Carolyne J. Montgomery

Nonopioid additives to local anaesthetics for caudal blockade in children: a systematic review

Background:  Caudal epidural injection with local anaesthetics is a popular regional technique used in infants and children. A disadvantage of caudal blockade is the relatively short duration of postoperative analgesia. Opioids have traditionally been added to increase the duration of analgesia but have been associated with unacceptable side‐effects. A number of nonopioid additives have been suggested to increase the duration of analgesia.

Plasma concentrations after high-dose (45 mg · kg−1) rectal acetaminophen in children

Although the recommended dose of rectal acetaminophen (25–30 mg · kg−1) is twice that for oral administration (10–15 mg · kg−1), the literature justifies the use of a higher dose when acetaminophen is administered via the rectal route. We measured’ venous plasma acetaminophen concentrations resulting from 45 mg · kg−1 of rectal acetaminophen in ten ASA 1, 15 kg paediatric patients undergoing minor surgery with a standardized anaesthetic. After induction of anaesthesia, a single 650 mg suppository (Abenol®, SmithKline Beecham Pharma Inc.) was administered rectally. Plasma was sampled at t = 0, 15, 30, 45, 60, 90, 120, 180, 240 min in the first five patients and at t = 0, 30, 60, 90, 120, 180, 240, 300, 420 min in the subsequent five. Acetaminophen plasma concentrations were determined’ using a TDxFLx® fluorescence polarization immunoassay (Abbott Laboratories, Toronto, Ontario). The maximum plasma concentration was 88 ± 39 μmol · L−1 (13 ± 6 μg · ml−1) and the time of peak plasma concentration was 198 ± 70 min (mean ± SD). At 420 min, the mean plasma concentration was 46 ± 18 μmol · L−1 (7.0 ± 0.9 μg · ml−1). No plasma concentrations associated with toxicity (> 800 μmol · L−1) were identified. A 45 mg · kg−1 rectal dose of acetaminophen resulted in peak plasma concentrations comparable with those resulting from 10–15 mg · kg−1 of oral acetaminophen at three hours after suppository insertion. It is concluded that the delayed and erratic absorption of acetaminophen after rectal administration leads to unpredictable plasma concentrations. Rectal acetaminophen will not be consistently effective for providing rapid onset of analgesia in children.RésuméLa dose rectale d’acétaminophène conseillée (25–30 mg · kg−1) est le double de la dose orale (10–15 mg · kg−1); les publications confirment la pertinence de cette dose lorsque l’acétaminophène est administré par la voie rectale. Les auteurs ont mesuré la concentration plasmatique veineuse de l’acétaminophène 45 mg · kg−1 administré chez dix enfants ASA 1 de 15 kg soumis à une chirurgie mineure sous anesthésie standardisée. Après l’induction de l’anesthésie, un suppositoire de 650 mg d’acétaminophène (Abenol®, SmithKline Beecham Pharmacologique Inc.) est administré par la voie rectale. Le plasma est analysé au t = 0, 15, 30, 45, 60, 90, 120, 240 min chez les cinq premiers patients et au t = 30, 60, 90, 120, 180, 240, 300, 360, 420 min chez les cinq patients suivants. Les concentrations plasmatiques d’acétaminophène sont mesurées au moyen de l’épreuve d’immunofluorescence par polarisation TDxFLx® (Laboratoires Abbott, Toronto, Ontario). La concentration plasmatique maximale est de 88 ± 39 (13 ± 6 μg · ml−1) et elle survient à 198 ± 70 min (moyenne ± ET). A 420 min, la concentration plasmatique moyenne est de 46 ± 18 μmol · L−1 (7,0 ± 0,9 μg · ml−1). Aucune concentration plasmatique ne peut être associée au niveau toxique (> 800 μmol · L−1). La dose rectale de 45 mg · kg−1 d’acétaminop`ene produit des concentrations plasmatiques comparables à celles de la dose orale de 10–15 mg · kg−1 trois heures après l’insertion du suppositoire. Les auteurs concluent que l’absorption retardée et irrégulière de l’acétaminophène rectal entraîne des concentrations plasmatiques imprévisibles. L’acétaminophène rectal ne procure pas toujours un analgésie rectale efficace et rapide chez les enfants.

