ANALGESIC RESPONSES TO I.V. LIGNOCAINE

The analgesic effect of i.v. lignocaine was evaluated in fivepatients with clinical neuralgic pain of varying aetiology.The response was compared with that on concurrently-inducedischaemic pain, initially of the same intensity Following ahigh dose infusion of 3 mg kg^–1 (lignocaine concentrationsgreater than 3 µg ml^–1 ) both pains were decreased,clinical pain to a significantly greater extent. Thereafter,at lower doses and blood concentrations, lignocaine was withouteffect on ischaemic pain, but almost totally suppressed thesame patient's clinical pain. The results suggest a divergencein the specificity of the analgesic action of lignocaine I.V.according to the nature of the pain-inducing process. Disordersmanifesting as deaffcrentation or central neuralgias appearto be affected favourably by lignocaine i.v., whereas pain ofperipheral origin is unaffected by lignocaine, except at bloodconcentrations which approach toxic values. ^*Present address for correspondence: Section of Anaesthetics,Department of Pharmacology and Clinical Pharmacology, Universityof Auckland School of Medicine, Auckland, New Zealand.     

OPTIMAL DOSE OF LIGNOCAINE FOR PREVENTING PAIN ON INJECTION OF PROPOFOL

The purpose of this study was to define the optimum dose oflignocaine required to reduce pain on injection of propofol.We conducted a prospective, randomized, double-blind trial on310 patients undergoing anaesthesia. Patients were allocatedto four groups according to the lignocaine dosage: group A (control),no lignocaine; group B, lignocaine 0.1 mg kg^–1; groupC, lignocaine 0.2mgkg^–1; group D, lignocaine 0.4mg kg^–1.Our results showed that a dose of lignocaine 0.1 mg kg^–1significantly reduced the incidence of pain and that there wasno improvement when the dose was increased.     

EFFECTS OF I.V. LIGNOCAINE ON AIRWAY REFLEXES ELICITED BY IRRITATION OF THE TRACHEAL MUCOSA IN HUMANS ANAESTHETIZED WITH ENFLURANE

We have investigated the effects of bolus administration oflignocaine 1.5 mg kg^–1 i.v. on respiratory responses toairway irritation induced by instillation of distilled waterinto the trachea in 10 patients anaesthetized with enflurane(1.5% end-tidal). Before administration of lignocaine, airwayirritation elicited not only the cough reflex, but also otherrespiratory reflexes such as expiration, apnoea and spasmodicpanting. Immediately after administration of i.v. lignocaine,when plasma concentrations of lignocaine exceeded 4.7 µgml^–1, tracheal irritation elicited only brief apnoea.Other reflex responses were suppressed completely; they recoveredgradually with progressive decrease in plasma concentrationof lignocaine. The apnoeic reflex was not eliminated at plasmalignocaine concentrations greater than 7.0 ug ml^–1, whereasthe expiration reflex, cough reflex and spasmodic panting wereeliminated effectively by plasma concentrations of lignocainegreater than 3.5, 2.8 and 2.2 ug ml^–1, respectively.     

PHARMACOKINETICS OF LIGNOCAINE IN CHILDREN FOLLOWING CAUDAL ANAESTHESIA

The time course of the plasma lignocaine concentration, followingcaudal anaesthesia, was studied in 11 healthy children (3.5–9yr). Plasma lignocaine concentrations were measured for up to6 h after administration (5 mg kg^–1). Peak plasma concentrationwas 2.05+0.08 µ ml^–1 and occurred at 28.2±2.9min after administration. Pharmacokinetic parameters determinedfrom a two-compartmental model were similar to those observedafter the i.v. or extradural administration of lignocaine inadults, except for a longer half-life of elimination (155±32min). Since the total body clearance of lignocaine was similarin children (15.4±1.2 ml min^–1 kg^–1) to thatin adults, the longer half-life of elimination was attributedto a larger volume of distribution in the children (3.05 ±0.40litre kg^–1).     

