Intravenous lidocaine infusions

Dr Ian McConachie FRCA FRCPC

Thank the organisers for inviting me.

No conflicts or disclosures

Lidocaine

• 1st amide local

anesthetic

• Synthesized in 1943

by Lofgren in

Sweden.

• 1st marketed in 1949.

2016

Epidural Lidocaine IV

IV Lidocaine infusions Timeline

1960s

• General

Analgesia

1970s

• MI

Arrythmias

1980s

• Chronic Pain

1990s

• Renewed

Interest in

Intraoperative

infusions

2000s 2010s

• Postoperative infusions

IV Lidocaine infusions Timeline

1960s

• General

Analgesia

1970s

• MI

Arrythmias

1980s

• Chronic Pain

1990s

• Renewed

Interest in

Intraoperative

infusions

2000s 2010s

• Postoperative infusions

Bartlett EE. Anesth Analg 1961 ; 40 : 296-304

IV Lidocaine infusions Timeline

1960s

• General

Analgesia

1970s

• MI

Arrythmias

1980s

• Chronic Pain

1990s

• Renewed

Interest in

Intraoperative

infusions

2000s 2010s

• Postoperative infusions

MI

• Lidocaine infusions for minimum of 24hrs

following MI were standard therapy in in

the 1970s and 1980s in an attempt to

reduce arrhythmias.

Doses of up to 4g in 1st 24hrs.

• Pharmacokinetics of IV Lidocaine were

extensively investigated.

IV Lidocaine infusions Timeline

1960s

• General

Analgesia

1970s

• MI

Arrythmias

1980s

• Chronic Pain

1990s

• Renewed

Interest in

Intraoperative

infusions

2000s 2010s

• Postoperative infusions

Lidocaine and chronic pain

Resurgence of interest in

IV Lidocaine for acute pain

came from chronic pain

studies in 80s and 90s

where brief, high dose IV

infusions ( eg 5mg/kg

over 30minutes) can result

in long term pain relief.

This role is well

established

• 3 doses 1,3 and 5mg/kg.

• 1 and 3 no better than placebo

• Implies need a minimum blood level for analgesia

A randomized, double-masked, placebo-controlled pilot

trial of extended IV lidocaine infusion for relief of ongoing

neuropathic pain. Clin J Pain. 2006 ; 22 : 266-71.

IV Lidocaine infusions Timeline

1960s

• General

Analgesia

1970s

• MI

Arrythmias

1980s

• Chronic Pain

1990s

• Renewed

Interest in

Intraoperative

infusions

2000s 2010s

• Postoperative infusions

Mechanisms of action of systemic

lidocaine

• Not likely classic local anesthetic effects

on Na channels

• Not fully understood

• Not conventional pain pathways

• systemic effect of lidocaine occurs

predominantly in damaged ( postop ) and

dysfunctional ( chronic pain ) nerves

• Peripheral nervous system

• Spinal and supraspinal mechanisms

• Suppression of both peripheral and central

hyperalgesia

• Active at Spinal NMDA receptors

• Selectively inhibit GPCRs which activate Gαq proteins.

• Anti inflammatory

Anti inflammatory actions

For the skeptics - TAH

Anesth Analg 2009 ; 109 : 1464–9

Placebo

Lidocaine

Cortisol stress repsonse - LSCS

Placebo

Lidocaine

Journal of Anesthesia 2009;23:215–21

Stress response - Abdominal

ANZ J Surg 85 (2015) 425–429

S

L

Is it safe ?

• Lidocaine is intrinsically

one of the least toxic

LA drugs

• Only lidocaine has

been considered safe

for IV use because of

its long history of

administration as an

antiarrhythmic drug.

• Plasma levels lower with infusion

• Levels often higher with other uses of Lidocaine eg BP block, epidural etc

• Safety also established in MI studies in 80s

• So….caution but not lightly dismiss potential benefits

Beneficial paradox ?

• No evidence for accumulation in healthy

individuals.

But

• The effect of intraoperative lidocaine

administration is sustained beyond its

infusion period and continues into the

post- operative period.

Plasma levels summary

Surgery Regime Levels μg/ml

Groudine SB

Anesth Analg 1998 ; 86

: 235-9.

Open

Prostatectomy

1.5mg/kg bolus

3mg/min

1.3-3.7

Koppert W

Anesth Analg 2004 ; 98

; 1050-5

Major Abdominal 1.5mg/kg bolus

1.5mg/kg/hr

1.9+/-0.7

Kaba A

Anesthesiology 2007 ;

106 : 11-18

Laparoscopic

colectomy

1.5mg/kg bolus

2mg/kg/hr

1.3-4.6

Herroeder S

Ann Surg 2007 ; 246 :

192-200

Colorectal surgery 1.5mg/kg bolus

2mg/min

1.1-4.2

Martin F

Anesthesiology 2008 ;

109 ; 118-123

Hip Arthroplasty 1.5mg/kg bolus

1.5mg/kg/hr

2.1+/-0.4

Bryson GL

Can J Anes 2010 ; 57 :

759-66

Total Abdominal

Hysterectomy

1.5mg/kg bolus

3mg/kg/hr

2.63 SD 0.6

Caution with comorbidities

• Caution if on drugs inhibiting Cyt P450

system eg

Ca Blockers SSRIs

Cimetidine Protease inhibitors

Ciprofloxacin Clarithromycin

Antifungals

Practical implication

Turn down the vapour !