Postoperative pain expression in preschool children : Validation of the child facial coding system

OBJECTIVE The purposes of the study were threefold: (a) to determine whether a measurement system based on facial expression would be useful in the assessment of post-operative pain in young children; (b) to examine construct validity in terms of structure, consistency, and dynamics of the facial display; and (c) to evaluate concurrent validity in terms of associations with global judgments of the childrens pain. PATIENTS One hundred children between the ages of 13 and 74 months were video-taped for a maximum of 1 hour after arrival in the postanesthesia care unit (PACU) at British Columbias Childrens Hospital. OUTCOME MEASURES Videotapes were edited into 20-second blocks, randomly selected from each 2-minute time period taped during the hour following surgery, and coded for the presence or absence of 13 facial actions in the Child Facial Coding System (CFCS). RESULTS Facial expressions were characterized primarily by the following constellation of actions: open lips, lowered brows, a deepened nasolabial furrow, mouth stretched wide in both horizontal and vertical directions, eyes squeezed shut or squinted, and raised cheeks. A principal components analysis indicated that these actions comprised a single factor, accounting for 55% of the variance in CFCS actions. Facial action summary scores were correlated with a visual analog rating of global pain, confirming that the CFCS has convergent validity. Facial action summary scores, i.e., pain displays, were at their lowest immediately after admittance to the PACU and just before the childs release from the PACU. CONCLUSIONS The present study demonstrated that the CFCS serves as a valid measurement tool for persistent pain in children.

Propofol anaesthesia reduces early post-operative emesis after paediatric strabismus surgery

Propofol anaesthesia may reduce postoperative emesis. The purpose of this study was to compare the incidence of emesis after propofol anaesthesia with and without nitrous oxide, compared with thiopentone and halothane anaesthesia, in hospital and up to 24 hr postoperatively, in outpatient paediatric patients after strabismus surgery. Seventy-five ASA class I or II, unpremedicated patients, aged 2–12 yr were randomly assigned to one of three groups: Thiopentone, 6.0 mg · kg− 1 iv induction followed by halothane and N2O/O2 for maintenance (T/H); propofol for induction, followed by propofol and oxygen for maintenance (P/O2); and propofol for iv induction, followed by propofol infusion and N2O/O2 for maintenance (P/N2O). All received vecuronium, controlled ventilation, and acetaminophen pr. Morphine was given as needed for postoperative analgesia. There were no differences in age, weight, number of eye muscles operated upon, duration of anaesthesia or surgery. The P/N2O group (255 ± 80 μg· kg− 1· min− 1) received less propofol than the P/O2 group (344 ± 60 μg · kg− 1· min− 1) (P ≤ 0.0001) and had shorter extubation (P < 0.001) and recovery (P < 0.01) times. Emesis in the hospital, in both the P/N2O (4.0%) and P/O2 group (4.0%) was less than in the T/H group (32%) (P < 0.01). Antiemetics were required in four patients in the T/H group (16.0%). Overall emesis after surgery was not different among the groups: T/H (48%), P/O2 (28%) and P/N2O (42%). The use of propofol anaesthesia with and without N2O decreased only early emesis. This supports the concept of a short-acting, specific antiemetic effect of propofol.RésuméOn attribue au propofol des propriété anti-émétiques postopératoires. Cette étude a pour objectif de comparer l’incidence des vomissements après l’anesthésie au propofol avec ou sans protoxyde d’azote, comparativement à l’anesthésie au thiopentone-halothane. Cette étude est réalisée à l’hôpital et jusqu’à 24 heures après l’opération chez des patients ambulatoires après chirurgie pour strabisme. Soixante-quinze patients ASA I et II, non prémédiqués, âgés de 2 à 12 ans sont assignés au hasard à un de trois groupes: induction au thiopentone, 6,0 mg· kg− 1 avec maintien à l’halothane-N2O, (T/ H); induction avec maintien au propofol-oxygène (P/O2) et induction au propofol avec maintien au protoxyde-oxygène (P/N2O). Tous reçoivent du vécuronium, une ventilation contrôlée et de l’acétaminophène rectal. De la morphine est administrée au besoin pour contrôler la douleur postopératoire. Il n’y a pas de différence d’âge, du poids, du nombre de muscles opérés et de durée anesthésique et chirurgicale. Les patients du groupe P/N2O (255 ± 80 μg· kg− 1· min− 1) reçoivent moins de propofol que le groupe P/O2 (344 ± 60 μg· kg− 1· min− 1, P < 0.001), sont intubés moins longtemps (P < 0.0001) et s’éveillent plus rapidement (P < 0.01). A l’hôpital, les vomissements dans les deux groupes P/N2O (4.0%) et P/O2 (4.0%) sont moins fréquents que dans le groupe T/H (32%). Des antiémétiques sont requis chez quatre patients du groupe T/H (16%). L’incidence générale des vomissements après la chirurgie est la même pour tous les groupes: T/H (48%), P/O2 (28%) et P/N2O(42%). L’utilisation du propofol en anesthésic avec ou sans N2O ne diminue que l’incidence des vomissements précoces, ce qui supporte le concept d’une activité anti-émétique brève et spécifique.

