Multimodal analgesia for TKR

Neil Agnew

Wrexham

March 2011

Overview

• Multimodal analgesia

• LIA

• Evidence for unusual drugs

• Data

What is ERAS?

An evidence-based approach to elective

surgery, ensuring that patients are in optimal

condition for treatment

Previously…

• Periop. opiates → drowsy, N+V, delay

mobilisation

• Femoral/sciatic nerve blocks – up to 48hrs

motor block, delaying mobilisation

• Staff (and patients) perceptions –

recovering in bed first 24hrs, IVI,

PCA, O2, limited physio

Copenhagen

• Premed: gabapentin 600mg, paracetamol 2g, celecoxib 400mg

• Spinal, tranexamic acid 500mg + 500mg

• IVI protocol – stop in recovery

• LIA:170 ml ropivacaine 0.2% + adrenaline

• 6 day pack: paracetamol, celecoxib 200mg bd, gabapentin 300mg am 600mg pm,

laxatives

• Oxynorm prn rescue

Wrexham

• Pregabalin 150mg premed

• GA or spinal; minimal opiates

• IVI + Magnesium 20 mmol started pre-incision

• Tranexamic Acid 2g IV bolus pre tourniquet

• IV paracetamol 1g

• IV Parecoxib 40 mg (or celecoxib 200mg premed)

• LIA: 150ml 0.1%levobupivacaine +1/150,000 adrenaline

Rapid recovery

• No PCA

• No nerve blocks

• No postop IVI

• ? Need for O2

• No urinary catheter

• Regular

NSAID/paracetamol

• Tramadol prn

• Mobilise ASAP

Local Infiltration Analgesia, (LIA)

• 150-170 ml 0.2% Ropivacaine + Ketorolac 30mg +10mcg/ml adrenaline

• Wound catheter top up 50 ml @15-20hrs

• TKA, n=64, db rct

• More satisfied

• Less pain

LIA

• Dbrct Sweden, TKA, n=48, LIA vs saline

• Morphine 0-48hr: 18mg vs 87mg p<0.001

Acta Orthopaedica 2010; 81 (3): 354–360

Orthopedics 33 (2), 75-80 (Feb 2010)

Pain Control After Total Knee Arthroplasty: A Prospective Study Comparing Local

Infiltration Anesthesia and Epidural Anesthesia

by Martin Thorsell, MD; Petter Holst, MD; Hans Christian Hyldahl, MD; Lars

Weidenhielm, MD

• 85 pts TKR

• LIA 200’ recovery vs 491’

• 76% LIA very satisfied with pain relief vs

40% epidural

• 66% LIA mobilising day 1 vs 3% epidural

• Lower pain scores in LIA

LIA vs Femoral nerve block

• rct, n=80, Denmark, TKA under spinal

• FNB 20ml 1%Ropiv + catheter 10ml/hr 2%

vs LIA

Acta Orthopaedica 2007; 78 (2): 172–179

LA Toxicity?

• LIA with Ropivacaine 400mg+adrenaline

– Blood levels 0.06µg/ml• JBJS 2006;88(5):959-963

– Blood levels 0.032µg/ml – 0.12µg/ml• Acta Orthopaedica 2010; 81 (3): 354–360

• Toxicity at 0.15µg/ml• BJA1997;78:507-14

Levobupivacaine vs Ropivacaine

Levobupivacaine vs Ropivacaine

Annals of Plastic Surgery. 55(3):258-261, September 2005

• Quality analgesia levo>ropiv

• Duration of analgesia = levo>ropiv (10hr vs 6hr)

• Cost levo<ropiv (BNF March 2010)

– L. £1.90 10ml 0.5%; £12.20 200ml bag 0.125%

– R. £2.65 10ml 0.75%; £14.45 200ml bag 0.2%

Levobupivacaine 0.125%

200ml bag• Add 1 mg adrenaline to 0.125% levo 200ml bag

making levo 0.125% + adrenaline 1/200 000

• Take out 3 x 50ml syringes totalling 150ml for use

OR

• 150ml as 3 x 50 ml syringes.

