Showing papers in "BJA: British Journal of Anaesthesia in 1985"
TL;DR: It is concluded that the more potent S(+) isomer of ketamine was associated with a more rapid recovery of psychomotor skills than the currently used racemic mixture.
Abstract: The clinical and electroencephalographic (EEG) effects of the individual ketamine isomers were compared with the racemic mixture in five volunteers who received each drug on a separate occasion. Racemic ketamine 275 ± 25 mg, s(+) ketamine 140 ± 21 mg or R(−) ketamine 429 ± 37 mg produced an anaesthetic state lasting 6 ± 2 min (mean ± SD). However, the EEG evaluation of the R(−) isomer revealed less overall slowing, and an absence of the large slow wave complexes produced by the s(+) isomer and the racemic mixture. The pharmacokinetic profiles for the individual isomers of ketamine did not differ significantly from the racemic mixture. Even though the apparent anaesthetic state produced in these healthy volunteers did not differ qualitatively between the three drug groups, recovery times (assessed using a standardized battery of psychometric tests) were consistently shorter following the individual isomers compared with the racemic mixture. The serum ketamine concentrations associated with regaining consciousness and orientation were consistent with an s(+):R(−) isomer potency ratio of 4:1. In terms of their ability to impair psychomotor function, the s(+):R(−) potency ratio varied from 3:1 to 5:1. After comparable degrees of CNS depression, we conclude that the more potent s(+) isomer of ketamine was associated with a more rapid recovery of psychomotor skills than the currently used racemic mixture.
352 citations
TL;DR: Brain ischaemia may be the single most important mechanism in the production of secondary brain dysfunction and damage after severe head injury.
Abstract: Brain ischaemia is a frequent and important sequel to brain injury. Areas of ischaemic brain damage are an almost invariable finding at postmortem in patients who have sustained severe head injury— that is, injury associated with coma (Graham, Adams and Doyle, 1978). Sequential computerized tomography of the head in disabled survivors of severe head injury frequently reveals sizeable cerebral infarcts (Miller et al., 1980). Traumatic brain laceration results also in ischaemia in the territory of divided vessels. Herniation of the medial temporal lobe of the brain through the tentorial hiatus and downward axial shift of the brain stem produce stretching and distortion of the brain arterial supply with ischaemia and infarction in the brain stem and occipital lobes (Miller and Adams, 1984). Brain ischaemia may therefore be the single most important mechanism in the production of secondary brain dysfunction and damage after severe head injury.
225 citations
TL;DR: Findings offer pharmacodynamic explanations for the differences in fentanyl and buprenorphine analgesic response profiles and suggest how binding interactions might be applied to therapeutic use.
Abstract: Receptor binding assays were undertaken in an attempt to elucidate the opioid binding characteristics of fentanyl and buprenorphine, and to investigate some of the differences between them. Buprenorphine showed slow receptor association (30 min), but with high affinity to multiple sites from which dissociation was very slow (T½ = 166 min) and incomplete (50% binding after 1 h). This contrasted with the receptor binding of fentanyl, which achieved rapid equilibrium (within 10 min) and dissociated equally rapidly (T½ = 6.8 min) and completely (100% by 1 h). Competitive displacement showed buprenorphine displacement of fentanyl binding was concentration-and time-dependent over ranges encountered in clinical use, but buprenorphine binding was displaced with only very high concentrations of other opioids. These findings offer pharmacodynamic explanations for the differences in fentanyl and buprenorphine analgesic response profiles and suggest how binding interactions might be applied to therapeutic use.
213 citations
211 citations
TL;DR: Physiologically, changes in blood volume pulsations depend on the distensibility of the vessel wall as well as on the intravascular pulse pressure, and it is shown that changes in the height of ventilatory waves may be of diagnostic significance.
Abstract: The optical principle of photo-electric plethysmography is described and the clinical significance of changes in the amplitude of the plethysmogram discussed. Physiologically, changes in blood volume pulsations depend on the distensibility of the vessel wall as well as on the intravascular pulse pressure. The importance of both factors in the interpretation of changes in the arterial pulse amplitude is illustrated by examples from 500 continuous recordings. In addition, it is shown that changes in the height of ventilatory waves maybe of diagnostic significance.
178 citations
TL;DR: The effects of the cutaneous application of EMLA cream (a eutectic mixture of lignocaine and prilocaine in their base form) were studied in volunteers, with the cream being most effective if left in contact with the skin for 60 min.
