Oral morphine dosing predictions based on single dose in healthy children undergoing surgery.

BACKGROUND: Oral morphine has been proposed as an effective and safe alternative to codeine for after-discharge pain in children following surgery but there are few data guiding an optimum safe oral dose. AIMS: The aim of this study was to characterize the absorption pharmacokinetics of enteral morphine in order to simulate time-concentration profiles in children given common oral morphine dose regimens. METHODS: Children (2-6 years, n = 34) undergoing elective surgery and requiring opioid analgesia were randomized to receive preoperative oral morphine (100 mcg·kg-1 , 200 mcg·kg-1 , 300 mcg·kg-1 ). Blood sampling for morphine assay was performed at 30, 60, 90, 120, 180, and 240 min. Morphine serum concentrations were determined by liquid chromatography-mass spectroscopy and pharmacokinetic parameters were calculated using nonlinear mixed effects models. Current data were pooled with published time-concentration profiles from children (n = 1059, age 23 weeks postmenstrual age - 3 years) administered intravenous morphine, to determine oral bioavailability (F), absorption lag time (TLAG ), and absorption half-time (TABS ). These parameter estimates were used to predict concentrations in children given oral morphine (100, 200, 300, 400, 500 mcg·kg-1 ) at different dosing intervals (3, 4, 5, 6, 8, 12 h). RESULTS: The oral morphine formulation had F 0.298 (CV 36.5%), TLAG 0.45 (CV 63.6%) h and TABS 0.71 (CV 55%) h. A single-dose morphine 100 mcg·kg-1 achieved a mean CMAX 10 mcg·l-1 . Repeat 4-hourly dosing achieved mean steady-state concentration 13-18 mcg·l-1 ; concentrations associated with good analgesia after intravenous administration. Serum concentration variability was large ranging from 5 to 55 mcg·l-1 at steady state. CONCLUSIONS: Oral morphine 200 mcg·kg-1 then 100 mcg·kg-1 4 h or 150 mcg·kg-1 6 h achieves mean concentrations associated with analgesia. There was high serum concentration variability suggesting that respiration may be compromised in some children given these doses.

Changes in QTc associated with a rapid bolus dose of dexmedetomidine in patients receiving TIVA: a retrospective study.

BACKGROUND: Clinical indications for the perioperative use of dexmedetomidine in pediatric anesthesia are accumulating. However, in 2013, dexmedetomidine was added to the list of medications with possible risk of prolonging the QT interval and/or inducing Torsades de Pointes. Unfortunately, current evidence for dexmedetomidine-induced QT prolongation is sparse and somewhat contradictory. OBJECTIVE: The purpose of this study was to evaluate temporal changes in corrected QT interval (QTc) after a rapid bolus administration of dexmedetomidine under total intravenous anesthesia (TIVA) with a standardized propofol and remifentanil administration. METHODS: Electrocardiography (ECG) and corresponding trend data were extracted from automated electronic data capture of physiological monitoring. Ten-second epochs of ECG data were extracted in 1-min intervals for 12 min, starting 1 min before dexmedetomidine bolus administration, and ending 10 min after. QT intervals were extracted using an automated routine in MATLAB, and corrected for heart rate (HR) using Bazett's (QTcB) and Fridericia's formulas (QTcF). QTcB and QTcF were compared using Wilcoxon signed-rank test between baseline measurements and the subsequent four interval values. RESULTS: Data from 21 subjects (17 male) with median (range) age 7.1 (5.4-9.5) yr, weight 23.6 (16.2-36.7) kg, and height 121 (103-140) cm were analyzed. Bolus administration of dexmedetomidine reduced HR in all subjects (median 22%), and caused transient reduction of QT interval, with its peak at 1-min postbolus administration: QTcB (median reduction 30.7 ms, P < 0.001) or QTcF (median reduction 15.4 ms, P = 0.001); QT shortening became statistically insignificant 4 min following dexmedetomidine bolus administration for QTcB and 2 min for QTcF. CONCLUSION: In this study, a rapid bolus of dexmedetomidine transiently shortened corrected QT intervals. However, these effects are confounded by dexmedetomidine-induced bradycardia. These findings should be confirmed in pediatric studies without concomitant TIVA administration and with optimized correction of baseline HR.

