2017 Pharmacy Education - ProCEs3.proce.com/res/pdf/CHS2017May17Handout.pdf2017 Pharmacy Education...

Multi‐Modal Surgical Pain ManagementCHS Pharmacy Education Series

ProCE, Inc.www.ProCE.com 1

2017 Pharmacy Education Series

May 17, 2017Multi‐Modal Surgical Pain Management

Featured Speakers:

Julie A. Golembiewski, PharmDTodd B. Edmiston, M.D.

2

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2016 Pharmacy Education Series

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It is the policy of ProCE, Inc. to ensure balance, independence, objectivity and scientific rigor in all of its continuing education activities. Faculty must disclose to participants the existence of any significant financial interest or any other relationship with the manufacturer of any commercial product(s) discussed in an educational presentation. Dr. Golembiewski has served as a content expert for Pacira. Dr. Edmiston does not have any relevant commercial and/or financial relationships to disclose

Please note: The opinions expressed in this activity should not be construed as those of the CME/CE provider. The information and views are those of the faculty through clinical practice and knowledge of the professional literature. Portions of this activity may include unlabeled indications. Use of drugs and devices outside of labeling should be considered experimental and participants are advised to consult prescribing information and professional literature.

May 17, 2017Multi‐Modal Surgical Pain Management

Featured Speakers:

Julie A. Golembiewski, PharmDTodd B. Edmiston, M.D.

CE Activity Information & Accreditation

ProCE, Inc. (Pharmacist and Pharmacy Technician CE)

– 2.0 contact hours

6

Funding:This activity is self‐funded through CHSPSC.



Multimodal Surgical Pain Management

Julie Golembiewski PharmDMay 17, 2017

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Multimodal Care• “No single element by itself will improve outcomes of surgery. • The approach to perioperative care must be multimodal, using all

available elements of care that improve recovery. • The key is to seek synergy between one process element and the next. • Since elements of ERAS are implemented by different departments, a

multidisciplinary approach is necessary.”

JAMA Surgery 2017;152(3):292-298

(ERAS)

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ENHANCED RECOVERY AFTER SURGERY PROTOCOL FOR TOTAL HIP OR KNEE REPLACEMENT SURGERY

Br J Anaesth 2016;117(S3):iii63 9

MULTIMODAL ANALGESIA

• Combination of therapies that target different mechanisms to provide analgesia

• Types of therapies may include non-pharmacological strategies, medications, interventions/procedures and/or psychosocial support

• Medication therapies may include non-opioids (e.g. acetaminophen, non-steroidal anti-inflammatory drugs, local anesthetic, gabapentin) and opioids

https://www.uptodate.com/contents/image?imageKey=PC%2F74589&topicKey=ANEST%2F398&source=outline_link

NSAIDAcetaminophen

Opioid

OpioidGabapentin

Local anesthetic(epidural)

NSAIDLocal anesthetic(local infiltration,nerve block)

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PREVENTIVE ANALGESIA• Interventions aimed at reducing:

– Postop pain

– Postop analgesic requirements

– Triggers for central sensitization pain that persists after normal tissue healing

• Interventions given prior to skin incision vs. after skin incision mixed results

• Multimodal interventions started preop andcontinued through postop period reduced postop pain and analgesic consumption, possibly allowing more rapid recovery and earlier discharge

Local and Regional Anesthesia 2014;4:7 17-22Indian Journal of Pain 2013;27(3):114-120Pain Physician 2013;16:E217-E226 11

ACETAMINOPHEN

Prevention Treatment

Oral Intravenous

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ACETAMINOPHEN FOR PREVENTING POSTOP PAIN

• Compared with no treatment, oral or IV acetaminophen: – Improved early (0-4 hr) pain control in some studies;

no difference in other studies 1

– Reduced opioid consumption by about 20% • Mean of 6.3 to 9 mg IV morphine 1

• Did not reduce opioid adverse effects1, however a recent meta-analysis concluded IV acetaminophen reduced postop nausea/vomiting possibly by a direct mechanism or by reducing pain2

1 Clin J Pain 2015;31:86082; Br J Anaesth 2005;94:505; Health Technol Assess 2010;14:1; Anesthesiology 2005;103;12962 Pain 2013;154;677 13

Children who received intra-op IV acetaminophen had a higher rate ofrequiring an IV opioid or other pain intervention in Post Anesthesia Care Unit (PACU) than children who did not receive IV acetaminophen

From the author:

“A number of studies that have shown efficacy for IV acetaminophenhave looked at multiple doses of the drug, particularly in patients undergoing orthopedic procedures. When single-dose IV acetaminophen has been studied, the results have been similar to what we found.”