Abstract: The effects of the cutaneous application of EMLA cream (a eutectic mixture of lignocaine and prilocaine in their base form) were studied in volunteers. When tested by pin-prick, EMLA cream 2.5% and 5% produced analgesia of the area tested, the cream being most effective if left in contact with the skin for 60 min. The pain produced by the insertion of an i. v. cannula was successfully blocked by the application of this formulation, especially if applied to the antecubital area. Temporary blanching of the skin areas was frequently observed on removal of the occlusive tape bandages, but prolonged, or repeated, application of 5% EMLA cream did not produce local skin reactions. Tests for delayed hypersensitivity reactions were negative. Plasma concentrations of lignocaine and prilocaine were low after a standard application.
177 citations
TL;DR: The new emulsion formulation of di-isopropyl phenol (propofol) was compared with methohexitone and thiopentone for induction of anaesthesia in day cases and post-anaesthetic recovery was superior with propofol, with virtual absence of side effects and rapid recovery with little impairment of psychomotor function 30 min after anaesthesia.
Abstract: The new emulsion formulation of di-isopropyl phenol (propofol) was compared with metho-hexitone and thiopentone for induction of anaesthesia in day cases. Propofol produced significantly smoresearch-article induction of anaesthesia, but caused more cardiovascular and respiratory depression. Pain on injection was significantly less than with methohexitone. Post-anaesthetic recovery was superior with propofol, with virtual absence of side effects, and rapid recovery with little impairment of psychomotor function 30 min after anaesthesia.
167 citations
TL;DR: The results indicate that the epiglottis and not the tongue is the main cause of obstruction of the upper airway and when methods are applied to displace the hyoid anteriorly, the airway will be cleared on most occasions.
Abstract: Airway patency was explored in patients breathing spontaneously under deep halothane anaesthesia. Opening and closing of the airway was observed with a flexible bronchoscope looking proximally from the nasopharynx at the epiglottis and the tongue. With the occiput elevated at various angles the smallest angle of retroflexion of the neck necessary to open the airway was measured. The influence of artificial airways on this angle of retroflexion was measured. Cadaveric preparations of the upper airway were studied to assess the mechanisms involved in airway patency. The results indicate that the epiglottis and not the tongue is the main cause of obstruction of the upper airway. When methods are applied to displace the hyoid anteriorly, the airway will be cleared on most occasions.
154 citations
TL;DR: Until more definitive knowledge is available concerning the influence of high-dose barbiturate therapy in treating different forms of cerebral ischaemia, its application should be viewed sceptically and limited to centres willing to create an organized data base for inter-institutional evaluation of this form of treatment.
Abstract: This review has indicated that barbiturates are useful in controlling ICP during anaesthesia in patients with intracranial hypertension. While laboratory data indicate that intraoperative administration of barbiturates during episodes of transient cerebral ischaemia, associated with surgical revascularization procedures, should be efficacious, current intraoperative results claiming benefit are anecdotal. Continuous high-dose barbiturate therapy (induced barbiturate coma) for occlusive stroke and persistently increased intracranial pressure is currently undergoing clinical trials. While it is clear that this therapy can often reduce increased ICP in head injured patients, its influence on neurological outcome remains to be determined by a multicentre trial at present in progress. Despite evidence that high-dose barbiturate therapy can reduce the area of infarction in occlusive stroke in the laboratory, organized clinical trials have not yet commenced. Until more definitive knowledge is available concerning the influence of high-dose barbiturate therapy in treating different forms of cerebral ischaemia, its application should be viewed sceptically and limited to centres willing to create an organized data base for inter-institutional evaluation of this form of treatment. If barbiturate therapy proves successful and the mechanisms involved are better understood, drugs with fewer side-effects and risks may become available to combat cerebral ischaemia.
143 citations
TL;DR: This study showed that sudden changes in pressure were closely followed by the Finapres, and the accuracy or reproducibility of each method, as expressed in intra-individual variance, diminished in the order Intra-Arterial-Line, Finapre, Accutorr.