PHARMACOKINETICS OF LIGNOCAINE IN CHILDREN AFTER INFILTRATION FOR CLEFT PALATE SURGERY

We have studied the pharmacokinetics of lignocaine in childrenafter local infiltration for cleft palate surgery. After inductionof anaesthesia, lignocaine 2.5 mg kg^–1 with adrenaline1.200000 was injected into the palate. Blood samples were collectedbefore and at 2, 5, 10, 15, 20, 30, 60 and 120 min after infiltration.Plasma concentrations of lignocaine were measured by a gas-liquidchromatographic technique. There were no signs of systemic toxicityon routine monitoring of the patients and the peak plasma concentrationswere less than the accepted toxic values. Mean half-life was72.9 (SEM9.9) min, similar to that found previously in adultsand children. However differences in mean clearance (24.6 (2.04)ml kg^–1 min^–1) and volume of distribution (0.80(0.07) litre kg^–1) were found between this and previousstudies.     

PLASMA LIGNOCAINE CONCENTRATIONS ASSOCIATED WITH EXTRADURAL ANALGESIA IN PATIENTS WITH AND WITHOUT MULTIPLE ORGAN FAILURE

We have measured plasma concentrations of ligno-caine afterthoracic extradural analgesia with continuous infusion of lignocainein eight intensive care patients with chest wall trauma or aftermajor upper abdominal surgery. Four patients developed multipleorgan failure (MOF). Plasma concentrations of lignocaine inarterial blood were measured 4, 8, 24 and 48 h after a continuousinfusion of lignocaine was commenced in the extradural space.Plasma concentrations of lignocaine were greater in all patientswith MOF (range 2.7–5.1 ng ml^–1) than in patientswithout MOF (range 0.8–1.2 fig mh^–1). Because plasmaconcentrations in patients with MOF were within the low toxicrange, extradural infusion of lignocaine should only be consideredin intensive care patients without MOF or when plasma concentrationsof lignocaine are monitored. (Br. J. Anaesth. 1992;69:513–516)     

EFFECT OF I.V. LIGNOCAINE ON PAIN AND THE ENDOCRINE METABOLIC RESPONSES AFTER SURGERY

Pain intensity, and blood glucose and plasma cortisol concentrationswere measured following abdominal hysterectomy in 18 patientsallocated randomly to receive either i.v. lignocaine 1.5 mgkg^–1 plus 2 mg kg^–1 h^–1, or saline. The administrationof lignocaine resulted in plasma conentrations between 1.5 and2.0 µg ml^–1 during the 2-h study period. However,the administration of lignocaine i.v. had no effect on the intensityof pain after surgery, or on the adrenocortical and hyperglycaemicresponses to surgery.     

FUNCTIONAL AND METABOLIC EFFECTS OF BUPIVACAINE AND LIGNOCAINE IN THE RAT HEART-LUNG PREPARATION

We have examined the effects of bupivacaine and lignocaine onmyocardial metabolism in the rat isolated heart-lung preparation.Bupivacaine 1, 5 or 25 µg ml^–1 or lignocaine 4,20 or 100 µg ml^–1 was administered 5 min after thestart of perfusion. Both bupivacaine 25 µg ml^–1and lignocaine 100 µg ml^–1 reduced heart rate significantly.Bupivacaine 25 µg ml^–1 was associated with a higherincidence of arrhythmias than the other groups. Three heartsin the bupivacaine 25 µg ml^–1 group (n = 8) andtwo hearts in the lignocaine 100 µg ml^–1 group (n= 8) failed (zero cardiac output) at the end of the experiment.Although there were no significant differences in myocardiallactate and glycogen concentrations between groups, ATP contentin the bupivacaine 25 µg ml^–1 and lignocaine 100µg ml^–1 groups was significantly less than thatin the control group. The results suggest that myocardial depressionand subsequent metabolic deterioration occurred with both thehigh doses of local anaesthetics; these findings do not accountfor the apparent increased cardiotoxicity of bupivacaine.     

