Effects of Adjuvants to Local Anaesthetics on Their Duration

The effects of addition of hyaluronic acid (sodium hyaluronate, Healon) to different local anaesthetics of the amide type on the duration of sensory or motor blocks following various regional anaesthetic procedures were studied in animal experiments. In the rat infra-orbital nerve block model, the addition of 0.1-0.5% hyaluronic acid (HA) to 2% prilocaine increased the duration of sensory block of varying degrees in a dose-dependent way by up to 500% of values obtained with plain prilocaine. The duration of degree 5 blocks produced by 0.5% etidocaine and 0.5% bupivacaine was also significantly prolonged when 0.4% HA was included to 206% and 282% of control, respectively, while blocks induced by 2% lidocaine were prolonged to 123% of control. The duration of motor block following spinal anaesthesia in the mouse was prolonged in a dose-dependent way when HA was added to prilocaine, bupivacaine and etidocaine. For solutions containing 0.4% HA, prolongations to 254%, 166% and 134% of control, respectively, were obtained. A concomitant increase of latency to onset of block and failure rate occurred with increasing concentrations of HA. The duration of corneal anaesthesia in the rabbit increased by 57% and 44% when 0.3% HA was added to prilocaine and bupivacaine, respectively. The duration of infiltration anaesthesia was not affected by the addition of HA to the local anaesthetic solutions. Addition of HA had no effect on the onset, depth and duration of prilocaine-induced block of the nervous transmission in vitro. The duration of infra-orbital nerve block and spinal anaesthesia shows a significant relation to the relative viscosity of the local anaesthetic solution.     

The prolongation of local anaesthetic action with dextran

Field blocks of the inguinal region were performed in two groups of patients, in one group using a mixture of 0.5% bupivacaine, 1:200 000 adrenaline and dextran 110 and in the second group using a mixture of 0.5% bupivacaine, 1:200 000 adrenaline and dextran 150; the study being performed in a double-blind fashion. The dextran 150 mixture produced a highly significant increase (p less than 0.01) in the duration of the block when compared with the dextran 110 mixture. The authors conclude that the use of dextran of increasing molecular weight increases the duration of action of local anaesthetics correspondingly.     

Duration of experimental nerve block by combinations of local anesthetic agents

The effects of bupivacaine-prilocaine and meperidine-lidocaine combinations (as compared with those of the agents used alone) on the duration of peripheral sensory nerve block were studied with the infraorbital nerve block model (IONB) in the rat, and those on motor block with spinal anesthesia (SA) in the mouse. The duration of bupivacaine-induced IONB was invariably prolonged when prilocaine was included in the solution. When included in 0.125% bupivacaine, 1.0% prilocaine had a slightly less pronounced enhancing efTect than 0.5% prilocaine (24–57% vs. 74%-104%, respectively). The duration of IONB with 1.0% prilocaine was significantly reduced (14–37%) by inclusion of 0.125% bupivacaine. In SA, inclusion in 0.125% bupivacaine of prilocaine (0.5% or 1.0%) prolonged motor block by 128% and 192%, respectively. When included in 0.25% bupivacaine, both 0.5% and 1.0% prilocaine significantly reduced the duration of SA, by 42% and 37%, respectively. With one exception, the duration of IONB by meperidine was significantly shortened (<44%) when lidocaine was included in the solution. In SA, inclusion of 2% lidocaine with 2% meperidine did not affect the duration of meperidine-induced motor block. The duration of SA obtained with the combination of 4% lidocaine and 4% meperidine was 45% shorter than that induced by 4% meperidine alone. The reasons for these variable effects are not clear, but may be due to interaction or antagonism at any of multiple sites.     

3-in-1 lumbar plexus block for muscle biopsy in malignant hyperthermia patients. Amide local anaesthetics may be used safely

A 3-in-1 lumbar plexus block with the aid of a nerve stimulator was performed in 32 patients and a psoas compartment block was performed in five patients for muscle biopsy of the upper leg for diagnosis of malignant hyperthermia (MH) susceptibility. Twenty-two patients were found to be MH susceptible by the in vitro contracture test. Twenty patients received 40 ml prilocaine 1.5% with epinephrine 1:200,000 and two received 40 ml bupivacaine 0.5% with epinephrine 1:200,000 without any untoward reaction. The 3-in-1 block provides a high success rate and excellent analgesia for muscle biopsy of the upper leg. Amide local anaesthetics are safe in MH-susceptible patients.     