Abstract: Two indirect arterial pressure monitors, the Finapres and the Accutorr, were investigated and compared with the direct measurement of intra-arterial pressure. Pressures in patients in a variety of circulatory states were measured and analysed in relation to two types of random error: first, the "intra-individual standard error" (within one session of measurement) and second, the "inter-individual standard error" (between sessions). (This distinction is important, since in routine monitoring of arterial pressure one is usually dealing with the first type of error only.) This study showed that sudden changes in pressure were closely followed by the Finapres. A pressure reading of the Accutorr takes about 15-20 s, meaning that, within this period, variations will not be observed. The accuracy or reproducibility of each method, as expressed in intra-individual variance, diminished in the order Intra-Arterial-Line, Finapres, Accutorr. The inter-individual variation decreased in the order Intra-Arterial-Line, Accutorr, Finapres. Most of the inter-individual variance of the Finapres is probably real because of the more peripheral position of its cuff. A correlation between malfunctioning of the Finapres and vasoconstriction or hypothermia of the finger could not be demonstrated.
140 citations
TL;DR: The efficacy of a topical anaesthetic formulation, EMLA 5% cream (Eutectic Mixture of Local Anaesthetics) in obtunding the pain produced by venepuncture, was determined in a double-blind randomized, cross-over study in 31 adult volunteers.
Abstract: The efficacy of a topical anaesthetic formulation, EMLA 5% cream (Eutectic Mixture of Local Anaesthetics) in obtunding the pain produced by venepuncture, was determined in a double-blind randomized, cross-over study in 31 adult volunteers. Pain was registered on a 10-cm visual analogue scale. In each subject the mean pain score after treatment with EMLA was compared with that following placebo. Twenty-eight subjects had lower pain scores with EMLA, and in the remaining three subjects EMLA and placebo were equi-effective. Transient skin reactions (blanching, erythema and oedema) were observed with both formulations. These reactions were not found to be aggravated by repeated applications.
TL;DR: A previously undiagnosed case of myotonic dystrophy presenting with apnoea of 2.5 h duration following thiopentone and anaesthetic implications noted are described.
Abstract: A previously undiagnosed case of myotonic dystrophy presenting with apnoea of 2.5 h duration following thiopentone is described. A review of the anaesthetic outcome from 49 operations in 17patientswith myotonic dystrophy in the Aberdeen area is presented. The type of operation and intra- and postoperative problems are analysed. The results reveal a 52 % complication rate in previously diagnosed cases and a 35% complication rate in undiagnosed cases. In the series, 29% of the anaesthetics were administered to symptomatic patients before formal diagnosis. To avoid potential hazards it behoves the anaesthetist to remain alert to the possibility of the undiagnosed disease. The symptomatology and associated findings of the 17 patients at initial diagnosis are presented. The literature has been reviewed and anaesthetic implications noted.
TL;DR: A biochemical effect of a single bolus dose of etomidate consistent with incomplete inhibition of adrenocortical mitochondrial 11 beta-hydroxylase activity is demonstrated, but no clinically significant adrenOCortical suppression is demonstrated.
Abstract: The effects of a single bolus dose of etomidate 0.3 mg kg − or thiopentone 5 mg kg − on the synthesis of corticosteroid hormones and adrenocorticotrophic hormone (ACTH), were compared for 24 h in 12 patients, undergoing minor surgery under general anaesthesia. Following opioid premedication i.m. and general anaesthesia, plasma cortisoi concentrations decreased transiently within the first hour of anaesthesia in all 12 patients. The six patients who received etomidate had statistically higher plasma 11-deoxycorticosterone concentrations at 4 and 24 h than those who had received thiopentone ( P
TL;DR: The pattern of selective vulnerability occurring after cerebral ischaemia is similar to that after status epilepticus and in the hippocampus, the pyramidal neurones in the CA1 and CA3 zones and the hilar polymorphic neurones are particularly vulnerable and the dentate granule cells are relatively resistant.
Abstract: The pattern of selective vulnerability occurring after cerebral ischaemia is similar to that after status epilepticus (Brierley, 1976; Corsellis and Meldrum 1976). In the hippocampus, the pyramidal neurones in the CA1 and CA3 zones and the hilar polymorphic neurones are particularly vulnerable and the dentate granule cells are relatively resistant. During status epilepticus induced experimentally in rats by the i. v. administration of bicuculline, allylglycine or kainic acid (Evans, Griffiths and Meldrum, 1983, 1984; Griffiths, Evans and Meldrum, 1983, 1984), selectively vulnerable neurones show condensation of perikaryal cytoplasm and swelling of mitochondria. The changes are evident after 30-90 min of continuous seizure activity. Severe condensation with a pyknotic nucleus and multiple, small, structureless vacuoles occur in a minority of vulnerable neurones after 90-150 min (Evans, Griffiths and Meldrum, 1984; Griffiths, Evans and Meldrum, 1984).