DEVELOPMENTAL NEUROPHYSIOLOGY OF MAMMALIAN PERIPHERAL NERVES AND AGE-RELATED DIFFERENTIAL SENSITIVITY TO LOCAL ANAESTHETIC

Using an in vitro nerve preparation, we have studied the relativeelectrophysiological properties of myelinated and unmyelinatednerve fibres in the vagus nerve of 1-, 9- and 36-month-old rabbitsand their sensitivity to local anaesthetic. The baseline (valuesbefore infusion of local anaesthetic) mean amplitude and conductionvelocity (CV) of the compound action potential (APc) were recordedand the nerve was exposed to a range of concentrations (0.5–4.0mmol litre^–1) of lignocaine for periods sufficient toattain equilibrium block. There was an increase in the amplitudeof the A fibre elevation from the 1-month to the 9- and 36-month-oldrabbits. The CV of the A and B fibres increased significantlywith age, while the CV of the C fibres did not change. The ED₅₀values of lignocaine for reduction of the A fibre elevationin the 1-, 9-and 36-month-old rabbits were 0.66, 0.94 and 0.85mmol litre^–1, respectively. The respective values forthe B fibres were 0.74, 1.21 and 0.82 mmol litre^–1, whilethose of the C fibres were 1.50, 2.44 and 2.07 mmol litre^–1.In general, nerves from young and old rabbits were more sensitiveto local anaesthetic-induced conduction blockade, suggestingthat smaller doses of local anaesthetic are required clinicallyfor anaesthesia in paediatric and older age groups.     

PLASMA CONCENTRATIONS OF LIGNOCAINE AFTER OBTURATOR NERVE BLOCK COMBINED WITH SPINAL ANAESTHESIA IN PATIENT'S UNDERGOING TRANSURETHRAL RESECTION PROCEDURES

Bilateral obturator nerve block has become a widely acceptedtechnique to avoid adductor contraction during transurethralresection of prostate or bladder tumours. However, little isknown about plasma lignocaine concentrations after the block.We conducted this study to assess a safe dose of lignocainefor injection in obturator nerve block. Bilateral obturatornerve block was performed with the aid of a peripheral nervestimulator in 12 patients after spinal anaesthesia. In groupI (n=6), patients received 2% lignocaine 10 ml (200 mg) forthe block; those in group II (n=6) received 2% lignocaine 15ml (300 mg). The block was satisfactory and no single adductorcontraction was observed in either group during surgery. Thepeak plasma concentrations of lignocaine were 2.28 (SD 0.29)pg ml^–1 and 3.75 (0.79) µg ml^–1 in groupsI and II, respectively. The greatest plasma concentration was5.07 µg ml^–1 in a patient of group II. There wereno symptoms suggesting systemic toxicity. We conclude that bilateralobturator nerve block may be performed safely and effectivelywith 2% lignocaine 10 ml with the aid of a peripheral nervestimulator in patients undergoing transurethral resection procedureswith spinal anaesthesia.     

EFFECTS OF ATRACURIUM, VECURONIUM OR PANCURONIUM PRETREATMENT ON LIGNOCAINE SEIZURE THRESHOLDS IN CATS

Among the non-depolarizing neuromuscular blocking drugs, atracuriumappears to be unique in its ability to produce cerebral stimulationin lightly anaesthetized animals. This effect is attributedto the atracurium metabolite, laudanosine. The following studieswere performed to determine if pretreatments with the non-depolarizingneuromuscular blockers pancuronium, atracurium or vecuroniumwould differ in their effects on the seizure threshold of lignocaine.Adult mongrel cats were anaesthetized with 1.0 MAC halothanein oxygen and nitrogen. Ventilation, blood-gas tensions, acidbasebalance and temperature were controlled. Cats received pancuronium0.2 mg kg^–1 i.v. (n= 7), atracurium 1.0 mg kg^–1i.v. (n = 7) or vecuronium 0.2 mg kg^–1 i.v. (n = 7). Tenminutes after the administration of the myoneural blocker, allcats received lignocaine 4 mg kg^–1 min^–1 i.v. untilthe onset of EEG evidence of generalized seizure activity. Atseizure onset, there were no statistically significant differencesamong the cumulative lignocaine doses or the serum lignocaineconcentrations in cats pretreated with pancuronium, atracuriumor vecuronium.     