• Add 10ml 0.5% levobupivacaine to 40 ml 0.9% saline and add 0.33mg adrenaline in each syringe making 0.1% levo +1/150,000 adrenaline

Reduce bleeding: No Drain

• Adrenaline in LIA

• Tranexamic Acid 2g

• COX2-I: Parecoxib 40mg IV or celecoxib po

• Tight bandage

• Magnesium reduces hypertension

Anti-fibrinolytic use for minimising perioperative

allogeneic blood transfusion (Review) 2007

Henry DA, Carsen PA et al

• Tranexamic Acid: RR for Tx 0.44 (ortho surgery)

2007

Tranexamic Acid

• RR DVT 0.77

Tranexamic Acid

• RR PE 0.55

Magnesium

• Multiple beneficial effects:– Analgesia

• NMDA antagonist (↓ wind up,↓central sensitisation)

• Ca channel blocker (↓dorsal horn excitability)

– ↓ anaesthetic and ↓ NM blocker requirement

– Antihypertensive

– Anticonvulsant

– Bronchodilator

– ↓ postop shivering +PONV

– Antiarrhythmic

• Mg levels fall postop by 9-27%

Magnesium analgesia

• Knee arthroscopy

• db rct; n = 46

• Anesth Analg 1998; 87:206-10

Hysterectomy (BJA 2008;100:397-403)

• Db pc rct; n=50

• Mg 50mg/kg + 15mg/kg/hr vs saline

• ↓ PONV (40%vs 76% );↓ shivering (4% vs 36%)

Lower limb surgery

• Db rct, n = 60. Spinal

• Mg2+ 8mg/kg vs

placebo

• Acta anaesthiol Scand

2009; 53: 1088-91

Time Mg2+ Control p

+1hr 1.1 2.5 < 0.0001

+3hr 1.1 2.3 < 0.0001

+6hr 1.3 2.6 < 0.0001

+12hr 1 2.2 < 0.01

+24hr 3.4 3.5 >0.05

Postoperative VAS

Lumbar arthrodesis

• Db rct , n=24 GA

• Mg2+ 50mg/kg vs saline• Anaesthesia 2003;58: 131-5

• Satisfaction:

• 14 RCT’s, 778 pts

• Mg signif. ↓ postop analgesic requirements

in 58% of studies and no diff in 36%

• 1 study (paed tonsills) – Mg ↑ VAS by 1

Anesth Analg 2007; 104:1532-9

• Prospective, db, rct; n=40

• THR under spinal

• Mg2+ 50mg/kg over 15 min(approx 3.5g),

then 15mg/kg/hr (approx 1g)

Hwang et al; BJA 2010;104:89-93

Magnesium levels

Hwang et al; BJA 2010;104:89-93

Mg2+ - Analgesia post THR

Hwang et al; BJA

2010;104:89-93

Other routes for Mg2+

• Epidural magnesium reduces postoperative

analgesic requirement – Br J Anaesth 2007;98:519-523

– Br J Anaesth 2008;101:694-699

• Intrathecal Mg2+ prolongs fentanyl analgesia– Anesth Analg 2002;95:661-666

• Intrarticular Mg2+ provides superior analgesia in

knee arthroscopy– Anesth Analg 2008;106:1548-1552

Gabapentinoids:

Mechanism of analgesia

• Binds α2δ unit of presynaptic voltage gated N-

type Ca channel

• Modulates Ca influx

• ↓ release of substance P, 5HT, Norad.,

dopamine, glutamate

• Attenuates postsynaptic excitability

• Spinal α2 adrenergic receptors

Pregabalin: Pharmacokinetics

• Rapid oral absorption – peak levels @ 1 hour

• No hepatic metabolism

• 98% renally excreted unchanged

• 6hr elimination half life

Pregabalin vs Gabapentin

• Higher affinity (x6) for Ca channel

• More linear pharmacokinetics

• Quicker onset (1hr vs 3hr)

• Less nausea and diarrhoea as SE’s

Pregabalin in THR

• Db rct, n=120Br J Anaesth 2008; 101: 535–41

Opioid sparing

Anesth Analg 2007;104:1545-9

Co-analgesia: Pregabalin/COX2-I

• Lumbar laminectomy, db rct; n=80Anesth Analg 2006; 103:1271-7

Pregabalin side effects

Optimum dose?

• Myomectomy

• Dbrct; n=80

Gabapentin

300mg

600mg

1200mg

placebo

Acta Anaesth Italica 2007;58:23-34

Dexamethasone

• Established antiemetic

• ↓ sedation of pregabalin

• Analgesic:

Methylprednisolone

BJA Feb 2011, 230-8

•Dbrct, n=48, TKR under spinal

•Methylpred 125mg vs saline

•Standard multimodal regime

•↓ PONV, CRP and fatigue

• THR under spinal, n=42, dbrct

• Gabapentin 1200mg, dex 8mg, ketamine 0.15mg/kg

vs placebos

• All had paracetamol, ketorolac and morphine pca

Multimodal analgesia

Cost ?

• Pregabalin 150 mg = £1.15 (gabapentin 900mg =£0.22)

• Magnesium 20mmol = £0.96

• Tranexamic acid 2g = £1.50

• Dexamethasone 8mg = £0.90

• Parecoxib 40 mg = £2.84 (celecoxib p.o. 400mg = £1.44)

Total = £5.02 - £7.35

vs

• No morphine intraop, No PCA, less antiemetics

• Reduced LOS

• Less chronic pain??

