Experimental gastrocarcinogenesis: the dynamics of morphological and biochemical changes

Nebulization of lignocaine is a common technique for preparing the airway prior to awake intubation. The aim of the study was to assay the serum levels of lignocaine. Ten ASA I volunteers had 6 mg/kg of 10% lignocaine solution nebulized via facemask. Blood assays for peak levels were performed. Mean peak serum lignocaine level was 0.29 mg/l with a highest measurement of 0.45 mg/l. This peak occurred 30 minutes following commencing nebulization. No subject developed symptoms or signs of lignocaine toxicity. Peak plasma lignocaine levels were an order of magnitude below the accepted toxic threshold of 5 mg/l. This indicates that supplemental doses of lignocaine via the bronchoscope can be given with safety.     

Evidence for safety margins of lignocaine local anaesthetics for peri-oral use

The evidence for the safety margins of doses of lignocaine local anaesthetics for standard injections for oral and dental purposes has been reviewed. Trials of peri-oral dosages leading to toxicity in humans have not been reported. The overwhelming evidence from trials of the normal dose range used clinically points to a restriction of total doses much lower than the 25 ml (500 mg) as published for 2% lignocaine with 1:80,000 adrenaline for a healthy adult. The recommendations are: 1. In mixtures of two pharmacologically active drugs (dual formulations) for peri-oral injections, to base the safety limit of local anaesthetic on the circulating level of lignocaine, rather than the amount of adrenaline contained in the injected volume. 2. Thus the suggested usual upper limit for dosage for a healthy adult patient is four and a half 2 ml (or 2.2-ml) cartridges of lignocaine with adrenaline (180-198 mg lignocaine or 2.57-2.82 mg/kg) body weight, if carefully given. 3. For some medically compromised patients, minimal doses only of lignocaine and adrenaline (about one cartridge) should be used and especial caution is necessary in patients likely to react adversely to the exogenous adrenaline of the dual formulation. 4. For both children and adults, the dosages should broadly be related to body size and note taken of the total dose which accrues from topical use of other formulations of lignocaine, such as pastes or creams or sprays. The doses injected should be the minimum that allow the treatment to proceed. If necessary the doses are better given at a series of appointments rather than as a large volume on one single occasion.     

Intra-arterial regional anaesthesia for hand surgery with alkalinized 0.5% lignocaine

Intra-arterial regional anaesthesia (IARA) for hand surgery is an old, forgotten technique. One of the causes of low popularity may be a scalding sensation in the hand during intra-arterial injection of lignocaine, which may be caused by low pH of lignocaine's solution. In this randomized, double-blind study, normal (pH 5.2-5.3) or alkalinized (pH 7.2-7.3) preservative-free 0.5% lignocaine 1.5 mg kg-1 was injected into the radial arteries of forty adult patients to produce anaesthesia for ambulatory hand surgery. Scalding sensation in the hand during intra-arterial injection (VAS) was less pronounced with alkalinized lignocaine (P = 0.04). The time of onset and regression of analgesia was similar in both groups. Four patients in group 1 (normal lignocaine) and six patients in group 2 (alkalinized lignocaine) needed supplemental analgesia at the start of surgery (NS). Cannulation time, operating conditions, motor blockade, surgical-, and tourniquet pain scores (VAS) and patient's acceptance were similar. Three patients (two in group 1 and one in group 2) had minor systemic adverse effects after tourniquet release (NS). Nine patients in group 1 and seven in group 2 developed minor bruises after cannulation (NS). No other sequelae of intra-arterial injections were observed. We conclude that alkalinized 0.5% lignocaine was less painful on injection than normal lignocaine and should be preferred for intra-arterial anaesthesia for hand surgery.     

Influence of physical activity upon bone mineralization of school age children of both sexes]

The effect of topical lignocaine applied to the eye muscles, on the incidence of the oculocardiac reflex during squint surgery of the medial rectus was investigated in 56 healthy children aged between 3-14 years. Three groups were studied. One (n = 16): stimulation of the reflex without lignocaine; 2 (n = 10): stimulation of the reflex after topical administration of 1 mg kg-1 lignocaine 2% to the medial part of the eye after induction of anaesthesia; 3 (n = 30): stimulation of the oculocardiac reflex without, and after a 5 min interval under the influence of lignocaine. Topical administered lignocaine significantly attenuated the OCR (105 vs. 68 bpm group II vs. group 1:82 vs. 63 bpm in group III). Severe bradycardiac rhythm disturbances, in particular cardiac stand-still, were not observed after lignocaine had been applied. Systemic side effects of lignocaine were not seen.     