Effects of Adjuvants to Local Anaesthetics on Their Duration

The effects of adding various macromolecular substances to 2% prilocaine on duration of rat infraorbital nerve block were investigated. The tested substances consisted of dextrans with lipophilic or charged substituents as well as other neutral or highly charged macromolecules. Most of the adjuvants caused significant prolongations of sensory block. For substituted dextrans the duration of sensory block degree 3 amounted to between 120% (3% capryldextran II) and 350% (3% carboxymethyldextran) in comparison to prilocaine plain. The corresponding values for hydroxypropylstarch (3%) alginic acid (0.5%), beta-cyclodextrin (1.5%) and hyaluronic acid (0.25%) were about 170%, 285% and 380%, respectively. The results suggest that the increased duration of local analgesia by prilocaine is related to increased viscosity of the solution produced by the macromolecular compounds. The mechanism seems to be of a physical character, and hyaluronic acid seems to be worthy of further studies.     

Epinephrine as an adjuvant to amino-amide local anesthetics does not prolong their duration of action in infraorbital nerve block in the rat

The effects of epinephrine as an adjuvant to local anesthetics were studied in the rat infraorbital nerve block (IONB) model, using solutions of 0.5% prilocaine, 0.5% mepivacaine, 0.125% bupivacaine or 0.125% ropivacaine in 50 mmol/l tris-hydroxymethylaminomethane (THAM) tested both without and with epinephrine (EPI) added at 2, 4, 8 or 16 micrograms/ml. Solutions of THAM and EPI in normal saline did not induce IONB. THAM-buffered solutions of bupivacaine induced IONB of longer duration than bicarbonate-buffered solutions. Intensity of block during onset was increased only when EPI at 2 and 16 micrograms/ml was included in bupivacaine solutions. The duration of block induced by prilocaine, bupivacaine and ropivacaine was not significantly prolonged by addition of EPI at any of the concentrations tested. Only at a concentration of 16 micrograms/ml did EPI significantly prolong the duration of mepivacaine-induced block (+48%). Low concentrations of EPI in solutions of bupivacaine and ropivacaine significantly reduced their duration of action by up to 22% and 57%, respectively. It is concluded that the duration of action of local anesthetics in buffered solutions is only moderately affected by the inclusion of EPI, the effects differing only slightly from one to another. The efficacy of EPI as an adjuvant would seem to be governed by factors affecting the local disposition of the main drugs, such as non-specific binding, buffering of solutions and tissue pH.     

Spinal Anesthesia in Sheep with Local Anesthetic Solutions at pH 4 and pH 7

Spinal anesthesia was performed in sheep, using five widely-used local anesthetic agents. The durations of sensory and motor block were shortest with procaine and longest with bupivacaine and tetracaine. The durations of block with prilocaine and mepivacaine fell between those of procaine and bupivacaine. These results agree with what we know about the relative durations of action of these agents in man. All solutions were tested at pH 4 and pH 7, but, except for prilocaine, there were no differences in the mean durations of sensory and motor block at the two pH levels. Sensory block with prilocaine solution at pH 7 was about 20% longer than at pH 4. With all the compounds except prilocaine, the frequency of motor block in the hind limbs was lower at pH 7 than at pH 4. We conclude that single injections of unbuffered solutions of these agents at pH 4 are as effective in terms of onset and duration as solutions at pH 7. The results of this study reconfirm the usefulness and reliability of the sheep as a model for evaluating and comparing spinal anesthetics.     

Effects of Adjuvants to Local Anaesthetics on Their Duration

A randomized study of the duration of ulnar nerve blockade induced with 2% prilocaine or 0.5% bupivacaine with and without 0.4% hyaluronic acid was performed in volunteers. In contrast to results in experimental animals, the addition of hyaluronic acid to the local anaesthetic solution did not affect the duration of sensory nerve block.     