Efficacy and complications of morphine infusions in postoperative paediatric patients

The aim of the study was to evaluate the efficacy and the incidence of clinically significant adverse drug reactions (ADRs) in paediatric patients receiving continuous intravenous morphine infusions for acute postoperative pain. Definitions were established for ADRs and data were collected in an immediately retrospective fashion for a maximum of 72 h in 110 patients ≥5 three months of age (0.3–16.7 years) receiving morphine infusions and admitted to a general ward over a three month convenience sampling period. Inadequate analgesia occurred in 65.5% of patients during the first 24 h of therapy and occurred most frequently in patients with infusion rates of 20 μg·kg−1·h−1 or less. Nausea/vomiting was the most commonly experienced ADR (42.5%). The incidence of respiratory depression was 0% (95% CI=0–3.3%). Other ADRs included: urinary retention (13.5%), pruritus (12.7%), dysphoria (7.3%), hypoxaemia (4.5%), discontinuation of morphine for treatment of an ADR (3.6%), and difficulty in arousal (0.9%). The most common ADRs associated with morphine infusions were inadequate analgesia (in the first 24 h) and nausea/vomiting. There were no cases of respiratory depression. Methods of avoiding initial inadequate analgesia and treating nausea and vomiting associated with morphine infusions are needed.

Emergence delirium in children: a randomized trial to compare total intravenous anesthesia with propofol and remifentanil to inhalational sevoflurane anesthesia

Emergence delirium (ED) refers to a variety of behavioral disturbances commonly seen in children following emergence from anesthesia. Vapor‐based anesthesia with sevoflurane, the most common pediatric anesthetic technique, is associated with the highest incidence of ED. Propofol has been shown to reduce ED, but these studies have been methodologically limited.

