Effect of Low Dose Lidocaine Infusions on Postoperative Analgesic RequirementsJ.E. Pellegrini, PhD, CRNA, DNP

LidocaineAmide AgentUsed as a local anesthetic & antiarrhythmic drugEpiduralSubarachnoidPercutaneousIntravenous

Can be used as a primary anesthetic agentNeuraxial administrationCentral or peripheral nerve blockadeEpiduralSpinalBier Block technique etc.Often used as an adjunct or bridging agent when given in conjunction with general anesthesiaMollify effects of propofol administration0.5-2 mg/kg to offset painRarely given as an integral part of anesthetic plan

Lidocaine

Often viewed as temporizing agent Treatment of acute pain or stimulationHas been shown to possess potent preemptive analgesic propertiesTraditionally preemptive properties associated with opioids or NSAIDsCan result in significant side effects when usedAlterations in hemodynamicsSedationPONVAltered Bowel and Bladder FunctioningCoagulation abnormalities (bleeding dyscrasias) Lidocaine

NSAIDsOften given to offset the side effects produced by opioidsNSAIDs have a positive effect on bowel and bladder functionNot as effective in treating pain from major muscle traumaSide effectsRenal damageBleeding disordersAllergic responses

Lidocaine

Lidocaine can be used as an agent for multimodal analgesic therapyLidocainePeripheral and Central Mode of actionPeripherallyLocalized anti-inflammatory responseCentrallySelectively decrease C-fiber activityLidocaine

LidocaineIntravenous lidocaine administration preoperatively & throughout procedure linked to decreasing incidence of hyperalgesia Anti-hyperalgesia- inhibits mechanoreceptors (prevents cascade of mechanoreceptor stimulation)Preemptive & Periop admin of IV lidocaine exhibits effects for 36 hrs after surgeryMost effective if given preemptively/ postemptively

Lidocaine InfusionFound to be useful in decreasing postoperative pain Noted decreases in incidence of postoperative ileus in patients undergoing major abdominal surgeryPostoperative ileus estimated to cost the health care system approximately 1 billion dollars annuallyThought to be caused from hyper-activation of the sympathetic nervous system and initiation of a pain response which causes inactivity in the gutMay block postoperative ileus by blocking sympathetic innervation allowing dominance of parasympathetic innervation in gutMay also work by decreasing postoperative inflammatory response (prostaglandin & other mediators) in gut

Act in similar fashion to NSAIDs in relation to maintenance of abdominal reflexesDecrease in postoperative illeusBest if administered preemptively and continued throughout the course of surgical interventionWill continue to provide effect for several hours after discontinuationRoutinely given in bolus of 1-2 mg/kg and maintenance infusion of 0.5-2 mg/kg/hrLidocaine

Useful adjunct in abdominal surgeriesHysterectomy patientsRetro pubic prostatectomy patientOpen CholecystectomyLaparoscopic CholecystectomyFound not to be useful when used in same admixture as morphine PCACassuto et al. (open cholecystectomy)

Lidocaine

Cassuto et al.Open cholecystectomy patient trialSmall study (20 patients)Bolus dose 100 mg followed by continuous infusion of 2 mg/kg/hr for next 24 hoursDecreased Pain Scores PostoperativelySignificant decrease in postoperative analgesic requirements (24 hour totals MSO4 Equiv)9.4 2 mg (Lidocaine group)29.4 2.5 mg (Control group)Lidocaine

From: Cassuto J et al. Inhibition of postoperative pain by continuous low-dose intravenous infusion of lidocaine. Anes Analg 1985; 64: 971-4.

From: Cassuto J et al. Inhibition of postoperative pain by continuous low-dose intravenous infusion of lidocaine. Anes Analg 1985; 64: 971-4.