TL;DR: There were no changes in plasma catecholamine concentrations in the 2 h following insertion of an i.v. cannula, suggesting that venous cannulation did not induce a measurable stress response, and a significant correlation was shown between mean percentage change in Linear Analogue Anxiety Score and mean percentage increase in plasma adrenaline concentrations.
Abstract: This study was designed to assess the value of measurement of plasma catecholamine concentrations as an objective index of anxiety. A preliminary study was undertaken on 11 healthy volunteers (medically qualified), to determine if venous cannulation per se produced any change in plasma catecholamine concentrations. There were no changes in plasma catecholamine concentrations in the 2 h following insertion of an i.v. cannula, suggesting that venous cannulation did not induce a measurable stress response. A second study was performed on 48 surgical patients who were asked to rate their perceived anxiety on a linear analogue scale immediately before premedication and immediately before induction of anaesthesia. Venous blood was obtained at the same time as these ratings. There were no significant changes in perceived anxiety or plasma noradrenaline concentrations following premedication. However, compared with values before premedication, there was a mean percentage increase in plasma adrenaline concentration of 40%before induction of anaesthesia. A significant correlation was shown between mean percentage change in Linear Analogue Anxiety Score and mean percentage change in plasma adrenaline concentrations (r = 0.32).
TL;DR: The effects of the inhalation of 50% nitrous oxide on somatosensory evoked potentials during a fentanyl-oxygen anaesthetic technique for central nervous system surgery were evaluated and suggest that they were attributable toNitrous oxide per se.
Abstract: The effects of the inhalation of50% nitrous oxide on somatosensory evoked potentials during a fentanyf-oxygen anaesthetic technique for central nervous system surgery were evaluated. The latency and amplitude of the first cortical wave were obtained using conventional somatosensory techniques with median or posterior tibialnerve stimulation. Data were collected before and after the inhalation of 50% nitrous oxide in oxygen introduced at the conclusion of the surgical procedure. The addition of nitrous oxide was associated with consistent decreases in the amplitude of somatosensory evoked potentials, but with no significant changes in latency. Since no electrical, physiological, or surgical event was associated with these changes, the results suggest that they were attributable to nitrous oxide per se.
TL;DR: The rapid (5-s) bolus dose of atracurium i.v. resulted in a significant increase in plasma histamine concentration (P less than 0.05) and was associated with a decrease in mean arterial pressure and an increase in heart rate, and administration of the same dose slowly prevented the increase, and abolished the subsequent haemodynamic response.
Abstract: This study was designed to determine the effects of a rapid bolus dose of atracurium 0.6 mg kg−1 on arterial pressure, heart rate and plasma histamine concentration (n = 9), and to compare these values with those obtained by (a) giving the same dose of atracurium slowly (over 75 s) (n = 9), or (b) pre-treating with H1- and H2- antagonists (n = 9). The rapid (5-s) bolus dose of atracurium i.v. resulted in a significant increase in plasma histamine concentration (P P > 0.05).
TL;DR: The patients given etomidate were easily distinguishable from those given saline, solely on the basis of changes in the early cortical peaks Pa and Nb, and the latencies of these peaks increased and their amplitudes decreased, linearly related to serum etomidates concentration.
Abstract: The effect of etomidate on the auditory evoked response was examined in a double-blind study carried out before the start of surgery. Fourteen patients were anaesthetized with 70% nitrous oxide and oxygen after induction with thiopentone. Ventilation was controlled. Seven of the patients received a continuous infusion of etomidate, increasing in five equal steps from 0.01 mg kg−1 min−1 to 0.05 mg kg−1 min−1 over a period of 50 min. The other seven received similarly an equivalent volume of saline. The patients given etomidate were easily distinguishable from those given saline, solely on the basis of changes in the early cortical peaks Pa and Nb. In the etomidate group the latencies of these peaks increased and their amplitudes decreased. These changes were linearly related to serum etomidate concentration. There was no effect of etomidate on the brainstem response.
TL;DR: The neurotoxic effects of each local anaesthetic tested as a continuous intrathecal infusion were dose related in the rat, which may be a useful model for screening other local anaesthetics.