The effectiveness of clonidine as an analgesic in paediatric adenotonsillectomy

PurposeTo compare the analgesic effects of preoperative oral clonidine with intraoperative intravenous fentanyl in children undergoing tonsillectomy or adenotonsillectomy.MethodsThis randomized, controlled, double-blind study of 36 ASA 1–11 children, age 7–12 yr undergoing adenotonsillectomy was conducted at a tertiary care paediatric teaching hospital. Either 4 μg·kg−1 clonidinepo was given 60–90 min preoperatively or 3 μg·kg−1 fentanyliv was given intraoperatively. Postoperatively visual analog pain scores (VAS) were recorded at rest and on swallowing every 10 min for the first 30 min and then every 15 min for two hours. Morphine 0.05 mg·kg−1iv was given for VAS ≥5. If > 3 doses were required, 1.5 mg·kg−1 codeinepo and 20 mg·kg−1 acetaminophenpo were given. Sedation and anxiety scores were recorded preoperatively. Haemodynamic changes, blood loss, recovery scores, and the incidence of vomiting, hypotension, and airway obstruction were recorded.ResultsChildren who received clonidine had a higher incidence of preoperative sedation (63%) than those receiving fentanyl (6%). Preinduction mean arterial pressure was lower in the clonidine group but required no intervention. VAS scores were similar throughout the observation period. There was no difference either in the number of morphine or codeine rescue doses administered or in the incidence of side effects.ConclusionOral clonidine is an effective analgesic and sedative for children undergoing tonsillectomy or adenotonsillectomy.RésuméObjectifComparer les effets analgésiques de l’administration orale de clonidine préopératoire et de fentanyl intraveineux peropératoire chez des enfants devant subir une amygdalectomie ou une adéno-amygdalectomie.MéthodeCette étude randomisée, contrôlée et à double insu a porté sur 36 enfants ASA 1–11, âgés de 7 à 12 ans, devant subir une adéno-amygdalectomie dans un hôpital universitaire de soins pédiatriques tertiaires. On a administré 4 ug·kg−1 de clonidinepo 60–90 min avant l’intervention ou 3 ug·kg−1 de fentanyliv au cours de l’intervention. Les niveaux de douleur ont été enregistrés après l’opération, à l’aide de l’échelle visuelle analogue (EVA), au repos et lors de la déglutition à toutes les 10 min pendant les 30 premières min et à toutes les 15 min pendant les deux heures suivantes. On a administré 0,05 mg·kg−1 de morphineiv pour des scores.-5 à l’EVA. Si plus de 3 doses étaient nécessaires, on a donné aussi 1,5 mg·kg−1 de codéinepo et 20 mg·kg−1 d’acétaminophènepo. Avant l’intervention, on a enregistré les niveaux de sédation et d’anxiété. Les changements hémodynamiques, les pertes sanguines, les niveaux de récupération et l’incidence de vomissements, d’hypotension et d’obstruction du conduit aérien ont été notés.RésultatsLes enfants qui ont reçu de la clonidine ont présenté une plus grande incidence de sédation préopératoire (63 %) que ceux qui ont reçu du fentanyl (6 %). Avant l’induction de l’anesthésie, la tension artérielle moyenne était plus basse dans le groupe qui avait reçu de la clonidine, mais cela n’a pas nécessité de traitement. Les valeurs de l’EVA ont été similaires tout au long de la période d’observation. Il n’y avait pas de différence non plus quant au nombre de doses de rattrapage de morphine ou de codéine administrées ou quant à l’incidence d’effets secondaires.ConclusionLa clonidine par voie orale est un analgésique et un sédatif efficace chez des enfants qui subissent une amygdalectomie ou une adéno-amygdalectomie.

Intravenous ketamine sedation for painful oncology procedures.

Background:  The aim of the study was to determine the efficacy and adverse effects of intravenous (i.v.) ketamine sedation administered by nonanesthetist physicians for painful procedures.

Skin Conductance Fluctuations Correlate Poorly with Postoperative Self-report Pain Measures in School-aged Children

Background:The number of fluctuations of skin conductance per second (NFSC) has been shown to correlate with induced pain and self-report pain scales. This study aimed to evaluate the validity and feasibility of NFSC as an objective measurement of nociception intensity in school-aged children after surgery. Methods:After approval by the research ethics board and obtaining consent, 100 subjects participated in this prospective observational study. Preoperatively, NFSC was measured for 60 s at rest and during response to a self-report pain scale (numeric rating scale [NRS], Faces Pain Scale-Revised) and anxiety scoring (NRS). Postoperative measurements were repeated every 10 min for 30 min or until NRS pain score was ≤ 4 for two consecutive scores. Spearman rank correlation coefficients were calculated to investigate the relationship between NFSC and NRS pain, Faces Pain Scale-Revised, and NRS anxiety. The clinical utility of using NFSC in determining NRS pain threshold was investigated using receiver operator characteristics analysis. For clinical relevance, a cutoff NFSC was chosen that optimizes both specificity and sensitivity. Although selecting a low cutoff value increases the sensitivity of the NFSC in diagnosing pain, it does so at the expense of specificity. Results:Data from 90 subjects (64.4% male) aged 7–17 yr (median age 13 yr) were analyzed (217 postoperative datasets). NFSC correlated weakly with NRS pain scores (P = 0.21; P < 0.002). NFSC did not correlate with NRS anxiety scores (P = 0.15, P < 0.03). NRS pain scores correlated strongly with Faces Pain Scale-Revised (P = 0.89, P < 0.0001) and weakly with NRS anxiety scores (P = 0.34, P < 0.0001). A threshold of 0.23 NFSC predicted severe pain (NRS ≥ 7) with 56.3% sensitivity (95% CI = 37.7–73.6%) and 78.4% specificity (95% CI = 71.7–84.1%). The area under receiver operator characteristic curve for NFSC was 69.1%. Conclusions:NFSC measurement is feasible in a perioperative setting but was not specific for postoperative pain intensity and was unable to identify analgesia requirements when compared with self-report measures.

