Both ropivacaine and bupivacaine are widely used in regional analgesia. The effective sensory block associated with reduced motor block and less cardiac and neurologically toxic effects are well-known properties of ropivacaine in adults. However, conflicting pharmacokinetic reports exist in children [1,2]. We therefore decided to examine the free plasma levels of ropivacaine and bupivacaine in children during our daily practice of outpatient hypospadias or groin surgery under caudal block. Equivalent dose and concentrations of both local anaesthetics were used.
Following institutional ethics committee approval and parental informed consent, 38 children ASA I aged between 10 months and 8 yr undergoing hypospadias or groin surgery in an ambulatory setting were included in this study. Children who had anatomic malformation of the spine, a history of convulsions or neuromuscular disease, skin infection of the caudal area, coagulopathy, renal or hepatic impairment, or delayed development were excluded. The children were not premedicated and were fasted for 6 h before surgery. After applying standard monitoring, general anaesthesia was induced using an intravenous (i.v.) technique, the trachea was intubated and each child placed in the left lateral decubitus position. The caudal epidural space was approached using an aseptic technique with a caudal needle (Braun Epican, 22-G 35 mm long) and identified by use of a saline filled syringe and the loss of resistance method. After negative aspiration of blood and cerebrospinal fluid, children were randomly allocated to receive 0.5 mL kg−1 of a 0.25% solution (1.25 mg kg−1) of either bupivacaine (n = 17) (Marcaine Astra Zeneca, Eczacibaşi, Turkey) or ropivacaine (n = 21) (Naropin, Astra, Sweden). All blocks were performed by the attending paediatric anaesthesiologist or the senior resident. To detect and avoid an i.v. or subarachnoid injection, the needle was repeatedly aspirated and local anaesthetic injected in increments while the electrocardiogram (ECG) was closely observed. Blood pressure (BP) and heart rate (HR) were recorded just before and after surgical incision and every 5 min thereafter until the end of anaesthesia. Venous blood samples (1 mL) were withdrawn from a peripheral i.v. catheter 1 and 2 h after the insertion of the block. The i.v. catheter was flushed with 1 mL heparinized saline. Blood samples which were collected in ethylene diamine tetraacetic acid (EDTA) containing glass tubes were subsequently separated by centrifugation and the plasma stored at −20°C until analysed. Free bupivacaine and ropivacaine levels were determined with gas chromatography and mass spectrometry by using a Hewlett Packard 6890 and 5973, GC-MS system (Hewlett Packard, Palo Alto, CA, USA). The gas chromatograph was fitted with an HP 5 (30 m × 0.25 mm × 0.25 μm thickness) film. Data was ana-lysed by t-test and is expressed as mean ± SD (range). P < 0.05 was considered statistically significant.
The distribution of age and the gender was similar between groups (Table 1). There were no changes in ECG traces throughout the operations. HR and BPs were stable unless there was traction on the hernial sac. Adequate analgesia was achieved during the operation and patients awoke free of pain. All of the patients were able to raise their lower limbs. There was no evidence of systemic local anaesthetic toxicity in any patient. In the bupivacaine group, bupivacaine concentrations were 46.8 ± 17.1 (27-98) ng mL−1 and 23.8 ± 8.1 (13-46) ng mL−1 at 1 and 2 h, respectively. In the ropivacaine group concentrations were 61.2 ± 8.2 (47-75) ng mL−1 and 49.5 ± 6.9 (39-63) ng mL−1 at 1 and 2 h, respectively. The difference between the groups was statistically significant.
It has been stated in the literature that central nervous system and cardiovascular system toxicity appear when free bupivacaine concentration is >0.25 μg mL−1 (250 ng mL−1) and ropivacaine concentration is >0.15-0.6 μg mL−1 (150-600 ng mL−1) [3-5]. None of the patients reached toxic levels. Several authors have reported that the maximum concentration occurs at around 60 min for ropivacaine in infants and young children after a single bolus dose of caudal epidural ropivacaine [2,6,7]. The duration of surgery for ambulatory procedures such as groin surgery is around 60 min. Pharmacokinetic studies in children have noted that bupivacaine concentration peaks at about 20 min which is generally during the operation [1,2]. Similar to previous studies, the free ropivacaine concentration in our study was significantly lower than 0.6 μg mL−1 at the first hour . When most of the patients were leaving the recov-ery room the free bupivacaine concentrations were 23.8 ng mL−1, a very safe concentration for toxicity.
We conclude that when using caudal 1.25 mg kg−1 ropivacaine or bupivacaine at a concentration of 0.25% the free plasma concentrations do not reach levels of potential toxicity.
This work was supported by the Research Fund of The University of Istanbul. Project No.: T 1140/ 18062001.
M. S. Cansever
1Department of Anaesthesia and Reanimation, Istanbul University, Cerrahpaşa Medical Faculty, Istanbul, Turkey
2Department of Paediatrics, Metabolism Division Laboratory, Istanbul University, Cerrahpaşa Medical Faculty Istanbul, Turkey
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