Dose Of Lignocaine Research Articles

Changes in intraocular pressure during low dose intravenous sedation with propofol before cataract surgery.

This study examined the effects on intraocular pressure, pulse rate, and blood pressure of low dose intravenous sedation with propofol. Twenty adult patients who were scheduled to undergo cataract surgery were given a single intravenous bolus (0.98 (SEM 0.4) mg/kg) of propofol for sedation before administering the local anaesthetic for cataract surgery. A small intravenous dose of lignocaine was the only other anaesthetic or sedative agent given. The intraocular pressure in the non-surgery eye, the pulse rate, and the blood pressure were measured before and after propofol induction. Compared with the preinduction baseline, there was a 17% to 27% (from 16.2 (0.7) mm Hg to 11.8 (0.7) mm Hg) decrease in intraocular pressure after propofol induction. A significant decrease in intraocular pressure occurred within the first minute and was still evident at 7 minutes when the measurements were stopped. There was also a 7%-12% increase in pulse rate during the first 4 minutes, a 12% decrease in mean systolic blood pressure, and a 7% decrease in mean diastolic blood pressure from baseline after propofol induction. A single low dose bolus of propofol used for sedation before cataract surgery caused a moderate reduction in intraocular pressure with minimal, easily managed side effects.

Maximum recommended doses of lignocaine are not toxic

The maximum recommended doses of lignocaine are frequently exceeded in clinical practice as some blocks may need more lignocaine to produce adequate anaesthesia. We have examined the success rate of brachial plexus block, possible toxic symptoms after a dose of lignocaine 900 mg with adrenaline, and the maximum plasma concentration of lignocaine produced in 17 adult patients. In all patients, the block was excellent and no toxic symptoms were encountered. The highest mean lignocaine plasma concentration was 2.9 micrograms ml-1 45 min after the block. We conclude that in brachial plexus block, the dose of lignocaine with adrenaline can be as high as 900 mg without fear of toxic symptoms.

Safety and efficacy of nebulized lignocaine in patients with cancer and breathlessness.

Although anecdotal reports suggest nebulized lignocaine may help breathlessness in patients with cancer this has not been examined formally. We report a pilot study comparing nebulized lignocaine 100 mg and 200 mg with saline in six patients with cancer who were breathless at rest. Nebulized lignocaine was well tolerated apart from mild bronchoconstriction in two patients after the 200 mg dose and the unpleasant taste; serum concentrations were below levels at which toxicity has been reported. The effort of breathing (measured on a visual analogue scale) did not differ between treatments, whereas the distress of breathing was less after saline than after either dose of lignocaine. These findings do not support the reported benefits of nebulized lignocaine.

I.V. BOLUS ADMINISTRATION OF SUBCONVULSIVE DOSES OF LIGNOCAINE TO CONSCIOUS SHEEP: RELATIONSHIPS BETWEEN MYOCARDIAL PHARMACOKINETICS AND PHARMACODYNAMICS

We have studied relationships between the time-courses of lignocaine concentrations in arterial and coronary sinus blood and myocardial tissue, and negative inotropic effects on the myocardium, after i.v. bolus administration of 50-, 75- or 100-mg doses of lignocaine to conscious, chronically instrumented sheep. Peak arterial and coronary sinus blood lignocaine concentrations occurred 26-38 s before and 29-78 s after the maximum decreases in myocardial contractility, respectively. Peak myocardial concentrations occurred simultaneously with the maximum decreases in myocardial contractility, except for the 100-mg doses. Anti-clockwise hysteresis occurred only between arterial blood lignocaine concentrations and the negative inotropic effect. It was concluded that, after short-term i.v. administration, only the myocardial concentrations of lignocaine were in pseudoequilibrium with the negative inotropic effects of the lignocaine on the myocardium.

I.V. BOLUS ADMINISTRATION OF SUBCONVULSIVE DOSES OF LIGNOCAINE TO CONSCIOUS SHEEP: MYOCARDIAL PHARMACOKINETICS

Mass balance principles were used to study the myocardial pharmacokinetics of lignocaine in conscious sheep. After i.v. bolus doses of lignocaine 50, 75 or 100 mg, arterial lignocaine concentrations reached a peak in approximately 16 s and these increased linearly with dose. Coronary sinus concentrations reached a peak between 83 and 129 s and the values showed poor relationships with dose. Net myocardial lignocaine uptake lasted for approximately 60 s--this was much shorter than the reported initial distribution half-life of lignocaine. The maximum rate of uptake was proportional to both the dose and the peak arterial lignocaine concentrations. At 15 min, the myocardial lignocaine concentrations were 46 (SD 22)% of their peak values. Pseudo-equilibrium between blood and myocardial lignocaine concentrations was not observed. It is concluded that, despite the myocardium being very well perfused, lignocaine myocardial concentrations were not well represented by blood lignocaine concentrations for at least 15 min. A greater understanding of the determinants of myocardial drug concentrations is required.