ASA Abstract A3021 October 24, 2016 14



ACETAMINOPHEN FOR TREATING POSTOP PAIN

• 75 studies (7,200 patients) received a single dose of IV acetaminophen or placebo

• Results – IV acetaminophen provides about 4 hours of

effective analgesia for 36% of patients experiencing postop pain (NNT = 5)

• IV acetaminophen patients required 26% less opioid over 4 hours with no reduction of opioid adverse effects

Cochrane Database Syst Rev 2016;CD007126 15

ORAL ACETAMINOPHEN• High bioavailability

• Rate of gastric emptying determines rate of absorption in small intestine

• When given before abdominal surgery * . . .– Lower maximum (peak) plasma concentration but overall

amount absorbed (area under curve) unchanged

– Small intestine begins to function normally about 6 hours after surgery

* Br J Anaesth 2006;97:171 16



IV VS. ORAL ACETAMINOPHEN

• Systematic literature review *• Results

– Efficacy (3 studies)• Opioid requirements significantly less with IV following CABG;

no difference in adverse effects or pain scores• No difference in opioid requirements or pain scores following

knee arthroscopy• Oral noninferior to IV following molar extraction

– Pharmacokinetic outcomes (4 studies)• Higher plasma concentration with IV

– Adverse events (4 studies)• No adverse events associated with use

• Conclusion– No strong evidence of superiority of IV over oral – No clear indication for IV over oral in patients with a

functioning GI tract who can take oral meds* Can J Hosp Pharm 2015;68:238 17

NSAIDS

• Treating postop pain 1

– Effective; NNT generally between 2 and 4.3

• Preventing postop pain 2

– Improved analgesia

– Reduced opioid requirements after surgery, often with reduced postop nausea/vomiting and sedation

NSAIDs = Nonsterioidal Anti-Inflammatory Drugs

1 Cochrane Database Syst Rev 2011;9:CD0086592 Health Technol Assess 2010;14:1; Anesthesiology 2005;103:1296; Can J Anaesth 2006;53:46; Anesth Analg 2012;114:424 18



ACETAMINOPHEN VS. NSAIDS

Cochrane Database Syst Rev 2015;CD008659

And, from a recent meta-analysis (Br J Anaesth 2017;118:22)

“A combination of acetaminophen with either an NSAID or nefopamwas superior to most analgesics other than morphine used alone.”

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NSAIDS –ADVERSE EFFECTS

• Cardiovascular (myocardial infarction, stroke)– Risk varies depending upon patient’s baseline CV event risk,

NSAID chosen and dose– Celecoxib may be preferred to nonselective NSAIDs for patients

with established heart disease

• Renal – Avoid in patients with chronic kidney disease (stage 3 or worse),

volume depletion or high risk for acute kidney injury

• Surgical bleeding (NOT celecoxib)– No association between ketorolac use and periop blood loss

except following tonsillectomy

• Bone healing– Short-term use does not affect fracture union– Studies demonstrating negative effect were following prolonged

(several weeks) useASA abstracts A2015, October 23, 2016

NSAIDs: Acute kidney injury (acute renal failure) UpToDate, Accessed April 18, 2017NSAIDs: Adverse cardiovascular effects. UpToDate Accessed April 18, 2017 20



GABAPENTIN AND PREGABALIN

• Improved analgesia

• Opioid-sparing with reduced opioid adverse effects (nausea, vomiting, urinary retention)

• Adverse effects– Dizziness, sedation

– Although analgesic effect is additive with opioid, addition of gabapentin or pregabalin may:

• Potentiate respiratory depressant effect of the opioid

• Adversely affect cognition

Acta Anaesthesiol Scand 2014;58:1165Anesthesiology 2016;124(1):141-149

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LOCAL ANESTHETICS

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MECHANISM OF ACTION

• Bind to fast sodium channels within axon membrane to block propagation of action potential (pain impulse)

• Inhibit local inflammatory response to injury, which normally sensitives nociceptors and contributes to pain

• Prevents central nervous system hypersensitivity, “wind-up” or sympathetic skin response

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Agent Onset Duration Max Dose * Comments

Chloroprocaine Fastest Short 800 (1,000) Epidural

Lidocaine Rapid Intermediate 300 (500) Most frequently used agent

Mepivacaine Moderate Intermediate 300 (500) Nerve block, epidural

Bupivacaine Slow Long **(up to 12 hrs)

175 (225) Local infiltration,nerve block, epidural, spinal

Bupivacaine liposome

Slow Longest (up to 72hrs)

266 Local infiltration only

Ropivacaine Slow Long **(up to 12 hrs)