Critical and heretical thoughts on the development of cardiology. Limits of mental and social compliance attitude of the population

100 patients with ASA risk I & II and undergoing perianal surgery were studied for anaesthetic effects and postoperative analgesia following either intrathecal pethidine or lignocaine. Saddle block was performed either with intrathecal pethidine 5% (50 mg/ml) 0.5 mg/kg or 1 ml of 5% lignocaine. Sensory and motor block postoperative analgesia, need for additional analgesia were studied. The onset of sensory and motor blockade with lignocaine was faster than pethidine. However the sensory and motor blockade lasted longer with pethidine. The duration of postoperative analgesia was 15.39 +/- 5.14 hours as against duration of postoperative analgesia with lignocaine which was 1.3 +/- 0.53 hours. Only 10% of patients in the pethidine group required intramuscular analgesic supplementation whereas 30% of patients in the lignocaine group required intramuscular analgesic supplementation.     

Analgesic and sedative concentrations of lignocaine shunt tonic and burst firing in thalamocortical neurones

The effects of lignocaine [lidocaine] HCl (0.6 microM(-1) mM) on the membrane electrical properties and action potential firing of neurones of the ventral posterolateral (VPL) nucleus of the thalamus were investigated using whole cell recording techniques in rat brain slices in vitro. Bath application of lignocaine reversibly decreased the input resistance (Ri) of VPL neurones. This effect was observed at low, clinically sedative and analgesic concentrations (i.e., maximal amplitude at 10 microM) whereas higher concentrations (300 microM(-1) mM) had no effect on Ri. Lignocaine (10-100 microM) depolarized VPL neurones up to 14 mV in a reversible manner. Consistent with a decreased Ri, low concentrations of lignocaine shunted the current required for spike generation in the tonic pattern. Lignocaine increased the threshold amplitude of current required for firing and decreased the tonic firing frequency, without concomitant elevation of the voltage threshold for firing or reduction in the maximal rate of rise (dV/dt(max)) of spikes. Low concentrations of lignocaine shunted low threshold spike (LTS) burst firing evoked either from hyperpolarized potentials or as rebound bursts on depolarization from prepulse-conditioned potentials. Higher concentrations of lignocaine (300 microM - 1 mM), not associated with a decrease in Ri, elevated the voltage threshold for firing and reduced the dV/dt(max) of spikes in a concentration-dependent fashion. In conclusion, low concentrations of lignocaine shunted tonic and burst firing in VPL neurones by decreasing Ri, a mechanism not previously described for local anaesthetics in the CNS. We suggest that a decreased resistance in thalamocortical neurones contributes to the sedative, analgesic, and anaesthetic properties of systemic lignocaine in vivo.     

Long-term treatment of bleeding caused by portal hypertension in children

We have compared the hypnotic requirements for i.v. thiopentone alone and in combination with i.m. lignocaine or bupivacaine. Ninety women, ASA I-II, undergoing minor gynaecological surgery were allocated randomly to nine groups of 10 patients to receive thiopentone combined with i.m. lignocaine, bupivacaine or saline, respectively. Thiopentone was administered in bolus doses of 0.5 mg kg-1 every 30 s until loss of response to verbal command. Lignocaine and bupivacaine significantly enhanced the hypnotic effect of thiopentone in a dose-dependent manner. The maximum doses tested (lignocaine 3.0 mg kg-1 and bupivacaine 1.0 mg kg-1) reduced the hypnotic dose of thiopentone by 39% and 48%, respectively. We conclude that if lignocaine or bupivacaine are injected into soft tissue before induction of anaesthesia by thiopentone, the i.v. dose of the latter should be modified accordingly.     

Effects of lignocaine on intramyocardial conduction in nonischaemic and ischaemic canine myocardium

The effect of lignocaine (USP: lidocaine) on intramyocardial conduction in ischaemic and nonischaemic areas of the left ventricular myocardium was determined in 11 mongrel dogs. Intramyocardial conduction times were assessed during control conditions, 15 min after coronary ligation, and following lignocaine administration. Coronary occlusion resulted in a disparity between the conduction velocities in the ischaemic and nonischaemic zones. Ater lignocaine administration conduction to the ischaemic area was further decreased. However, conduction to the nonischaemic area was decreased to a relatively greater extent, resulting in a significant decrease in the disparity of conduction velocities in the two areas. It is concluded (1) that lignocaine exerts dissimilar quantitative effects on the nonischaemic and acutely ischaemic myocardium and (2) that these differential effects decrease the inhomogeneity of intraventricular conduction. It is possible that this action may play a role in the suppression of re-entrant arrhythmias.     

