Margot Semsroth

The dose-response of caudal ropivacaine in children.

BACKGROUND Ropivacaine, a new local anesthetic, is less cardiotoxic in adults and is less likely to cause motor blockade than is bupivacaine. The authors evaluated the clinical effectiveness and hemodynamic effects of ropivacaine compared with bupivacaine and the pharmacokinetics of ropivacaine when given for caudal blocks in 56 children 4.1 +/- 1.2 yr old (mean +/- SD). METHODS Patients scheduled for inguinal hernia repair were randomly given a caudal injection (0.75 ml/kg) of ropivacaine, 0.25% (R0.25 group); ropivacaine, 0.5% (R0.5 group); or bupivacaine, 0.25% (B0.25 group). Postoperative measurements included the duration of analgesia, which was our primary outcome variable, and hemodynamic and respiratory monitoring for 4 h in the recovery room. Thereafter, analgesic requirements for the following 24 h were assessed by an independent observer on the ward using an observational pain-discomfort scale, which gives a cumulative score from 5 to 15 to estimate the quality of analgesia by assessment of behavioral objective parameters. Plasma levels of ropivacaine were measured before the procedure was started and 5, 10, 15, 20, 25, 30, and 45 min and 1, 2, 4, 6, 8, and 24 h after caudal block. RESULTS A significantly longer (P < 0.0001) duration of analgesia (median [range]) was observed in the R0.5 group (1,440 [335-1,440] min), whereas the R0.25 group (208 [175-340] min) and the B0.25 group (220 [100-390] min) were comparable. All groups showed a significant decrease in mean arterial blood pressure and heart rate from baseline values, but differences between groups were not observed. CONCLUSION Ropivacaine is well tolerated and provides effective analgesia when given for caudal blockade in small children for inguinal hernia repair.

The Efficacy and Safety of a Clonidine/bupivacaine Combination in Caudal Blockade for Pediatric Hernia Repair

We evaluated the analgesic efficacy and hemodynamic and respiratory safety of clonidine when added to bupivacaine for caudal blocks in 58 children aged 38 +/-2 mo (mean +/- SEM). Patients scheduled for ambulatory hernia repair were randomly given a caudal injection (0.75 mL/kg) of either saline placebo (P group), bupivacaine, 0.25% (B group), bupivacaine plus epinephrine 1:200,000 (BE group), bupivacaine plus clonidine 1 micro g/kg (BC1 group), or bupivacaine plus clonidine 2 micro g/kg (BC2 group). Postoperative measurements included duration of analgesia, hemodynamics, and respiratory monitoring for 6 h. Thereafter, parents assessed their childs analgesic requirements at home every 3 h for 18 h. The duration of analgesia (median [range]) was significantly longer (P < 0.05) in the BC1 and BC2 groups (360 [270-360] min and 360 [355-360] min, respectively) compared with the P (77[45-190]), B (346[105-360]), or BE group (300[75-360]). Similarly, the BC1 and BC2 groups required less additional analgesic within the first 24 h. All groups showed a significant decrease in mean arterial pressure compared with baseline values, but the differences among the groups were not significant. Bradycardia and respiratory depression were not observed. Clonidine 1 and 2 micro g/kg can be safely added to bupivacaine caudal blockade in small children for ambulatory hernia repair to achieve an increased duration of analgesia compared with bupivacaine alone or bupivacaine plus epinephrine. Implications: The addition of clonidine, an antihypertensive drug with analgesic properties, to local anesthetics in caudal blocks prolongs postoperative pain relief and reduces the need for additional pain treatment in children after hernia operation.