Chronic post op pain?

• 52% moderate pain (VAS 30-59 mm), and 16% severe pain (VAS > or = 60 mm) when walking 1 month post TKR Anaesthesia May 2009;64(5):508-13

• 6 months, 21% of placebo gp. had pain at rest in the operated hip versus 8% in the ketamine group (n=154,P = 0.036, odds ratio 0.33, risk reduction 67%)

Anesth Analg Dec 2009;109 (6), 1963-71

Pregabalin reduces chronic pain

• Buvanendran A. et al. Anesth Analg 2010;110:199-207

• r db pct, n=240 TKR

• 300mg Pregabalin pre and 14/7 postop

• Less intraop opioids P=0.005

• Chronic pain: 0% vs 8.7% @ 3 months

0% vs 5.2% @ 6 months

• 2004-2008, n=1977 consecutive,unselected

Wrexham Data

Audit July 09 – June 10

• 73 Patients (79 replacements)

• BMI 28.5 (19 – 41)

• ASA 1 – 6 pts

• ASA 2 – 53 pts

• ASA 3 – 13 pts

• ASA 4 – 1 pts

• GA:Spinal 44:30

• TT – 35 mins (22-86)

Post-Op Analgesia

0

5

10

15

20

25

30

35

40

45

50

0 1 2 3

6 hours

12 hours

18 hours

24 hours

Post-Operative Nausea &

Vomiting

0

0.5

1

1.5

2

2.5

0 1 2 3 4

6 hours

12 hours

18 hours

24 hours

Length of stay

• All: mean 2.5 days (1-5)

• Unis: 1.6 days (1-3)

• TKR: 2.8 days (2-5)

3 month follow up questionnaire

• 95% response rate (n=70)

• 93% happy to go home

• 93% able to control pain at home

• 52% (n=37) visited gp

• 97% would recommend enhanced recovery

• OKS 37/48

Maelor Hospital Data:

Apr 2009-Sept 2010

• n= 138 primary tkrs

• m:f 51:87

• Av. age 70yrs (41 – 89)

• BMI 31.0 (24 – 48)

• Av. l.o.s. 3.8 days (1 – 19)

In hospital data

• Mobilisation day of surgery 130/138

• Mean pain score day of surgery 1

• Mean pain score day one 1.4

• Mean pain score day two <1

• PONV post op 8/138 pts

Pilot 2 (11.11.08)Pilot 1 (22.07.08 -24.07.08)Baseline LoS (All Cons)

20

15

10

5

0

Lo

S (

Da

ys)

6.02941

3.66667

2.66667

Results of Enhanced Recovery Pilot with Mr Anthony Smith (Commenced July 08)

Length of stay

0

1

2

3

4

5

6

7

Rapid

Recovery

Best Practice

Mr Smith English Peer BCULHB

Len

gth

of

Sta

y (

days)

Not Everyone Discharged Day 3

• But everyone benefits from programme

Distribution Of Patients According to Length of Stay

0

5

10

15

20

25

30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Length of Stay (days)

Perc

en

tag

e

Pre Rapid Recovery

Rapid Recovery

Complications

• One significant post op haematoma as an

I/P

• Readmission within 30 days = 2 cases

– 1 DVT

– 1 superficial wound infection (IVAB’s)

PROM’s

Fig 4 – Oxford Knee Scores – Wrexham Maelor Hospital v English Average

Average Score at

Pre-Op

Average Score 6

Months Post-Op

Average Health Gain

(Points)

Wrexham (n=76) 16.9 31.4 14.5

England (n=162) 18.7 33.4 14.7

Average Increase in Points for Oxford Knee Score

Between Pre-Op Assessment & Six Months Post-Op

0.000

2.000

4.000

6.000

8.000

10.000

12.000

14.000

16.000

18.000

20.000

Comparison Against All English Trusts (April 2009 - August 2010)

Avera

ge In

cre

ase in

Hip

Sco

re (

Po

ints

Wis

e)

Wrexham Maelor Hospital

> 14.52

1 2 3

Efficiency Outcomes

If we can roll-out Rapid Recovery ‘Knees’

to all Orthopaedic Consultants in BCULHB

the following savings can be made: -

• Bed Days Released - 2610

• Potential Extra Activity - 874

Summary

• Multimodal analgesia with LIA safe and effective

• Growing evidence for atypical analgesics

• Whole system change at every step of patient pathway for ERAS to work

Multimodal analgesia:

Future studies

• Timing

• Duration

• Optimum dose

• Quantify side effects

• Chronic pain

Any Questions ?