Die kombinierte „3-in-1“/Ischiadicus-Blockade Blockadeerfolg,Serumspiegel und Nebenwirkungen bei Einsatz von je 700 mg Mepivacain 1% ohne und mit Adrenalin sowie Prilocain 1%

A high dose of local anaesthetic is necessary for the combined “3-in-1”/sciatic nerve block. Prilocaine is recommended for its low toxicity. However, in some patients prilocaine results in pronounced methaemoglobin formation due to toludine. Little has been known hitherto about the use of high-dose mepivacaine for the combined 3-1/sciatic nerve block. This study was undertaken to compare the use of 700?mg mepivacaine 1% and of 700?mg prilocaine 1%. Methods. The study was approved by the ethics committee of our hospital. Once their informed consent had been obtained in writing 3×20 patients (ASA 1–2) undergoing planned surgery on the foot or ankle joint were enrolled in the study. The patients were randomized to the following three groups on a double-blind basis: group 1,700?mg mepivacaine without epinephrine; group 2,700?mg mepivacaine with 0.2?mg epinephrine (1:350000); group 3,700?mg prilocaine 1%. Arterial blood samples for determination of local anaesthetic serum levels were collected over a 120-min period. We determined methaemoglobin and oxygen saturation before and 120?min after the blockade and continued these measurements for 6?h in group 3. At 15-min intervals, all patients were questioned about early signs of toxicity. The perioperative monitoring including blood pressure, ECG and pulse oximetry. Data were analysed using ANOVA and Student's t-test, P<0.05 considered statistically significant. Results. The blocking efficacy did not differ among the groups (groups 1, 2, 3: 90%, 95%, 90%). The maximum mepivacaine serum level in group 1 was 3.91?μg/ml ±0.95 and 2.94?μg/,ml ±0.58 in group 2 (Fig. 2). Over the entire observation period the addition of epinephrine resulted in a significant reduction of the serum level (between 60.3% at t=15 min and 19.7% at t=120?min). In the prilocaine group the maximum serum level was 2.07?μg/ml ±0.56, significantly less than in either mepivacaine group. No patient showed signs or symptoms of local anaesthetic toxicity. In the prilocaine group there was wide variation in methaemoglobin formation among the patient, with a median of 10.1% (Fig. 3, Table 3). Three patients showed a maximum methaemoglobinemia between 16% and 17%. Five patients were still cyanotic after 6?h when they were transferred to the ward. The fractional SaO₂ values amounted to 88% (median) with a minimum of 80.3%. Conclusion. Both mepivacaine 1% and prilocaine 1% are appropriate local anaesthetics for the combined 3-in-1/sciatic nerve block at a dose of 700?mg. There was no difference in the blocking efficacy. No patient showed clinical signs or symptoms of a local anaesthetic toxicity. Following prilocaine we are sometimes faced with high methaemoglobinemia, which may necessitate prolonged monitoring.     

Comparative study between 5% prilocaine and 2% mepivacaine by the subarachnoid route in transurethral resections

OBJECTIVE: To compare the duration of spinal block with 5% prilocaine and 2% mepivacaine in short procedures for transurethral resection and to assess possible complications in the immediate postoperative period. MATERIAL AND METHODS: Fifty-seven patients scheduled for transurethral resection of the prostate or a vesical tumor. Patients were ASA I-III, over 55 years of age and randomly assigned to two groups to receive 5% prilocaine (1 mg/kg, n = 27) or 2% mepivacaine (0.8 mg/kg, n = 30). We collected data on anesthetic technique, levels of extension of motor and sensory blockades, duration of blockades and complications within the first 24 hours after surgery. RESULTS: Demographic data, ASA classification and duration of surgery were similar in both groups. We found statistically significant differences (p < 0.05) in duration of sensory blockade (120.92 +/- 36.21 min with prilocaine and 145.83 +/- 35.81 min with mepivacaine) and in motor blockade (106.29 +/- 38.16 min with prilocaine and 133.16 +/- 42.21 min with mepivacaine). Five cases of hypotension and 4 of bradycardia occurred in each group and one patient in the mepivacaine group suffered slight postoperative cephalea. CONCLUSIONS: Both local anesthetics offer good surgical conditions with hemodynamic stability and few complications. The duration of sensory and motor blockade is shorter with prilocaine than with mepivacaine, making prilocaine more appropriate for short interventions.     