I.V. BOLUS ADMINISTRATION OF SUBCONVULSIVE DOSES OF LIGNOCAINE TO CONSCIOUS SHEEP: EFFECTS ON CIRCULATORY FUNCTION

We have studied the effects of subconvulsive doses of lignocaine on circulatory function in five conscious, chronically instrumented sheep. In the absence of overt signs of central nervous system toxicity, 50-, 75- or 100-mg i.v. bolus doses of lignocaine induced reductions in myocardial contractility, as assessed by the maximum rate of increase in left ventricular pressure (LV dP/dtmax), of 17 (SD 4)%, 25 (4)% and 33 (4)%, respectively. The durations of these reductions in myocardial contractility were 2-3.5 min. There were no significant changes in cardiac output, coronary artery blood flow, mean arterial pressure, heart rate or left ventricular systolic and diastolic pressures. It is concluded that the initial toxic effects of lignocaine are on the heart rather than the central nervous system, as is generally believed. This negative inotropic effect of lignocaine in vivo may be more deleterious to myocardial function when the heart is compromised by pre-existing disease, or the co-administration of other myocardial depressive drugs.

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 accepted technique to avoid adductor contraction during transurethral resection of prostate or bladder tumours. However, little is known about plasma lignocaine concentrations after the block. We conducted this study to assess a safe dose of lignocaine for injection in obturator nerve block. Bilateral obturator nerve block was performed with the aid of a peripheral nerve stimulator in 12 patients after spinal anaesthesia. In group I (n = 6), patients received 2% lignocaine 10 ml (200 mg) for the block; those in group II (n = 6) received 2% lignocaine 15 ml (300 mg). The block was satisfactory and no single adductor contraction was observed in either group during surgery. The peak plasma concentrations of lignocaine were 2.28 (SD 0.29) micrograms ml-1 and 3.75 (0.79) micrograms ml-1 in groups I and II, respectively. The greatest plasma concentration was 5.07 micrograms ml-1 in a patient of group II. There were no symptoms suggesting systemic toxicity. We conclude that bilateral obturator nerve block may be performed safely and effectively with 2% lignocaine 10 ml with the aid of a peripheral nerve stimulator in patients undergoing transurethral resection procedures with spinal anaesthesia.

Spinal local anaesthetic actions on afferent evoked responses and wind-up of nociceptive neurones in the rat spinal cord: combination with morphine produces marked potentiation of antinociception

Lignocaine was tested either alone or in combination with a low dose of morphine by intrathecal administration on the C- and A-beta evoked responses of nociceptive neurones in the dorsal horn of the halothane-anaesthetized rat. In addition the effect of prilocaine was compared to lignocaine. The effects of lignocaine on wind-up, a frequency-dependent increase in the responses of the cells produced by repeated C-fibre stimulation was also tested. Lignocaine produced dose-dependent inhibitions of the C-, A-delta and A-beta evoked responses of the cells which became more selective for the noxious evoked responses as the dose increased. The effective doses corresponded well to those used clinically. Wind-up was also decreased by lignocaine. In combination with a low dose of morphine, threshold doses of lignocaine produced a highly marked potentiation of the inhibitions of the C-fibre evoked responses compared to either agent alone. No potentiation of the inhibitions of the A-beta responses was observed. The potentiated inhibitory effects on the C-fibre responses were rapidly reversed by intrathecal naloxone. The finding that spinal local anaesthetic and morphine potentiate markedly to reduce spinal nociception is discussed both in terms of mechanisms of action of the agents and their clinical application.

EFFECT OF ADRENALINE ON EXTRADURAL ANAESTHESIA, PLASMA LIGNOCAINE CONCENTRATIONS AND THE FETO-PLACENTAL UNIT DURING ELECTIVE CAESAREAN SECTION

Extradural anaesthesia was induced with either 2% lignocaine or 2% lignocaine with adrenaline 1:200,000 in 20 patients undergoing elective Caesarean section. With the adrenaline-containing solution, a smaller dose of lignocaine was required to produce an adequate block and the lignocaine concentrations in both mother and neonate were significantly smaller compared with the plain solution. Arterial pressures were less in the adrenaline group, but there was no difference in umbilical flow velocity waveform, fetal heart rate or fetal outcome. Neither feto-placental circulation nor fetal outcome were affected adversely by episodes of hypotension or the ephedrine used for treatment.

