Peter A. Stoddart

Reversal of Rocuronium-induced Neuromuscular Blockade with Sugammadex in Pediatric and Adult Surgical Patients

Background:Sugammadex reverses neuromuscular blockade by chemical encapsulation of rocuronium. This phase IIIA study explored efficacy and safety of sugammadex in infants (28 days to 23 months), children (2–11 yr), adolescents (12–17 yr), and adults (18–65 yr). Methods:Anesthetized patients (American Society of Anesthesiologists class 1–2) received 0.6 mg/kg rocuronium and were randomized to receive sugammadex (0.5, 1.0, 2.0, or 4.0 mg/kg) or placebo at reappearance of T2. Neuromuscular monitoring was performed using acceleromyography. Primary endpoint was time from sugammadex/placebo administration to recovery of the train-of-four ratio to 0.9. Adverse events and electrocardiograms were recorded, and blood samples were collected for safety and determination of sugammadex and rocuronium plasma concentrations. Results:A dose-response relation was demonstrated in children (n = 22), adolescents (n = 28), and adults (n = 26), but not infants because of the small sample size (n = 8). After placebo, median recovery time of train-of-four to 0.9 was 21.0, 19.0, 23.4, and 28.5 min in infants, children, adolescents, and adults, respectively. After 2.0 mg/kg sugammadex train-of-four 0.9 was attained in 0.6, 1.2, 1.1, and 1.2 min, respectively. The sugammadex plasma concentrations were similar for the children, adolescent, and adult age groups across the dose range. Sugammadex was well tolerated: No reoccurrence of blockade, inadequate reversal, significant QT prolongation, or other abnormalities were observed. Conclusions:Sugammadex is a new reversal agent that rapidly, effectively, safely, and with similar recovery times reverses rocuronium-induced neuromuscular blockade in children, adolescents, adults, and the small number of infants studied.

A critique of elective pediatric supraglottic airway devices

In 1988, when the Laryngeal Mask Airway‐Classic™ (Intavent Orthofix, Maidenhead, UK), was introduced there were only two choices of airway management: tracheal tube or facemask. The supraglottic airway, as we now understand the term, did not exist. Yet, 20 years later, we are faced with an ever increasing choice of supraglottic airway devices (SAD). For many SADs, with the exception of the LMA‐ClassicTM and LMA‐ProsealTM (Intavent Orthofix, Maidenhead, UK), there is a lack of high quality data of efficacy. The best evidence requires a randomized controlled trial comparing a new device against an established alternative, properly powered to detect clinically relevant differences in clinically important outcomes. Such studies in children are very rare. Safety data is even harder to establish particularly for rare events such as aspiration. Therefore, most safety data comes from extended use rather than high quality evidence which inevitably biases against newer devices. For reason of these factors, claims of efficacy and particularly safety must be interpreted cautiously. This narrative review aims to present the evidence surrounding the use of currently available pediatric SADs in routine anesthetic practice.

Efficacy, safety, and pharmacokinetics of levobupivacaine with and without fentanyl after continuous epidural infusion in children a multicenter trial

Background Levobupivacaine, the levo-enantiomer of bupivacaine, is as potent as bupivacaine but less toxic. Therefore, the authors investigated the efficacy, safety, and pharmacokinetics of perioperative epidural levobupivacaine with and without fentanyl in children. Methods After Research Ethics Board approval and informed written consent, 120 healthy children aged 6 months to 12 yr who were scheduled to undergo urologic or abdominal surgery were randomized in a double-blinded and concealed manner to receive one of four epidural solutions as a continuous infusion for 24 h: 0.125% levobupivacaine; 0.0625% levobupivacaine; 1 &mgr;g/ml fentanyl; or the combination, 0.0625 levobupivacaine and 1 &mgr;g/ml fentanyl. After induction of anesthesia and tracheal intubation, a lumbar epidural catheter was sited, a loading dose was administered (0.75 ml/kg levobupivacaine, 0.175%), and the epidural infusion was commenced. The primary endpoint was the need for rescue analgesia (morphine) in the first 10 h after surgery. Pain, motor strength, and side effects were recorded for 24 h. Venous blood was collected from 18 children to determine the plasma concentrations of levobupivacaine and/or fentanyl before and 2, 4, 8, 16, 24, and 26 or 30 h after the start of the epidural infusion. Results Of the 114 children who were analyzed for intention to treat, a similar number of children in each group reached the 10-h mark. The time to the first dose of morphine in the first 10 h was less in the plain fentanyl group (P < 0.044). All other effects were similar among the four groups. The plasma concentration of levobupivacaine increased during the infusion period, reaching a maximum of 0.76 ± 0.11 &mgr;g/ml in the 0.125% group and 0.48 ± 0.12 &mgr;g/ml in the 0.0625% group by 24 h. The plasma concentration of fentanyl also increased steadily, reaching a maximum concentration of 0.37 ± 0.11 ng/ml by 24 h. Conclusion We conclude that 0.0625% levobupivacaine without fentanyl is an effective perioperative epidural solution in children when infused at a rate of 0.3 ml · kg−1 · h−1. The plasma concentrations of 0.125% and 0.0625% levobupivacaine and fentanyl (1 &mgr;g/ml) at the end of a 24-h infusion are low.

