Percutaneous minimal-access fetoscopic surgery for spina bifida aperta. Part II: maternal management and outcome.

OBJECTIVE: To assess maternal morbidity and outcome in women undergoing minimal-access fetoscopic surgery for spina bifida aperta. METHODS: This was a retrospective study of 51 women undergoing minimal-access fetoscopic surgery to improve postnatal neurological outcome of spina bifida aperta, at a mean gestational age of 24 weeks, at our center between July 2010 and June 2013. We analyzed various perioperative complications of surgery, namely: maternal and fetal death, need for maternal blood transfusion, placental abruption, pulmonary edema, spontaneous labor, oligohydramnios, chorioamnionitis, chorioamniotic membrane separation, duration of hospitalization, amniotic fluid leakage, gestational age at delivery and status of hysterotomy site. RESULTS: In none of the 51 women was there maternal demise, spontaneous labor, placental abruption or a need for maternal blood transfusion in the perioperative period. Chorioamniotic membrane separation occurred in one patient, mild pulmonary edema occurred in one and oligohydramnios occurred in seven. All fetuses survived surgery, but there was one very early preterm delivery 1 week after the procedure and this neonate died immediately, from early postoperative chorioamnionitis. Amniotic fluid leakage occurred in 43 patients, at a mean gestational age of 29.7 (range, 22.6-37.3) weeks; two of these patients developed chorioamnionitis. Duration of maternal hospitalization after surgery was 7.2 (range, 4-12) days. Mean gestational age at delivery was 33 (range, 24.6-38.1) weeks. All abdominal and uterine trocar insertion sites healed well. CONCLUSION: Minimal-access fetoscopic surgery for spina bifida aperta is apparently safe for most maternal patients. Despite the common occurrence of amniotic leakage, the majority of women deliver beyond 32 weeks of gestation.

Intercostal nerve block, interpleural analgesia, thoracic epidural block or systemic opioid application for pain relief after thoracotomy?

The purpose of this study was to investigate the effect of different pain-relief methods (regional and systemic) following thoracotomies on the cardiovascular system, pulmonary gas exchange, various endocrine parameters and subjective perception. A further aspect was to evaluate the benefits of interpleural analgesia as a new regional technique against already established regional techniques, such as intercostal nerve block and thoracic epidural block. All postoperative pain methods led to a significant time-dependent reduction of the adrenaline concentrations in plasma while the noradrenaline concentrations did not change significantly. There were no statistical differences in catecholamine concentrations among the different study groups, although the mean concentrations of adrenaline in patients having a thoracic epidural block for pain relief were lower in comparison to the findings in other groups. The plasma concentrations of the "stress metabolites", such as glucose, free fatty acids and lactate, as well as the haemodynamic (mean arterial pressure, heart rate) and pulmonary parameters (blood gas analyses), showed no significant differences among groups. In contrast to the other pain-relieving methods, interpleural analgesia did not lead to sufficient pain relief in that 7 out of 10 patients needed supplementary systemic opioid therapy. Therefore, interpleural analgesia for pain relief following thoracotomies cannot be recommended.

[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.

[Ultrafiltration as a fast and simple method for determination of free and protein bound prilocaine concentration. Clinical study following high-dose plexus anesthesia]. / Ultrafiltration als schnelle und einfache Methode zur Bestimmung von freier und proteingebundener Prilocain-Konzentration. Klinische Untersuchungen nach hochdosierter Plexusanaesthesie.

Ultrafiltration as a Fast and Simple Method to Separate Free and Protein Bound Concentrations of Local Anesthetics/Pharmacokinetic studies following high-dose anesthesia of the axillary plexus. As many other drugs amide-type local anesthetics are protein bound in plasma. The extent of binding varies between local anesthetics. The free, non protein-bound fraction of these drugs is mainly responsible for cardiovascular and central-nervous side effects. If high doses are necessary for regional anesthetic procedures it seems reasonable to determine the pharmacological active, non protein-bound fraction in addition to the total concentration of the local anesthetic drug. Analyses of protein binding was performed using an ultrafiltration method which is discussed in this paper. Total (HPLC) and unbound plasma levels (combination of ultrafiltration and HPLC) of the local anesthetic drug in central venous blood were studied in 20 healthy orthopedic patients, undergoing plastic surgery of the upper limb (elbow, forearm, hand), over a time period of 90 min, when performing axillary plexus block with 30 ml prilocaine (CAS 721-50-6) 2% (= 600 mg). Separation of the local anesthetic fractions was achieved using the ultrafiltration system MPS-1, equipped with a YMT-membrane. These membranes have a narrow pore size retaining molecules larger than 30000 Dalton. Ultrafiltration was accomplished by subjecting 1.2 ml of plasma to centrifugation at 2000 x g for 60 min at 30 degrees C using a clinical centrifuge equipped with a 35 degree angle head rotor. The plasma samples were adjusted to physiological pH (7.40) with a sodium-potassium-phosphate buffer. The tightness of the used membrane was controlled by a micromethod for protein estimation (sensitivity 10 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

[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.

[Maternal and neonatal bupivacaine plasma levels in peridural anesthesia for relief of labor pain]. / Maternale und neonatale Bupivacain-Plasmakonzentrationen bei Periduralanästhesien zur Dämpfung der Wehenschmerzen.

Peripheral venous blood samples were drawn for bupivacaine analyses (gas chromatography) from 24 patients under epidural anaesthesia, used to reduce pain caused by contractions. The specimens were taken 10, 20, 30 and up to 45 minutes following a first injection of 11 to 13 ml bupivacaine 0.25%, before, 15 as well as 30 minutes after each repetitive dose and at childbirth. Immediately after cord clamping, blood sampling in the neonate was performed to evaluate bupivacaine concentrations in the umbilical artery and vein. Additionally, apgar scores and blood gas parameters were checked and compared with those of neonates, born without analgesic treatment of their mothers. Using bupivacaine 0.25% (average 12 ml) for epidural anaesthesia, the peak plasma levels (mean = 0.2 micrograms/ml) were found 10 minutes after application of the analgesic dose. In one patient a maximum bupivacaine plasma concentration (0.47 micrograms/ml) was determined 15 minutes after the second repetitive dose of 5 ml bupivacaine 0.25%. Apgar scores and results of blood gas analyses demonstrated no significant difference between neonates born spontaneously under regional anaesthesia or without any analgesic treatment of their mothers, respectively. Using bupivacaine 0.25% in epidural anaesthesia for pain relief in labour, we found maternal and neonatal plasma concentrations of the local anaesthetic drug far below the accepted threshold level which might produce systemic toxic reactions.