Pharmacokinetic profiles of epidural bupivacaine and ropivacaine following single-shot and continuous epidural use in young infants

Aims: The primary aim of this study was to describe the pharmacokinetics of total and unbound bupivacaine and ropivacaine following epidural bolus and infusion in neonates and young infants. Secondary aims were to investigate the influence of alpha‐1‐acid glycoprotein (AAG) on the concentration–time profiles and to determine the efficacy and adverse event profile of the epidural regimen. Methods/Materials: Thirty‐one infants aged 40–63 weeks of postmenstrual age (PMA) undergoing hernia repair or abdominal surgery received an epidural injection of 1.5 mg·kg^?1 bupivacaine (0.25%) or ropivacaine (0.2%) followed 2 h later by an infusion of 0.2 mg·kg^?1·h^?1 in those undergoing abdominal surgery. Total and unbound concentrations of bupivacaine and ropivacaine were analyzed using nonmem . Hourly pain scores and adverse effects were recorded. Results: Bupivacaine data were available from 11 infants (five had infusions) and ropivacaine from 13 infants (four had infusions). Alpha‐1‐acid glycoprotein and total bupivacaine and ropivacaine concentrations accumulated during infusions, but unbound concentrations did not. Maximum unbound concentrations for bupivacaine and ropivacaine were 0.12 mg·l^?1 (bupivacaine) and 0.13 mg·l^?1 (ropivacaine). Typical clearance/bioavailability estimates of total (unbound) bupivacaine were 0.215 (4.65) l·h^?1·kg^?1 and of total (unbound) ropivacaine were 0.288 (3.31) l·h^?1·kg^?1. Pain scores requiring pain team referral occurred once with bupivacaine and four times with ropivacaine. No toxicity was observed. Conclusions: Epidural infusions of 0.2 mg^?1·kg^?1·h^?1 bupivacaine or ropivacaine appeared to be well tolerated and efficacious in this population. No accumulation of unbound drug concentrations occurred.     

The effect of volume of local anesthetic on the anatomic spread of caudal block in children aged 1-7 years

Objectives: To examine the anatomic spread of caudal local anesthetic solution in children aged 1–7 years. Aim: To determine whether incremental increases in the volume of caudal injections of 0.5, 0.75, and 1.0 ml·kg^?1 result in reliable (>90%) and potentially clinically significant increases in the number of vertebral segments reached. Background: Caudal block is one of the most frequently performed pediatric regional analgesic techniques. Traditional formulae suggest that changes in the volume of caudal injectate in the range 0.5–1.0 ml·kg^?1 would have clinically useful effects. Methods: In a single blind design, 45 children aged 1–7 years undergoing caudal block received one of the three predetermined volumes (0.5, 0.75, and 1 ml·kg^?1) of local anesthetic solution containing radio‐opaque contrast under controlled conditions. Following X‐ray examination, the anatomic spread of the block was reported by a radiologist blinded to the volume of solution received. Results: There were 15 children in each group, and they were similar in terms of age, height, and weight. Spread was observed between the 5th lumbar (L5) and 12th thoracic (T12) vertebral levels. A volume of 1 ml·kg^?1 results in a small but significantly greater spread of solution than 0.5 ml·kg^?1 (P < 0.05), but there was no difference between 0.5 and 0.75 ml or between 0.75 and 1.0 ml. No volume reliably reached a level higher than the second lumbar vertebra (L2). Conclusions: Incrementally increasing the volume of injectate between 0.5 and 1.0 results in a modest increase in the spread of the caudal solution. It is unlikely that volumes of <1 ml will reliably reach a vertebral level that is higher than L2.     

Continuous caudal anaesthesia with chloroprocaine as an adjunct to general anaesthesia in neonates

Purpose

The authors prospectively evaluated the use of a continuous caudal epidural infusion of chloroprocaine as an adjunct to genera! anaesthesia during intra-abdominal surgery in neonates.