Apnea after Awake Regional and General Anesthesia in Infants: The General Anesthesia Compared to Spinal Anesthesia Study-Comparing Apnea and Neurodevelopmental Outcomes, a Randomized Controlled Trial

Background:Postoperative apnea is a complication in young infants. Awake regional anesthesia (RA) may reduce the risk; however, the evidence is weak. The General Anesthesia compared to Spinal anesthesia study is a randomized, controlled trial designed to assess the influence of general anesthesia (GA) on neurodevelopment. A secondary aim is to compare rates of apnea after anesthesia. Methods:Infants aged 60 weeks or younger, postmenstrual age scheduled for inguinal herniorrhaphy, were randomized to RA or GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born less than 26 weeks gestation. The primary outcome of this analysis was any observed apnea up to 12 h postoperatively. Apnea assessment was unblinded. Results:Three hundred sixty-three patients were assigned to RA and 359 to GA. Overall, the incidence of apnea (0 to 12 h) was similar between arms (3% in RA and 4% in GA arms; odds ratio [OR], 0.63; 95% CI, 0.31 to 1.30, P = 0.2133); however, the incidence of early apnea (0 to 30 min) was lower in the RA arm (1 vs. 3%; OR, 0.20; 95% CI, 0.05 to 0.91; P = 0.0367). The incidence of late apnea (30 min to 12 h) was 2% in both RA and GA arms (OR, 1.17; 95% CI, 0.41 to 3.33; P = 0.7688). The strongest predictor of apnea was prematurity (OR, 21.87; 95% CI, 4.38 to 109.24), and 96% of infants with apnea were premature. Conclusions:RA in infants undergoing inguinal herniorrhaphy reduces apnea in the early postoperative period. Cardiorespiratory monitoring should be used for all ex-premature infants.

Double-blind randomized placebo-controlled trial of the effect of ketamine on postoperative morphine consumption in children following appendicectomy

Background: Ketamine has an opioid sparing effect following surgery in adults. This study investigated whether a similar effect is seen following appendicectomy in paediatric patients.

Intravenous paracetamol overdose: two case reports and a change to national treatment guidelines.

Two cases of 10-fold accidental overdose with intravenous paracetamol are presented. Case 1: A 5-month-old child with intussusception received 90 mg/kg intravenous paracetamol over an 8 h period. She was not initially treated with an antidote and developed hepatic impairment. Case 2: A 6-month-old child received a single dose of 75 mg/kg intravenous paracetamol. The child was treated with N-acetylcysteine and remained well without hepatic impairment. Therapeutic errors such as 10-fold overdosing are relatively common in children. Case 1 demonstrates that intravenous paracetamol is a potentially dangerous drug. This should be taken into consideration when prescribing the intravenous formulation. The concentration–time nomogram used following oral paracetamol overdose should be used with caution following intravenous overdose. Significant overdose should be discussed with the National Poisons Information Service whose guidance suggests intervention with antidote following an overdose above 60 mg/kg.

