Intravenous lidocaine infusions. Dr Ian McConachie FRCA FRCPC

Intravenous lidocaine infusions Dr Ian McConachie FRCA FRCPC

Thank the organisers for inviting me. No conflicts or disclosures

Lidocaine 1 st amide local anesthetic Synthesized in 1943 by Lofgren in Sweden. 1 st marketed in 1949.

2016 Epidural Lidocaine IV

IV Lidocaine infusions Timeline 1960s 1970s 1980s 1990s 2000s 2010s General Analgesia MI Arrythmias Chronic Pain Renewed Interest in Intraoperative infusions Postoperative infusions

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

IV Lidocaine infusions Timeline 1960s 1970s 1980s 1990s 2000s 2010s General Analgesia MI Arrythmias Chronic Pain Renewed Interest in Intraoperative infusions 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 1 st 24hrs. Pharmacokinetics of IV Lidocaine were extensively investigated.

IV Lidocaine infusions Timeline 1960s 1970s 1980s 1990s 2000s 2010s General Analgesia MI Arrythmias Chronic Pain Renewed Interest in Intraoperative infusions 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 1970s 1980s 1990s 2000s 2010s General Analgesia MI Arrythmias Chronic Pain Renewed Interest in Intraoperative infusions 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 Placebo Lidocaine Anesth Analg 2009 ; 109 : 1464 9

Cortisol stress repsonse - LSCS Placebo Lidocaine Journal of Anesthesia 2009;23:215 21

Stress response - Abdominal S L ANZ J Surg 85 (2015) 425 429

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 Cimetidine Ciprofloxacin SSRIs Protease inhibitors Clarithromycin Antifungals

Practical implication Bolus 1.5mg/kg Infusion 1.5mg/kg/hr Turn down the vapour! 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 1 st 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.

IV Lidocaine infusions Timeline 1960s 1970s 1980s 1990s 2000s 2010s General Analgesia MI Arrythmias Chronic Pain Renewed Interest in Intraoperative infusions 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 Noted for clear age, gender increase and in chronic opioid use. Lidocaine Lidocaine infusions usage intraop during were period 2-3mg/kg/hr, reduced of study 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

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 1 st 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