[The effect of flumazenil on the endocrine stress reaction following modified neuroleptanesthesia]. / Der Einfluss von Flumazenil auf die endokrine Stressreaktion nach modifizierten Neuroleptanästhesien.

This study was undertaken to investigate in a prospective randomized way the influence of the benzodiazepine antagonist flumazenil on endocrine stress response and haemodynamic parameters after modified neuroleptanaesthesia. A total of 24 patients (ASA scores I or II) aged between 18 and 60 who were scheduled for major gynaecological surgery, were investigated. For modified neuroleptanaesthesia, midazolam, fentanyl and vecuronium were administered in standardized doses. After extubation, patients of the flumazenil group received initial injections of 0.2 mg flumazenil to antagonize the residual effect of midazolam and additional doses of 0.1 mg per minute until the desired level of vigilance was reached (awareness of person, time and place). In the control group no flumazenil was used. Endocrine stress parameters and haemodynamic parameters were measured at 7 different times, from before induction of anaesthesia up to 60 minutes after the operation. In both groups, a marked increase in endocrine stress response was observed. Adrenaline, noradrenaline, antidiuretic hormone, adrenocorticotropic hormone, cortisol, glucose and lactate, however, were not additionally influenced by the antagonism. No influence of flumazenil on mean arterial pressure, heart rate and arterial oxygen saturation was observed. After modified neuroleptanaesthesia, a careful antagonism of midazolam with small doses of flumazenil is not disadvantageous with respect of endocrine stress response and haemodynamic reactions.

[Endocrine and hemodynamic effects of naloxone following modified neuroleptanesthesia]. / Endokrine und hämodynamische Effekte von Naloxon nach modifizierter Neuroleptanästhesie.

This study was undertaken to investigate the influence of the opiate-antagonist naloxone on the endocrine stress response and haemodynamic parameters after modified neuroleptanaesthesia in a randomized, prospective design. A total number of 22 patients (ASA-scores I or II) between 18 and 60 years scheduled for major gynaecologic surgery were included. For modified neuroleptanaesthesia, midazolam, fentanyl and vecuronium were administered in standardized doses. After extubation, patients of the naloxone-group received injections of 2 x 0.1 mg naloxone; in controls, no naloxone was used. Endocrine stress parameters and haemodynamic parameters were measured 7 times before induction of anaesthesia and up to 60 minutes after the operation. In both groups, remarkable increases in adrenaline, noradrenaline, antidiuretic hormone, adrenocorticotropic hormone, cortisol, glucose and lactate took place in the postoperative period. This stress response was comparable in both groups and not increased by naloxone. No significant influence of naloxone on mean arterial pressure, heart rate and arterial oxygen saturation was observed. After neuroleptanaesthesia, a careful opiate antagonism with small doses of naloxone is not disadvantageous with respect to endocrine stress response and haemodynamic reactions.

[The simultaneous determination of ketamine and midazolam using high pressure liquid chromatography and UV detection (HPLC/UV)]. / Die simultane Bestimmung von Ketamin und Midazolam mittels Hochdruck-Flüssigkeits-chromatographie und UV-Detektion (HPLC/UV).

In order to prevent some negative side effects of ketamine during "dissociative anaesthesia", this substance is regularly combined with benzodiazepines, e.g., midazolam. This study was undertaken to develop a simple and effective method for the simultaneous detection of ketamine and midazolam in plasma by high-pressure liquid chromatography with UV-detection (HPLC/UV). METHODS. The chromatographic system consisted of a 300 x 3.9-mm C18 column for reversed-phase chromatography and a mobile phase of 30% acetonitrile and 70% 0.05 M sodium phosphate buffer, pH 4.45. The flow rate was 1 ml/min. UV-detection took place at a wavelength of 210 nm. Blood samples were preferably taken from a central venous or arterial line. After plasma separation, 1 microgram (100 microliters) etidocaine was added to 1 ml plasma as an internal standard. The samples were alkalinised and extracted with ether, followed by back-extraction of the organic phase in 250 microliters 0.05 N sulphuric acid; 50 microliters of this solution was injected into the system. RESULTS. Sample preparation by trained personnel was reliable and led to adequate results. Separation of ketamine and midazolam was very satisfactory. Standard curves for both drugs were linear from 15-4000 ng/ml (ketamine r = 0.9998; midazolam r = 0.9996). Recovery rates for ketamine in plasma were above 95%, for midazolam 70%-75%. Coefficients of variation for ketamine in plasma were between 0.6% and 1.3%, for midazolam between 2.0% and 2.6%. The detection limit was lower than 5 ng/ml. CONCLUSION. The method is suitable for clinical practice and allows the simultaneous detection of two anaesthetics in wide-spread combined use.