Abstract: Neurotoxicity after subarachnoid infusion of bupivacaine, lignocaine and 2-chloroprocaine was studied in a chronic rat model. Hartmann's solution 100 microliter h-1 was infused as a control, and 0.5% bupivacaine, 1.5% lignocaine and 2.0% 2-chloroprocaine were infused at 100 microliter h-1 for 3, 6 or 24 h, to five rats in each group. No residual paralysis occurred in the control group, but 27 of 45 rats (60%) which received an infusion of local anaesthetic had residual paralysis lasting until sacrifice at 7 days. The incidence of paralysis was dependent on the duration of exposure to the local anaesthetic, but there were no significant differences in incidence between any of the local anaesthetics tested. Abnormal histology, in the form of neuronal vacuolation, was not a sensitive index, being present in control rats, but more intense in those receiving lignocaine and 2-chloroprocaine than in those given bupivacaine; no correlation with clinical findings could be established. The neurotoxic effects of each local anaesthetic tested as a continuous intrathecal infusion were dose related in the rat, which may be a useful model for screening other local anaesthetics.
TL;DR: The results suggest that the incidence of major adverse reactions occurred during or after anaesthesia, and the incidence was not influenced by the rate of injection.
Abstract: Sixty unpremedicated patients (30 male) were randomly allocated to three groups. They received an induction dose of propofol 2 mg kg-1 over 5, 20 or 60 s to a forearm vein. Anaesthesia was maintained with conventional inhalation anaesthetic agents. Anaesthesia was induced satisfactorily in all 20 of the patients in the 5-s group, in 19 of the patients in the 20-s group and in 18 of the patients in the 60s group. The rate of injection had a significant influence on induction time. Mean induction time increased from 21.5 to 34.7 and 50.5s, when injection time was increased from 5- to 20 to 60s, respectively. Similar induction times were found in male and female patients. There was no significant difference between the groups, in depth of anaesthesia obtained — as assessed by the eyelash reflex. Mean arterial pressure decreased to the same extent in all three groups. Two minutes after induction, mean systolic arterial pressure was reduced by 15.1, 13.5 and 19.3 mm Hg in the 5-, 20- and 60-s groups, respectively, and mean diastolic arterial pressure by 10.3, 13.2 and 13.7 mm Hg. Heart rate changes were insignificant. Apnoea of more than 10 s duration was seen frequently in all three groups, but the results suggest that the incidence was not influenced by the rate of injection. Three patients experienced mild pain at the time of injection. No major adverse reactions occurred during or after anaesthesia.
TL;DR: The pharmacokinetics of midazolam were studied in surgical patients given 0.3 mg kg-1 i.v. for either the induction of anaesthesia, or postoperative sedation following cardiopulmonary bypass.
Abstract: The pharmacokinetics of midazolam were studied in surgical patients given 0.3 mg kg-1 i.v. for either the induction of anaesthesia, or postoperative sedation following cardiopulmonary bypass. The short elimination half-life of midazolam (2.4 h in patients less than 50 yr undergoing minor surgery) was significantly, although not markedly, prolonged with age (4.1 h in patients greater than 50 yr undergoing minor procedures) and by the nature of the operation (3.8 h after major operative procedures). These changes were the result of alterations in clearance and volume of distribution with age, and in volume of distribution with nature of operation.
TL;DR: All suggestion patients were completely amnesic for the intraoperative spoken suggestion, despite inquiries which included hypnotic regression to the operation.
Abstract: In a double-blind study, 33 patients (herniorraphy, cholecystectomy and orthopaedic) were randomly assigned to either suggestion or control groups. Under known clinical levels of nitrous oxide and enflurane or halothane anaesthesia, suggestion patients were exposed to statements of the importance of touching their ear during a postoperative interview. Compared with controls, suggestion patients did touch their ear (tetrachoric correlation 0.61, P
TL;DR: It is concluded that, although ester hydrolysis is the major metabolic pathway of atracurium degradation, Hofmann elimination provides a "safety net" in its clinical use.
Abstract: The degradation of atracurium and the formation of laudanosine was examined in vitro in both Sorensen buffer and human plasma using sensitive, specific high pressure liquid chromatographic assays to determine drug concentrations. At normal physiological pH and temperature, the degradation of atracurium was threefold more rapid in plasma than in buffer. Laudanosine is the major end-product of atracurium degradation in buffer or in plasma; its production is more rapid in plasma than in buffer. Dilution of plasma constituents or the use of diisopropylfluorophosphate (a potent esterase inhibitor), slows the degradation of atracurium and the production of laudanosine. We conclude that, although ester hydrolysis is the major metabolic pathway of atracurium degradation, Hofmann elimination provides a "safety net" in its clinical use.