Spinalanästhesie in der Tageschirurgie

BACKGROUND: Since prilocaine is being increasingly used for day case surgery as a short acting local anaesthetic for spinal anaesthesia and because of its low risk for transient neurological symptoms, we compared it to bupivacaine. PATIENTS AND METHODS: Patients (n=88) who were scheduled for lower limb surgery with spinal anaesthesia randomly received 15 mg hyperbaric bupivacaine 0.5% or 60 mg hyperbaric prilocaine 2% (administered in a sitting position). Onset time, intensity, duration of the sensomotoric block, vital parameters and time of spontaneous miction were recorded and patients were questioned on satisfaction with the anaesthesia procedure and the occurrence of adverse side-effects after 24 h. RESULTS: Bupivacaine caused a significantly higher sensory block than prilocaine (T6 vs. T8). Both groups were similar in reaching an analgesic level of at least T12, block intensity and onset times. Median analgesic levels at T12 were maintained for 60 min with prilocaine versus 120 min with bupivacaine, regression of the motor block was 135 min versus 210 min, sensory block S1 was 240 min versus 360 min, and time for spontaneous miction was 306 min versus 405 min, respectively (differences for all comparisons were statistically significant). CONCLUSION: Under the present study conditions, hyperbaric prilocaine 2% was superior to hyperbaric bupivacaine 0.5% due to a shorter effect profile but otherwise equivalent quality of block. However, puncture in a sitting position and positioning with elevated torso for restriction of the cranial expansion of block spread might cause an enhanced sacral block with delayed recovery of bladder function.     

Regional anaesthesia for surgery of the forearm and hand

Eighty patients who presented for surgery of the forearm or hand were allocated randomly to one of two groups. In Group A, surgery was performed under supraclavicular brachial plexus block only; a mixture of equal parts of prilocaine 1% and bupivacaine 0.5% without adrenaline was used. In Group B, supraclavicular brachial plexus block was performed using prilocaine 1% alone, but in addition discrete nerve blocks were performed at elbow level using 0.5% bupivacaine without adrenaline. Patients in Group B had a significantly shorter duration of unwanted postoperative motor blockade and a significantly longer duration of postoperative analgesia (p less than 0.005).     

Evaluation of dextran with local anaesthesia for short-stay inguinal herniorraphy.

A prospective randomised study of 40 patients undergoing unilateral inguinal herniorrhaphy under local anaesthesia was undertaken. Half the patients received the local anaesthetic (0.25% bupivacaine) mixed with dextran 40 solution. Subjective and objective assessments were made of the postoperative pain experienced in the first 48 h after operation. The use of 0.25% bupivacaine local inguinal block results in a postoperative pain-free period of approximately 10 h. Simple oral analgesics are adequate for postoperative pain relief in 87.5% of patients and are required relatively infrequently. The addition of dextran 40 to the local anaesthetic has no significant effect on its duration of action.     

Failure of spinal anesthesia. Evaluation of the practice at a university hospital

There is little data concerning failures in spinal anaesthesia. A retrospective analysis of 337 spinal anaesthesias performed in a teaching hospital gave a 9.8% failure rate. A failure was defined as the need to carry out part or all of a surgical act under general anaesthesia when spinal anaesthesia had been carried out. The main causes of failure were insufficiently or excessively extended neural blockade, insufficient duration or a poor quality sensory blockade with the patient feeling surgical or tourniquet pain. The local anaesthetics used were hyperbaric 0.5% tetracaine with and without 0.1 mg metaraminol, hyperbaric 0.5% prilocaine and isobaric 0.5% bupivacaine. The failure rate was 19.4% with plain hyperbaric tetracaine, 7.6% with tetracaine with metaraminol, 5% with prilocaine and 2.9% with isobaric bupivacaine. This rate was related neither to the experience of the anaesthetist, nor to the clinical features of the patients, nor to the position nor to the needle size. Although there were more failures during orthopaedic procedures, probably because of tourniquet pain, this was not significant. These results confirmed that spinal anaesthesia was a reliable technique. Hyperbaric plain tetracaine did not always guarantee a successful anaesthesia and isobaric bupivacaine should be more commonly used.     