Clinical features

The technique was used in 25 neonates ranging in age from 1 to 28 days and in weight from 2.2 to 4.9 kg. Following anaesthetic induction and tracheal intubation, an initial bolus dose of chloroprocaine 3% (1 or 1.5 ml · kg^?1) was followed by a continuous infusion of 1 or 1.5 ml · kg^?1 · hr^?1 administered through a caudal epidural catheter. No parenteral opioids were administered. The duration of the surgical procedures varied from one hour five minutes to three hours 15 min. The first three neonates received a bolus dose of 1.0 ml kg^?1 followed by an infusion of 1.0 ml · kg^?1 · hr^?1 chloroprocaine 3%. These three neonates required an additional bolus dose followed by an increase in the infusion to 1.5 ml · kg^?1 · hr^?1 to provide surgical anaesthesia. Adequate intraoperative anaesthesia was achieved in all 25 neonates with an infusion of 1.5 ml · kg^?1· hr^?1 of chloroprocaine 3%. This was evidenced by a lack of haemodynamic response to surgical manipulation. No neonate required more than 0.2% isoflurane or 70% nitrous oxide in oxygen. No episodes of haemodynamic instability (decreased blood pressure/bradycardia) related to the caudal epidural anaesthesia were noted. Twenty-three of 25 of the neonates’ tracheas were extubated immediately (within 10 minutes) following the surgical procedure.

Conclusions

Caudal anaesthesia with a continuous infusion of chloroprocaine can be used as an adjunct to general anaesthesia during abdominal surgery in neonates. Our initial experience suggests that the combined technique may eliminate the need for parenteral opioids and limit the intraoperative requirements for inhalational anaesthetic agents.     

Adequacy of caudal analgesia in children after penoscrotal and inguinal surgery using 0.5 or 1.0 ml·kg−1 bupivacaine 0.125%

To determine the optimal volume of bupivacaine 0.125% for postoperative caudal analgesia, we compared the effectiveness of 0.5 ml·kg^?1 and 1 ml·kg^?1 of bupivacaine 0.125% with 1:200,000 epinephrine in 80 children undergoing penoscrotal and inguinal surgery. The adequacy of caudal analgesia and supplemental analgesic requirements did not differ between the two groups at any time during the first 12 hr after surgery. We conclude that 0.5 ml·kg^?1 of bupivacaine 0.125% with 1:200,000 epinephrine is as effective as 1 ml·kg^?1 of the same solution and recommend its use for penoscrotal surgery. The evidence for ss of 0.5 ml·kg^?1 of bupivacaine 0.125% for inguinal owever, is inconclusive because of an insufficient patients studied.     

The relationship between age and morphine infusion rate in children

Aim: We performed a retrospective audit of intravenous morphine infusion administered to children in an effort to characterize the relationship between dose and age. Methods: A retrospective audit of morphine infusions was reviewed for a 24‐months period and included all children who received continuous intravenous nurse‐controlled morphine infusions and patient‐controlled analgesia; a population undergoing acute and elective surgical procedures, as well as medical and oncological treatments. The relationship between age and infusion rate was investigated using nonlinear mixed effects models. Results: There were 886 children whose data were acceptable for review. Morphine dose increased with age from 9.97 (CV 28%) μg·kg^?1 per h in neonates. The Hill equation with an exponential of 1.5 best described these changes. Morphine rate reached 90% of its mean final rate of 22.5 (CV 167%) μg·kg^?1 per h, observed in teenagers, at approximately 5 years of age. There was considerable uncertainty of this age–morphine rate profile, and the maturation half‐life of this profile was 20 months of age (CV 632%). An increase in dosing variability was observed with increasing age. Conclusions: Morphine infusions at steady‐state did not mirror clearance maturation in children nursed in our hospital. We suggest that initial infusion rates in children are started at 10 μg·kg^?1 per h in neonates, 15 μg·kg^?1 per h in toddlers and 25 μg·kg^?1 per h in children above the age of 5 years. The large variability associated with infusion rates means that subsequent infusion rates will depend on feedback from pain scores, adjuvant medications and adverse effects.     