[The present status of interpleural analgesia]. / Gegenwärtiger Stellenwert der interpleuralen Analgesie.

Since the introduction of interpleural administration of local anaesthetics by Kvalheim and Reiestad in 1984, this technique has been applied to treat postoperative pain after cholecystectomy, renal, thoracic and unilateral abdominal surgery. Other indications are pain control in patients who suffered multiple rib fractures and in patients with chronic pain due to pathological processes in the pancreas. Due to the fact that interpleural analgesia is considered a new anaesthetic procedure, a number of questions still have to be answered regarding the mechanism of action, the appropriate local anaesthetic solution to be employed and, most importantly, the benefit/risk ratio associated with this technique. The purpose of this review article is to give a detailed account of the knowledge and obtained clinical experiences present to date regarding interpleural analgesia, and to give a critical evaluation of this method.

[Is the plasma protein binding of lidocaine modified by the simultaneous administration of midazolam?]. / Beeinflussung der Plasmaproteinbindung von Lidocain durch gleichzeitige Midazolam-Applikation?

Perioperative antiarrhythmic therapy with lidocaine (bolus dosage 100 mg followed by infusion of 200 mg/h) was performed in 24 patients; 12 of them simultaneously received an intravenous injection of 10 mg midazolam with the bolus of lidocaine (group I: with midazolam; group II: without midazolam). Central venous blood samples were collected over a period of 1 h (1, 3, 5, 10, 20, 30, and 60 min after the bolus) to evaluate unbound and total (protein-bound + unbound) plasma concentrations of lidocaine, thus calculating plasma protein binding. One minute after intravenous administration of lidocaine peak plasma concentrations occurred: in group I 5.38 +/- 1.99 micrograms/ml (mean +/- SD), in group II 5.25 +/- 1.90. Up to 60 min there was only a gradual decrease in plasma concentrations in both groups. There was no significant difference between the two groups (group I: mean free concentration 0.67-0.80 micrograms/ml; mean total concentration 4.84-5.38 micrograms/ml; mean plasma protein binding 83%-86%; group II: 0.69-0.89 micrograms/ml; 4.62-5.25 micrograms/ml; 82%-85%). We draw the conclusion that midazolam administration is safe in patients undergoing antiarrhythmic therapy or regional anesthesia with lidocaine.

[Pharmacokinetic studies of blood protein binding of bupivacaine following acute preoperative hemodilution]. / Pharmakokinetische Untersuchungen zur Plasmaproteinbindung von Bupivacain nach akuter präoperativer Hämodilution.