Antimicrobial activity of ropivacaine and other local anaesthetics.

BACKGROUND AND OBJECTIVE: It is claimed that local anaesthetics have antimicrobial properties. Our aim was to investigate the antimicrobial effects of different concentrations of ropivacaine, bupivacaine, lidocaine and prilocaine on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. METHODS: All local anaesthetic dilutions were exposed to microorganisms for 0, 30, 60, 120, 240 min at room temperature. The inoculums taken from diluted suspensions were reinoculated on blood agar and incubated for 18-24 h at 35 degrees C and then the colonies were counted. RESULTS: Ropivacaine did not inhibit any of the microorganisms tested. Bupivacaine reduced the viable cells of P. aeruginosa at 0.5% and 0.25% solutions. Lidocaine 5% and 2% and prilocaine 2.0% dilutions reduced the viable cells of all microorganisms tested. Prilocaine 1.0% reduced the viable cells of E. coli, S. aureus and P. aeruginosa. Lidocaine 1% reduced only the viable cells of P. aeruginosa and prilocaine 0.5% reduced only E. coli. CONCLUSION: Ropivacaine had no antimicrobial effect on microorganisms tested. Bupivacaine showed poor antimicrobial effectiveness. Lidocaine and prilocaine had more powerful antimicrobial effects than the other two local anaesthetics.     

Transpulmonary disposition of prilocaine, mepivacaine, and bupivacaine in humans in the course of epidural anaesthesia

The pulmonary first-pass kinetics of the amide-linked local anaesthetics prilocaine, mepivacaine and bupivacaine were studied in 33 patients after a single epidural injection. Drug concentrations were monitored before and after lung passage, i.e. in samples withdrawn simultaneously from mixed venous and arterial blood. In most cases, maximum plasma concentrations were observed 10 min after injection (range 2 to 30 min). Two min after injection the local anaesthetics were distinctly extracted by the lung (prilocaine 40%, mepivacaine 20%, and bupivacaine 12%). Prilocaine was retained by the lung more effectively than bupivacaine and mepivacaine. However, a transpulmonary concentration gradient could be observed only for a short time, i.e. maximum 15 min. Altogether, in the case of accidental fast absorption, e.g. inadvertent intravenous injection, arterial peak concentrations of these drugs will be attenuated by passage of the lung. However, the lung will not substantially lower the risk of toxicity by amide-linked local anaesthetics during normal conditions of regional anaesthesia where slow absorption occurs.     

Isobaric spinal anaesthesia with bupivacaine and tetracaine (author's transl)]

4 ml 0.5% solutions of bupivacaine and tetracaine without the addition of a vasoconstrictor, approximately isobaric, were used for spinal anaesthesia on patients in the sitting position. The sensory and motor block due to the two local anesthetics was tested and compared. The mean time on onset of complete analgesia was the same for both local anaesthetics (9 and 11 min), as was also the highest level of analgesia (T10). The duration of maximal extension of analgesia was on an average 45 min longer due to tetracaine (bupivacaine 105 min, tetracaine 150 min). The duration of maximal spread of the blocked sensation of pain, temperature, pressure and touch was similar for each of both local anesthetics. The regression of these sensory qualities, blocked in a dissoaciated manner, took a parallel course. With tetracaine the motor block of the lower extremities developed faster and lasted longer (Bromage 3 for bupivacaine 192 min, for tetracaine 220 min). Motor function and proprioception normalized in a synchronized manner. Isobaric spinal anaesthesia with these two solutions of local anaesthetics was found to be reliable and controllable, especially when administered to the sitting patient. Tetracaine is a good alternative to bupivacaine, currently controversial for intrathecal use.     

Prolonged local analgesia for inguinal herniorrhaphy with bupivacaine and dextran.

In a randomised double-blind trial 40 patients undergoing unilateral inguinal herniorrhaphy were each locally anaesthetised with one of a series of 8 solutions. These contained bupivacaine, both with and without adrenaline, mixed with an equal volume of dextran 40, dextran 70, dextran 110, or saline. Significant prolongation of local analgesia was achieved with high-molecular-weight dextran and this was most consistently obtained when the solution used contained adrenaline. The possible influence of the pH of the solutions used, together with the ways in which dextran may affect the duration of action of bupivacaine are discussed.     