Cassuto TrialSerum levels obtained and no toxicity notedNo systemic toxic effects observedGreater analgesia afforded beyond 24 hour infusion time periodProblems24 hour infusion requiring PACU staySmall number of patientsOnly done on healthy open cholecystectomy patients

Lidocaine

Groudine et al TrialEnrolled Patients undergoing Retro pubic radical prostatectomyBolus dose of 1.5 mg/kgInfusion started (2-3 mg/kg/hr) immediately after induction and continued throughout surgeryInfusion DCd 60 minutes following skin closureNoted significant decreases in pain scores and analgesic requirements postoperatively

Lidocaine

Groudine et al StudyDischarge to Home4 0.69 days (Lidocaine Group)5.1 2.18 days (Control Group)Total Pain Scores4.67 3.94(Lidocaine Group)13.25 7.65 (Control Group)

Groudine et al StudyFlatus Return28.5 13.4 hours (Lidocaine Group)42.1 16.0 hours (Control Group)Bowel Movement61.8 13.2 hours (Lidocaine Group)73.9 16.3 hours (Control Group)

Groudine et al StudyDiffered from Cassuto study in designBolusInfusionNo toxic levels (serological) seen nor systemic toxicity noted in groupDid not require extensive monitoring postoperativelyProblemsSmall number (40 subjects total)Less analgesic effectsOnly enrolled radical prostatectomy patients

Ching-Tang et al. StudyUsed a multimodal approach using lidocaine infusion and IM dextromethorphan Laparoscopic cholecystectomy patients4 group design (Lidocaine infusion, Lido-Dex, Control-Dex, Control only)Lidocaine Group (3 mg/kg lidocaine infusion started 30 minutes before incision & concluded at skin closure)Lidocaine

Ching-Tang et al. Study

Time to 1st Analgesic21.7 23.8 hours (Lidocaine Group)8.2 17.7 hours (Control Group)Time to 1st Flatus22.1 1.6 hours (Lidocaine Group)22.9 1.8 hours (Control Group)

Ching-Tang et al. Study

Validated analgesic benefit from short term infusion of lidocaine in laparoscopic cholecystectomy patientsInconclusive evidence in relation to return of bowel functionInclusion of Dextromethorphan conflicting variable (study not designed to analyze lidocaine group as independent group didnt use Soloman design properly)No data reported in relation to time to discharge nor time to first bowel movement

Systemic Lidocaine(Effect on Bowel Function)Lidocaine infusions linked to earlier return of bowel functionVariable results on postoperative analgesic efficacyDefinite advantages in reducing intraoperative analgesic requirementsLidocaine infusions dont appear to slow the time to emergence from GETABolus dose 1-1.5 mg/kg on inductionContinuous infusion of 2 mg/kgMost trials continue infusions into post-operative period

Herroeder S, Pecher s, Schnherr M, Kaulitz G, et al. Systemic lidocaine shortens the length of hospital stay after colorectal surgery: A double-blind, randomized, placebo-controlled trial. Ann Surg 2007; 246(2): 192-200.Enrolled 66 patients undergoing colorectal surgery & randomly assigned to placebo or lidocaine infusion groupBolus dose of 1.5 mg/kg with inductionContinuous infusion of 2 mg/kg initiated immediately after induction 4 hrs postopMeasured inflamatory mediators

Herroeder S, Pecher s, Schnherr M, Kaulitz G, et al. Systemic lidocaine shortens the length of hospital stay after colorectal surgery: A double-blind, randomized, placebo-controlled trial. Ann Surg 2007; 246(2): 192-200.

Herroeder S, Pecher s, Schnherr M, Kaulitz G, et al. Systemic lidocaine shortens the length of hospital stay after colorectal surgery: A double-blind, randomized, placebo-controlled trial. Ann Surg 2007; 246(2): 192-200.CytokinesAttenuated levels of IL-6, IL-8, IL-1ra and C3aDifferences noted during surgery and following surgeryNoted that plasma levels of TNF- and IL-1 did not increase during surgery and IL-10 was unaffected at any time point (anti-inflammatory cytokine)Cytokines are well known to play role in inflammatory response Inflammation plays key role in promotion of ileus following surgerySome evidence suggests lower postoperative infection rates

Herroeder S, Pecher s, Schnherr M, Kaulitz G, et al. Systemic lidocaine shortens the length of hospital stay after colorectal surgery: A double-blind, randomized, placebo-controlled trial. Ann Surg 2007; 246(2): 192-200.