Superior vena cava syndrome after heart transplantation: percutaneous treatment of a complication of bicaval anastomoses

The aims of this study were to establish a working rabbit heart model of regional myocardial ischaemia in which electrophysiologic parameters and arrhythmogenesis could be correlated and to explore the mechanisms underlying the antiarrhythmic activity of lignocaine. Monophasic action-potential duration (MAPD90), effective refractory period (ERP), and conduction delay were measured at three ventricular sites in isolated hearts paced at 3.3 Hz. The hearts were treated before and throughout 30 min of ischaemia and 15 min of reperfusion with a vehicle or 20 microM lignocaine. In both groups, ischaemia produced a similar shortening in MAPD90. Lignocaine decreased ERP shortening during ischaemia from -56+/-4 to -32+/-6 ms. An ischaemia-induced increase in conduction delay was greater in the lignocaine than the control group (49+/-7 vs. 11+/-2 ms). Ischaemia-induced dispersion of repolarisation was reduced by lignocaine from 66+/-4 to 32+/-7 ms, and dispersion of refractoriness was decreased from 57+/-6 to 16+/-3 ms. Lignocaine decreased inducibility of ventricular fibrillation (VF) during ischaemia from 86 to 25%. We conclude that, in this model, the antiarrhythmic activity of lignocaine during regional ischaemia is associated with an increase in ischaemia-induced conduction delay and reduced dispersion of repolarisation and refractoriness.     

Haemostatic changes caused by i.v. regional anaesthesia with lignocaine

The various components of i.v. regional anaesthesia (IVRA), that is ischaemia, tourniquet compression and the presence of high concentrations of local anaesthetics in the blood vessels of the extremity, may affect haemostatic mechanisms. We performed a cross-over study in 10 healthy male volunteers to examine the role of lignocaine in IVRA on several haemostatic variables, and those indicating fibrinolysis and platelet function in particular. Venous blood samples were obtained from the test arm and the opposite arm before IVRA, at the time of tourniquet cuff deflation and 30 min thereafter. Metal needle punctures were used, and for the sample from the test arm at the time of cuff deflation, cuff pressure was reduced from 300 mm Hg to individual mean arterial pressure. The IVRA technique included exsanguination by arm elevation and axillary artery compression, inflation of the tourniquet cuff for 20 min and deflation of the cuff in one step (after obtaining the venous sample). Each subject received, in random order, either 0.5% lignocaine 3 mg kg-1 or the corresponding volume of saline i.v. All fibrinolysis markers, that is, D-dimer, tissue plasminogen activator antigen (t-PA antigen), tissue plasminogen activator activity (t-PA activity), plasminogen activator inhibitor activity (PAI) and protein C indicated enhanced fibrinolysis by IVRA, but only t-PA antigen and PAI showed greater changes in the lignocaine compared with the saline group in the exposed arm at the time of cuff deflation. Platelet function tests (ADP-induced platelet aggregation, beta-thromboglobulin and thrombelastogram (TEG)) indicated no differences between the lignocaine and saline groups. Although IVRA appeared to induce some platelet dysfunction, there was a small increase in TEG amplitude indicative of improved fibrin-platelet interaction in the lignocaine-exposed arm at the time of cuff deflation. We conclude that the presence of high i.v. lignocaine concentrations (median 144.4 micrograms ml-1 in cubital veins at the end of the tourniquet time) potentiated ischaemia-induced fibrinolysis activation during IVRA. Concomitant platelet dysfunction was not aggravated by lignocaine.     