Influence of intravenous local anaesthetics upon quadriceps muscle function

This study was undertaken to assess the effects of intravenous administration of mepivacaine and etidocaine on muscle function. Seven male volunteers were given mepivacaine (5 mg/kg) and etidocaine (50 mg) intravenously, on separate occasions. A reference group of 11 male volunteers received 0.9% saline solution intravenously. Muscle function was tested by measurements of isometric muscle force of knee extension and by quantitative electromyographic (EMG) recordings from the quadriceps muscle during knee extension at different degrees of isometric muscle force. At the end of the mepivacaine and etidocaine infusions, the mean venous plasma concentrations of the two anaesthetic agents were 2.9 and 1.2 micrograms/ml, respectively. The muscle strength remained unchanged during infusion of the two local anaesthetics. Mepivacaine had a minor effect on the mean rectified EMG amplitudes at the end of the infusion at maximal voluntary muscle contraction, but no such effect was observed at submaximal knee extension force. However, at the plasma concentrations mentioned above, the clinical influence of intravenous infusion of the local anaesthetics on muscle function was negligible.     

Plasma levels of lignocaine during tumescent local anaesthesia in children with burns

The aim of the study was to assess the changes in plasma lignocaine concentrations over time when the tumescent solution is injected into subcutaneous tissue of children undergoing surgical treatment of burns. Sixteen consecutive children with burns were studied using a prospective study design. After induction of general anesthesia, tumescent lignocaine solution 0.1% with adrenaline in nine patients (adrenaline group) for the treatment of postburn sequelae, or without adrenaline in seven patients (no-adrenaline group) for the treatment of acute burns, was injected into the subcutaneous tissue of burned and donor areas. The maximum dose of lignocaine was 7 mg/kg. Blood samples were collected before the start of the injection as well as at 5, 10, 20, 30, 45, 60, 90 minutes and 2, 4, 8, 12, 24 hours after the infiltration was completed. The course of lignocaine plasma levels was chaotic in the adrenaline group and biphasic during the first hour in the no-adrenaline group. The maximum plasma concentration of lignocaine was 2.09 microg/ml in the adrenaline group and 1.98 microg/ml in the no-adrenaline group. No adverse reactions were noted. Tumescent injection in burned children resulted in lignocaine plasma concentrations that were always lower than the often quoted value of 5 microg/ml, considered to be the toxic plasma threshold in adults. These data lend support to the use of lignocaine using the tumescent technique in burned paediatric patients.     

Prilocaine or mepivacaine for combined sciatic-femoral nerve block in patients receiving elective knee arthroscopy

AIM: The aim of this study was to evaluate the onset time of surgical block, recovery of motor function and duration of post-operative analgesia of combined sciatic-femoral nerve block performed with either mepivacaine or prilocaine. METHODS: With Ethical Committee approval and written informed consent, 30 ASA physical status I-II patients, undergoing elective arthroscopic knee surgery, received a combined sciatic-femoral nerve block with 30 ml of either 2% mepivacaine (n=15) or 1% prilocaine (n=15). An independent observer recorded the onset time of sensory and motor blocks, the need for intraoperative analgesia supplementation, recovery of motor function, and first request of post-operative pain medication. RESULTS: Onset time of nerve block required 15+/-5 min with prilocaine and 12+/-7 min with mepivacaine (p=0.33). No patient required general anesthesia to complete surgery; 3 patients receiving prilocaine (20%) and 2 patients receiving mepivacaine (13%) required 0.1 mg fentanyl intravenously to complete surgery (p=0.99). Recovery of motor function and first request of post-operative pain medication occurred after 238+/-36 min and 259+/-31 min with prilocaine, and 220+/-48 min and 248+/-47 min with mepivacaine (p=0.257 and p=0.43, respectively). Patient satisfaction was good in all studied patients. CONCLUSION: Prilocaine 1% provides adequate sensory and motor block for arthroscopic knee surgery, with a clinical profile similar to that produced by 2% mepivacaine, and may be a good option for surgical procedures of intermediate duration and not associated with severe postoperative pain.     

