advancement in the use of multimodal analgesia for acute...

Advancement in the use of multimodal analgesia for acute postoperative pain

Ratan K. Banik, M.D., Ph.D.

Assistant Professor

Department of Anesthesiology

University of Minnesota,

Minneapolis, USA

4 October 2017

Role of an anesthesiologist

- Acute pain service

- Chronic pain clinic

- Critical care service

- Preop clinic

- Ambulatory surgery service

The Scope of the Problem

Post-Operative Pain

• Incidence 80%

• 25% of patients report sufficient post-op pain relief

• Moderate-Severe Pain

– 41% on DOS

– 15% on POD #4

Wu and Raja, Lancet 2011

Post-Op Pain Time Course

Brennan TJ Pain (2011) 152:S33

The Mission

• Pain

– Minimize post-operative pain and suffering

• Early return of function

– Ambulation

– Feeding

– Activities of daily living

• Treatment Course

– Reduce inpatient length of stay

– Earliest possible return to normal daily activities

– Prevention of persistent post surgical pain

A System for the Mission

Multimodal Therapy:

A method of providing superior analgesia and reduced side-effects by combining interventional techniques and/or medications of different classes.

Overview

• Components of Multimodal Analgesia

– Pre/Post-Operative Medications

• COX inhibitors

• Gabapentinoids

• Paracetamol

• Tramadol

– IV PCA

– Epidurals

– Regional anesthesia with emphasis on ultrasound guided techniques

Perioperative COX Inhibitors

• Inhibition of cyclooxygenase (COX)

– COX-1: constitutive

– COX-2: inducible

• Caveats to usage:

– Renal function

– GI bleeding

– Platelets function

Klabunde cvphysiology.com


• Multiple Perioperative Doses

– Orthopedic surgery

– 200 mg BID-TID x 5 d

– Pain over 5 days

– Maximal pain intensity

– Rescue medication

– Medication adverse events

Celecoxib

Derry and Moore (2012) Cochrane 3 Gimbel (2001) Clin Ther (2001) 23(2):228.

Scott Reuben Controversy At least 12 Coxib related retractions


• Multiple Perioperative Doses

– Limit to 15 mg IV Q 6 hrs

– Limit to 2-3 days

– Joint decision with surgeon

• Caution

– Renal dysfunction

– Single kidney

– > 65 years old

Ketorolac

De Oliveira et al. (2012) AA 114(2):424 Storm et al. JAMA (1997) 275(5):376

Overview



• COX inhibitors

• Gabapentinoids

• Paracetamol

• Tramadol

– IV PCA

– Epidurals


• The perioperative Enhanced Recovery System

Perioperative Gabapentinoids

• GABA analog without significant direct GABAergic activity

• Bind a2d subunit of VG Ca2+ channels

– Ca2+ influx at presynaptic terminals

– release of Glutamate

– release sP/CGRP

• Clinically effective

– Post-surgical pain

– Neuropathic pain

Melrose et al. Neurosci Lett (2007) 417(2):187


• Meta-analysis of single pre-operative dose

• static and dynamic pain for 24 hrs

• MEDD

• dose has larger in MEDD

• Sedation

• Unclear effect of subsequent dosing

Gabapentin

Hurley et al. RAPM (2006) 31(3) Seib and Paul. Can J Anesth (2006) 53(5): 461


• Meta-analysis of peri-operative dosing

• Hysterectomy, mastectomy, cholecystectomy, spine surgery, hip arthroplasty, dental extractions

• Static pain

• Unclear effect on dynamic pain

• MEDD

• Effects more robust for doses > 300 mg/d

• Dizziness, headache, and visual disturbance

Pregabalin

Zhang et al. BJA (2011) 106(4):454

Overview



• COX inhibitors

• Gabapentinoids

• Paracetamol

• Tramadol

– IV PCA

– Epidurals


• The perioperative Enhanced Recovery System at MD Anderson

Perioperative Paracetamol • Centrally acting analgesic

• Debated mechanism

– COX isoenzymes

– Cannabinoids

– Vanilloid (TRPA1)