I.V. LIGNOCAINE IN REFLEX AND ALLERGIC BRONCHOCONSTRICTION

The protection against bronchospasm afforded by infusions oflignocaine was tested in dogs anaesthetized with thiamylal bychallenge with aerosols of citric acid (CAA) or ascaris antigen(AAA). During the infusion of lignocaine, the response to CAAwas blocked or markedly attenuated, but AAA still elicited alarge increase in pulmonary resistance (R_L). In untreated dogs,CAA increased R_L from 0.14±0.05 (mean±SEM) kPalitre^–1 s to 1.09±0.18, whereas in dogs treatedwith lignocaine, R_L was 0.19±0.09 before challenge withCAA and 0.44±0.13 after challenge. AAA increased R_L.from 0.14±0.06 kPa litre¹ s to 3.01±0.65 in untreateddogs, and from 0.34±0.10 kPa litre^–1 to 1.85±0.69in dogs treated with lignocaine. Blood concentrations of lignocainewere 1.5±0.3 and 2.5±0.6µg ml^–1 duringchallenge with CAA and AAA, respectively. We conclude that lignocaine,at blood concentrations which will reduce the risk of cardiacarrhythmia, markedly reduces reflex bronchoconstriction, buthas relatively little effect on that initiated by allergic mediators.     

INTRATHECAL SUFENTANIL AS A SUPPLEMENT TO SUBARACHNOID ANAESTHESIA WITH LIGNOCAINE

The combination of low-dose sufentanil with lignocaine for subarachnoidanaesthesia was studied in a double-blind comparative trialin 40 urological patients. Patients were allocated randomlyto two groups and received 5% heavy lignocaine 1.5 ml togetherwith either 1.5 ml of sufentanil 5 µg ml^–1, or physiologicalsaline 1.5 ml. No statistically significant differences wereobserved between the two groups with respect to analgesia oranaesthesia. The only clear benefit of the addition of a lowdose of sufentanil to lignocaine was the significantly longerperiod of postoperative analgesia. There was no significantdifference in the number of patients requiring supplementaryanalgesics. Side-effects were similar in both groups.     

EXPERIMENTAL EPIDURAL ANAESTHESIA IN THE CAT WITH LIGNOCAINE AND AMETHOCAINE

In cats with permanently implanted catheters in the lumbar epiduralspace, the typical responses to the epidural administrationof lignocaine and amethocaine were a flaccid paralysis of thehind limbs and a block of the flexion reflex. The responsesto periodic injections of lignocaine were consistent up to fourteenweeks after surgery. The effects of lignocaine were enhanced(1) when the total dose was increased from 7.5 to 37.5 mg, (2)when the pH of the injection solution was increased from 3.4to 7.5, and (3) in the presence of adrenaline 1: 100,000. Amethocainewas distinctly more potent and more toxic than lignocaine. Althoughthe criteria for measuring the responses in the cat and in mandiffer, it is concluded that epidural anaesthesia in the twospecies is remarkably similar. ^*Present address: New England Research and Development Laboratories,Worcester, Massachusetts,U.S.A.     

TRACHEAL INTUBATION AFTER INDUCTION OF ANAESTHESIA WITH PROFOL, ALFENTANIL AND I.V. LIGNOCAINE

We have assessed trachea/ intubating conditions in 60 AS A Ior II patients after induction of anaesthesia with propofol2.5 mg kg^-1 and alfentanil 10 or 20 fig kgr' with or withouti. v. lignocaine 1 mg kg1. No neuromuscular blocking agentswere administered. Patients were allocated randomly to fourgroups: group 1 = propofol-alfentanil 10 fig kg^-1; group 2 =propofol-alfentanil 10 fig kg^-1-lignocaine Imgkgr1; group 3= propofol-alfentanil 20 jig kg^-1; group 4 = propofol-alfentanil20 fig kg^-1-lignocaine 1 mgkgr. Intubating conditions were assessedas acceptable or unacceptable on the basis of a scoring systemdependent on ease of faryngoscopy, vocal cord position and coughingon insertion of the trachea/ tube. Intubating conditions wereacceptable in 20% 73, 73% and 93% of patients in groups 1–4,respectively. Intubating conditions were better and there wasless coughing in the lignocaine group. (Br. J. Anaesth. 1993;70: 163–166)     

I.V. LIGNOCAINE FAILS TO ATTENUATE THE CARDIOVASCULAR RESPONSE TO LARYNGOSCOPY AND TRACHEAL INTUBATION

I.v. lignocaine has been used with varying success to attenuatethe cardiovascular responses to laryngoscopy and tracheal intubation.We determined the optimal time of administration in 45 ASA Iand II Chinese patients premedicated with morphine and hyoscine,and anaesthetized with thiopentone and suxamethonium. Patientswere allocated randomly to a control group or three treatmentgroups to receive lignocaine 1.5 mg kg^–1 i.v. 1, 2, or3 min before laryngoscopy. Analysis of variance for measuredand derived cardiovascular variables failed to show any significantdifference between any of the groups. Present addresses: Department of Anaesthesia, Stobhill GeneralHospital, Balornock Road, Glasgow G21 Department of Cardioanaesthesia, Freeman Hospital, High Heaton,Newcastle Upon Tyne NE7 7DN.     