Addition of fentanyl to prilocaine for intravenous regional anaesthesia

Fifteen volunteers underwent intravenous regional anaesthesia on two occasions using 40 ml 0.5% prilocaine, to which had been added either 2 ml 0.9% saline or 0.1 mg fentanyl (resultant concentration 2.5 micrograms/ml). There was no difference in the rate of onset of blockade of cold sensation from an ethyl chloride spray, or to sharp and touch pinprick sensation in either group. There was an increase in the incidence of nausea after tourniquet release in the fentanyl group. It is concluded that the addition of fentanyl 2.5 micrograms/ml to prilocaine 0.5% confers no benefit in intravenous regional anaesthesia.     

Intrathecal mepivacaine and prilocaine are less neurotoxic than lidocaine in a rat intrathecal model

BACKGROUND AND OBJECTIVES: Histologic evidence of the comparative neurotoxicity of lidocaine, mepivacaine, and prilocaine is incomplete. We compared the intrathecal neurotoxicity in rats among these 3 drugs based on morphologic and neurofunctional findings. METHODS: Rats (n=169) randomly received 0.12 microL/g of 0%, 2%, 5%, 7.5%, 10%, or 20% lidocaine, mepivacaine, or prilocaine or 25% glucose dissolved in distilled water via a chronically implanted intrathecal catheter. The effect of the agents on neurofunction was evaluated by movement of the hind limb (behavior test) and by sensory threshold (paw-stimulation test). The L1 spinal cord, the posterior and anterior roots, and the cauda equina were removed en bloc 5 days later and examined by light and electron microscopy. RESULTS: A significant decrease in sensory threshold or irreversible hind-limb limitation was observed only in rats receiving 20% lidocaine. Morphologic abnormalities characterized by axonal degeneration were observed in rats receiving > or =7.5% lidocaine, 20% mepivacaine, and 20% prilocaine, at the posterior white matter and the proximal portion of the posterior root just at the entrance into the spinal cord. The incidence of lesions was significantly higher in rats receiving lidocaine than mepivacaine and prilocaine. CONCLUSION: It is suggested that intrathecal mepivacaine and prilocaine are less neurotoxic than highly concentrated lidocaine in a rat intrathecal model.     

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.     

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.     

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.     

Lack of Impairment in Skills Related to Driving after Intramuscular Administration of Prilocaine or Mepivacaine

A saline placebo, 3 mg/kg of 2% plain prilocaine, and 3 mg/kg of 2% plain mepivacaine were injected into the deltoid muscles of 10 healthy subjects in a doubleblind, cross-over trial. Before and at 0.5, 1.5 and 3 h after injection, psychomotor skills related to driving were measured. When compared to the saline placebo, neither prilocaine nor mepivacaine impaired the parameters of psychomotor function measured. Blood concentrations of prilocaine were significantly (P less than 0.001) lower than those of mepivacaine during the whole observation period. It was concluded that in comparison to lidocaine, bupivacaine, or etidocaine, which have been tested previously and found to impair psychomotor performance, mepivacaine and, especially, prilocaine are the anaesthetic agents to be preferred when effects on central nervous system should be avoided, e.g. in outpatient practice.     