A smartphone version of the Faces Pain Scale-Revised and the Color Analog Scale for postoperative pain assessment in children.

BACKGROUND: Effective pain assessment is essential during postoperative recovery. Extensive validation data are published supporting the Faces Pain Scale-Revised (FPS-R) and the Color Analog Scale (CAS) in children. Panda is a smartphone-based application containing electronic versions of these scales. OBJECTIVES: To evaluate agreement between Panda and original paper/plastic versions of the FPS-R and CAS and to determine children's preference for either Panda or original versions of these scales. METHODS: ASA I-III children, 4-18 years, undergoing surgery were assessed using both Panda and original versions of either the FPS-R or CAS. Pain assessments were conducted within 10 min of waking from anesthesia and 30 min later. RESULTS: Sixty-two participants, median (range) age 7.5 (4-12) years, participated in the FPS-R trial; Panda scores correlated strongly with the original scores at both time points (Pearson's r > 0.93) with limits of agreement within clinical significance (80% CI). Sixty-six participants, age 13 (5-18) years, participated in the CAS trial. Panda scores correlated strongly with the original scores at both time points (Pearson's r > 0.87); mean pain scores were higher (up to +0.47 out of 10) with Panda than with the original tool, representing a small systematic bias, but limits of agreement were within clinical significance. Most participants who expressed a preference preferred Panda over the original tool (81% of FPS-R, 76% of CAS participants). CONCLUSION: The Panda smartphone application can be used in lieu of the original FPS-R and CAS for assessment of pain in children. Children's preference for Panda may translate to improved cooperation with self-report of pain.

Identifying a rapid bolus dose of dexmedetomidine (ED50) with acceptable hemodynamic outcomes in children.

BACKGROUND: Dexmedetomidine is a highly sensitive, specific α2 adrenoceptor agonist with anxiolytic, sedative, and analgesic effects. Administration is recommended as a loading dose infused over 10 min. Clinical experience and a previous study suggested a shorter time frame might be used without causing adverse hemodynamic effects. OBJECTIVE: To determine the dexmedetomidine dose that can be given as a rapid 5 s bolus to healthy children during total intravenous anesthesia (TIVA) without causing significant hemodynamic effects. METHODS: ASA I-II children, aged 5-9 years, having elective surgery under TIVA were recruited. The up-and-down sequential study design was employed to determine the effective dose of dexmedetomidine, starting at 0.3 mcg·kg(-1) with 0.1 mcg·kg(-1) intervals, which caused no hemodynamic response in half the subjects (ED50). Positive responses were defined as mean blood pressure (MAP) and/or heart rate (HR) changes ≥30% from baseline. Three parametric estimators and one nonparametric estimator were used to determine the ED50. RESULTS: Twenty-one subjects with median age 7.1 (range 5.4-9.5) years and median weight 23.6 (range 16.2-36.7) kg were recruited. A maximum median HR decrease of 20 b·min(-1) occurred at 50 s and a maximum median MAP increase of 12.5 mmHg occurred at 100 s after bolus dose administration. Fifteen subjects (71%) had a HR <60 b·min(-1) while one subject had a HR <40 b·min(-1) (minimum 35 b·min(-1)) for 60 s following the dexmedetomidine bolus. Four estimators led to an ED50 estimate for dexmedetomidine of 0.49 mcg·kg(-1) [95% CI 0.26-0.80 mcg·kg(-1)]. CONCLUSION: The ED50 of dexmedetomidine administered over 5 s without significant hemodynamic compromise is 0.49 mcg·kg(-1). Further work is needed to determine the 'safe' (ED5 or less) and effective dose for desired perioperative clinical outcomes.