200 (200) Local infiltration, nerve block, epidural

* In milligrams; epinephrine containing solution in parenthesis** May be given as a continuous infusion for local infiltration, epidural, peripheral nerve block

AGENTS

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PERIOPERATIVE ROUTES OF ADMINISTRATION OF LOCAL ANESTHETICS

Topical

Subcutaneous,deep tissue

Transversusabdominis plane*

Tumescenttechnique

Intra- orperiarticular

Spinal

Epidural

Intravenous(lidocaine only)

Peripheralnerve block

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SPINAL AND EPIDURAL ANESTHESIA

Spinal needle

Anesthesiaor

Analgesia

Primarily Anesthesia

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NERVE BLOCK ANESTHESIA(PERINEURAL INJECTION)

Femoral nerve block Sciatic nerve block

Source: http://www.privatehealth.co.uk/private-operations/Anaesthesia/femoral-nerve-block/http://www.privatehealth.co.uk/private-operations/Anaesthesia/sciatic-nerve-block/

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LOCAL INFILTRATION AROUND SURGICAL WOUND

Single injection –Limited by duration of action of local anesthetic agent

Continuous infusion via a catheter prolongs duration of action

Subcutaneous and/or Deep Tissue Injection

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OTHER ROUTES OF ADMINISTRATION

• Transversus abdominis plane (TAP) block– Local anesthetic is injected into plane between internal

oblique and transversus abdominis muscles

• Tumescent infiltration– Large volumes of very dilute lidocaine and epinephrine

infiltrated into subcutaneous tissues swollen, firm, anesthetized tissue cannulas placed for liposuction

• Intra- or periarticular injection– Direct injection into areas of

knee or hip with pain receptors

• Topical• Intravenous

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LIPOSOMAL BUPIVACAINE INFILTRATION AT SURGICAL SITE

• Cochrane review• Results

– Pain intensity over first 72 hours (3 studies)• Lower cumulative pain scores vs. placebo• No difference vs. bupivacaine HCl (2 studies)• Lower mean pain score at 12 hours vs. bupivacaine HCl (1 study)

– Longer time to first opioid dose vs. placebo (2 studies)– Lower total opioid consumption vs. placebo (1 study) but not vs.

bupivacaine HCl (1 study)– Percent of patients who did not require an opioid over first 72 hours

(3 studies)• Higher % of patients vs. placebo (1 study) • No difference vs. bupivacaine HCl (1 study) or placebo (1 study)

• Conclusion– Liposome bupivacaine reduces pain vs. placebo – Limited evidence at present time does not demonstrate

superiority to bupivacaine HClCochrane Database of Systematic Reviews 2017;Issue 2. Art. No. CD011419 30



LOCAL ANESTHETIC TOXICITY –CLASSIC TEACHING

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HOWEVER …

• Nearly half of reports of local anesthetic systemic toxicity are in patients either < 16 years old (16%) or > 60 years old (30%)

• More than one third of reports of toxicity involved patients with underlying cardiac, neurologic, renal, hepatic, pulmonary or metabolic disease

• Dose reduction and heightened vigilance may be warranted in such patients, particularly if they’re at the extremities of age

Neal et. al. Reg Anesth Pain Med 2010;35:152Rosenberg et. al. Reg Anesth Pain Med 2004;29:564 32



ASRA Checklist for Treatmentof Local Anesthetic Systemic

Toxicity 2012

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OPIOIDS

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Property Morphine Hydromorphone

(Dilaudid)Fentanyl

Onset 5 min ≤ 5 min ≤ 2 min

Peak 15 - 20 min 10 – 20 min 5 – 7 min

Duration(dose dependent)

3 – 4 hours 2 – 3 hours 30 – 60 min

Renal dysfunction Active metabolite can accumulate

OK OK

Equianalgesic dose 1 mg 0.2 mg 12.5 mcg

IV OPIOIDS

When IV route is needed for postop analgesia for more than a few hours, Patient-Controlled Analgesia (PCA) is preferred to intermittent IV boluses

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ORAL OPIOIDSPREFERRED ROUTE FOR

PATIENTS WHO CAN TAKE ORAL MEDS

Opioid Oral Bioavailability

Potency Metabolism

Hydrocodone (Norco, Vicodin)

Good Similar to oralmorphine

Analgesic on its own, metabolized by CYP2D6 to hydromorphone

Oxycodone Good Strong opioid (1.5 x more potent than oral morphine)

Analgesic on its own; metabolized by CYP2D6 to oxymorphone

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CODEINE: TWO KEY PROBLEMS# 1: Codeine is a prodrug; & must be converted to morphine for analgesic effect