EFFECTS OF I.V. LIGNOCAINE ON PSYCHOLOGICAL PERFORMANCE AND SUBJECTIVE STATE IN HEALTHY VOLUNTEERS

In order to assess the effects of different doses of lignocaine on performance, nine healthy volunteers aged 21-34 yr received i.v. infusions of saline, low and high dose lignocaine (mean plasma concentrations 0.92 and 1.78 micrograms ml-1, respectively) in a double-blind randomized order. The Digit-Symbol Substitution Test (DSST) and Visual Analogue Scales (VAS) were performed repeatedly and a battery of performance tests once. The median (lower, upper quartile) number of correct responses for the DSST during the infusion period was: placebo 69 (67, 77); low 74 (71, 80); high 66 (61, 75) (P less than 0.001, General Linear Models; all pairwise comparisons P less than 0.05). None of the measures in the full battery showed any significant changes. VAS showed that subjects felt more interested (P less than 0.05), drowsy (P less than 0.01), dizzy, tense, abnormal, drunk and muzzy (P less than 0.001) with lignocaine than with placebo. These results confirm that lignocaine can produce acute performance effects (both improvements and impairments). Subjects were clearly aware of the presence of lignocaine, suggesting that subjective reports may be a useful indicator of its CNS effects.

HEART RATE RESPONSE TO AN I.V. TEST DOSE OF ADRENALINE AND LIGNOCAINE WITH AND WITHOUT ATROPINE PRETREATMENT

In order to evaluate the sensitivity of an adrenaline test dose for detecting intravascular injection and the effect of atropine pretreatment, 90 ASA physical status I and II patients were allocated randomly to two groups, to receive i.v. saline 1 ml (n = 46) or i.v. atropine 0.5 mg (n = 44). Five minutes later, all patients received an i.v. test dose of 2% lignocaine 3 ml with adrenaline 15 micrograms at a rate of 1 ml s-1. The groups were similar with respect to basal heart rate (HR). HR remained unchanged after saline injection, but increased slightly 5 min after atropine injection (mean 78 (SD 15) beat min-1 vs 87 (20) beat min-1 (P less than 0.05). After the test dose of lignocaine with adrenaline, HR increased significantly in both groups at 30 s, 1 and 2 min, and remained increased at 3 min in the atropine group. The maximum increase in HR was greater in the atropine group than in the saline group (31 (4) beat min-1 vs 26 (11) beat min-1 (P less than 0.05). However, when individual maximum HR changes are considered, five patients in the saline group and four in the atropine group had an increase less than or equal to 10 beat min-1, and three patients in the saline group had no change or a decrease in HR. Defining a positive result to a test dose as an increase in HR of greater than 10 beat min-1, the sensitivity of the adrenaline test dose was 83 (5.5)% in the saline group and 91 (3.5)% in the atropine group (ns).(ABSTRACT TRUNCATED AT 250 WORDS)

OPTIMAL DOSE OF LIGNOCAINE FOR PREVENTING PAIN ON INJECTION OF PROPOFOL

The purpose of this study was to define the optimum dose of lignocaine required to reduce pain on injection of propofol. We conducted a prospective, randomized, double-blind trial on 310 patients undergoing anaesthesia. Patients were allocated to four groups according to the lignocaine dosage: group A (control), no lignocaine; group B, lignocaine 0.1 mg kg-1; group C, lignocaine 0.2 mg kg-1; group D, lignocaine 0.4 mg kg-1. Our results showed that a dose of lignocaine 0.1 mg kg-1 significantly reduced the incidence of pain and that there was no improvement when the dose was increased.

Myocardial uptake of lignocaine: pharmacokinetics and pharmacodynamics in the isolated perfused heart of the rabbit