This randomized study was designed to determine the effects of isovolemic hemodilution and lumbar epidural anesthesia on plasma concentrations of bupivacaine in patients scheduled for endoprosthetic hip surgery. PATIENTS, MATERIALS AND METHODS. The patients were randomly assigned to two groups. In a hemodilution group (n = 15), which included patients undergoing lumbar epidural anesthesia following isovolemic hemodilution (15 ml/kg body weight), withdrawn blood was substituted by colloidal solution (hydroxyethyl starch solution 6%, 450/0.7; ratio of replacement 1:1). Controls were 15 patients who were not subjected to isovolemic hemodilution; epidural anesthesia only was performed. Both groups had identical fluid pretreatment (1000 ml Ringer's solution) before injection of the epidural bupivacaine dose (mean 14 ml, 0.75%); central venous blood samples were drawn at short intervals over 180 min. Both, the total plasma concentrations and the free bupivacaine fractions were determined by HPLC and ultrafiltration. RESULTS. Peak bupivacaine plasma levels (mean 1.30 microgram/ml) were found 10 min after application of the analgesic dose in the control patients. In contrast, in hemodiluted patients mean maximum plasma levels of bupivacaine were measured between the 20th and 30th min, with peak levels of only 0.75 microgram/ml plasma. The unbound bupivacaine levels were not significantly different in both groups over the entire measuring period despite the differing total bupivacaine concentrations. Therefore, protein binding of bupivacaine was about 6% lower in the hemodilution group, especially during the period shortly after injection. DISCUSSION. We conclude that isovolemic hemodilution leads to lower plasma bupivacaine concentrations after epidural anesthesia, probably due to an increased volume of distribution. Protein binding of bupivacaine is reduced by hemodilution; the free, non-protein-bound concentrations of local anesthetic were not associated with any systemic side effects in this study.

[Pharmacokinetics and pharmacodynamics of local anesthetics]. / Pharmakokinetik und Pharmakodynamik von Lokalanästhetika.

In clinical practice the efficacy of local anaesthesia is judged by the time of onset, duration and the quality of sensory and motor blockade. Apart from the physicochemical properties of local anaesthetics, a sufficient blockade depends on the volume and the concentration which are applied. Generally increasing the dose leads to a better quality of blockade as well as a higher risk of toxicity. This dilemma is evident in procedures, where, due to continuous or repetitive application within one day, the applied total dosage exceeds the recommended maximum limit. The values regarding maximum doses published in the German Pharmacopeia ("Rote Liste") can be defined as being more or less the product of the volume of distribution and the toxic concentration in the plasma. According to that formula the maintainance doses for continuous techniques in regional anaesthesia are derived from the product of the elimination half-life and the toxic plasma concentration. The values for toxic plasma concentrations are difficult to define since only the free protein-unbound fraction of a local anaesthetic is responsible for undesired side-effects. This fraction can be influenced by acidosis, body temperature and shortage of specific binding protein. Some well documented case reports show that another major cause of acute toxicity is nearly always due to inadvertent intravascular injections. This event can occur nearly unnoticed and leads to life-threatening complications even with lower doses than the recommended maximum doses. Only the application of high concentrations into well vascularised regions is followed by a similarly quick development of high plasma levels. Typical kinetics of local anaesthetics are presented for various methods of regional anaesthesia informing the anaesthetist on corresponding plasma concentrations if the recommended maximum doses are exceeded and thus he gets useful information for his daily work.

[Proposals for standardized documentation of regional anesthetic techniques in anesthesia protocols]. / Vorschläge zur einheitlichen Dokumentation regionaler Anaesthesietecniken im Narkoseprotokoll.

The wide-spread use and wide variety of regional anesthetic procedures makes it essential to insist on careful documentation in the anesthetics record, with special emphasis on technique, effects and complications. With a view to possible medico-legal problems, data should be recorded in considerable detail with each technique applied specified. Documentation is discussed according to the different procedures and their clinical relevance, with various examples.

[Maternal and neonatal plasma concentrations of bupivacaine during peridural anesthesia for cesarean section]. / Maternale und neonatale Bupivacain-Plasmakonzentrationen bei Periduralanaesthesien zur Sectio caesarea.