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

BACKGROUND: 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. OBJECTIVE: To conduct a randomized-controlled trial comparing the incidence of ED in children following sevoflurane (SEVO) anesthesia and propofol-remifentanil total intravenous anesthesia (TIVA). METHODS: One hundred and twelve children, ASA I-II, aged ≥ 2 and ≤ 6 years, undergoing strabismus repair, were assigned to receive TIVA (intravenous induction and maintenance of anesthesia with propofol and remifentanil) or SEVO (inhalational induction and maintenance of anesthesia with sevoflurane). Parent-child induction behavior was scored using the Perioperative Adult Child Behavior Interaction Scale (PACBIS). Postoperatively, ED was assessed by a masked investigator using the Pediatric Anesthesia Emergence Delirium (PAED) Scale and pain using the Face, Legs, Activity, Cry, Consolability (FLACC) Scale every 5 min. RESULTS: Data are reported for 94 subjects. Incidence of ED was higher with SEVO (38.3% vs 14.9%, P = 0.018). There was no difference in the median PACBIS score. A higher FLACC score was seen with SEVO (median 3 vs 1, P = 0.033). Subjects experiencing ED had higher FLACC scores vs those unaffected by ED (median 7 vs 1, P < 0.0001). CONCLUSION: There was a lower incidence of ED after TIVA. Both intravenous and inhalational inductions were similarly well-tolerated. The use of TIVA was associated with reduced postoperative pain as measured using FLACC scores.

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 or= 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.

The effect of age on the dose of remifentanil for tracheal intubation in infants and children.

INTRODUCTION: This study aimed to determine the age-specific bolus dose of remifentanil (ED(50)) to facilitate tracheal intubation without the use of neuromuscular blocking agents. METHODS: ASA 1-2 subjects were recruited into three groups of 0-3 months (group I), 4-12 months (group II), and 1-3 years (group III) of age. A sequential up-and-down design determined the remifentanil bolus dose, which was initially started at 3 mcg x kg(-1) and adjusted in 1 mcg x kg(-1) increments (range 1-6 mcg x kg(-1)). Following pretreatment with glycopyrrolate 10 microg x kg(-1) and an induction dose of propofol 5 mg x kg(-1), remifentanil was administered with a blinded study investigator commencing tracheal intubation after 60 s. After tracheal intubation, the time to return of spontaneous ventilation was measured. Logistic regression was used to predict the ED(50) and ED(95) of remifentanil. RESULTS: Sixty-four subjects were recruited. Tracheal intubation was successful at first attempt in over 90% of subjects in each age group. Satisfactory intubating conditions were achieved in 85%, 63%, and 75% of subjects in groups I, II, and III, respectively. The logistic regression results for ED(50) (95% CI) were 3.1 (2.5-3.8), 3.7 (2.0-5.4), and 3.0 (2.1-3.9) mcg x kg(-1), and ED(95) (95% CI) were 5.0 (3.0-7.0), 9.4 (1.5-17.4), and 5.6 (2.9-8.4) mcg x kg(-1) in groups I, II, and III, respectively. Infants aged 4-12 months (group II) showed a marked variability in dose response; however, the mean ED(50) and ED(95) were not different to groups I and III. Older children had a longer duration of apnea than infants, 331 vs 180 s (P < 0.05). DISCUSSION: The ED(50) of remifentanil for tracheal intubation was higher in all age groups than previously reported. Ideal intubating conditions were achieved in 50% of subjects with remifentanil doses of 3.1-3.7 mcg x kg(-1). Higher doses will be required for higher success rates and with anticholinergic pretreatment, doses of up to 6 mcg x kg(-1) were tolerated, without adverse effects, in two patients. Further investigation of the variability in dose response in infants and assessment of the safety this technique is warranted.

Telephone and web-based pediatric day surgery questionnaires.