Minimum local analgesic concentration of ropivacaine for intra‐operative caudal analgesia in pre‐school and school age children

We compared the minimum local analgesia concentration of ropivacaine for intra‐operative caudal analgesia in pre‐school and school age children. Fifty‐one boys, undergoing hypospadius repair surgery, were stratified into pre‐school or school age groups. After induction of anaesthesia, caudal block was performed with ropivacaine 1 ml.kg^?1 of the desired concentration. The first child in each group received ropivacaine 0.125%, and subsequent concentrations were determined by the analgesic response of the previous patient using Dixon’s up‐and‐down method. Under general anaesthesia with 0.7 minimum alveolar concentration of sevoflurane, the minimum local analgesia concentration of ropivacaine for intra‐operative caudal block was 34% greater in school age than in pre‐school age boys (0.143% (95% CI 0.132–0.157%) vs 0.107% (95% CI 0.089–0.122%), respectively; p < 0.001). This study indicates that a higher concentration of ropivacaine is needed for school age than pre‐school age children to provide intra‐operative caudal analgesia when combined with general anaesthesia.     

The effect of caudal vs intravenous morphine on early extubation and postoperative analgesic requirements for stage 2 and 3 single-ventricle palliation: a double blind randomized trial

Background: High‐dose single‐shot caudal morphine has been postulated to facilitate early extubation and to lower initial analgesic requirements after staged single‐ventricle (SV) palliation. Methods: With Institutional Review Board approval and written informed parental consent, 64 SV children aged 75–1667 days were randomized to pre‐incisional caudal morphine–bupivacaine (100 μg·kg^?1 morphine (concentration 0.1%), mixed with 0.25% bupivacaine with 1 : 200 000 epinephrine, total 1 ml·kg^?1) and postcardiopulmonary bypass (CPB) intravenous (IV) droperidol (75 μg·kg^?1) (‘active caudal group’) or pre‐incisional caudal saline (1 ml·kg^?1) and post‐CPB IV morphine (150 μg·kg^?1) with droperidol (75 μg·kg^?1) (‘active IV group’). Assignment remained concealed from families and the care teams throughout the trial. Early extubation failure rates (primary or reintubation within 24 h), time to first postoperative rescue morphine analgesia, and 12‐h postoperative morphine requirements were assessed for extubated patients. Results: Thirty‐one (12 stage 2) SV patients received caudal morphine and 32 (15 stage 2) received IV morphine. Extubation failure rates were 6/31 (19%) for caudal and 5/32 (16%) for IV morphine. For successfully extubated patients (n = 54), active caudal treatment significantly delayed the need for postoperative rescue morphine in stage 3 patients (P = 0.02) but not in stage 2 patients (P = 0.189) (Kaplan–Meier survival analysis with LogRank test). The reduction in 12‐h postoperative morphine requirements with active caudal treatment did not reach significance (P = 0.085) but morphine requirements were significantly higher for stage 2 compared with stage 3 patients (P < 0.001) (two‐way anova in n = 50 extubated patients). Conclusions: High‐dose caudal morphine with bupivacaine delayed the need for rescue morphine analgesia in stage 3 patients. All stage 2 patients required early rescue morphine and had significantly higher postoperative 12‐h morphine requirements than stage 3 patients. Early extubation is feasible for the majority of stage 2 and 3 SV patients regardless of analgesic regimen. The study was underpowered to assess differences in extubation failure rates.     

Ultrasound guidance characteristics and efficiency of suprazygomatic maxillary nerve blocks in infants: a descriptive prospective study