Herroeder S, Pecher s, Schnherr M, Kaulitz G, et al. Systemic lidocaine shortens the length of hospital stay after colorectal surgery: A double-blind, randomized, placebo-controlled trial. Ann Surg 2007; 246(2): 192-200.

Herroeder S, Pecher s, Schnherr M, Kaulitz G, et al. Systemic lidocaine shortens the length of hospital stay after colorectal surgery: A double-blind, randomized, placebo-controlled trial. Ann Surg 2007; 246(2): 192-200.

Herroeder S, Pecher s, Schnherr M, Kaulitz G, et al. Systemic lidocaine shortens the length of hospital stay after colorectal surgery: A double-blind, randomized, placebo-controlled trial. Ann Surg 2007; 246(2): 192-200.Study demonstrated that perioperative systemic lidocaine significantly shortened length of hospital stay by 1 dayNo differences in length of PACU stay76 74 versus 84 77 minutes (control vs lido) Postoperative ileus estimated to increase the cost of abdominal surgery by 1 billion dollars per year in U.S.Definite advantage in decreasing inflammatory mediatorsConflicting results as to how it differs from patients administered thoracic epidural analgesia (Kuo et al)Small sample sizeWeak exclusionary criteria (allowed patients on corticosteroids)Less impact on postoperative analgesia than other studiesDid not report overall intraoperative and postoperative analgesic requirements

Lidocaine InfusionsSome trepidation over infusion of > 1 mg/kg/min secondary to concerns of possible toxicity over timeOne research study investigated the use of a low dose lidocaine infusion in conjunction with a PCA morphine in patients undergoing major abdominal surgery

40 patients allocated to lidocaine or saline groups Lidocaine group1.5 mg/kg with induction2 mg/kg intraoperatively1.33 mg/kg for 24 hrs postoperativelyMeasured pain scores, opioid consumption, fatigue scores, time to first flatus and defecation

Abdominal DiscomfortOpioid Consumption

Small pilot study enrolling 22 patients receiving major abdominal surgeryR or L Colectomies, Ant Sigmoid resection, Small Bowel resectionsExcluded patients with;Known sensitivity to lidocaine, preexisting significant heart disease, taking beta blockers or cimetidineAll subjects were administered a PCA morphine for postoperative analgesia and randomized to receive either a continuous IV infusion of placebo (NS) or a lidocaine infusion of 1 mg/kg/minLidocaine infusions (1.5g lidocaine/250 ml NS) @ 10 ml/hrNormal saline infusions @ 10 ml/hrMeasured overall analgesic requirements, VAS pain scores, time to first flatus-bowel movement, discharge from hospital Lidocaine infusions discontinued 24 hours following surgery

No adverse events noted related to lidocaine infusionsOverall lower VAS scores for pain reported in lidocaine groupHowever noted higher overall morphine requirements in Lidocaine groupMore importantly; noted faster time to flatus, bowel movement & hospital dischargeDespite increased morphine consumption

ConclusionsLidocaine has been shown to be safe to useUseful in decreasing intraoperative and postoperative analgesic requirementsExcept in one clinical trialNo Toxicity reported in clinical trials when doses of < 3 mg/kg/hr infusions usedDefinite reduction in postoperative illeus noted in 4 clinical trials Lower total hospital stay requirements when used in major abdominal surgeryLower overall hospital costsFurther studies are needed current study underwayLidocaine

Lidocainepellegrini@son.umaryland.edu