• Bolus 1.5mg/kg

• Infusion 1.5mg/kg/hr

Time to extubation :

14.43 +/- 3.5 min

v

6.73 +/-1.76 min

Nepal Med Coll J 2010; 12 :

215-220

Different intraoperative regimens !

Bolus : Infusion rate :

100mg 2mg/min

1.5mg/kg 3mg/min

1.5mg/kg 2mg/kg/hr

1.5mg/kg 1.5mg/kg/hr

2mg/kg 3mg/kg/hr

- 3mg/kg/hr

100mg 3mg/min

2mg/kg 1.5mg/kg/hr

“The dose of i.v. lidocaine necessary for

analgesia in the peri- operative period is 1–2

mg kg−1 as an initial bolus followed by a

continuous infusion of 0.5–3 mg kg−1 h−1.

The most widely reported and clinically

effective dose range appears to be from 1 to

2 mg kg−1 h−1.”

BJA Education 2016 ; 16 (9) : 292–298

Clinical results

• Several meta analyses and systematic

reviews have been published.

• Many in Surgical journals !

• Most recent systematic review is abridged

version of 2015 Cochrane review :

Weibel S, Jokinen J, Pace NL, Schnabel A et al. Efficacy

and safety of intravenous lidocaine for postoperative

analgesia and recovery after surgery : a systematic review

with trial sequential analysis.

Br J Anaesth 2016 ; 116 : 770-83

2011 Meta Analysis

Can J Anes 2011 ; 58 : 22–37

GI recovery : time to 1st flatus

Cumulative postoperative opioid

consumption

Length of stay

Lidocaine related side effects

• Eighteen of the 21 included trials reported no significant

lidocaine-related adverse events.

• One trial reported cardiac arrhythmia with stable vital

signs in 1 patient receiving lidocaine intervention.

• One study reported mild headache in 10% of patients in

the lidocaine group.

• Another study reported that the incidence of

lightheadedness and dry mouth was significantly higher

in the lidocaine group.

Lidocaine related side effects

• Eighteen of the 21 included trials reported no significant

lidocaine-related adverse events.

• One trial reported cardiac arrhythmia with stable vital

signs in 1 patient receiving lidocaine intervention.

• One study reported mild headache in 10% of patients in

the lidocaine group.

• Another study reported that the incidence of

lightheadedness and dry mouth was significantly higher

in the lidocaine group.

IV Lidocaine infusions Timeline

1960s

• General

Analgesia

1970s

• MI

Arrythmias

1980s

• Chronic Pain

1990s

• Renewed

Interest in

Intraoperative

infusions

2000s 2010s

• Postoperative infusions

Postoperative Lidocaine

infusions • Double blind placebo

controlled RCT

• Open cholecystectomy

• 100mg bolus 30min prior to

incision then 2mg/min IVI

for 24hr versus saline.

• Levels of 1.75 +/- 0.34

μg/ml at 20hrs

• Pain scores and analgesia

requirements reduced

Anesth Analg 1985 ; 64 :971-4

No benefit added to PCA

• Double blind RCT

• Morphine 1mg/ml v

Morphine 1mg/ml +

lidocaine 10 or 20mg/ml

• No difference in pain

scores, opioid use or side

effects

• No benefit from adding

Lidocaine to Morphine

PCA

Anesth Analg 1996 ; 83 :102

APS experience

• Some receive 1-2hrs in PACU.

• Others ( especially chronic pain patients )

receive up to 3 days.

• We require ECG telemetry monitoring,

Ottawa does not.

• APS monitoring as for PCA etc.

• Education of nursing staff important.

• Intralipid on arrest cart.

• Ottawa have most experience in post

operative Lidocaine infusions – since

2009.

• Protocol and brief summary of their

experience and results have been

published.

Eipe N, Gupta S, Penning J. Intravenous lidocaine for

acute pain: an evidence-based clinical update. BJA

Education 2016 ; 16 (9) : 292–298

Comparison with Epidurals

• 1 study found epidural provided best

analgesia but IV Lidocaine better than

PCA Reg Anesth Pain Med 2011; 36 : 241-248

• 1 study found equivalent analgesia in

infusions given for up to 5 days postop. Reg Anesth Pain Med 2010 ; 35 : 370-376

IV Lidocaine for ERAS ?

• Retrospective comparison of epidural and IV

lidocaine analgesia. 108 patients each.

• Matched for age, gender and chronic opioid use.

• Lidocaine infusions intraop were 2-3mg/kg/hr,

reduced to 0.5-1mg/kg/hr postop.