On the relative potency of amino–amide local anaesthetics in vivo

With the aim of comparing the analgesic effectiveness of lidocaine, prilocaine, bupivacaine and etidocaine in vivo , a study of the relationships between dose and duration of infraorbital nerve block (IONB) of various intensities (IONB degrees 3–10) was performed in the rat. With increasing doses longer durations of action were obtained. Further analyses were performed using multiple regression analysis. The log (dose) – duration lines for bupivacaine and etidocaine were found to be linear, whereas those for lidocaine in degree 3 and degree 10 IONB and for prilocaine in degree 10 IONB were so only after omission of some data. The only comparisons yielding no deviation from parallelism of log (dose) – duration lines were etidocaine vs. lidocaine at IONB degree 10 and lidocaine vs. prilocaine and bupivacaine vs. etidocaine at IONB degree 3. The difference between these agents with respect to their duration of action at all dose levels amounted to 113 minutes (M s.e.m.) for etidocaine vs. lidocaine (IONB degree 10), 27 4 min for prilocaine vs. lidocaine and 54 5 min for bupivacaine vs. etidocaine (IONB degree 3). For all other comparisons the log (dose) duration lines deviated from parallelism, i.e. differences between agents with respect to their duration of action were found to be dose–dependent. The slopes of the log (dose) – duration lines were found to correlate closely to the log (partition coefficient) and log (protein binding) of the investigated agents.     

THE DURATION OF ACTION OF BUPIVACAINE, PRILOCAINE AND LIGNOCAINE

The duration of analgesia and of hypoaesthesia produced by avariety of solutions has been examined by skin weal testing;each separate study was carried out in twenty female volunteersunder double-blind conditions. First, bupivacaine, lignocaineand prilocaine were compared with and without 1 in 200,000 adrenaline.Bupivacaine was found to give significantly longer analgesiathan prilocaine and significantly longer hypoaesthesia thanboth the other agents. Adrenaline significantly lengthened theaction of all three drugs, this prolongation being greatestwith lignocaine. The second part of the trial compared the durationof action of hospital-prepared and commercially prepared solutionsof the three local analgesics plus adrenaline. The commercialampoule preparations provided significantly longer action thanthe corresponding drugs in hospital-prepared multidose vials.The third group of experiments studied the effect of doublingthe concentrations of the solutions; there was no great increasein duration of analgesia but the duration of hypoaesthesia waslengthened, significantly so with bupivacaine. Throughout allthe above studies the individual results with bupivacaine showeda greater range of variation than those with the other agents.Finally the analgesic effect of saline (with and without adrenaline)was investigated; it was found that both agents generally produceda similar brief period of hypoaesthesia. The findings and theirpractical implications are discussed. Present address: Princess Alexandra Hospital, Harlow, Essex.,     

Comparison of clonidine and tramadol added to prilocaine brachial plexus block - analgesia, sensory and motor block

In a randomized, double-blind study we investigated the effect of clonidine and tramadol added to prilocaine on duration of analgesia, sensory and motor brachial plexus block. 60 patients were randomized in three groups. Group A received 40 ml prilocaine 1,5 % with tramadol 1,5 mg/kg KG, group B 40 ml prilocaine 1,5 % plus clonidine 1,5 microg/kg KG and group C 40 ml prilocaine 1,5 % without any additional medication. We recorded heart rate, blood pressure, oxygen saturation and sedation score at regular intervals. The onset of sensory and motor block was tested every five minutes for thirty minutes. The duration of analgesia, sensory and motor block were evaluated by using a questionnaire. There was no difference between the three groups concerning onset of brachial plexus block and duration of analgesia. But there was a significant prolongation of the duration of sensory and motor block in group B. Haemodynamic parameters remained stable in all patients, there were no significant changes in blood pressure and sedation.     

Transient Neurologic Symptoms after Spinal Anesthesia: A Lower Incidence with Prilocaine and Bupivacaine than with Lidocaine

Background: Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs.

Methods: Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure.

Results: Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05).