PURPOSE: Patient questionnaires are popular tools for assessing and improving service quality, especially as administrators are increasingly expected to consider the patient's voice in their decision making. Despite web-based questionnaire advantages, they have not been previously compared to telephone questionnaires for assessing quality. The purpose of this paper is to compare telephone questionnaire administration with a web-based version. DESIGN/METHODOLOGY/APPROACH: Day surgery patients from a tertiary pediatric hospital completed a telephone interview and a web-based questionnaire with identical questions. The appropriateness of the web version as a telephone version substitute was ascertained by comparing the number of changes in responses, non-responses, differences in means, the number of non-substantive responses and reliability. FINDINGS: The web-based questionnaire tended towards more negative responses. The mean number of missing responses did not differ between versions, although the web-questionnaire had more "not sure" responses. Inter-rater reliability was acceptable. RESEARCH LIMITATIONS/IMPLICATIONS: Parents without internet access were unable to participate. PRACTICAL IMPLICATIONS: The web-based questionnaire is a good substitute for telephone-administered questionnaires. ORIGINALITY/VALUE: The paper shows that parents were able to rate items more candidly owing to the increase in privacy and lack of interviewer bias, which is crucial for improving health service quality.

Stability of Hydromorphone-Ketamine Solutions in Glass Bottles, Plastic Syringes, and IV Bags for Pediatric Use.

OBJECTIVES: To evaluate the stability of mixtures of hydromorphone and ketamine in 0.9% sodium chloride (normal saline [NS]) after storage for up to 7 days at room temperature (25°C). METHODS: The stability of 3 standard mixtures of hydromorphone and ketamine (hydromorphone 0.2 mg/mL + ketamine 0.2 mg/mL, hydromorphone 0.2 mg/mL + ketamine 0.6 mg/mL, and hydromorphone 0.2 mg/mL + ketamine 1.0 mg/mL) in NS was studied. Portions of each mixture were transferred to 3 brown glass bottles (100 mL), 3 plastic syringes (50 mL), and 3 IV bags (50 mL), which were then stored at room temperature (25°C). Physical characteristics, including pH, colour, and precipitation, were evaluated daily. Three 1.5-mL samples were collected from each bottle, syringe, and IV bag at baseline, at 24, 48, and 72 hours, and on day 7. Samples were analyzed in triplicate by a stability-indicating high-performance liquid chromatography method. Solutions were considered stable if they maintained 90% of the initial concentration of each drug. Samples from syringes and IV bags were subjected to standard sterility testing by incubation for 5 days in an enriched culture media. RESULTS: No notable changes in pH or colour were observed, and no precipitation occurred in any of the solutions. All formulations maintained more than 90% of the initial concentration of each drug on day 7. No bacterial growth was observed in any of the samples tested. CONCLUSIONS: Mixtures of hydromorphone and ketamine were stable for up 7 days at 25°C, and the sterility of the preparations was maintained. Because stability alone does not guarantee efficacy, it is recommended that clinical studies be conducted to evaluate the pharmacokinetics and pharmacodynamics of these formulations.

Validity of Simplified Versus Standard Self-Report Measures of Pain Intensity in Preschool-Aged Children Undergoing Venipuncture.

There are inadequate age-specific data to support the use of current self-report pain scales in 3- and 4-year-old children. Most preschool-aged children also lack the necessary cognitive development to use standard scales. We aimed to evaluate the validity and feasibility of 2 novel simplified scales (Simplified Faces Pain Scale, S-FPS; Simplified Concrete Ordinal Scale, S-COS) for preschool-aged children. These simplified scales used a 2-step self-report method: children were first asked whether they have pain (yes/no); only if yes, then pain intensity was self-reported using a 3-point scale with visual aids signifying mild/moderate/severe. We recruited 180 3- to 6-year-old children undergoing routine blood collection. Each child was randomly assigned 2 of 3 scales-S-FPS, S-COS, Faces Pain Scale-Revised (FPS-R)-to self-report pain before venipuncture, immediately after, and 5 minutes later, using both scales at each time-point. Pain was also assessed using observation (Face Legs Activity Cry Consolability) at each time point. The ability to discriminate pain from no pain was improved with S-FPS and S-COS, compared with the FPS-R, among 4-year-olds, but not 3-year-olds. Correlation with Face Legs Activity Cry Consolability was moderate to strong and cooperation rates were similar for all self-report scales. The simplified scales can improve and simplify pain assessment for 4-year-olds. Quantitative pain rating remains challenging for 3-year-olds. PERSPECTIVE: This study evaluated 2 novel simplified pain assessment tools for preschool-aged children undergoing blood sampling. These scales demonstrated good validity and feasibility compared with the FPS-R, suggesting these simplified pain scales may have a role in clinical practice for children as young as 4 years.