A cohort evaluation of the pediatric ProSeal laryngeal mask airway in 100 children

but both groups in our study were in the flexed position therefore we considered that it will not have an impact on the results. Dr Garg’s most important comment is the probable engorgement effect of gravity on epidual veins that we missed to mention. We also agree with Dr Garg who states ‘it needs to be studied whether higher CSF pressures predominates over increased epidural vein engorgement or vice versa..’. The present literature regarding the effect of gravity on epidural veins reflect the results of adults. While our results show that 45 head up positioning is only effective in children younger than 12 month of age which may have more compliant tissues and spinal structures compared with older children or adults. The only present evidence in young children is by Molina and Fons (1) which show an increase in subarachnoid space width with the increase in hydrostatic pressure in neonates. They did not measure the changes in the epidural structures. Ours results suggest that further similar studies should also focus on young children who are prone to unsuccessful LPs. Another point to remind is that, bloody tap incidence was not our primary outcome measure therefore we are not sure that the power of the study is sufficient for evaluating this cause of LP failure. This aspect was mentioned in our article. Finally, it is our routine practice to insert spinal needles with cephalad orientation of the bevels including Atraucan needles therefore we cannot comment on its effects on spinal block properties. Ates Duman * Seza Apiliogullari† Cemile Oztin Ogun* *Department of Anaesthesia and Intensive Care, Medical Faculty, Selcuk University, Konya, Turkey †Department of Anaesthesia and Intensive Care, Dr Faruk Sukan Obstetrics and Children’s Hospital, Konya, Turkey (email: dumanates@yahoo.com)

Anesthesia for thymectomy in children with myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease with antibodies directed against the acetylcholine receptor at the neuromuscular junction (NMJ). Anesthetists have a special interest in myasthenia gravis because of its interaction with various anesthetic agents and because many myasthenics require a thymectomy to control their disease. Much has been written about the critical care management and anesthesia for adult myasthenic patients (1–6), but there is very little relating to modern pediatric anesthetic practice (7,8). In 1990, Brown et al. described the use of tubocurare and alcuronium in myasthenic children (7); neither of these drugs is currently available in the UK. This article discusses the anesthesia of children with autoimmune (or juvenile) myasthenia who present for thymectomy. However, it should be noted that the pediatric anesthetist may encounter two other forms of myasthenia gravis: neonatal myasthenia, a transient condition caused by the passage of antibodies from myasthenic mothers across the placenta and congenital myasthenia, a genetically inherited autosomal recessive disorder affecting the motor endplate (2,7,9,10). Neither of these conditions are associated with an abnormal thymus, so thymectomy is not indicated. We report three cases of thymectomy in children with juvenile myasthenia gravis and describe the clinical and physiological features of the disease. A discussion of the relevant pharmacology and the factors affecting anesthetic management is presented.

Predictors of Failure of Awake Regional Anesthesia for Neonatal Hernia Repair: Data from the General Anesthesia Compared to Spinal Anesthesia Study-Comparing Apnea and Neurodevelopmental Outcomes

Background:Awake regional anesthesia (RA) is a viable alternative to general anesthesia (GA) for infants undergoing lower abdominal surgery. Benefits include lower incidence of postoperative apnea and avoidance of anesthetic agents that may increase neuroapoptosis and worsen neurocognitive outcomes. The General Anesthesia compared to Spinal anesthesia study compares neurodevelopmental outcomes after awake RA or GA in otherwise healthy infants. The aim of the study is to describe success and failure rates of RA and report factors associated with failure. Methods:This was a nested cohort study within a prospective, randomized, controlled, observer-blind, equivalence trial. Seven hundred twenty-two infants 60 weeks or less postmenstrual age scheduled for herniorrhaphy under anesthesia were randomly assigned to receive RA (spinal, caudal epidural, or combined spinal caudal anesthetic) or GA with sevoflurane. The data of 339 infants, where spinal or combined spinal caudal anesthetic was attempted, were analyzed. Possible predictors of failure were assessed including patient factors, technique, experience of site and anesthetist, and type of local anesthetic. Results:RA was sufficient for the completion of surgery in 83.2% of patients. Spinal anesthesia was successful in 86.9% of cases and combined spinal caudal anesthetic in 76.1%. Thirty-four patients required conversion to GA, and an additional 23 patients (6.8%) required brief sedation. Bloody tap on the first attempt at lumbar puncture was the only risk factor significantly associated with block failure (odds ratio = 2.46). Conclusions:The failure rate of spinal anesthesia was low. Variability in application of combined spinal caudal anesthetic limited attempts to compare the success of this technique to spinal alone.

Pain management in 100 episodes of severe mucositis in children.

Objective:  We aimed to review the pain management in 100 episodes of severe mucositis in children and determine the incidence of associated side effects.