1. The uptake kinetics and pharmacodynamics of lignocaine were studied in isolated perfused heart of the rabbit. 2. Six hearts were perfused with increasing concentrations of lignocaine in a modified Krebs-Henseleit buffer. The effluent concentration together with the increase in QRS duration were measured during lignocaine infusion and during 20 min after cessation of lignocaine infusion. 3. Lignocaine disposition and elimination were best described by a two-compartment open model. Terminal half-life was 11.0 +/- 2.9 min. The unidirectional transfer was slower from central to peripheral compartment than from peripheral to central compartment (T1/2.12 = 42.6 +/- 10.5 min whereas T1/2.21 = 10.7 +/- 2.8 min). The myocardium/perfusate concentration-ratio was 4.7 +/- 0.4. 4. The pharmacodynamic effect was best described in the central compartment by using the Hill equation. Calculated maximum QRS duration (Emax) was 77 +/- 8 ms. Emax was also directly measured in four additional rabbits by infusing ten times the dose of lignocaine used in the main experiment: the value of Emax measured in these conditions was 92.5 +/- 9.6 ms, i.e. a QRS widening of 150%. The steady-state perfusate concentration producing half the effect (C50) was 15.7 +/- 7.6 micrograms ml-1. 6. In conclusion, the specific lignocaine binding leading to increase in QRS duration appeared to be more closely related to the vascular stream than non specific binding leading to a deeper accumulation process.

EFFECT OF LIGNOCAINE ON CORONARY BLOOD FLOW, SYSTOLIC MYOCARDIAL FUNCTION AND MYOCARDIAL HIGH ENERGY PHOSPHATE STORES IN SWINE

1. To investigate the effect of lignocaine upon coronary blood flow, myocardial systolic wall function and high energy phosphate stores, lignocaine was administered as a rapid intravenous injection to 14 open chest anaesthetized swine. 2. Before and after injection, measurements were made of coronary blood flow by electromagnetic flow probe, per cent wall thickening by ultrasonic crystals, adenosine triphosphate (ATP) and creatine phosphate (CP) content by myocardial biopsy, and arterial pressure by central aortic catheter. The animals were divided into two groups based on whether or not they received a continuous low-dose infusion of lignocaine prior to the study. Group I received the continuous low-dose infusion of lignocaine and group II did not. 3. With a 2 mg/kg lignocaine injection, peak diastolic coronary flow rose significantly in groups I and II by 27 +/- 7 and 29 +/- 7% respectively. This was followed by a significant decline in per cent wall thickening in groups I and II of -11 +/- 2 and -19 +/- 6% respectively. In group I myocardial CP content decreased after lignocaine injection by 58 +/- 6% and ATP tended to rise even though systolic and diastolic pressure did not change significantly. In group II neither CP nor ATP changed significantly, but systolic and diastolic blood pressure decreased significantly. 4. Repeat lignocaine injections were given over a wider dosage range (0.5-4.0 mg/kg) to determine dose-response for lignocaine versus coronary blood flow. Coronary blood flow increased and per cent wall thickening decreased as doses of lignocaine were increased. 5. It was concluded that rapid intravenous lignocaine injection appeared to cause a dose-dependent coronary dilatation and systolic dysfunction. Pre-treatment with low-dose continuous infusion of lignocaine appeared to result in a decrease in CP and a rise in ATP when compared with no pre-treatment--despite a similar effect on myocardial function and coronary blood flow.

Local anaesthesia for fibreoptic bronchoscopy: transcricoid injection or the "spray as you go" technique?

Local anaesthesia for fibreoptic bronchoscopy should be given by a safe technique that is not unpleasant to the patient and should provide acceptable conditions for the bronchoscopist. Single injection transcricoid local anaesthesia was compared with the "spray as you go" technique in patients having day case fibreoptic bronchoscopy. Patients were randomised to receive either 100 mg lignocaine by a single cricothyroid puncture or 240 mg lignocaine instilled through the bronchoscope under direct vision. Further doses were given by the operator to both groups as required. The 30 patients receiving transcricoid lignocaine coughed less (3.56 (SD 3.1) coughs/min) than the 32 patients receiving lignocaine through the bronchoscope (5.89 (4.8)/min) despite receiving a lower total dose of lignocaine (322 (25.9) v 451 (20.9) mg). Cricothyroid puncture was not associated with any complications and was not unpleasant for the patients.

Changes in haemodynamics and plasma catecholamine concentrations after field block for inguinal herniorrhaphy using lignocaine with adrenaline

Haemodynamic changes and plasma catecholamine concentrations were measured in 12 patients aged 24 to 87 years after performance of a field block for elective repair of inguinal or femoral hernia. The local anaesthetic used comprised a mixture of lignocaine 0.5% with adrenaline 1:200,000; the dose of lignocaine administered varied from 3.8 mg/kg to 4.9 mg/kg. Plasma adrenaline increased by 326% and plasma noradrenaline by 75% at 10 minutes after completion of the block. Mean heart rate increased from 75 to 94 beats/minute after 20 minutes, whilst there were no obvious changes in systolic and diastolic arterial pressures. Potentially serious arrhythmias developed in two patients, thought to be related to the peak plasma concentrations of adrenaline produced. It is recommended that the dose of adrenaline used as described for this block should be reduced.