Many anesthesiologists prefer epidural anesthesia for cesarean section because of the potential risks of general anesthesia such as Mendelson's syndrome. For this indication, the local anesthetic of first choice is the long-acting substance bupivacaine. The aim of the following study was to determine maternal and neonatal plasma concentrations of bupivacaine 0.5% following epidural anesthesia for cesarean section in order to give critical statements about the systemic toxicity of the local anesthetic. MATERIALS and METHODS. Central venous blood samples were collected for bupivacaine analysis (gas chromatography) in 15 patients (Table 1) undergoing cesarean section with epidural anesthesia over a period of 60 min after injection of 14 to 23 ml bupivacaine 0.5%. Six of these patients had received the epidural anesthesia earlier to relieve labor pain. Before administering the anesthetic dose, a blood sample was taken to determine the baseline value. Immediately after cord clamping, blood sampling was done to determine bupivacaine concentrations in the umbilical artery and vein. Apgar scores and blood gases were also checked and compared with those of neonates born by cesarean section under general anesthesia. RESULTS. Ten to 15 min following epidural application of 70 to 115 mg bupivacaine (mean = 99 mg), peak plasma concentrations occurred (mean = 0.41 micrograms/ml) The maximum plasma level of 0.7 micrograms/ml bupivacaine was found in a patient who had received epidural anesthesia for pain relief during labor. In this case, the baseline bupivacaine level after several epidural injections (125 mg in 15 h) before the anesthetic dose for cesarean section was 0.2 micrograms/ml. Immediately after delivery the mean plasma bupivacaine concentrations in the umbilical vein and artery were 0.11 micrograms/ml and 0.07 micrograms/ml respectively. Apgar scores and blood gas analyses showed no significant difference between neonates born by cesarean section under regional or general anesthesia. DISCUSSION. Using bupivacaine 0.5% for epidural anesthesia for cesarean section, we found maternal and neonatal plasma concentrations of the local anesthetic far below the accepted threshold level for producing systemic toxic reactions. In contrast to others, we obtained good analgesia and sufficient motor blockade accompanied by low plasma levels. In our opinion, there is no need to use 0.75% bupivacaine, especially since peak plasma concentrations of more than 2 micrograms/ml occur shortly after its epidural administration.

[Intravenous regional anesthesia of the foot using prilocaine. Clinical aspects, pharmacokinetic and pharmacodynamic studies]. / Die intravenöse Regionalanaesthesie (IVRA) des Fusses mit Prilocain. Klinische Aspekte, pharmakokinetische und -dynamische Untersuchungen.

Intravenous regional anesthesia (IVRA) of the foot is a rarely used but alternative method to other regional techniques and general anesthesia, especially when operating on the distal portion of the lower limb. The present report describes our method and experience with this type of anesthesia in approximately 500 patients, including pharmacokinetic and -dynamic aspects. MATERIALS AND METHODS. Pharmacological studies were performed in 17 orthopedic outpatients undergoing operations on the foot following an IVRA technique with prilocaine. A plastic cannula was inserted into a peripheral vein of the forefoot and a pneumatic tourniquet (350 mm Hg) applied proximally and close to the malleoli after achieving exsanguination with an Esmarch bandage. If there was no sufficient analgesia (pinprick testing) 5 min after injection of 200 mg prilocaine, IVRA was supplemented with another 100 mg of local anesthetic. Peripheral venous blood samples were collected at short intervals for up to 2 h before and after cuff release to determine total plasma concentrations of prilocaine (HPLC) and the degree of methemoglobinemia (CO-Oximeter). RESULTS. Administration of 200-300 mg prilocaine resulted in complete analgesia in 15 of 17 cases that was sufficient for operations lasting up to 85 min. The tourniquet was tolerated for up to 105 min without any complaints. Plasma concentrations after 200 (n = 12) and 300 mg prilocaine (n = 3) peaked between 10 and 20 min after cuff release, respectively, with maximum levels of 0.96 micrograms/ml (means = 0.56 micrograms/ml) and 1.45 micrograms/ml. The extent of methemoglobin formation was low (maximum 3.8% of total hemoglobin). DISCUSSION. In addition to conventional anesthetic techniques, IVRA deserves a firm place in modern anesthesiological practice and should be used more widely. In order to avoid systemic toxic reactions, the use of prilocaine is recommended. Prolocaine plasma concentrations and methemoglobin formation were both far below toxic levels. Failure of IVRA was probably caused by premature outflow of the local anesthetic solution, as shown by the course of prilocaine plasma concentrations and methemoglobinemia.