A study of sexual behavior among rural residents of China

Besides the fast tetrodotoxin-sensitive Na+ current, small dorsal root ganglion neurones of rats also possess a slower tetrodotoxin-resistant Na+ current. The blocking effect of commonly used local anaesthetics upon the tetrodotoxin-resistant Na+ current was investigated in the present paper. Dorsal root ganglia were dissected from adult rats and cells were enzymatically isolated. The whole-cell patch clamp technique was then used to measure inward Na+ currents of small dorsal root ganglion neurones. Externally applied local anaesthetics reversibly blocked the tetrodotoxin-resistant Na+ current in a dose-dependent manner. Half-maximal blocking concentrations for tonic block were: lignocaine, 326 microM; prilocaine, 253 microM; mepivacaine, 166 microM; etidocaine, 196 microM bupivacaine, 57 microM procaine, 518 microM benzocaine, 489 microM; tetracaine, 21 microM; and dibucaine, 23 microM. Blocking of the current by lignocaine was independent of temperature. The quaternary lignocaine derivative OX-314 did not have any effect upon the tetrodotoxin-resistant Na+ current when applied externally. High concentrations of tetrodotoxin also blocked the tetrodotoxin-resistant Na+ current with a half-maximal blocking concentration of 115 microM. The block by high tetrodotoxin concentrations did not compete with the lignocaine block, suggesting that there were two independent blocking mechanisms for the two substances. The tetrodotoxin-resistant Na+ currents also showed a marked sensitivity to phasic (use-dependent) block by local anaesthetics.     

Nucleotide sequence of DR-B exon of major histocompatibility complex from an Indian zebu cattle breed

Somatosensory evoked potential, locomotion and vocalisation upon tail pinch in rats was studied in order to determine whether intrathecal magnesium sulphate administration causes spinal anaesthesia. In Wistar rats with indwelling intrathecal catheters, cortical somatosensory evoked potential was recorded following stimulation via electrodes inserted into the hind paw under chloral hydrate anaesthesia before and after intrathecal administration of 10 microliters of either magnesium sulphate (12.3% or 24.6%) or lignocaine (4% or 8%). Locomotion and vocalisation after tail pinch were tested following intrathecal administration of the same two drugs in conscious rats. Somatosensory evoked potential amplitude was diminished after administration of lignocaine (p < 0.05) but did not change after magnesium sulphate. Latency of P1 was increased by lignocaine and by magnesium sulphate 12.3% (p < 0.05). Although lower extremity paralysis was observed in both groups, its duration with magnesium sulphate was much longer than with lignocaine. Vocalisation was recognised after magnesium sulphate 12.3%, but was not observed after lignocaine 8% during paralysis (p < 0.05). We believe that magnesium sulphate caused motor paralysis, but not complete analgesia.     

Farnesyltransferase inhibitors versus Ras inhibitors

BACKGROUND: Intra-arterial regional anaesthesia (IARA) may be useful for ambulatory hand surgery in patients with poor veins. This randomized, double-blind study assessed which of the three doses of lignocaine gives the optimal analgesia with a minimum of adverse effects. METHODS: A preservative-free, alkalinized 0.5% lignocaine 1, 2 or 2.89 mg/kg body weight was injected into the radial arteries of 60 adult patients, allocated to three equal groups, to produce anaesthesia for carpal tunnel releases, capsulotomies, tenosynovectomies, palmar fasciectomies, Z-plastics, arthroplastics, arthrodeses etc. RESULTS: Surgical analgesia and motor block were best in group 3 (P < 0.01), whereas injection and tourniquet pain scores were similar in the three groups. Onset of analgesia was similar in all groups, and varied between 2 and 15 min. Cannulation time, surgery start time and tourniquet time were also similar in all groups, as were operating conditions and patient's acceptance of the method. No significant cardiovascular changes were observed after tourniquet release in any of the groups. Plasma lignocaine concentrations were lowest in group 1 (1 mg/kg) (P < 0.001). Five patients in group 1, seven in group 2 and seventeen in group 3 developed small bruises at the cannulation site (P < 0.001). Six patients (two in group 1, three in group 2 and one in group 3) had minor symptoms of lignocaine toxicity after tourniquet release (NS). No other complications were observed. CONCLUSIONS: The highest dose of lignocaine produces best surgical analgesia, without increasing the risk of toxicity. However, many patients receiving this dose will develop bruises at the injection site, and an occasional patient may need supplemental analgesia.     

A double-blind trial comparing subacromial methylprednisolone and lignocaine in acute rotator cuff tendinitis

Fifty-five patients with shoulder pain due to rotator cuff tendinitis of less than 12 weeks' duration were randomized to receive either 40 mg methylprednisolone and lignocaine or lignocaine alone. No statistically significant difference could be discerned between the two groups during 12 weeks of follow-up.     