Faces scales for the measurement of postoperative pain intensity in children following minor surgery.

OBJECTIVES: Faces scales are commonly used to obtain self-reports of pain intensity from children. Previous research using hypothetical vignettes and pain following venepuncture has found differences in children's pain ratings as a function of the type of faces scale used. The purpose of the present study was to determine whether scales beginning with a smiling rather than neutral "no pain" face would produce higher ratings in the assessment of postoperative pain intensity in children and to compare ratings using different faces scales to those reported with an additional independent measure of pain intensity. METHODS: Participants were 78 children between the ages of 5 and 13 years undergoing surgery, one of their parents, and their postoperative care nurse. Following surgery, children were asked to provide a rating of their current pain intensity using a set of 5 successively administered faces scales and the Colored Analog Scale (CAS). Parents and nurses provided independent ratings using the same measures. RESULTS: Results showed that parents and nurses rated significantly more pain when using scales with a smiling rather than a neutral "no pain" face. This pattern was not as clear for the children's ratings, although their highest ratings were provided when using a smiling "no pain" faces scale. Children's and nurses' ratings on the CAS were generally more similar to their ratings using scales with neutral "no pain" faces, whereas parents' CAS ratings tended to fall in between ratings provided on the smiling and neutral "no pain" faces scales. Scale preference, age and sex differences in pain ratings, and child-parent-nurse agreement in pain ratings are also examined. DISCUSSION: Children's and parents' ratings of postoperative pain intensity are influenced by the presence of a smiling "no pain" face at the beginning of faces scales, with such scales producing significantly higher ratings than scales with neutral "no pain" faces. Ratings on the independent CAS measure were more comparable to those provided on faces scales with neutral "no pain" faces. Nurses are also susceptible to the influencing effect of a smiling face at the beginning of a faces scale.

A Compartmental Analysis for Morphine and Its Metabolites in Young Children After a Single Oral Dose.

BACKGROUND AND OBJECTIVES: Currently, the majority of the surgical procedures performed in paediatric hospitals are done on a day care basis, with post-operative pain being managed by caregivers at home. Pain after discharge of these post-operative children has historically been managed with oral codeine in combination with paracetamol (acetaminophen). Codeine is an opioid, which elicits its analgesic effects via metabolism to morphine and codeine-6-glucuronide. Oral morphine is a feasible alternative for outpatient analgesia; however, the pharmacokinetics of morphine after oral administration have been previously described only sparsely, and there is little information in healthy children. METHODS: The clinical trial included 40 children from 2 to 6 years of age, with an American Society of Anaesthesiologists physical status classification of 1 or 2, who were undergoing surgical procedures requiring opioid analgesia. Morphine was orally administered prior to surgery in one of three doses: 0.1 mg/kg, 0.2 mg/kg and 0.3 mg/kg. Blood samples were collected for plasma morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations at 30, 60, 90, 120, 180 and 240 min after administration. All analyses were performed with the non-linear mixed-effect modelling software NONMEM version 7.2, using the first-order conditional estimation (FOCE) method. RESULTS: A pharmacokinetic model was developed to simultaneously describe the plasma profiles of morphine and its metabolites M3G and M6G after a single dose of oral morphine in young children (2-6 years of age). The disposition of morphine, M3G and M6G in plasma was best described by a one-compartment model. M3G and M6G metabolite formation was best described by a delay transit compartment, indicating a delay in the appearance of these two major metabolites. CONCLUSION: This model provides a foundation on which to further evaluate the use of oral morphine and its safety in young children. Longer follow-up time for morphine oral doses and incorporation of other important covariates, such as phenotype, will add value and will help overcome the limitations of the presented population pharmacokinetic analysis.