• Route: IV, PO, PR

• IV route with double CSF concentration

• In cancer population

– Hepatic toxicity

– Temperature monitoring

Andersson et al. Nature Comm (2011) 2: 551

Perioperative Paracetamol

• Single pre-operative oral dose

– 500-1,000 mg

– pain for 4-6 hours

• NNT 3.5

– Poor dose-response curve

– 50% needed for additional analgesia

– Few adverse events

• Multiple IV Doses

– Q6 hr paracetamol vs placebo (RCT)

– 24 hrs after laparoscopic surgery

– pain

– time to first rescue opioid

– MEDD

McNicol et al. BJA (2011) 106(6):764 Apfel et al. Pain (2013) 154:677 Wininger et al. Clin Ther (2010) 32: 2348 Toms et al. Cochrane (2012) 4

Overview



• COX inhibitors

• Gabapentinoids

• Paracetamol

• Tramadol

– IV PCA

– Epidurals



Perioperative Tramadol • Multiple mechanisms of

action

– Weak MOR agonist (relatively selective)

– Augments release 5-HT

– NE reuptake inhibition

• Oral form only in US

• Caution

– Previous seizures

– Brain metastasis

– Patients taking SSRI and SNRI

– Neuroendocrine tumors

Perioperative Tramadol

• Single pre-operative oral dose

• Abdominal, ortho, gyn, OB, and dental

• pain with 50-150 mg

– Excellent dose response curve

• Increased efficacy when combined with paracetamol

Moore and McQuay. Pain (1997) 69:287-294

Perioperative Tramadol

• Multiple perioperative oral doses

• Lumbar disc, groin, and laproscopic surgery

• 200-600 mg/d

• pain over 24 hrs

• Similar efficacy to

– Codeine/APAP 30/500 mg

– Naproxen 500 mg

• No RCT with tramadol ER

Grond and Sablotzki. Clin Pharma 92004) 43:879

Overview



• COX inhibitors

• Gabapentinoids

• Paracetamol

• Tramadol

– IV PCA

– Epidurals



Patient Controlled Analgesia (IV-PCA)

• Self-administered small doses of IV opioid

• Lock-out interval for safety

• Basal infusion for opioid tolerant patients only (if at all)

• Loading dose necessary

• Morphine

– M6G (MOR active) accumulation in renal failure

– M3G (MOR inactive) accumulation in renal failure neuroexcitatory

• Hydromorphone and Fentanyl

– No meaningful active metabolites

– Renal dysfunction in cancer patients

Grass A&A 2005 Viscusi et al. NYSORA.com 2008


• Traditional Teaching

– analgesic gaps

– opioid needed for same level of analgesia

– opioid related side effects

– nursing and pharmacy staff time

• $400 / d in U.S.

– patient satisfaction

– sense of control


• Recent meta-analysis of 55 RCT’s

– Mixed surgical types

– pain vs control

– patient satisfaction

– nursing and pharmacist staff costs

– other adverse SE

– hospital LOS

– total opioid

– itching

Hudcova et al. Cochrane (2012) 6

Overview



• COX inhibitors

• Gabapentinoids

• Paracetamol

• Tramadol

– Intra-Operative Medications

• Ketamine

• Lidocaine

– IV PCA

– Epidurals



Epidural Recipients

• Thoracotomies

• Upper Abdominal Surgery

• Lower Abdominal Surgery

• Urological/Gynecological

• Othropaedic

Epidural Location

• Target: dermatomal midpoint of surgical site

– Thoracotomy: T4-7

– Upper abdomen: T6-8

– Mid abdomen: T8-10

– Lower abdomen: T10-L1

Epidural Catheters

0

500

1000

1500

2000

2500

Epidurals per Year

0

1

2

3

4

5

6

7

8

9

Average Epidural Days per Year

Anticoagulation: ASRA Guidelines PLUS

• Placing Epidural

– INR < 1.4 and Platelets > 100K

– No VEGF inhibitors in last 3-4 weeks

• Removing Epidural

– INR < 1.7 and Platelets > 70K

– Check thrombo-elastogram (TEG)

– 2% patients require transfusion

Epidurals and Health Outcomes

• Analgesia

– Lower pain score vs systemic opioids

– Improved static and dynamic pain scores

• Gastrointestinal

– Decreased duration of post-operative ileus

• Pulmonary

– Decreased duration of mechanical ventilation

– Less atalectasis and hypoxemia

– Decreased overall post-op pulmonary complications

• Metabolic

– Attenuates post-op nitrogen excretion sparing muscle mass

• Cardiovascular

– May lower risk MI or dysrhythmias

• Mortality

– Small reduction at 30-days

Popping DM et al. Arch Surg (2008) 143:990-99.