• Most patients also had PCA. Multimodal

analgesia for all.

• Epidural v Lidocaine based on personal

preference.

Reg Anesth Pain Med 2016;41: 28–36

• Retrospective comparison of epidural and IV

lidocaine analgesia. 108 patients each.

• Matched for age, gender and chronic opioid use.

• Lidocaine infusions intraop were 2-3mg/kg/hr,

reduced to 0.5-1mg/kg/hr postop.

• Most patients also had PCA and multimodal

analgesia.

• Epidural v Lidocaine based on personal

preference.

Reg Anesth Pain Med 2016;41: 28–36

Noted clear increase in

Lidocaine usage during period

of study !

IV lidocaine :

• Not inferior to epidural analgesia overall with

respect to pain scores. Inferior 12-24hrs.

• Inferior to epidural analgesia with respect to

opioid consumption.

• Fewer episodes of hypotension and less

postoperative nausea and vomiting, pruritus,

and urinary retention. Earlier 1st GI function.

• Mental status similar.

• Hypotension necessitating changes in analgesic

therapy (either holding or dose adjustment)

occurred in approximately 25% of patients on

POD1 and approximately 10% of patients on

POD2 in the epidural patients.

• Pruritus (probably resulting mainly from

neuraxial opioid) also almost eliminated.

• Nausea and vomiting were reduced by 50%.

• Trend toward earlier discharge by 24hr in

Lidocaine group.

Implications for ERAS protocols

• Most protocols include epidural analgesia.

However, epidural analgesia often results

in increased IV fluids because of

hypotension and decreased mobilization.

• In addition, the rate of failure and

reductions in infusion rates because of

hypotension are problemaric.

• Using IV lidocaine may be an attractive

option.

• Their colorectal ERAS program now uses

subarachnoid morphine before surgery

and IV lidocaine thereafter.

• Results have been very positive, with a 2

day reduction in length of hospitalization

as compared with historical controls (most

of whom received epidural analgesia).

Poor man’s epidural

• Will not mimic all beneficial effects of epidural infusion of LA.

• Nevertheless, may be of benefit in patients who cannot or will not have an epidural

Medical Hypotheses 2004 ; 63 : 386–389

Preventive analgesic effect ?

• Preventive analgesia is defined as a reduction of

post operative pain for more than 5.5 half-lives

of a drug ie approximately 8hrs for lidocaine.

• 13 of 16 studies demonstrated preventive

analgesia by IV administration of lidocaine.

• “IV lidocaine administration may be a

reasonable analgesic approach when regional

techniques are contraindicated or not

performed.”

Anesth Analg 2013 ; 116 : 1141–61

•

Additional potential benefits

• Prevent development of chronic pain Clin J Pain 2012 ; 28 : 567–572

• Attenuate the “stress” response Anesth Analg 1987 ; 66 : 1008-13

• Improve quality of recovery scores Anesth Analg 2012 ; 115 : 262-7

• Improve ability to ambulate British Journal of Anaesthesia 2009 ; 103 : 213–19

• Treat postoperative paralytic ileus Anesth Analg 1990 ; 70 : 414-9.

Which Patients Could Benefit?

• Patients with pre-existing chronic pain

• Patients with pre-existing opioid use

– Chronic pain

– Drug abuse or methadone maintenance

• Patients who have contraindications to or

refuse a regional technique

• Patients in whom a laparoscopic

procedure unexpectedly converts to an

open procedure

• Suggested that extent/magnitude of

surgery determines the success or failure

of IV Lidocaine.

• Thus, Lidocaine more effective for open v

laparoscopic prostatectomy and open v

laparoscopic colectomy.

Anesth Analg 2009 ;109 :1718–9

Cochrane Review – 2 broad

conclusions

“Thus, the effects of a relatively simple

intervention such as the administration of

intravenous lidocaine should be considered

relevant and worthwhile to be discussed with

patients if the site of the surgical procedure

or the expected pain level is appropriate.”

Cochrane Database of Systematic Reviews 2015, Issue 7. Art. No.:

CD009642.DOI: 10.1002/14651858.CD009642.pub2.

“The described effects may be considered

especially relevant if conditions are

prevalent that worsen the risk-to-benefit ratio

of more invasive treatments such as

(thoracic) epidural analgesia or peripheral

regional analgesia techniques."

Cochrane Database of Systematic Reviews 2015, Issue 7. Art. No.:

CD009642.DOI: 10.1002/14651858.CD009642.pub2.

Conclusions

• Despite some concerns re quality of the

evidence, it seems that Intraoperative IV

Lidocaine provides analgesic benefit

especially in the 1st 24hrs.

• Some ( less convincing evidence ) for

other benefits such as reduced LOS.

• Postoperative infusions, on limited

evidence seem to show promising benefit

especially in selected patients.

Final thought : Systemic effects

of Blocks

British Journal of Anaesthesia 2008 ; 101 : 45–7