Simultaneous analysis of lignocaine and bupivacaine enantiomers in plasma by high-performance liquid chromatography

A sensitive analytical procedure is described for the simultaneous determination of lignocaine and the enantiomers of bupivacaine in biological fluids using diazepam as an internal standard. After solvent extraction into hexane, the local anaesthetics were separated using an alpha1-acid glycoprotein (AGP) column and detected at 214 nm. Calibration curves were linear (r2>0.99) in the concentration range of 5 to 500 ng/ml for the enantiomers of bupivacaine and 12.5 to 1000 ng/ml for lignocaine. The corresponding limits of detection were 4 ng/ml and 10 ng/ml, respectively. The method was applied to the analysis of plasma from a healthy woman undergoing tubal ligation.     

Injection pain with propofol. Reduction with aspiration of blood

A randomised, controlled, single-blind study was performed on 100 patients to investigate a new method of reducing pain on propofol injection. Aspiration of 2 ml of the patient's blood into a syringe of propofol immediately before injection was compared with the addition of lignocaine 20 mg or normal saline 2 ml to the propofol before injection. The addition of blood was significantly more effective in reducing pain on injection than the addition of saline (p < 0.001), but was not significantly more effective than the addition of lignocaine.     

Variation in taste of topical lignocaine anaesthesia for gastroscopy

AIM: To study the distribution and determinants of taste variation for lignocaiine spray (Xylocaine; Astra Pharmaceuticals, King's Langley, UK). METHODS: Sixty-nine patients (male:female 49:20, mean age 48.5 years) attending for open access upper gastrointestinal endoscopy were studied. Taste perceived after applying 4 doses (40 mg) of lignocaine spray to the oro-pharynx was recorded prior to endoscopy. RESULTS: 37/69 (54%, 95% CI: 41-66%) perceived the taste of the lignocaine spray as bitter. whilst 24/69 (35%, 95% CI: 24-47%) and 6/69 (9%, 95% CI: 3-18%) perceived the taste as either fruity/sweet or tasteless. The variation in taste did not correlate with either demographic features or H. pylori inflection, but duodenal ulceration was slightly more common amongst bitter tasters. CONCLUSION: The taste of lignocaine is not uniform, but the basis of this variability is uncertain.     

Pouch of Douglas block for laparoscopic sterilisation

The use of local anaesthetic has been shown to reduce the incidence of pain after laparoscopic sterilisation and the need for opioid analgesia from day surgery. We investigated a technique in which a catheter is placed in the pouch of Douglas allowing repeated administration of local anaesthetic in the postoperative period. Forty patients were randomly allocated pre-operatively into one of two groups to receive in a double-blind manner either lignocaine 1% or normal saline. Pain was assessed using visual analogue and subjective scoring systems. Postoperative pain scores were significantly reduced (p < 0.05) after injection of lignocaine through the catheter. There were no complications related to the technique and no evidence of local anaesthetic toxicity. Lignocaine instilled into the Pouch of Douglas is an effective method for postoperative pain relief after laparoscopic sterilisation.     

Toxigenic fungi and mycotoxin content in poultry feedstuff ingredients

There is continuing controversy over what dose of what drug should be used to identify an accidental intravascular or subarachnoid catheter placement in obstetric epidural anaesthesia. The purpose of this randomized, double-blind study was to evaluate the dose-effect relationship for the production of central nervous system (CNS) symptoms by intravenous lignocaine. Sixty first-trimester, pregnant patients divided into groups of 10 received saline or one of five doses of lignocaine (0.39, 0.5, 0.63, 0.79, and 1.0 mg kg-1) i.v. An ED95 of 1.12 mg kg-1 was calculated to produce reliable CNS symptoms when injected intravascularly. Lignocaine is an effective and reliable marker for intravenous injection in pregnant women.     

Urethral stricture following transurethral resection of the prostate. The role of local anaesthetics

In a multicentre prospective study, 261 patients undergoing transurethral resection of the prostate (TURP) in 17 urology departments were randomised to receive lubricating jelly containing either 3% tetracaine hydrochloride, 1% lignocaine hydrochloride, or no local anaesthetic. No patient had a history of urethral instrumentation or a previous urethral stricture. After 6 months' follow-up, 25/79 patients (32%) treated with 3% tetracaine jelly developed urethral strictures, as did 4/92 patients (4%) who received 1% lignocaine and 2/90 (2%) who received the jelly without anaesthetic. It was concluded that the use of 3% tetracaine jelly is associated with a high incidence of post-TURP urethral strictures.