Plasma concentrations of flumazenil following intranasal administration in children

Purpose: A pharmacokinetic study in children to determine plasma flumazenil concentrations after the intranasal administration of 40 µg·kg−1.Methods: Following institutional approval and informed written consent, II ASA physical status I–II patients, aged two to six years, undergoing general anesthesia for dental surgery were recruited. After induction, 40 µg·kg−1 flumazenil Anexate®, Roche, 0.1 mg·mL−1 (0.4 mL·kg−1)) were administered via a syringe as drops, prior to nasal intubation. Venous plasma samples were drawn prior to administration of flumazenil (t=0), and then at 2, 4, 6, 8, 10, 15, 20, 30, 40, 60, and 120 min thereafter. The plasma samples were immediately processed by the onsite laboratory and then stored at −70°C, before batch analysis via high performance liquid chromatography assay. Pharmacokinetic data calculations were performed using WinNonLin software (Scientific Consulting Inc.).Results: Eleven patients were studied, but data for one patient were discarded due to insufficient sampling. The median age was 4.3 yr (range 3 to 6), with a median weight of 18.9 kg (range 14.9 to 22.2). There were seven boys and three girls. Mean Cmax was 67.8 ng·mL−1 (SD 41.9), with Tmax at two minutes. The calculated half-life was 122 min (SD 99).Conclusion: The mean plasma concentrations of flumazenil attained were similar to those reported after intravenous administration, and may be sufficient to antagonize the side-effects of benzodiazepines. This route of administration may be useful when the intravenous route is not readily available.RésuméObjectif: Déterminer, par une étude pharmacocinétique chez des enfants, la concentration plasmatique de flumazénil après l’administration intranasale de 40 µg·kg−1.Méthode: Après avoir obtenu les autorisations écrites de l’institution et des parents, on a recruté II patients, d’état physique ASA I–II, âgés de deux à six ans, qui devaient subir une intervention dentaire sous anesthésie générale. À la suite de l’induction, 40µg·kg−1 de flumazénil (Anexate®, Roche, 0,1 mg·mL−1 (0,4 mL·kg−1)) ont été administrés en gouttelettes au moyen d’une seringue avant l’intubation nasale. Des échantillons plasmatiques veineux ont été pris avant l’administration de flumazénil (t=0), et ensuite à 2, 4, 6, 8, 10, 15, 20, 30, 40, 60, et 120 min. Les échantillons plasmatiques ont été immédiatement traités au laboratoire sur place et conservés à −70 °C, avant l’analyse du tout par chromatographie à haute performance. Les calculs pharmacocinétiques ont été réalisés avec le logiciel WinNonLin (Scientific Consulting Inc.).Résultats: Les données d’un seul patient sur II ont été refusées pour échantillons insuffisants. L’âge moyen des en fants, dont sept garçons et trois filles, était de 4,3 ans (limites de 3 à 6), et le poids moyen était de 18,9 kg (limites de 14,9 à 22,2). La Cmax moyenne était de 67,8 ng·mL−1 (écart type de 41,9), et un Tmax à deux minutes. La demi-vie était de 122 min (écart type de 99).Conclusion: Les concentrations plasmatiques moyennes de flumazénil obtenues ont été similaires à celles qui suivent l’administration intraveineuse et peuvent être suffisantes pour contrer les effets secondaires des benzodiazépines. L’administration par voie nasale peut se révéler utile lorsque la voie intraveineuse n’est pas facilement accessible.