[Neurologic complication following spinal anesthesia for manual detachment of the placenta]. / Neurologische Komplikation nach Spinalanästhesie zur manuellen Planzentalösung.

Long-term paralysis of the lower extremities was observed in a 31-year-old fourth-gravida patient, undergoing a curettage under spinal anaesthesia because of placenta accreta. The patient recovered within three days from her neurological signs and symptoms, consisting of complete paresis of the hip and knee flectors and severe headache. Clinical investigations including a neurological examination, spinal puncture, x-ray pictures of the lumbosacral area and haemograms revealed no evidence for an infection, abscess or haematoma. With regard to the fact, that neurological deficiency disappeared completely within three days, it seems probable, that the symptoms were caused by the longer lasting gynaecological position (Steinschnitt-position) during the period of delivery and curettage thereafter.

[The significance of the sampling site in the determination of plasma levels of local anesthetics using 0.75% bupivacaine as an example]. / Die Bedeutung des Entnahmeortes bei der Bestimmung von Lokalanaesthetikakonzentrationen im Plasma am Beispiel von Bupivacain 0.75%.

Knowledge of the actual concentrations of local anesthetic administered by various techniques is essential requisite when undesirable side effects and possible toxicity of a substance are to be evaluated. Therefore, numerous studies of plasma concentrations have been presented, which were carried out with the additional purpose of analyzing the kinetics of different local anesthetics with respect to limiting-value concentrations in the organism. Despite a sufficient degree of precision in the analysis of amide local anesthetics, it is uncertain whether the results of the different studies are comparable, because blood samples have been taken variously from peripheral veins, central veins or arteries. In the present study changes in bupivacaine concentrations were monitored by means of a standardized method consisting in simultaneous sampling of blood in peripheral veins, central veins and arteries. METHODS. Each of 12 patients undergoing orthopedic hip surgery received average 17 ml bupivacaine (0.75%) via peridural lumbar catheter. After the administration of bupivacaine, blood samples were taken simultaneously from peripheral veins, central veins and arteries at 1, 3, 5, 10, 15, 30, 45, 60, and 90 min after injection. Placement of an arterial cannula and central venous catheter was indicated in all patients (hip-joint revision arthroplasty). Quantitative analysis of bupivacaine concentration was carried out by means of high-pressure liquid chromatography (HPLC). All patients had given their informed consent. RESULTS. All patients showed a rapid increase in bupivacaine concentration in the central venous blood within the first few minutes after administration, the maximum being reached between 3 and 10 min after. A similar course was observed with arterial plasma concentrations; absolute values, however, were an average of 10-20% lower at 15 min following administration. Bupivacaine concentrations in peripheral veins rose more slowly and reached a maximum between 15 and 30 min. At 30 min after peridural application the concentration curves in blood from all three sites were similar. DISCUSSION. In earlier studies the influence of the site of blood sampling has often been underestimated. According to our results, central venous and arterial plasma concentrations correspond closely at all times following peridural application. The observed uniform differences in concentrations at the various sites of sampling can be explained by the fact that pulmonary uptake of local anesthetics causes the lower arterial levels. Especially in the early phase of resorption after administration of local anesthetics, the concentration in peripheral blood does not seem to be representative, because an equilibrium is not established between arterial and central venous blood until 30 min after administration at the earliest. In our opinion the peripheral venous concentrations are unreliable, particularly in the early phases, for the evaluation of unwanted effects or toxicity of local anesthetics, because the initial low values and the delayed increase in these could lead to a false sense of security.

[The sympatho-adrenergic stress reaction in ear surgery using various anesthesia technics]. / Die sympathoadrenerge Stressreaktion bei Ohroperationen unter verschiedenen Anästhesietechniken.