Quality-of-life outcomes after surgical correction of pectus excavatum: a comparison of the Ravitch and Nuss procedures.

PURPOSE: The purpose of this study was to compare clinical and health-related quality-of-life (HRQL) outcomes within a group of patients treated for pectus excavatum (PE). METHODS: A retrospective 3-year review of patients undergoing Nuss or Ravitch correction of PE was performed. Health-related quality-of-life assessment was performed using the Child Health Questionnaire (CHQ-CF87) and the 17-item Pectus Excavatum Evaluation Questionnaire, and results were compared between groups and with age-matched CHQ-CF87 normative data. RESULTS: Forty-three patients (39 males; 91%) underwent surgery; 19 (44%) by Nuss procedure. Duration of postoperative opioid analgesia and length of hospital stay (LOS) were significantly longer in Nuss patients. The overall survey response rate was 53%. The groups differed significantly in the CHQ on one item (Change in Health). On the Pectus Excavatum Evaluation Questionnaire, Nuss patients reported being "less bothered" by the appearance of their chest. Compared to Australian age-matched norms, the aggregate PE sample showed better scores for family activity domain and worse scores in mental health, general health perceptions, change in health, bodily pain, and self-esteem. CONCLUSIONS: Patients undergoing surgery for PE by either Nuss or Ravitch procedure have similar clinical and HRQL outcomes, but as a group have poorer HRQL scores than age-matched population norms.

Measuring the quality of pediatric day surgery care.

This brief report describes the process of developing a valid and reliable questionnaire for quality measurement of pediatric day surgery care from the families' perspective. Questionnaire items were generated through a literature search and interviews with clinicians and parents. A computer-assisted telephone interview was used to administer the questionnaire to 448 parents within 72 hours of patient discharge. Tests of reliability and validity were administered, and questionnaire items were improved or omitted based on the results. The investigators plan to readminister the improved questionnaire to confirm its validity and reliability.

Intravenous nalbuphine 50 microg x kg(-1) is ineffective for opioid-induced pruritus in pediatrics.

PURPOSE: This investigation evaluated the efficacy of nalbuphine in treating postoperative opioid-induced pruritus (Pr) in pediatric patients. METHODS: After Ethics Board approval, the dual site, tertiary care teaching centre study recruited 212 subjects, age > or = seven years, who received opioid analgesia postoperatively. A modified, self-report colour analogue scale (CAS) scored pruritus intensity (PrI). Subjects who reported PrI score > or = 5/10 were randomized to treatment with nalbuphine 50 microg x kg(-1) iv (max 5 mg) or saline placebo. A pruritus intensity difference (PrID) > or = 50% was considered a positive outcome. RESULTS: Of 260 subjects approached, 212 consented and 184 received opioids. Median age was 13 yr (range 7-19) and median weight was 51 kg (range 19.6-134.8 kg). Pruritus intensity > or = 5/10 occurred in 37 (20.1%) subjects. Intravenous morphine [patient-controlled analgesia (PCA)/continuous infusion] was associated with Pr in 68% of subjects over a wide dose range (9.4-63.2 mug.kg(-1).hr(-1)). Pruritus occurred in 36% of patients in the PCA group compared to continuous opioid infusion (27%) and epidural administration (27%). Pruritus intensity difference > or = 50% was achieved in 55.6% of nalbuphine and 57.9% of saline-treated subjects. CONCLUSION: This preliminary report suggests that nalbuphine 50 microg x kg(-1) iv is not effective in treating postoperative opioid-induced pruritus in pediatric patients. The modified CAS score and PrID warrant further investigation.

Intravenous nalbuphine 50 µg·kg(-1) is ineffective for opioid-induced pruritus in pediatrics.