Plasma lignocaine levels during paediatric endoscopy of the upper respiratory tract. Relationship with mucosal moistness.

Plasma lignocaine levels were measured at 5, 10 and 15 minutes following local application (4 mg/kg) to the upper airway in children who underwent endoscopy under general anaesthesia. These levels were then correlated with the appearance of the moistness of the airway mucosa secondary to premedication with atropine. This latter assessment was carried out by one anaesthetist who used a predetermined scale of 1-5, where 1 was very dry and 5 very wet. Significantly higher (p less than 0.05) plasma levels of lignocaine were achieved when the mucosa was 'very dry' especially in children under 2 years of age. The total dose of lignocaine applied to the upper airway of children should probably be reduced, in the presence of a 'dry' mucosa after effective antisialogogue premedication, and especially when less than 2 years of age.

EFFECTS OF LIGNOCAINE AND BUPIVACAINE ON REGIONAL MYOCARDIAL FUNCTION AND CORONARY BLOOD FLOW IN ANAESTHETIZED DOGS

Empirical i.v. doses of lignocaine or bupivacaine of equal local anaesthetic potency were administered to halothane-anaesthetized dogs. Both local anaesthetics caused the expected depression of global haemodynamic function. Regional myocardial systolic shortening was depressed similarly by both agents. Regional myocardial dysfunction, seen as post-systolic shortening, occurred to a similar extent with both lignocaine and bupivacaine. Coronary blood flow and coronary perfusion pressure were significantly correlated during the administration of lignocaine; bupivacaine had erratic effects on coronary blood flow and no correlation between coronary blood flow and coronary perfusion pressure was seen. These results suggest that regional myocardial dysfunction occurs with both local anaesthetics and does not account for the apparent increased cardiotoxicity of bupivacaine. Bupivacaine did, however, cause wider individual variations compared with lignocaine with respect to coronary blood flow.

Postal survey of bronchoscopic practice by physicians in the United Kingdom.

In 1983 a postal survey of the bronchoscopic practice of chest physicians in the United Kingdom produced a 90% response rate. Two hundred and thirty one physicians were carrying out bronchoscopy; they had performed about 40 000 bronchoscopies in the preceding year, 87% of these being fibreoptic procedures with topical anaesthesia. The mortality rate of fibreoptic bronchoscopy was 0.04%, with a 0.12% incidence of major complications. Transbronchial biopsy carried both an appreciably higher mortality rate of 0.12% and a major complication rate of 2.7%. There is wide variation in the use and choice of sedative drugs for fibreoptic bronchoscopy. Many of the drug combinations could be criticised on pharmacological grounds. The mean dose of lignocaine was 342 mg, most operators exceeding the usual maximum recommended dose; but adverse reactions were rare. Routine supplemental oxygen was given by only 18% of bronchoscopists. Basic resuscitation equipment was often inadequate. Radiological screening was used for transbronchial lung biopsy by 53% of respondents and significantly reduced the incidence of pneumothorax from 2.9% to 1.8%. Both the number of bronchoscopies performed and the complication rate were higher than previous estimates. Bronchoscopists should re-examine their policy on drugs and safety precautions to minimise the risks of the procedure.

Patient comfort and plasma lignocaine concentrations during fibreoptic bronchoscopy.

In a preliminary prospective study, eleven outpatients undergoing fibreoptic bronchoscopy using a titrated dose of topical lignocaine anaesthesia were studied. Patient comfort, lignocaine dosage and resultant plasma concentrations were measured at four stages during the procedure. Large total doses, mean 512 (SD 55) mg lignocaine, were frequent and systemic absorption was unpredictable with two patients having plasma concentrations in the toxic range (greater than 5 micrograms/ml). Peak plasma concentrations, mean 2.3 (SD 1.4) micrograms/ml, occurred 30 to 40 minutes after commencement of topical application and coincided with completion of the procedure. No correlation was found between the individual dose of lignocaine administered and either the resultant plasma concentration or patient comfort scores. In an effort to minimise potential lignocaine toxicity, a fixed total dose technique (lignocaine 370 mg) was studied in a further twenty-one patients. No change in patient comfort scores and no toxic plasma concentrations were observed. Mean completion plasma concentration was 2.0 (SD 1.0) micrograms/ml. No clinical toxicity was observed in either group. Fibreoptic bronchoscopy in both groups using topical lignocaine anaesthesia without premedication or intravenous supplementation was well tolerated.