The aim of the present study was to investigate the effects of various anaesthetic procedures on the endocrine stress responses during ear microsurgical operations. Simple mastoidectomies, radical mastoidectomies and tympano plastics were carried out in 49 patients under the following randomised anaesthetic procedures: Group 1 halothane anaesthesia and retroauricular infiltration anaesthesia with lidocaine and ornipressin (n = 14), Group 2 fentanyl anaesthesia and retroauricular anaesthesia with lidocaine and ornipressin (n = 10), Group 3 fentanyl anaesthesia and retroauricular infiltration anaesthesia with lidocaine and epinephrine (n = 14), and Group 4 retroauricular infiltration anaesthesia with prilocaine and epinephrine (n = 14). The plasma levels of epinephrine, norepinephrine, glucose, lactate and free glycerol were measured in addition to mean arterial pressure (MAP) and heart rate (HR) immediately before anaesthesia, 10 minutes after skin incision, 10 minutes after having started bone drilling, at the end of the operation and 3 hours after operation. All data were subjected to covariance analysis including the age factor. Plasma catecholamine concentrations remained within the normal range during the investigation in patients subjected to general anaesthesia (Groups 1-3). Plasma catecholamines (epinephrine and norepinephrine) increased significantly in Group 4 (retroauricular infiltration anaesthesia). There were no group variabilities with regard to MAP and HR. The plasma levels of epinephrine and norepinephrine demonstrate a direct response to stress followed by a secondary change in glucose, lactate and free glycerol. The beneficial effect of general anaesthesia is documented by normal plasma levels of epinephrine and norepinephrine throughout the operation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Initial experiences with a novel nerve stimulator for use in axillary plexus anesthesia]. / Erste Erfahrungen mit einem neuartigen Nervenstimulator bei axillären Plexusanaesthesien.

The advantages of an electrical nerve stimulator for detection of the axillary neurovascular sheath have been frequently described in the literature and are now well known. In most of these techniques, stimulation is achieved by a fixed electrical voltage and variable amplification. The new nerve stimulator presented here offers the possibility of measuring the current at the site of stimulation ("test" position). PATIENTS AND METHODS. Axillary block was performed in 23 patients undergoing orthopedic surgery. Identification of the neurovascular sheath was first achieved by the "loss of resistance" technique, after which the injection cannula was connected to the new device. Stimulation was started at 1.0 mA. In case of a negative response to stimulation the actual electric current was checked by means of the test position in order to exclude an error in the circuit system. In these cases, the position of the cannula was altered so as to maintain a response at the lowest possible current (less than 0.5 mA). After removal of the inner solid steel stylet of the cannula, the local anesthetic was injected while compressing the distal part of the neurovascular sheath in order to avoid downstream diffusion. RESULTS. All 23 patients were operated upon under axillary block after nerve stimulator control without any additional drugs. Table 2 indicates the lowest stimulation current that still evoked a response. Disturbances in the circuit system were found twice, one caused by a short circuit, the other by a desiccated gel pad on the adhesive electrode. After elimination of the defect, stimulation produced a response. DISCUSSION. Since it is now well known that induction of paresthesias in locating peripheral nerves can cause irreversible lesions, the use of electrical nerve stimulators is preferred to locate the cannula as near as possible to the nerve without direct contact. The mode of operation of the stimulator presented here, which defines the chosen technical starting impulse as well as the actual current, allows much better localization of nerves during local anesthesia. Thus, disturbances in the circuit between nerve stimulator and patient, as shown in the two cases, can be detected. According to our experience, the intensity of stimulation for successful nerve blockade should be approximately 0.5 mA or lower. Consequently, universally applicable stimulating instruments with constant electrical tension should allow fine tuning of the current in 0.1-mA aliquots.

[Does the development of methemoglobin in the newborn infant affect the suitability of prilocaine for pudendal anesthesia? A clinical study in the peripartum phase]. / Beeinträchtigt die Met-Hämoglobin-Entwicklung des Neugeborenen die Einsatzmöglichkeit von Prilocain zur Pudendusanaesthesie? Eine klinische Untersuchung in der peripartalen Phase.