Caudal clonidine prolongs analgesia from caudal S(+)-ketamine in children

We performed a prospective randomized double-blinded study to test preservative-free S(+)-ketamine alone or in combination with clonidine for intra- and postoperative caudal blockade in pediatric surgery over a 24-h period. Fifty-three children (1–72 mo) scheduled for inguinal hernia repair were caudally injected with either S(+)-ketamine 1 mg/kg alone (Group K) or with additional clonidine (Group C1 = 1 &mgr;g/kg; Group C2 = 2 &mgr;g/kg) during sevoflurane anesthesia via a laryngeal mask. Intraoperative monitoring included heart rate, blood pressure, and pulse oximetry; postoperative monitoring included a pain discomfort scale and a sedation score. No additional analgesic drugs were required during surgery. The mean duration of postoperative analgesia was 13.3 ± 9.2 h in Group K, 22.7 ± 3.5 h in Group C1, and 21.8 ± 5.2 h in Group C2 (P < 0.0001, Group K versus other groups). Groups C1 and C2 received significantly fewer analgesics in the postoperative period than Group K (15% and 18% vs 63%;P < 0.01). The three groups had similar postoperative sedation scores. We conclude that the combination of S(+)-ketamine 1 mg/kg with clonidine 1 or 2 &mgr;g/kg for caudal blockade in children provides excellent analgesia without side effects over a 24-h period.

Analgesic Effects of Caudal and Intramuscular S (+)-Ketamine in Children

BackgroundPrevious studies suggest that caudal administration of ketamine cause effective analgesia. The purpose of the current study was to compare the clinical effectiveness and plasma concentrations of S(+)-ketamine after caudal or intramuscular administration in children to distinguish between local and systemic analgesia. MethodsAfter induction of general anesthesia, 42 patients, aged 1 to 7 yr, scheduled to undergo inguinal hernia repair randomly received a caudal (caudal group) or intramuscular (intramuscular group) injection of 1 mg/kg S (+)-ketamine. Intraoperatively, heart rate (HR), mean arterial pressure (MAP) and arterial oxygen saturation were measured. Postoperative measurements included duration of analgesia, a four-point sedation score, and hemodynamic and respiratory monitoring for 6 h in the recovery room. Analgesic requirements in the recovery room were assessed by an independent blinded observer using an observational pain/discomfort scale (OPS). Plasma samples for determination of ketamine concentrations were obtained before and 10, 20, 30, 45, 60, 90, 120, and 180 min after injection of S (+)-ketamine. ResultsA significantly longer duration of analgesia (P < 0.001) was observed after caudal administration (528 min [220–1,440 min]; median [range]) when compared with intramuscular administration (108 min [62–1,440 min]) of S (+)-ketamine. Plasma levels of ketamine were significantly lower from 10 to 45 min after caudal administration than after intramuscular injection. ConclusionCaudal S (+)-ketamine provides good intra- and postoperative analgesia in children. Despite similar plasma concentrations during most of the postoperative observation period, caudal S (+)-ketamine provided more effective analgesia than did intramuscular S (+)-ketamine, indicating a local analgesic effect.

Incidence and therapy of midazolam induced hiccups in paediatric anaesthesia.

A prospective, randomized and double blind study was undertaken to determine the incidence and a possible dose‐ or age‐dependence of hiccups in children premedicated with rectal midazolam and to investigate the treatment of hiccups by intranasal ethyl chloride spray application. Two hundred ASA physical status 1 and 2 children, weighing 3.0 to 15.0 kg, scheduled for minor surgery, were randomly assigned to be given either 0.5 mg·kg−1 midazolam(n=100) or 1.0 mg·kg−1 midazolam (n=100) administered rectally. If hiccups were observed during a period of 20 min after premedication with midazolam, these children were treated after 3 min of hiccups with two short intranasal applications of ethyl chloride spray. Hiccups occurred in 22% of children in the 0.5 mg·kg−1 group and 26% in the 1.0 mg·kg−1 group (n.s.). The intranasal application with ethyl chloride was successful in 100% in both groups. The mean age levels between children with or without hiccups were 5±9 months vs 21±19 months (P<0.01) in the 0.5 mg·kg−1 group and 6±7 months vs 20±14 months (P<0.01) in the 1.0 mg·kg−1 group. Intranasal application of ethyl chloride spray seems to be an effective therapy for midazolam induced hiccups in paediatric anaesthesia. The incidence of these hiccups is highly age significant, but not dose dependent.