Background: Bilateral suprazygomatic maxillary nerve blocks approach improves pain relief after palate surgery. We report the feasibility and efficiency of ultrasound‐guided suprazygomatic maxillary nerve blocks in cleft palate repair in children. Methods: Twenty‐five children scheduled to undergo surgical cleft palate repair were included. Ultrasound‐guided suprazygomatic maxillary blocks were performed according to landmarks previously defined. The ultrasound probe was located optimally over the maxilla and under the zygomatic bone to visualize the pterygopalatine fossa. 0.15·ml·kg^?1 of 0.2% ropivacaine was injected bilaterally. Feasibility of block, spread of local anesthetic, pain scores and side effects were noted. Results: Fifty ultrasound‐guided suprazygomatic maxillary nerve blocks were performed in 25 children. The needle movement was seen in all cases using an out‐of‐plane approach. The spread of LA was clearly observed in 94% (47/50) of cases. A poor ultrasound imaging was found in 4% (2/50), and the spread of LA was not identified in 2% of case (1/50). The median time to perform the block was 56 s (35–120 s). The median pain scores and consumption of nalbuphine were low during the study period. 80% of patients did not require continuous opioid infusion. No complication related to maxillary blocks was reported. Conclusion: With a very low technical failure rate and a good clinical success rate, ultrasound appears to be a useful and simple tool to aid suprazygomatic maxillary nerve block in children.     

Clonidine does not improve quality of ropivacaine axillary brachial plexus block in children

Background: The addition of clonidine to peripheral nerve blocks is controversial in children. Objective: The aim of our study was to evaluate the effect of clonidine added to ropivacaine in pediatric axillary brachial plexus block (ABPB). Methods: Children aged 1–6 years, scheduled to undergo forearm or hand surgery, were recruited into this prospective, double‐blind controlled trial. Patients were randomly allocated to receive an ABPB either with ropivacaine 0.2% 0.4 ml·kg^?1 plus saline in 1 ml (RS) or ropivacaine 0.2% 0.4 ml·kg^?1 plus clonidine 1 μg·kg^?1 in 1 ml (RC). Primary endpoints were quality of postoperative analgesia as assessed by pain scores and total 24‐h postoperative analgesia requirements. Secondary outcomes were time to first analgesia request and duration of motor blockade. Results: Sixty patients were recruited (n = 30 per group) into the study. Pain scores were comparable throughout the first 24 h between the two groups. Ten children in the (RS) and six in (RC) groups required supplementary analgesia during the first 24 h (P = 0.24). Children who required further analgesia did so after 288 ± 94 min in the (RS) and 437 ± 204 min in the (RC) group (P = 0.06). There was no difference in the duration of motor block [186 ± 71 and 154 ± 56 min, P = 0.12 for (RS) and (RC), respectively]. Conclusion: Ropivacaine (0.2% 0.4 ml·kg^?1) for ABPB provides sufficient postoperative analgesia in children scheduled for forearm or hand surgery. The addition of clonidine to ABPB does not improve overall postoperative analgesia but may increase the time to first analgesia request.     

The effects of caudal or intravenous clonidine on postoperative analgesia produced by caudal levobupivacaine in children

Background: Clonidine is used increasingly in pediatric anesthesia practice to prolong the duration of action of caudal block with a local anesthetic agent. Which route of administration of clonidine is the most beneficial remains unknown. We compared the effects of caudal and intravenous clonidine on postoperative analgesia produced by caudal levobupivacaine. Methods: Sixty ASA I and II children, aged 2–8 undergoing inguinal hernia repair or orchidopexy surgery received standardized premedication with midazolam and general anesthesia. The children were randomized in a double‐blind fashion to three groups. Group L (n = 20) patients received 0.75 ml·kg^?1 of caudal 0.25% levobupivacaine and i.v. 5 ml saline, Group L‐Ccau (n = 20) patients received 0.75 ml·kg^?1 of caudal 0.25% levobupivacaine + 2 μg·kg^?1 clonidine and i.v. 5 ml saline, Group L‐Civ (n = 20) patients received 0.75 ml·kg^?1 of caudal 0.25% levobupivacaine and i.v. 2 μg·kg^?1 clonidine in 5 ml of saline. Mean arterial blood pressure, heart rate, peripheral oxygen saturation, and end‐tidal carbon dioxide values were recorded. Postoperative pain [Children and Infants Postoperative Pain Scale (CHIPPS) score], sedation (Ramsay Sedation Scale) and motor blockade (Modified Bromage Scale) were assessed at predetermined time points during the first 24 h after surgery. Results: Caudal clonidine significantly delayed the time to first rescue analgesic and fewer patients required rescue analgesia in the 24 h after surgery. No motor block was observed in any of the three groups on awakening or during the study period. In Group L‐Ccau, the CHIPPS score was lower than in Group L at all times through 240 min (P < 0.05), while the pain scores were lower in Group L‐Civ only at extubation and at 240 min (P < 0.05). Conclusions: Caudal clonidine prolongs the duration of analgesia produced by caudal levobupivacaine without causing significant side effects and this is because of a spinal mode of action.     

