidine

Post-operative

Titration of opioids, adjuvant medications, and regional techniques to patient comfort:


Expect postoperative opiate requirements to be up to 2 to 4 times the dose required in an opioid nave person. Individuals requirements can not be predicted with confidence. Titrate opioids aggressively to achieve adequate pain control in the postoperative care unit. If oral route is available, start with 1.5 times the preoperative oral opioid dose and PCA for breakthrough pain. If oral route is unavailable, consider basal rate for PCA. Administer at least half of the preoperative opiate requirement systemically. Consider use of high-potency opioids such as fentanyl/sufentanil in place of morphine for epidural management.

Start opioid PCA:


In patients undergoing a regional technique :


Post-operative

Continue acetaminophen 1,000 mg every 6 hours, and/or NSAID, or COX-2 inhibitor for several days with attention to renal function and risk of bleeding. Continue ketamine if started in OR, or institute ketamine infusion if pain proves refractory to other measures. Monitoring for over sedation and opioid withdrawal:

Chronically opioid-consuming patients are at higher risk for respiratory depression than are opioid nave patients and must be monitored appropriately with regular evaluation of sedation and oxygen saturation.

Ketamine

Single low dose bolus 0.15-0.5 mg/kg Low-dose infusion 2-4 mcg/kg/min Avoid fixed dose ratio with opioids Psychotropic SEs are common Unclear:

Combined administration of benzo Who benefits more?


1. 2. 3. 4. 5. 6. 7. 8.

Dix Paediatr Anaesth 2003;13:422-426. Duncan. J Pain Symptom Manage 2002;24:8-11. Eilers. Anesth Analg 2001;93:213-214. Unlugenc. Eur J Anaesthesiol 2003;20:416-421. Unlugenc. Acta Anaesthesiol Scand 2002;46:1025-1030. Jahangir. Bangladesh Med Res Counc Bull 1993;19:21-27. Sveticic. Anesthesiology 2003;98:1195- 1205. Edwards. Anaesthesia 1993; 48:124-

Small-Dose Ketamine Enhances MorphineInduced Analgesia After Outpatient Surgery

IV coadministration of ketamine 50-100 g/kg with morphine 50 g/kg 15 min before the end of the operation 1. Although opiates produce antinociception through receptor agonist activity, they activate NMDA receptors, resulting in hyperalgesia and the development of tolerance to opiates. 2. The marked reduction in both pain score and morphine requirement may be explained by the interaction of ketamine with NMDA receptors that had been activated by perioperative nociceptive inputs, as well as by the administration of morphine.
Manzo Suzuki, Kentaro Tsueda, et al. Anesth Analg 1999;89:98-103

Intraoperative Ketamine Reduces Perioperative Opiate Consumption in Opiate-dependent Patients with Chronic Back Pain Undergoing Back Surgery

Randomized, prospective, double blinded, and placebocontrolled trial involving opiate-dependent patients 52 patients in the treatment group were administered 0.5 mg/kg IV ketamine on induction of anesthesia, and infusion 10mcg/kg/min and terminated at wound closure 50 patients in the placebo group received saline of equivalent volume. Patients were observed for 48 h postoperatively and followed up at 6 weeks. The primary outcome was 48-h morphine consumption
Randy Loftus et al. Anesthesiology 2010

Results: Total morphine consumption (or equivalents) was significantly reduced in the treatment group 48 h after the procedure. It was also reduced at 24 h and at 6 weeks. The average reported pain intensity was significantly reduced in the post anesthesia care unit and at 6 weeks.
Randy Loftus et al. Anesthesiology 2010

NSAIDs

Often omitted Efficacy supported by several reviews and meta-analyses As a component of multimodal treatment Concerns: Renal, gastric, coagulation, cardiac

1. Barden J. Cochrane Database Syst Rev 2003;CD004233. 2. Kokki. Paediatr Drugs 2003;5:103-123. 3. McCrory. Anesth Analg 2002; 95:169-176. 4. Katz. Cleve Clin J Med 2002;69(suppl 1):SI65-SI75. 5. Hyllested. Br J Anaesth 2002;88:199-214. 6. White. Anesth Analg 2002;94:577-585. 7. Gilron. Anesthesiology 2003; 99:1198-1208.

Scientific Evidence

Levels of evidence
I Evidence obtained from a systematic review of all relevant randomized controlled trials. II Evidence obtained from at least one properly designed randomized controlled trial III-1 Evidence obtained from well-designed pseudo-randomized controlled trials (alternate allocation or some other method)

Levels of evidence
III-2 Evidence obtained from comparative studies with concurrent controls and allocation not randomized (cohort studies), case-controlled studies or interrupted time series with a control group III-3 Evidence obtained from comparative studies with historical control, 2 or more single-arm studies, or interrupted time series without a parallel control group IV Evidence obtained from case series, either post-test or pre-test and post-test

Pre-emptive and preventive analgesia

The timing of a single analgesic intervention (pre incisional versus post incisional), defined as preemptive analgesia, does not have a clinically significant effect on postoperative pain relief (Level I). There is evidence that some analgesic interventions have an effect on postoperative pain and/or analgesic consumption that exceeds the expected duration of action of the drug, defined as preventive analgesia (Level I). NMDA (n-methyl-D-aspartate) receptor antagonist drugs in particular may show preventive and analgesic effects (Level I).

Organizational requirements

Preoperative education improves patient or carer knowledge of pain and encourages a more positive attitude towards pain relief (Level II). Implementation of an acute pain service may improve pain relief and reduce the incidence of sideeffects (Level III-3). Staff education and the use of guidelines improve patient assessment, pain relief and prescribing practices (Level III-3). Even simple methods of pain relief can be more effective if attention is given to education, documentation, patient assessment and provision of appropriate guidelines and policies (Level III-3).

Patient-controlled analgesia
1. 2. 3. 4. 5.

6.

Intravenous opioid PCA provides better analgesia than conventional parenteral opioid regimens (Level I). Patient preference for iv PCA is higher when compared with conventional regimens (Level I). Opioid administration by iv PCA does lead to lower opioid consumption, hospital stay or lower adverse effects (Level I). The addition of ketamine to PCA morphine does improve analgesia or reduce the incidence of opioid-related adverse effects (Level I). PCEA for pain results in the use of lower doses of LA, less motor block and fewer anesthetic interventions (Level I).

Take Home

Mind like parachute, does not work if not open Charlie Chan

God heals and the Doctor can claim the fees


Benjamin Franklin 1740

Thank You

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