Combined spinal and epidural anesthesia for cesarean section: a retrospective study with 0.5% hyperbaric bupivacaine

BACKGROUND: We investigated retrospectively the relationship between the intrathecal dose of 0.5% hyperbaric bupivacaine and the use of 2% mepivacaine through an epidural catheter. METHODS: Forty-nine patients undergoing cesarean section with combined spinal and epidural anesthesia (CSEA) were analyzed. They were divided into two groups; with (CSEA group) and without additional epidural injection group (spinal group). RESULTS: In the CSEA group (24 patients received 1.2 +/- 0.4 ml of 0.5% hyperbaric bupivacaine), 5-10 ml of 2% mepivacaine were required to achieve the adequate surgical anesthesia. In the spinal group (25 patients received 1.6 +/- 0.3 ml of 0.5% hyperbaric bupivacaine), cesarean section was performed without additional mepivacaine before delivery. The analgesic level and the amount of fluid infusion were similar in the two groups. However, 20% of patients in the spinal group showed hypotension (systolic blood pressure below 80 mmHg), although no patients in the CSEA group developed hypotension. The amount of ephedrine used before delivery was significantly larger in the spinal group (8.9 +/- 7.7 mg) than in the CSEA group (3.9 +/- 4.3 mg). CONCLUSIONS: Spinal anesthesia induced by 1.2 ml of 0.5% hyperbaric bupivacaine with sequential epidural block induced by 5-10 ml of 2% mepivacaine caused no hypotension during cesarean section.     

Fentanyl-prilocaine mixture for intravenous regional anaesthesia in patients undergoing surgery

The effect of the addition of 0.1 mg or 0.2 mg fentanyl to 40 ml 0.5% prilocaine in intravenous regional anaesthesia of the arm was investigated in 37 patients in a randomised, double-blind study. The characteristics of the sensory and motor block were studied. There was no difference in the speed of onset of analgesia in the groups (mean latency approximately 4 min in each group). However, significantly more patients in the fentanyl 0.2 mg group (7/12) had complete anaesthesia at 15 min than in the fentanyl 0.1 mg group (1/13) and the control group (2/12) (p less than 0.05). There were no differences in the incidence of tourniquet pain immediately before cuff deflation (tourniquet time 45-87 min). After cuff deflation, in those patients who complained of wound pain within 30 min, on average the pain appeared later in the fentanyl 0.2 mg group (six patients, mean 14.3 min) than in the control group (eight patients, mean 9.4 min) (ns). In the fentanyl groups, the incidence of central nervous system side effects was greater than in the control group (fentanyl 0.1 mg 7/13 patients, fentanyl 0.2 mg 6/12 patients, control 1/12 patients) (p less than 0.05). The plasma concentrations of prilocaine after cuff deflation were higher, in a dose-dependent fashion, in the fentanyl groups than in the control group, but the concentrations of prilocaine and fentanyl did not correlate with the symptoms. Postoperative nausea occurred only in the patients who had received fentanyl.     

PHARMACOKINETIC AND CLINICAL PHARMACOLOGICAL STUDIES WITH MEPIVACAINE AND PRILOCAINE

The tolerance and pharmacokinetic properties of mepivacaineand prilocaine were compared following i.v. infusion of 250mg (0.88 and 0.97 mmol respectively) of each drug in five healthyvolunteers. Side-effectrs were minor and occurred in only twosubjects during the infusion of mepivacaine. Plasma concentrationsof mepivacaine were greater in each subject than the correspondingvalues for prilocaine. The elimination half-life of mepivacainewas generally longer than that for prilocaine, whereas the totalbody clearance of prilocaine was consistently greater than thecorresponding value for mepivacaine. For each subject the clearanceof prilocaine substantially exceeded normal heptic blood flowand therefore an extra-hepatic site of metabolism of prilocainehas been postulated.     