# 2: Genetic variability in CYP2D6 enzymes can result in too low or too high morphine plasma concentration with “usual” dose of codeine in some patients

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Pediatric Anesthesia 2013;23:677

Impact of other factors on a child with multiple copies of CYP2D6 allele

4-20-2017

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ADVERSE EFFECTS• Anticipate, prevent and manage

– RR = 1.5 for any adverse effect– RR = 4 for stopping the opioid because of an adverse effect

• Common adverse effects– Sedation (15 – 30%)– Concentration/memory deficits (20 – 25%)– Dizziness (10 – 20%)– Constipation (20 – 40%), nausea, vomiting – Pruritus (10%)

• Occur at all dose ranges; frequency increases with: – Daily use (vs. PRN)– Higher doses – Long-term therapy– Polypharmacy– Decreased renal or hepatic function

• Tolerance develops to most side effects EXCEPT constipation

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SUMMARY:POSTOPERATIVE PAIN MANAGEMENT

The Journal of Pain 2016;17(2):131

Agent Suggested Use

Acetaminophen and NSAIDs

Use as a component of multimodal analgesia (foundation)No clear difference between IV and oral

Oral opioids Use as a component of multimodal analgesia (rescue)Preferred route for those who can take orals

IV opioids Use when parenteral route is neededPCA preferred when IV route is needed for analgesia for more than a few hours

Gabapentin, pregabalin Consider as a component of multimodal analgesia in patients who underwent major surgery

Local infiltrationIntra- or peri-articular

Use in surgical procedures for which there is evidence of benefit

Peripheral nerve block Use in surgical procedures for which there is evidence of benefit

Epidural analgesia Use for major thoracic, abdominal, cesarean delivery and lower extremity surgery

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Multi-Modal Surgical Pain Management

May 17th, 2017

Todd Edmiston, MD

South Baldwin Regional Medical Centera CHS facility in Foley, Alabama

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Disclosures

None

Fellowship training in Sports and Adult Reconstruction

Director of Orthopaedic Center, South Baldwin Regional Medical Center, Foley Alabama

Chief of Staff, South Baldwin Regional Medical Center, Foley Alabama

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Multi-Modal– adjective

adjective: multi-modalcharacterized by several different modes of activity or occurrence.

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Goal

Prevent Pain– Keep the patient comfortable

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Goal

Prevent Complications (of Opiates)

–Urinary Retention

– Ileus

–Respiratory Depression

–Nausea/Vomiting

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Definition:

Combination of 2 or more analgesic agents or techniques that act by different mechanisms

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Pre-Op

“Pain Management and Best Outcomes Begin with Pre‐Op Planning” TBE

Brain, Cortex

– Education, Setting Expectations

– Pre‐Load

• Celecoxib (Celebrex®) (Cox2) 200‐400mg PO

• Oxycodone HCl (Oxycontin®) 10‐20mg PO

• Acetaminophen 500mg PO

• Metoclopramide (Reglan®) 10mg IV

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Intra-Op

Spinal Anesthetic

Epidural Injection

– Cox2

• Blocks Transmission

50




Intra-Op

– Inflammatory Cells

– Sensory Neurons

Peri-Articular Injection (PAI)

– Cocktail

• Ropivicaine

• Morphine

• Ketorolac (Toradol)

• Epinephrine

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Post-Op Recovery Room

– Peripheral Nerve Block

• Adductor Canal

• ICE


• Opioid IV or PO

• DVT Prophy

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Post-Op Floor

• ICE


• Opioid PO

• Opioid IV

• DVT Prophy

• Therapy

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IV Acetaminophen

– Affects Central Pain

– IV vs PO

– Liver toxicity

– Costly

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History of Pain Management during Total Knee Arthroplasty

– 1980s ‐ IV Opiates

– 1990s ‐ IV Opiates and PCA pump

– Urinary Retention

– Ileus

– Respiratory Depression

– Nausea/Vomiting

» +15%

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– 2000s ‐Multi‐Modal Pain Management

• Peripheral Nerve Block

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2000s ‐Multi‐Modal Pain Management

• Peripheral Nerve Block

IV & PO Opioid vs MMPN with PNB

– Femoral Nerve Blocks and Sciatic Nerve Blocks

• Reduced Opioid Requirements

• Lower Pain Scores

• Faster Time to Discharge

Hebl JR et al, Reg Anesth & Pain Med 33, 2008

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– 2000s ‐MMPM with Peripheral Nerve Block

– 2010s ‐MMPM with Peri-Articular Injection

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2010s ‐MMPM with Peri-Articular Injection

Total Knee Arthroplasty with MMPM and PAI• Literature Review

• Lower Pain Scores

• Reduced Narcotic Requirements

• No change in Length of Stay

Gibbs et al, JBJS 94B, 2012

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Prospective Randomized Trial Comparing PNB and PAIfor pain management following Total Knee Arthroplasty.