TL;DR: After operation, the incidence of deep vein thrombosis was found to be 40% in the SAB group, which was significantly lower than the incidence in the GA group, and may account for the previously reported effect of SAB in reducing early postoperative mortality.
Abstract: Forty patients with fractured neck of femur were allocated randomly to undergo surgery under general anaesthesia (GA) or subarachnoid anaesthesia (SAB). After operation, the incidence of deep vein thrombosis (DVT), assessed by venography, was found to be 40% in the SAB group, which was significantly lower than the incidence (76.2%) in the GA group. These observations may account for the previously reported effect of SAB, in comparison with GA, in reducing early postoperative mortality in this category of patient.
TL;DR: It is suggested that, to avoid SCN toxicity (plasma SCN greater than 1.75 mumol litre-1), in the absence of SCN monitoring, the total SNP dose should be less than 70 mg kg-1 in patients with normal renal function.
Abstract: Blood cyanide (HCN) or plasma thiocyanate (SCN) concentrations, or both, were measured in 30 patients (ages 11 months-72 yr) receiving sodium nitroprusside (SNP) for 12-314 h. Sequential measurements in three of these patients (infused 5, 12 and 13 days) showed that HCN concentrations varied with dose rate, while SCN concentrations increased linearly with increasing SNP dose. The accumulated data confirmed that the rate of administration (0.3-6.5 micrograms kg-1 min-1) determined the plasma HCN concentrations (0-3.8 mumol litre-1; y = 0.267 X -0.0733; r = 0.64; n = 51; P less than 0.001). Thus, if prolonged exposure to plasma HCN concentrations greater than 1 mumol litre-1 is to be avoided, the maximum safe sustained dose rate of SNP will lie near to 4 micrograms kg-1 min-1. Likewise, the SCN results (30--880 mumol litre-1) confirmed the close relationship between plasma concentrations and the total SNP dose (0.44-32.9 mg kg-1; y = 24.6x + 74.9; r = 0.95, n = 51, P less than 0.001). Therefore, we suggest that, to avoid SCN toxicity (plasma SCN greater than 1.75 mumol litre-1), in the absence of SCN monitoring, the total SNP dose should be less than 70 mg kg-1 in patients with normal renal function.
TL;DR: It was concluded that, as a result of the moderate degree of imprecision, it is unwise to rely totally on the absolute values of alfentanil plasma concentrations predicted by a computer-regulated infusion pump such as TIAC, but such devices can be used to attain rapidly a relatively stable plasma concentration that can be adjusted to the requirements of an individual patient during anaesthesia.
Abstract: The accuracy of using average alfentanil pharmacokinetic data in a computer assisted infusion pump (TIAC) to predict alfentanil plasma concentrations was tested in 35 patients {divided into three groups) receiving alfentanil and nitrous oxide in oxygen anaesthesia for lower and upper abdominal surgery. By frequently measuring the arterial plasma concentration, it was possible to determine the average prediction error for individual patients and for groups of patients. For the groups, there were no significant systematic over- or underpredictions of the alfentanil plasma concentrations (bias). However, there existed a moderate degree of variability (imprecision) within the groups, caused by deviations of measured and predicted plasma concentrations in the individual patients within each group. As a result, prediction errors of 22.2-32.5% can be expected with the average pharmacokinetic data used in this study to drive TIAC. It was concluded that, as a result of the moderate degree of imprecision, it is unwise to rely totally on the absolute values of alfentanil plasma concentrations predicted by a computer-regulated infusion pump such as TIAC. However, such devices can be used to attain rapidly a relatively stable plasma concentration that can be adjusted (titrated) to the requirements of an individual patient during anaesthesia.
TL;DR: Investigation of the vascular effects and duration of action of two ester-linked local anaesthetics, procaine and amethocaine, and four amide-linked national anaesthetic drugs found them to be concentration-dependent, with slopes of the log dose--duration plots reflecting the observed vasoactivity.
Abstract: The vascular effects and duration of action of two ester-linked local anaesthetics, procaine and amethocaine, and four amide-linked local anaesthetics, cinchocaine, lignocaine, mepivacaine and prilocaine, were investigated in 10 volunteers by intradermal injection using a double-blind technique. Procaine and amethocaine produced marked vasodilatation; weal formation was observed at 80% of the amethocaine injection sites. Mepivacaine had a marked vasoconstrictor effect; the other three agents produced more variable vasoactivity. Duration of action was concentration-dependent for all six drugs, the slopes of the log dose-duration plots reflecting the observed vasoactivity.