Effect of epidural clonidine on minimum local anesthetic concentration (ED50) of levobupivacaine for caudal block in children

Background: Clonidine has the potential to significantly prolong the duration of caudal epidural anesthesia. We investigated the effect of the addition of clonidine to the MLAC of levobupivacaine in a randomized controlled dose–response trial. Methods: A group of 120 children aged <6 years of age received caudal anesthesia with levobupivacaine and 1, 2, or 3 μg·kg^?1 of clonidine. The MLAC was determined according to a Dixon‐Massey protocol. The primary outcome was effective surgical anesthesia. Secondary outcomes were the duration of postoperative analgesia, postoperative pain scores, clonidine side effects, and time to hospital discharge. Results: The MLAC of caudal levobupivacaine was 0.106%, 0.077%, and 0.035% with 1, 2, and 3 μg·kg^?1 of clonidine, respectively. There were significant dose‐dependent increases in median duration of analgesia. The incidence of delayed discharge, somnolence, and PONV was significantly increased in the 3 μg·kg^?1 of clonidine group. Conclusions: Clonidine produces a local anesthetic sparing effect with a dose‐dependent decrease in levobupivacaine MLAC for caudal anesthesia. In addition, there is a dose‐dependent prolongation of postoperative analgesia following lower abdominal surgery in children. A dose of 2 μg·kg^?1 of clonidine provides the optimum balance between improved analgesia and minimal side effects.     

Changes of dorsalis pedis artery flow pattern after caudal block in children: observational study using a duplex sonography

Objective: To evaluate the changes of the flow velocity, the volume flow, and the diameter of dorsalis pedis artery using a duplex ultrasonography after caudal block with sevoflurane anesthesia in children. Aim: To know the acute change in peripheral arterial flow patterns of sympathetically blocked lower limbs in anesthetized children. Background: Caudal analgesia in combination with general anesthesia may affect the circulatory hemodynamics due to sympatholytic vasodilating effects. Methods: After approval by the Ethics Committee, we evaluated the changes of peripheral hemodynamics using a duplex ultrasonography before and after a caudal block in sevoflurane‐anesthetized children. Results: A caudal block using 0.15% ropivacaine 1.5 ml·kg^?1 significantly altered the arterial flow patterns; increased peak velocity (24%) and volume flow (76%), and the diameter of the dorsalis pedis artery (20%) in children. However, blood pressures and heart rates were not affected significantly by caudal block. Conclusions: Duplex sonographic measurements indicate that a caudal block changes the flow patterns of the dorsalis pedis artery significantly in the anesthetized children.     

Measuring circulating blood volume in newborn infants using pulse dye densitometry and indocyanine green

Background: Circulating blood volume (BV) is an important, but often unconsidered, variable in newborn infants undergoing intensive care. The data on validation and repeatability of BV measurement are limited. Aim: To validate and test the repeatability of measuring BV in newborn infants using indocyanine green (ICG) and pulse dye densitometry (PDD). Methods: Validation– Paired measurements of BV were made using the fetal hemoglobin (HbF) dilution and the PDD method. Repeatability– The BV was measured twice at an interval of 30–40 min in a second group of infants. Results: Validation– Data from three of 13 infants studied were excluded because of probe dislodgement or ICG injection error. The median (range) birth weight of the 10 infants whose data were analyzed was 1032 g (740–2384 g) and seven (70%) were receiving either mechanical ventilation or nasal CPAP. The median BV measured by HbF dilution was 66.2 ml·kg^?1 (43.7–81.0 ml·kg^?1) and by the PDD method was 68.9 ml·kg^?1 (49.3–101.0 ml·kg^?1). The mean difference was 5.92 ml·kg^?1 (sd 17.33 ml·kg^?1). Repeatability– Twelve infants were studied and three excluded because of probe dislodgement/motion artifact or ICG injection error. The median weight of the nine infants whose data were analyzed was 1208 g (795–2600 g). The median (range) BV1 and BV2 were 70.5 ml·kg^?1 (53.1–160 ml·kg^?1) and 87.5 ml·kg^?1 (38.0–248.0 ml·kg^?1), respectively. Mean difference of the two BV estimates (BV1–BV2) was ?24.6 ml·kg^?1 (sd 33.3 ml·kg^?1) and coefficient of repeatability was 66.5 ml·kg^?1. Conclusion: Pulse dye densitometry can be used to measure BV in the newborn infant at the cotside but the repeatability measurements suggest that its use is limited.     