PURPOSE: This investigation evaluated the efficacy of nalbuphine in treating postoperative opioid-induced pruritus (Pr) in pediatric patients. METHODS: After Ethics Board approval, the dual site, tertiary care teaching centre study recruited 212 subjects, age ≥ seven years, who received opioid analgesia postoperatively. A modified, self-report colour analogue scale (CAS) scored pruritus intensity (PrI). Subjects who reported PrI score ≥ 5/10 were randomized to treatment with nalbuphine 50 µg·kg(-1) iv (max 5 mg) or saline placebo. A pruritus intensity difference (PrID) ≥ 50% was considered a positive outcome. RESULTS: Of 260 subjects approached, 212 consented and 184 received opioids. Median age was 13 yr (range 7-19) and median weight was 51 kg (range 19.6-134.8 kg). Pruritus intensity ≥ 5/10 occurred in 37 (20.1%) subjects. Intravenous morphine [patient-controlled analgesia (PCA)/continuous infusion] was associated with Pr in 68% of subjects over a wide dose range (9.4-63.2 µg·kg(-1)·hr(-1)). Pruritis occurred in 36% of patients in the PCA group compared to continuous opioid infusion (27%) and epidural administration (27%). Pruritus intensity difference ≥ 50% was achieved in 55.6% of nalbuphine and 57.9% of saline-treated subjects. CONCLUSION: This preliminary report suggests that nalbuphine 50 µg·kg(-1) iv is not effective in treating postoperative opioidinduced pruritus in pediatric patients. The modified CAS score and PrID warrant further investigation. OBJECTIF: Évaluer l'efficacité de la nalbuphine contre le prurit (Pr) postopératoire induit par les opioïdes chez des patients pédiatriques. MéTHODE: Nous avons recruté 212 sujets de ≥ sept ans qui ont reçu une analgésie opioïde postopératoire. Une échelle analogique de couleur (EAC) modifiée pour l'auto-évaluation a mesuré les scores d'intensité du prurit (IPr). Répartis au hasard, les sujets dont les scores d'IPr étaient ≥ 5/10 ont reçu de la nalbuphine à 50 µg·kg(-1) iv (5 mg maximal) ou un placebo salin. Une différence d'intensité de prurit (DIPr) ≥50% était considérée positive. RéSULTATS: Des 260 sujets rencontrés, 212 ont participé à l'étude et 184 ont reçu des opioïdes. L'âge moyen a été de 13 ans (7-19) et le poids moyen de 51 kg (19,6-134,8 kg). Un prurit ≥ 5/10 a été noté chez 37 (20,1 %) des sujets. De la morphine intraveineuse [en analgésie auto-contrôlée (AAC) ou en perfusion continue] a été associée à du Pr chez 68 % des sujets pour un grand éventail de doses (9,4-63,2 µg·kg(-1)·h(-1)). Le prurit s'est manifesté chez 36 % des patients avec l'AAC comparée à la perfusion d'opioïde continue (27 %) et à l'administration péridurale (27 %). Une différence d'intensité du prurit ≥ 50 % a été atteinte chez 55,6 % des sujets qui recevaient la nalbuphine et 57,9 % de ceux qui avaient le placebo. CONCLUSION: La nalbuphine iv à 50 µg·kg(-1) n'est pas efficace pour traiter le prurit postopératoire induit par les opioïdes chez des patients pédiatriques. Le score modifié à l'EAC et la DIPr devront être étudiés plus à fond.