Prilocaine Plasma Levels and Methemoglobinemia in Patients Undergoing Tumescent Liposuction Involving Less Than 2,000 ml

Background As a reaction to reported adverse outcomes after lidocaine infiltration in tumescent liposuction, prilocaine has gained increasing popularity. Previous studies investigating large-volume liposuction procedures found maximum prilocaine levels and methemoglobinemia up to 12 h postoperatively, suggesting that liposuction should be performed as a hospital procedure only. The aim of this study was to determine prilocaine plasma levels and methemoglobinemia in patients after low- to average-volume liposuction for the purpose of defining the required postoperative surveillance period.Methods In 25 patients undergoing liposuction involving less than 2,000 ml prilocaine levels and methemoglobinemia were measured over 4 h postoperatively. Liposuction was conducted after the tumescent technique using a 0.05% hypotonic prilocaine solution with epinephrine.Results The average prilocaine dose was 6.8 + 0.8 mg/kg, with a maximum dose of 15 mg/kg. The peak prilocaine plasma level of 0.34 g/ml occurred 3 h after the infiltration. The mean methemoglobinemia at this time point was 0.65%. Only one patient demonstrated a slightly elevated methemoglobin level of 1.4%, but lacked any clinical signs of methemoglobinemia. The prilocaine recovery in the aspirate averaged 36 ± 4%, indicating that a large amount is removed by suctioning.Conclusions The patients did not experience high plasma levels of prilocaine or methemoglobinemia undergoing liposuction involving less than 2,000 ml using a 0.05% hypotonic prilocaine solution. The authors therefore conclude that this procedure can be performed safely with a monitoring period of 12 h.     

Blood Concentrations of Lidocaine, Mepivacaine and Bupivacaine During Caudal Analgesia in Children

The venous blood concentrations of lidocaine, mepivacaine and bupivacaine were measured in children following the caudal epidural administration of these local anaesthetic solutions with adrenaline. The mean maximum concentrations of lidocaine and mepivacaine were 2.20 μg/ml and 2.53 ug/ml, respectively, which occurred at 45 min after injection of lidocaine or mepivacaine 11 mg/kg. By combined administration of 5.5 mg/kg equally of lidocaine and mepivacaine, the blood concentration of mepivacaine was significantly higher than that of lidocaine. The mean maximum concentration of bupivacaine was 0.67 μg/ml and occurred at 45 min after injection of bupivacaine 3.7 mg/kg. The blood concentration of bupivacaine was consistently significantly lower than that of lidocaine or mepivacaine. These results demonstrate that the blood concentrations of the three local anaesthetics following caudal administration are all below the toxic levels in spite of application of the maximum dosage recommended for adults.     

Systemic absorption of lignocaine ointment from tracheal tubes

Arterial plasma concentrations of lignocaine were studied in fifteen adult patients following insertion of a tracheal tube whose cuff area was smeared with 5% lignocaine ointment. Twelve patients had 2 ml of ointment (114 mg) and samples were taken every 5 minutes until 30 minutes and in eight of the 12 patients at 40, 50 and 60 minutes after insertion and inflation of the tracheal tube and cuff. Three patients had 1 ml of ointment on the tube and were studied over 60 minutes. Plasma concentrations were determined using gas liquid chromatography. In the 2 ml lignocaine group mean plasma lignocaine levels were 1.9 (SD 0.9) micrograms/ml at 10 minutes, 2.3 (SD 0.8) micrograms/ml at 20 minutes, 2.3 (SD 0.8) micrograms/ml at 30 minutes and 1.7 (SD 1.0) micrograms/ml at 60 minutes. After 1 ml of lignocaine, levels were 1.2 (SD 0.1) micrograms/ml at 10 minutes, 1.1 (SD 0.7) micrograms/ml at 20 minutes, 0.8 (SD 0.3) micrograms/ml at 30 minutes and 0.75 (SD 0.1) micrograms/ml at 60 minutes.     