INFLUENCE OF PREMEDICATION ON LIGNOCAINE-INDUCED ACUTE TOXICITY AND PLASMA CONCENTRATIONS OF LIGNOCAINE

The effects were studied, in eight healthy volunteers, of premedicationwith diazepam 0.14 mg kg^–1 by mouth or hyoscine 6 µgkg^–1 ³ morphine 0.2 mg kg ¹ i.m., or no premedication,on toxic symptoms and plasma concentrations after rapid i.v.injection of lignocaine 1 mg kg^–1. The ₁-acid glycoprotein(AAG) and albumin plasma protein fractions were assessed. Avariety of mild central nervous system (CNS) symptoms were experiencedafter the bolus of lignocaine. However, there was no correlationbetween premedication and degree of severity or number of CNSsymptoms. The highest single arterial plasma concentration oflignocaine was 11.0 µg ml^–1, 1 min after injection.There was no correlation between plasma concentration of lignocaineand occurrence of CNS symptoms. Furthermore, there was no correlationbetween AAG or albumin plasma concentrations and lignocaineplasma concentrations.     

A COMPARISON OF THE HYDROCHLORIDE AND CARBONATED SALTS OF LIGNOCAINE FOR CAUDAL ANALGESIA IN OUT-PATIENTS

Plain solutions of 1.73 per cent carbonated lignocaine and theequivalent concentration of lignocaine hydrochloride were comparedfor caudal anaesthesia in 64 patients, 46 of whom were ambulatoryout-patients. The carbonated solution produced rapid intenseblockage 4.5 times faster than the hydrochloride solution, andthe segmental spread of analgesia was 46 per cent more extensive.This was achieved with no increase in toxicity. The advantagesof caudal block for perineal surgery in out-patients were shownto include the absence of adverse cardiac and laryngeal vagalreflexes and persistence of sacral analgesia postoperativelytogether with rapid mobilization. The rapid and extensive analgesiaof carbonated lignocaine was shown to further enhance this technique. ^*Present address: Department of Anesthesia, Stanford UniversitySchool of Medicine, Stanford, California 94305, U.S.A.     

EFFECTS OF I.A. LIGNOCAINE ON ADRENALINE-INDUCED VASOCONSTRICTION

The effects of i.a. administered lignocaine on the in vivo responseof the vascular bed supplied by the lingual, external maxillaryand posterior auricular branches of the common carotid arterywere studied in the rat. Infusions of lignocaine in concentrationsof 10–1000 µg ml^–1 administered at the rateof 0.05 ml min^–1 for 10 min did not affect vascular resistanceor arterial pressure in the common carotid artery. However,following such infusions, the increase of vascular resistancecaused by bolus doses of adrenaline (20–120 ng in 0.1ml) was inhibited, indicating lignocaine-adrenaline antagonism.Responses to adrenaline remained significantly depressed 60min after the termination of a 100-µg ml^–1 or higherlignocaine infusion. ^* Present address: Turner Dental School, University of Manchester,Bridgeford Street, Manchester M15.     

Maximum recommended doses of lignocaine are not toxic

The maximum recommended doses of lignocaine are frequently exceededin clinical practice as some blocks may need more lignocaineto produce adequate anaesthesia. We have examined the successrate of brachial plexus block, possible toxic symptoms aftera dose of lignocaine 900 mg with adrenaline, and the maximumplasma concentration of lignocaine produced in 17 adult patients.In all patients, the block was excellent and no toxic symptomswere encountered. The highest mean lignocaine plasma concentrationwas 2.9 µg ml^–1 45 min after the block. We concludethat in brachial plexus block, the dose of lignocaine with adrenalinecan be as high as 900 mg without fear of toxic symptoms