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. METHODS: A single-agent, procedural sedation protocol using titrated doses of ketamine i.v. (maximum 2 mg.kg(-1)) was conducted in outpatient pediatric oncology patients undergoing lumbar puncture (LP), bone marrow biopsy/aspiration (BMBx/A) or combination (LP/BMBx/A) in a tertiary care setting. The efficacy of analgesia and sedation (ability to perform the procedure), procedure duration, recovery time and the occurrence of adverse events are described. RESULTS: Fifty-eight subjects of a median age of 5 years (1-13) and median weight of 20 kg (10.5-68) underwent 119 sedations. An LP was performed in 73% of cases, a BMBx/A in 13% and LP/BMBx/A in 13%. Efficacy was 100% and the mean dose of ketamine was 1.3 mg.kg(-1) (0.4). The mean duration of the procedure was 6.6 min (4.2) and the recovery time was 11 min (4-45). Two subjects (1.7%) had a hypoxemia (SpO2 of <94%). No major airway complications occurred. The prevalence of hypertension (systolic > 20% at 5 min) was 54%. The median pain visual analogue score (VAS) for an observer was 0 (range 0-3) and caregiver was 0 (range 0-4). The median VAS for satisfaction (observer) was 10 (range 7-10) and caregiver VAS was also 10 (range 5-10). At 24 h after discharge, the incidence of bad dreams was 3.3%; vomiting, 10.8%; and abnormal behavior, 4.2%. CONCLUSION: Ketamine i.v. up to 2 mg.kg(-1) is an effective sedative for oncology procedures using a defined protocol.

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. METHODS: A systematic review was conducted to identify randomized control trials comparing the use of local anaesthetic to local anaesthetic with nonopioid additives for caudal blockade in children. The increase in duration of analgesia and side-effects were compared. RESULTS: The addition of clonidine to the local anaesthetic solution produces an increase in the duration of analgesia following caudal blockade in children (pooled weighted mean difference of 145 min with 95% confidence interval of 132-157 min). Side-effects include sedation and the potential for neonatal respiratory depression. Ketamine and midazolam further increase the duration of analgesia, however, the potential for neurotoxicity remains a concern. CONCLUSION: The evidence examined shows an increased duration of analgesia with clonidine, ketamine and midazolam. However, we are not convinced that the routine use of these adjuvants in the setting of elective outpatient surgery shows improved patient outcome. It is unclear if the potential for neurotoxicity is outweighed by clinical benefits. Further testing, including large clinical trials, is required before recommending routine use of nonopioid additives for caudal blockade in children.

The analgesic efficacy of preoperative high dose (40 mg x kg(-1)) oral acetaminophen after bilateral myringotomy and tube insertion in children.

BACKGROUND: The purpose of this study was to measure the plasma levels and analgesic effectiveness of a dose of 40 mg x kg(-1) of preoperative oral acetaminophen. METHODS: Thirty children aged 55 (17-72) months undergoing bilateral myringotomy and tube insertion (BMT) received acetaminophen 40 mg x kg(-1) p.o. preoperatively. Plasma levels were measured, at 29 (10-51) min and at 60 min in the postanaesthesia care unit (PACU). Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), for all subjects and the Poker Chip Tool (PCT) a self-report scale for subjects aged > 4 years, were used. After discharge, 24-h analgesic efficacy was evaluated using an observer Visual Analogue Scale (VAS) score and further acetaminophen use was recorded. RESULTS: Plasma concentrations were 259 (60-391) micromol x l(-1) and 250 (135-450) micromol x l(-1), respectively. All 60 min plasma concentrations were > or = 70 micromol x l(-1) (ED50 for adenotonsillectomy) and less than 800 micromol x l(-1) (associated with toxicity). Twenty-six subjects (87%) had adequate analgesia (CHEOPS < or = 8). The PCT was only understood in the PACU by 13 of the 21 children > 4 years (62%). The median worst 24-h observer VAS was 0.5 (0-5.5) (27 subjects). No further analgesic was required after discharge in 16/28 (57%). A higher plasma level was associated with fewer doses of acetaminophen after discharge (r = -0.36, P=0.05). CONCLUSIONS: No relationship was evident between age, the 60 min plasma acetaminophen level and the CHEOPS carried out at the same time. Acetaminophen 40 mg x g(-1) p.o. results in 60 min plasma levels of 250 (135-450) micromol x l(-1). The in-hospital analgesic efficacy was 87% (CHEOPS < 9, no further analgesics) and the 24-h efficacy was 57% (need for further acetaminophen).