Pudendal block is a well established method of achieving analgesia during the second stage of labor. Whenever a large amount of a local anesthetic has to be injected in well vascularized tissue, local anesthetic drugs with low systemic toxicity should be used, to minimize side effects. This means that prilocaine is the drug of choice. It is well known that the metabolites of prilocaine induce methemoglobinemia, and thus the question arises as to whether the methemoglobinemia affects the fetus. PATIENTS AND METHODS. Pudendal block was achieved with 2 x 10 ml prilocaine 1% in each of 17 mothers. Plasma concentrations of the local anesthetic in the second stage of labor were determined by gas chromatography in blood samples drawn from the mother and the newborn at the moment of childbirth. In addition, the time course of methemoglobinemia was determined by capillary blood samples from the neonate up to 6 h. To evaluate methemoglobinemia in the newborn, 125 microliters heparinized capillary blood was diluted with 200 microliters 0.9% sodium chloride; methemoglobin was detected by absorbance spectrometry. RESULTS. Before the pudendal block maternal methemoglobin concentrations were about 0.2% of the total hemoglobin concentration and within the physiological range. At the moment of delivery it was increased only to a small extent, without statistical significance. In the neonates mean methemoglobin concentrations were about 1% of total hemoglobin immediately after delivery, increasing up to 1.8% in the next 2 h and then decreasing continuously in all. At the moment of childbirth maternal mean prilocaine concentrations were 0.57 micrograms/ml on an average and 0.29 micrograms/ml in the newborn. DISCUSSION. With respect to systemic toxicity, prilocaine is the drug of choice in local anesthetic procedures when a long duration of anesthesia is not required; it guarantees short latency and adequate relief of pain. Methemoglobinemia induced by its metabolites is not a contraindication for its use in humans. Formerly prilocaine was judged to be contraindicated in pregnant women during delivery because of the small redox capacity of fetal erythrocytes. Our study, however, demonstrates that 200 mg prilocaine for pudendal block does not induce methemoglobinemia in newborns to any significant extent. One explanation for this may be the increased renal elimination of local anesthetics in newborns and the low fetomaternal ratio.

[The quantitative analysis of amide local anesthetics using high pressure liquid chromatography and ultraviolet detection (HPLC/UV)]. / Die quantitative Analyse von Amid-Lokalanaesthetika mittels Hochdruck-Flüssigkeits-Chromatographie und UV-Detektion (HPLC/UV).

This study was undertaken to develop a time- and cost-effective method for the detection of lidocaine, mepivacaine, prilocaine, bupivacaine, and etidocaine by HPLC/UV. The chromatographic system consisted of a C18-column (300 x 3.9 mm) for reversed-phase chromatography and a mobile phase of 30% acetonitrile and 70% 0.05 M sodium phosphate buffer. For the analysis of lidocaine, mepivacaine, and prilocaine, the buffer was adjusted to pH 5.8. The buffer for the analysis of bupivacaine and etidocaine was adjusted to pH 3.5. The flow rate was 1 ml/min. UV detection took place at a wavelength of 210 nm. All blood samples were taken from a central venous line. After plasma separation, 1 microgram (100 microliters) of internal standard was added to 1 ml plasma. The samples were alkalized and extracted with ether, followed by the extraction of the organic phase in 250 microliters 0.05 N sulphuric acid; 50 microliters of this solution was injected into the system. The chromatographic system allowed the separation of bupivacaine and etidocaine (pH 3.5) as well as lidocaine and mepivacaine or prilocaine (pH 5.8). Separation of prilocaine and mepivacaine in one run was not satisfactory. Recovery rates for all local anesthetic substances were about 90%, standard variations below 3%, and coefficients of variation below 2%. The detection limit was about 30 ng/ml. The method is suitable for clinical practice. Only minor methodological modifications are necessary for the detection of the amide local anesthetics in current clinical use.