Comparison of mepivacaine and lidocaine for intravenous regional anaesthesia: pharmacokinetic study and clinical correlation

Background. Limitations to the use of lidocaine for intravenousregional anaesthesia (IVRA) include lack of optimal intraoperativeanalgesia and systemic toxic reactions.This randomized double-blindstudy was conducted to compare intraoperative and postoperativeanalgesia, adverse effects, and plasma concentrations of mepivacaineor lidocaine, on release of the tourniquet in patients undergoingIVRA for distal upper limb surgery. Methods. Forty-two adult patients were randomly allocated toreceive either a 0.5% lidocaine solution 3 mg kg^–1 (n=20)or mepivacaine 5 mg kg^–1 (n=22). Plasma concentrationsof both anaesthetic agents were measured at 5, 10, 20, 30, 45,and 60 min after deflation of the tourniquet by gas chromatography. Results. Although plasma concentrations of mepivacaine and lidocainewere comparable 5 min after deflation, concentrations of lidocainedecreased significantly thereafter, whereas plasma concentrationsof mepivacaine were similar over the 60-min study period. Supplementaryanalgesia during the intraoperative period was required by 45%of patients in the lidocaine group as compared with 9% in themepivacaine group (P=0.02). No adverse effects were observedin patients given mepivacaine. In the lidocaine group, adverseeffects were observed in 10% of the patients. The total ischaemiatime, volume of the local anaesthetic, and duration of the surgicalprocedure were not significantly different between the two groups. Conclusions. Mepivacaine 5 mg kg^–1 ensured better intraoperativeanalgesia than lidocaine 3 mg kg^–1 when used for IVRA.Plasma concentrations of lidocaine decreased significantly between5 and 60 min following tourniquet deflation, whereas blood concentrationsof mepivacaine remained below the toxic concentration. Br J Anaesth 2002; 88: 516–19     

Studies in man with a constant-rate infusion of tubocurarine.

Tubocurarine (dTC) was administered to twenty patients by intravenous infusion at a predetermined constant rate, and the twitch responses recorded at stimulus intervals of 10 seconds (0.1 Hz). In half the group dTC plasma concentrations were measured both during and following the infusion. This provided data for derivation of the pharmacokinetic parameters, two plasma concentration-response curves and the dose-response curve. The mean effective dTC plasma concentration for 50% paralysis during the infusion (onset) was 0.93 micrograms/ml, but was lower post-infusion (offset) (0.54 micrograms/ml, p less than 0.001). The steady state dTC plasma concentration which should produce 95% paralysis was predicted to lie between 0.95 and 1.67 micrograms/ml. In the range 20 to 80% paralysis the slopes of the two (log) concentration-response lines were similar, although steeper than the associated (log) dose-response regression line, the test for parallelism showed no statistical difference. Combination of the plasma concentration-response curve with pharmacolkinetic models was used to predict the time course of paralysis in patients with normal and impaired renal function. Dose-response curves for the other 10 patients were also constructed to stimulus frequencies from 0.02 to 5 Hz. In the range 20 to 80% paralysis the regression lines appeared to be parallel. The results were pooled for all patients at a stimulation rate of 0.1 Hz, giving a mean effective dose of dTC at 95% paralysis of 0.53 mg/kg, and an ED50 of 0.22 mg/kg.     

Protein binding of prilocaine in human plasma: influence of concentration, pH and temperature

Protein binding of prilocaine was investigated in vitro under various conditions of changing pH, temperature and total plasma concentration by means of HPLC with UV-detection and ultrafiltration. Whereas changes in temperature (25 degrees C-40 degrees C) and pH (pH 5-pH 10) influenced protein binding markedly, rising plasma concentrations up to 16 micrograms/ml did not affect plasma protein binding significantly. This may be a possible explanation for clinical evidence of low toxicity associated with the use of prilocaine. Discussions concerning protein binding of local anaesthetics should always be based on defined ambient conditions (pH, temperature, concentration).