Surgical outcome in children undergoing hypospadias repair under caudal epidural vs penile block

Aim and Objective: To evaluate the effect of penile block vs caudal epidural on the quality of analgesia and surgical outcome following hypospadias repair. Background: Intraoperative penile engorgement because of caudal epidural may result in tension on surgical sutures and alter surgical outcome. Methods: Fifty‐four ASA I and II children were randomly allocated to group P (penile block, 0.25% bupivacaine, 0.5 mg·kg^?1; n = 27) and group C (caudal epidural, 0.25% bupivacaine, 0.5 ml·kg^?1; n = 27), respectively. Quality of analgesia was assessed by visual analog scale (VAS) score recorded at 0, 0.5, 3, 6, 12, 24 h, and once a day for the next 4 days. Duration of analgesia was calculated from the institution of block to the first analgesic demand by child or VAS > 5. Total morphine consumption in the first 48 h and oral paracetamol consumption till 5th day were recorded. Children were regularly followed up in their respective outpatient clinic for early or late complications. Results: In group P, lower mean VAS scores were seen from 0.5 h after surgery till day 3 and analgesia lasted for significantly longer duration (82 min) when compared with caudal epidural, P < 0.001. Incidence of urethral fistula formation after primary hypospadias repair was 19.2%, and all had received caudal epidural. An increase of 27% in penile volume from baseline value was observed 10 min after caudal epidural placement, P < 0.05. Conclusion: Penile block provided better analgesia when compared with caudal epidural in children undergoing primary hypospadias repair. Postoperative urethral fistula formation was more likely in children who received caudal epidural.     

Impact of propofol on electrocardiographic alterations during intravascular application of bupivacaine--a study in piglets

Background: Intravascular application of a small dose of local anesthetics (LA) with epinephrine as well as larger doses of LA under sevoflurane anesthesia results in increase in T‐wave amplitude in the electrocardiogram (ECG). The aim of this study was to elucidate whether propofol anesthesia affects these ECG alterations or not. Methods: Thirty neonatal pigs were randomized into two groups. Group 1 was anesthetized with sevoflurane, group 2 with sevoflurane plus continuous propofol infusion (10 mg·kg^?1·h^?1). A test dose of 0.2 ml·kg^?1 bupivacaine 0.125% + epinephrine 1 : 200 000 was injected intravenously. Arterial pressure was monitored. ECG was analyzed for changes in T‐wave amplitude (positive if ≥25% baseline) and heart rate. In another setting, bupivacaine 0.125% was intravenous infused at a rate of 4 mg·kg^?1·min^?1. ECG was analyzed for alteration in T‐wave amplitude and heart rate at 1.25, 2.5, and 5 mg·kg^?1 bupivacaine infused. Results: T‐wave elevation after the administration of an epinephrine containing LA test dose was similar between the two groups. Increase in heart rate caused by the test dose were significantly higher in group 2 (P = 0.008). During continuous bupivacaine administration, T‐wave elevation occurred in 40% and 71% (group 1 and 2) at 1.25 mg·kg^?1, in 80% and 100% at 2.5 mg·kg^?1, and in 93% and 86% at 5 mg·kg^?1 bupivacaine infused. Conclusion: Continuous propofol infusion does not suppress the ECG signs of a systemically administered epinephrine containing LA test dose nor does it suppress the ECG signs caused by high doses of intravenous applied bupivacaine.     