Cardiovascular criteria for epidural test dosing in sevoflurane- and halothane-anesthetized children.

This study was designed to determine the detectability of a simulated IV test dose in children during administration of general anesthesia by using heart rate (HR), systolic blood pressure (SBP), and T wave criterion. Forty-two children (0.5–8 yr old) received an IV injection containing epinephrine 0.5 &mgr;g/kg and another IV injection containing saline during either halothane or sevoflurane anesthesia administration at 1.0 minimum alveolar concentration in nitrous oxide. A positive test response was defined as a change in T wave amplitude ≥25%, SBP increase ≥15 mm Hg, and HR increase ≥10 bpm. By using the T wave, SBP, and HR criteria, a positive response rate to epinephrine was 100%, 95%, and 71%, respectively, during sevoflurane, and 90%, 71%, and 71%, respectively, during halothane anesthesia administration. These data suggest that the T wave criterion is superior to conventional hemodynamic criteria, and that sevoflurane attenuates T wave and SBP responses less than halothane; however, chronotropic responses are similar to halothane. Implications: We found a greater reliability of the T wave criterion over conventional hemodynamic criteria for detecting intravascular injection of a simulated epidural test dose. Sevoflurane may increase the likelihood of recognition of an accidental intravascular injection of epinephrine-containing solutions in clinical practice compared with halothane.

Simulation of an epidural test dose with intravenous isoproterenol in awake and in halothane-anesthetized children.

Background An epidural test dose containing epinephrine does not reliably produce hemodynamic responses in children under halothane anesthesia. The purpose of this study was to determine hemodynamic responses to intravenous isoproterenol in both awake and halothane‐anesthetized children. Methods After obtaining institutional review board approval and parental informed consent, 72 ASA physical status 1 or 2 children (2.8 +/‐1.7 yr) undergoing elective minor surgery were studied before and during anesthesia with 1.2 minimum alveolar concentration halothane. A bolus containing 0.25 mg/kg bupivacaine and 0.05 micro gram/kg, 0.075 micro gram/kg, or 0.1 micro gram/kg isoproterenol, or bupivacaine and saline was injected via a peripheral arm vein to simulate intravascular injection of an epidural test dose. Results Before induction of anesthesia, all patients showed a positive test response after isoproterenol injection (heart rate increase greater or equal to 20 beats/min). During anesthesia, 79% of patients receiving 0.05 micro gram/kg, 89% of patients receiving 0.075 micro gram/kg, and 100% of patients receiving 0.1 micro gram/kg met the criterion of a positive test response. Among each treatment group, all infants showed a positive test response. Blood pressure did not differ among the groups at any time. Transient benign dysrhythmias occurred in only one patient under halothane anesthesia receiving 0.075 micro gram/kg isoproterenol. Conclusion Isoproterenol at a dose of 0.1 micro gram/kg is a sensitive indicator for intravascular injection of a test dose in children anesthetized with halothane and nitrous oxide. Isoproterenol at a dose of 0.05 micro gram/kg approximates a minimal effective dose in awake children and in infants. After detailed studies on neural toxicity, isoproterenol could be of value as an epidural test agent in children.

S(+)-ketamine for rectal premedication in children.