Nishimori M et al. Cochrane Database Syst Rev (2006) 3:

CD005059

Joshi GP et al. Anesth Analg (2008) 107:1026-40

Wijeysundera DN et al. Lancet (2008) 372:562-69.

Latterman et al. Pain Med (2007) 32: 227

Wu CL et al. RAPM (2004) 29:525-33.

Liu SS and Wu CL. Anesth Analg (2007) 689-702

Marret E et al. Br J Surg (2007) 94: 665-73.

Fischer HB et al. Anaesthesia (2008) 63: 1105-23.

“Splitting”

• Difficult clinical scenario

– Pain + Hypotension

– Patchy epidural

– Unilateral epidural

– Pain at non-surgical site

• Solution is “splitting”

– Local anesthetics alone in the epidural

– Provide systemic opioids through IV PCA or PO route

• Clinical rule: Do not mix neuraxial and systemic opioids

– Too difficult for patient

– Provider may forget about other source

Surgery Specific Duration of Catheter

• Thoracic Surgery

– After chest tube removed

– Pneumonectomy POD #5

– Esophagectomy POD #7

• Abdominal Surgery

– After tolerating full liquid diet OR tube feeds at 40 ml/hr

• Ortho

– When PT goals achieved

Epidural Misadventures

• No block

– Not in epidural space

– Migration

• Missing segments

– Unilateral block (catheter depth)

– Patchy block

• Wrong level

• Pain somewhere else

• Hypotension

– Fluid sparing anesthesia

• Motor block

• Sedation

• Dural puncture ~1%

• Post-Operative radicular pain 0.3%

Overview



• COX inhibitors

• Gabapentinoids

• Paracetamol

• Tramadol

– Intra-Operative Medications

• Ketamine

• Lidocaine

– IV PCA

– Epidurals



Peripheral Nerve Blocks

• Rapidly expanding and changing

– Ultrasound guidance

– Catheters

• Mostly orthopedic surgeries in studies

• pain compared to systemic opioids

• MEDD

• Earlier mobilization

• Possible length of stay

Viscusi et al. NYSORA.com 2008

Supraclavicular Plexus Block

Neuraxiom.com NYSORA.com

Femoral n. Block

Neuraxiom.com NYSORA.com

Transversus Abdominis Plane Block

• Nerves blocked:

– Anterior rami of T7-L1

– Best block generally T10-L1

Transversus Abdominis Plane Block

NYSORA.com

Further Learning

USRA.ca NYSORA.com

Innovative Medications

• Extended release local anesthetics

– Liposomal bupivacaine

– Long acting single shot technique

– Unknown safety

POST-OP ANALGESIA

Epidural/Peripheral Bupivacaine Na+ Channel Block

Gabapentinoids N-type Ca2+ channel inhib

NSAIDs Cyclooxygenase inhib

Tramadol SNRI + weak MOR agonist

Paracetamol TRPA1 agonist (?)

Dexmedetomidine a2 agonist

Ketamine NMDA-R antagonism

Lidocaine (infusion) Systemic Na+ channel inhib

Opioids Strong MOR agonists

Difficult Clinical Scenario #1

Obstructive Sleep Apnea • Higher risk of respiratory

complications post-op

• Strongly push for neuraxial or regional technique if applicable

• Utilize home CPAP/BiPAP immediately after extubation

• Maximize non-opioid medications

• Minimum effective opioid dose

• Vigilant post-op monitoring


Opioid tolerant patient

• Often misunderstood by physicians

• Continue pre-operative opioid

• MORE opioid needed in the perioperative period

• Strongly push for neuraxial or regional technique if applicable

• Patient must have access to opioids to prevent perioperative withdrawal

• IV PCA to determine new opioid requirement

• Pain score will be higher than the average patient

• Remember careful titration


The Unhappy Triad • Maximize non-opioid

medications

• Consider regional techniques

• Eliminate other sedating medications

– Benzodiazepines, anti-emetics, anti-histamines

• Ensure adequate fluid status

• Safety first

Questions

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