The hemodynamic effects of newborn caudal anesthesia assessed by transthoracic echocardiography: a randomized, double-blind, controlled study

Background: Caudal anesthesia has been increasingly used in abdominal, urinary tract, and lower extremity surgery of infants. However, little was known about the hemodynamic effects of caudal anesthesia in them, especially in neonates. The purpose of this prospective study was designed to investigate the hemodynamic alterations by transthoracic echocardiography in newborn baby after caudal anesthesia with plain Bupivacaine or with epinephrine added Bupivacaine. Methods: Thirty full‐term newborn infants scheduled for lower abdominal or urinary tract surgery were randomly allocated into three groups (n = 10 each) as follows: (i) GA group: general anesthesia with sevoflurane; (ii) GA+CP group: GA with sevoflurane, combined with caudal anesthesia of plain Bupivacaine (1.25 ml·kg^?1 of 0.2%); (iii) GA+CA group: sevoflurane GA combined with caudal anesthesia of epinephrine‐added Bupivacaine (1.25 ml·kg^?1 of 0.2% Bupivacaine plus 1/200 000 epinephrine). Cardiac output (CO), arterial blood pressure, and heart rate were measured before (T‐5) and 5(T5), 10(T10), 15(T15) min after performance of caudal anesthesia. Results: In GA group, no significant hemodynamic alteration was observed in comparison with T‐5, except HR, which decreased by 7% at T15; In GA+CP group, compared with T‐5, HR decreased significantly at T5, T10 and T15, respectively, by 6%, 7% and 10%. And also CO decreased significantly at T15 by 8% compared with T‐5; In GA+CA group, no significant hemodynamic alteration was observed expect diastolic arterial blood, which decreased significantly at T15 by 10% compared with T‐5; At T15, the larger decrease of systolic arterial blood in GA+CP group and GA+CA group vs (GA) group (P < 0.05). Conclusions: The study shows the stability of hemodynamic variables during caudal anesthesia with Bupivacaine and with epinephrine‐added Bupivacaine in newborn infants.     

Resuscitation strategies from bupivacaine-induced cardiac arrest

Objectives: Local anesthetic (LA) intoxication with cardiovascular arrest is a potential fatal complication of regional anesthesia. Lipid resuscitation has been recommended for the treatment of LA‐induced cardiac arrest. Aim of the study was to compare four different rescue regimens using epinephrine and/or lipid emulsion and vasopressin to treat cardiac arrest caused by bupivacaine intoxication. Methods: Twenty‐eight piglets were randomized into four groups (4 × 7), anesthetized with sevoflurane, intubated, and ventilated. Bupivacaine was infused with a syringe driver via central venous catheter at a rate of 1 mg·kg^?1·min^?1 until circulatory arrest. Bupivacaine infusion and sevoflurane were then stopped, chest compression was started, and the pigs were ventilated with 100% oxygen. After 1 min, epinephrine 10 μg·kg^?1 (group 1), Intralipid^® 20% 4 ml·kg^?1 (group 2), epinephrine 10 μg·kg^?1 + Intralipid^® 4 ml·kg^?1 (group 3) or 2 IU vasopressin + Intralipid^® 4 ml·kg^?1 (group 4) were administered. Secondary epinephrine doses were given after 5 min if required. Results: Survival was 71%, 29%, 86%, and 57% in groups 1, 2, 3, and 4. Return of spontaneous circulation was regained only by initial administration of epinephrine alone or in combination with Intralipid^®. Piglets receiving the combination therapy survived without further epinephrine support. In contrast, in groups 2 and 4, return of spontaneous circulation was only achieved after secondary epinephrine rescue. Conclusions: In cardiac arrest caused by bupivacaine intoxication, first‐line rescue with epinephrine and epinephrine + Intralipid^® was more effective with regard to survival than Intralipid^® alone and vasopressin + Intralipid^® in this pig model.     