Our purpose for this prospective, randomized, and double-blinded study was to evaluate the anesthetic efficacy of S(+)-ketamine, an enantiomer of racemic ketamine, compared with a combination of S(+)-ketamine and midazolam, and plain midazolam for rectal premedication in pediatric anesthesia. Sixty-two children, ASA physical status I and II, scheduled for minor surgery, were randomly assigned to be given rectally one of the following: 1.5 mg/kg preservative-free S(+)-ketamine, a combination of 0.75 mg/kg preservative-free S(+)-ketamine and 0.75 mg/kg midazolam, or 0.75 mg/kg midazolam. Preoperative anesthetic efficacy was graded during a period of 20 min by using a five-point scale from 1 = awake to 5 = asleep. Tolerance during anesthesia induction via face mask was graded by using a four-point scale from 1 = very good to 4 = bad. A sufficient anesthetic level (≥3) after rectal premedication was reached in 86% in midazolam/S(+)-ketamine premedicated children, in 75% in midazolam premedicated children, but only in 30% in S(+)-ketamine premedicated children (P < 0.05 S(+)-ketamine versus midazolam/S(+)-ketamine and midazolam groups). The incidence of side effects after rectal premedication was rare. Whereas the mask acceptance score was comparable in the three study groups, a 25% rate of complications during anesthesia induction via face was observed in the S(+)-ketamine study group (P < 0.05 versus other study groups). Our conclusions are that S(+)-ketamine for rectal premedication in the dose we chose shows a poor anesthetic effect and a frequent incidence of side effects during induction of anesthesia via face mask compared with the combination of midazolam/S(+)-ketamine and plain midazolam. Dose-response studies of S(+)-ketamine for rectal premedication in pediatric anesthesia may be warranted. IMPLICATIONS In contrast to racemic ketamine, neither plain S(+)-ketamine (1.5 mg/kg) nor the addition of S(+)-ketamine (0.75 mg/kg) with midazolam shows advantages compared with plain midazolam for rectal premedication in children for anesthetic potencies or facilitation of induction of anesthesia via face mask.

Effective pain relief with continuous intrapleural bupivacaine after thoracotomy in infants and children

The effect of continuous intrapleural bupivacaine on pain relief after lateral thoracotomy was studied in nine infants (≤ 15 kg body weight) and 11 children (> 15 kg body weight). An intrapleural catheter was inserted under direct vision during surgery. After extubation, the patients were transferred to the ICU where vital signs and pain scores were monitored. An intrapleural infusion of bupivacaine 0.25% with adrenaline was given at a loading dose of 0.625 mg˙kg−1 body weight followed by a continuous infusion with a starting rate of 1.25 mg˙kg−1˙h−1. Haemodynamic and respiratory parameters did not differ significantly from control values throughout the study period in either group. The mean infusion rate could be reduced stepwise in both groups to 0.75 ± 0.32 mg˙kg−1˙h−1 and 0.73 ± 0.38 mg˙kg−1˙h−1 respectively. The pain score indicated a rapid onset of analgesia in both groups and remained low during the study period. The degree of analgesia amongst other factors was position dependent. The lack of any recognizable side effects or complications related to this method has been most encouraging. Only one child required a supplementary dose of an opioid. We conclude that continuous intrapleural access has proved to be a safe and suitable route for pain relief in infants and children following thoracotomy.

Simulation of an epidural test dose with intravenous isoproterenol in sevoflurane- and halothane-anesthetized children.

Isoproterenol has been suggested as an alternative marker for epidural test dosing in children receiving halothane anesthesia.The purpose of this prospective, randomized, double-blind study was to determine the chronotropic response to IV isoproterenol in sevoflurane-anesthetized children. Thirty-six ASA physical status I children (0.5-8 yr) were anesthetized with either halothane or sevoflurane at 1 minimum alveolar anesthetic concentration adjusted for age in 70% nitrous oxide. Patients received incremental IV injections of isoproterenol until their heart rate increased >or=to20 bpm above baseline. The minimal effective dose of isoproterenol required to produce an increase of >or=to20 bpm was 55 ng/kg (42-72 ng/kg; 95% confidence interval) in sevoflurane-anesthetized children and 32 ng/kg (26-38 ng/kg; 95% confidence interval) in halothane-anesthetized children (P < 0.05). This dose-response study suggests that sevoflurane antagonizes beta-adrenergic-mediated chronotropic responses to isoproterenol more than halothane. These observations also suggest that larger doses of isoproterenol will be necessary for epidural test dosing in children receiving sevoflurane rather than halothane anesthesia. Implications: Isoproterenol has been suggested as an alternative marker for epidural test dosing in children receiving halothane anesthesia. This isoproterenol dose-response study indicates that larger doses of isoproterenol will be necessary for epidural test dosing in children undergoing sevoflurane rather than halothane anesthesia. (Anesth Analg 1998;87:549-52)