– Same surgery technique, Same implant, Same post op medications

– PNB ‐ Femoral NB and Sciatic NB

– PAI ‐ Ropivicaine, Morphine, Ketorolac (120ml)

• Pain Scores Equal in both groups

• Length of Stay was 1/2 day shorter in PAI group

Spanghel, Clarke et al, CORR, 2015

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Prospective Randomized Trial Comparing PNB and PAI for pain management following Total Knee Arthroplasty.

• Length of Stay was 1/2 day shorter in PAI group

–Earlier mobilization in PAI group

• PNB group had 12% nerve injury rate at 6 weeks f/u


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Prospective Randomized Trial Comparing PNB and PAI for pain management following Total Knee Arthroplasty.

• No statistical difference in complication rate

–3 Falls in PNB group

–0 Falls in PAI group


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Bupivicaine– Long acting local anesthetic

– Half‐Life = 3.5 hrs

– Effects typically last up to 9 hrs

63


Liposomal Bupivicaine

– Up to 72 hours of pain relief

– Does not disperse into the soft tissues as well

– Limited data to show superiority

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Dosing Study Comparing Liposomal Bupivicaine vs Bupivicaine HCl

Liposomal Bup ‐ 133mg, 266mg, 399mg, 532mg

Standard Bup ‐ 150mg

Only the 532mg of Liposomal showed a superior effect over 150mg Standard

– 4x the dose

Bramlett et al, The Knee, 2012

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PAI Study with single variable = Liposomal Bupivicaine

– 2 Groups each with PAI cocktail

– Substituted Liposomal Bupivicaine with regular Bupivicaine in the Traditional PAI cocktail

First 24 hrs = No Statistical Difference in Pain Scores

After 24 hrs = Better pain scores in the regular cocktail group

– Liposomal Bupivicaine had inferior pain management after 24 hours

Meneghini et al, J Arthroplasty, 2014

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PAI Study comparing Liposomal Bupivicaine with the traditional cocktail

–No Difference in Narcotic Usage

–No Benefit to use of Liposomal

• Liposomal Bupivicaine ~$300

• Standard Bupivicaine ~$5

Shroer et al, J Arthroplasty, 2015

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PAI Study comparing Liposomal Bupivicaine with the Ranawatcocktail

• Dr. Ranawat's cocktail is same as described with addition of Clonidine.

–No Difference in Narcotic Usage

Collis et al, J Arthroplasty, 2016

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Is PAI Technique dependant?• Several different injection techniques compared

• Infiltrate the tissues

• Avoid filling the joint

–No Difference in outcome

Meneghini et al, J Knee Surg, 2016

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Peri-Articular Multi-Modal Drug Injections

• PA Injections offer better pain control over PCA alone or Epidural alone.

– Cocktail:

• Bupivicaine or Ropivicaine

• Morphine 5‐10mg

• Ketorolac 30mg

• Volume increased with NS up to 60‐120ml

Martin Roche, 2015

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Technique

– Peri-Articular Injections

• Multiple Branches

• Multiple Injections

• Liposomal Bupivicaine

– Decreased Dispersement

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Technique

– Peri-Articular Injections

• 60cc ‐120cc

• Infiltrate into the tissues

• Subperiosteal tissue

• Posterior

• Subcutaneous

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Technique

– Adductor Canal Injections

– Peripheral Nerve Block

• 30cc

• 0.5% Bupivicaine

• Infiltrate into the canal

• Block sensory not motor fibers

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My Protocol

Pre‐Op

– Education & Expectations

Intra‐Op

– PAI

Recovery Room

– Lite Adductor Block (sensory)

Floor

– Cryotherapy

– Compression

– Elevation

– Early Mobilization w Therapy

– PO and IV Opioids

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My PAI Injection

My Potion: $13.85

– Ropivicaine 0.2% — 20ml

– NACL IV 0.9% — 37ml

– Morphine — 2mg

– Ketorolac (Toradol) — 15mg

– Epinephrine 1:1000 — 0.3ml

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Thank You76



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Jerry H. Reed, MS, RPh, FASCP, FASHP

Senior Director, Pharmacy Services

Community Health Systems

Update on Current Pharmacy Initiatives and Strategies



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2017 Pharmacy Education - ProCEs3.proce.com/res/pdf/CHS2017May17Handout.pdf2017 Pharmacy Education...

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