A novel isotonic balanced electrolyte solution with 1% glucose for intraoperative fluid therapy in neonates: results of a prospective multicentre observational postauthorisation safety study (PASS)

Background: Neonates have a higher metabolic rate and an increased risk of perioperative hypoglycemia and lipolysis, but during anesthesia, both oxygen consumption and metabolic rate are decreased, and this may lead to reduced intraoperative glucose requirements. Objective: The objective of this prospective multicentre observational postauthorisation safety study was to evaluate the intraoperative use of a novel isotonic balanced electrolyte solution with a low glucose concentration of 1% (BS‐G1) in neonates with a particular focus on changes in acid‐base, electrolyte, and glucose concentrations. Methods: Following the local ethics committee approval, neonates with a postmenstrual age under 45 weeks and an ASA risk score of I–IV undergoing intraoperative administration of BS‐G1 were enrolled. Patient demographics, the performed procedure, adverse drug reactions, hemodynamic data, and the results of blood gas analysis before and after infusion were documented with a focus on changes in acid‐base, electrolyte, and glucose concentrations. Results: In 66 neonates (ASA I–IV; postmenstrual age 38 ± 4, range 25–45 weeks; body weight 2.9 ± 0.9, range 0.65–4.6 kg), the mean infusion rate was 10.4 ± 3.2 (range 4.5–19.6) ml·kg^?1·h^?1 BS‐G1. During the infusion, hemoglobin, hematocrit, bicarbonate, base excess, anion gap, strong ion difference, and calcium decreased, and chloride and glucose increased significantly within the physiological range. All other measured parameters including sodium and lactate remained stable. Neither hypoglycemia (glucose < 3 mm ) nor hyperglycemia (glucose > 10 mm ) was documented after BS‐G1 infusion. No adverse drug reactions were reported. Conclusion: The study shows that the intraoperative use of an isotonic balanced electrolyte solution with 1% glucose and a mean infusion rate of 10 ml·kg^?1·h^?1 helps to avoid acid‐base dysbalance, hyponatraemia, hypoglycemia, ketoacidosis, and hyperglycemia in surgical neonates. A careful intraoperative monitoring and adaptation of the infusion rate as needed is crucial because the glucose and fluid requirements may vary widely between subjects.     

Comparison of epinephrine vs lipid rescue to treat severe local anesthetic toxicity – an experimental study in piglets

Objectives: Local anesthetic (LA) intoxication with severe hemodynamic compromise is a potential catastrophic event. Lipid resuscitation has been recommended for the treatment of LA‐induced cardiac arrest. However, there are no data about effectiveness of Intralipid^® for the treatment of severe cardiovascular compromise prior to cardiac arrest. Aim of this study was to compare effectiveness of epinephrine and Intralipid^® for the treatment of severe hemodynamic compromise owing to bupivacaine intoxication. Methods: Piglets were anesthetized with sevoflurane, intubated, and ventilated. Bupivacaine was infused with a syringe driver via a central venous catheter at a rate of 1 mg·kg^?1·min^?1 until invasively measured mean arterial pressure (MAP) dropped to 50% of the initial value. Bupivacaine infusion was then stopped, and epinephrine 3 μg·kg^?1 (group 1), Intralipid^® 20% 2 ml·kg^?1 (group 2), or Intralipid^® 20% 4 ml·kg^?1 (group 3) was immediately administered. Survival, hemodynamic course, and ET_CO2 were recorded. Results: Twenty‐one piglets (3 × 7), with median age of 26 days (19–43) and weighing 4.9 kg (4.3–5.8), were investigated. All animals in group 1 (100%) but only four of seven (57%) piglets in group 2 and group 3, respectively, survived. Normalization of hemodynamic parameters (HR, MAP) and ET_CO2 was fastest in group 1 with all piglets achieving HR and MAP values at or above baseline within 1 min. Conclusion: For the treatment of severe hemodynamic compromise owing to bupivacaine intoxication in piglets, first‐line rescue with epinephrine was more effective than Intralipid^® with regard to survival as well as normalization of hemodynamic parameters and ET_CO2.