A randomized double-blind trial of intranasal dexmedetomidine versus intranasal esketamine for procedural sedation and analgesia in young children.

BACKGROUND: Procedural sedation and analgesia are commonly used in the Emergency Departments. Despite this common need, there is still a lack of options for adequate and safe analgesia and sedation in children. The objective of this study was to evaluate whether intranasal dexmedetomidine could provide more effective analgesia and sedation during a procedure than intranasal esketamine. METHODS: This was a double-blind equally randomized (1:1) superiority trial of 30 children aged 1-3 years presenting to the Emergency Department with a laceration or a burn and requiring procedural sedation and analgesia. Patients were randomized to receive 2.0 mcg/kg intranasal dexmedetomidine or 1.0 mg/kg intranasal esketamine. The primary outcome measure was highest pain (assessed using Face, Legs, Activity, Cry, Consolability scale (FLACC)) during the procedure. Secondary outcomes were sedation depth, parents' satisfaction, and physician's assessment. Comparisons were done using Mann-Whitney U test (continuous variables) and Fisher's test (categorical variables). RESULTS: Adequate analgesia and sedation were reached in 28/30 patients. The estimated sample size was not reached due to changes in treatment of minor injuries and logistical reasons. The median (IQR) of highest FLACC was 1 (0-3) with intranasal dexmedetomidine and 5 (2-6.75) with intranasal esketamine, (p-value 0.09). 85.7% of the parents with children treated with intranasal dexmedetomidine were "very satisfied" with the procedure and sedation compared to the 46.2% of those with intranasal esketamine, (p-value 0.1). No severe adverse events were reported during this trial. CONCLUSIONS: This study was underpowered and did not show any difference between intranasal dexmedetomidine and intranasal esketamine for procedural sedation and analgesia in young children. However, the results support that intranasal dexmedetomidine could provide effective analgesia and sedation during procedures in young children aged 1-3 years with minor injuries. TRIAL REGISTRATION: Eudra-CT 2017-00057-40, April 20, 2017. https://eudract.ema.europa.eu/.

Educational Intervention to Strengthen Pediatric Postoperative Pain Management: A Cluster Randomized Trial.

BACKGROUND: Pediatric postoperative pain is still undertreated. AIMS: To assess whether educational intervention increases nurses' knowledge and improves pediatric postoperative pain management. DESIGN: Cluster randomized controlled trial with three measurement points (baseline T1, 1 month after intervention T2, and 6 months after intervention T3). PARTICIPANTS/SUBJECTS: The study was conducted in postanesthesia care units at six hospitals in Norway. Nurses working with children in the included units and children who were undergoing surgery were invited to participate in this study. METHODS: Nurses were cluster randomized by units to an intervention (n = 129) or a control group (n = 129). This allocation was blinded for participants at baseline. Data were collected using "The Pediatric Nurses' Knowledge and Attitudes Survey Regarding Pain: Norwegian Version" (primary outcome), observations of nurses' clinical practice, and interviews with children. The intervention included an educational day, clinical supervision, and reminders. RESULTS: At baseline 193 nurses completed the survey (75% response rate), 143 responded at T2, and 107 at T3. Observations of nurses' (n = 138) clinical practice included 588 children, and 38 children were interviewed. The knowledge level increased from T1 to T3 in both groups, but there was no statistically significant difference between the groups. In the intervention group, there was an improvement between T1 and T2 in the total PNKAS-N score (70% vs. 83%), observed increase use of pain assessment tools (17% vs. 39%), and children experienced less moderate-to-severe pain. CONCLUSIONS: No significant difference was observed between the groups after intervention, but a positive change in knowledge and practice was revealed in both groups. Additional studies are needed to explore the most potent variables to strengthen pediatric postoperative pain management.

Rapid systemic uptake of naloxone after intranasal administration in children.

BACKGROUND: Naloxone has a high affinity for the µ-opioid receptor and acts as a competitive antagonist, thus reversing the effects of opioids. Naloxone is often administrated intravenously, but there is a growing interest in the intranasal route in treating patients with opioid overdose, and in reversing effects after therapeutic use of opioids. As administration is painless and no intravenous access is needed, the intranasal route is especially useful in children. AIM: The aim of this study was to investigate the uptake of naloxone 0.4 mg/ml during the first 20 min after administration as a nasal spray in a pediatric population, with special focus on the time to achieve maximum plasma concentration. METHODS: Twenty children, 6 months-10 years, were included in the study. The naloxone dose administered was 20 µg/kg, maximum 0.4 mg, divided into repeated doses of 0.1 ml in each nostril. Venous blood samples were collected at 5, 10, and 20 min after the end of administration. RESULTS: All patients had quantifiable concentrations of naloxone in venous blood at 5 min, and within 20 min, peak concentration had been reached in more than half of the children. At 20 min after intranasal administration, the plasma naloxone concentrations were within the range of 2-6 nanogram/ml. CONCLUSION: This study confirms the clinical experience that the rapid effect of naloxone after intranasal administration in children was reflected in rapid systemic uptake to achieve higher peak plasma concentrations than previously reported in adults.

Postoperative pain, pain management, and recovery at home after pediatric tonsil surgery.

PURPOSE: To explore the severity and duration of postoperative pain, the management of analgesics, and postoperative recovery in children undergoing tonsil surgery. METHOD: Participants included 299 children aged 4-17 years undergoing tonsillotomy ± adenoidectomy (TT ± A) or tonsillectomy ± adenoidectomy (TE ± A). Data were collected up to 12 days. The child rated pain on the Face Pain Scale-Revised (FPS-R) and recovery using the Postoperative Recovery in Children (PRiC) questionnaire. Caregivers assessed their child's pain, anxiety, and nausea on a numeric analog scale and kept a log of analgesic administration. RESULTS: High pain levels (FPS-R ≥ 4) were reported in all surgical and age groups (TT ± A age 4-11, TE ± A age 4-11, TE ± A age 12-17), but there were variations in pain intensity and duration within and between groups. The TE ± A group scored more days with moderate to very excruciating pain and lower recovery than the TT ± A group, with the worst outcomes reported by older TE ± A children. The majority of the children used paracetamol + COX-inhibitors at home, but regular administration of analgesics was lacking, particularly during late evening and at night. Few were received rescue medication (opioid or clonidine) despite severe pain. Physical symptoms and daily life activities were affected during the recovery period. There was moderate agreement between child and the caregiver's pain assessment scores. CONCLUSION: Children reported a troublesome recovery with significant postoperative pain, particularly older children undergoing tonsillectomy. Pain treatment at home was suboptimal and lacked regular analgesic administration. Patient information needs to be improved regarding the importance of regular administration of analgesics and rescue medication.

Children's views on postsurgical pain in recovery units in Norway: A qualitative study.

AIMS AND OBJECTIVES: To explore children's postsurgical experiences with pain and pain management in the recovery unit. BACKGROUND: Children's pain is underestimated and undertreated. Untreated pain can cause unnecessary suffering, increased complication risks and may lead to chronic pain. Research exploring children's experiences with postoperative pain and pain management is limited. DESIGN: A qualitative, exploratory study. The study complied with the Consolidated Criteria for Reporting Qualitative Research (COREQ). METHODS: Children (N = 20), 8-16 years old, took part in semi-structured interviews about their experiences with pain and postoperative pain management while they were in a recovery unit. Data were collected at two university hospitals in Norway. Content analysis was used to analyse the data. RESULTS: Three themes emerged from the interviews: "children's experiences of what felt unpleasant and painful," "children's experiences with pain management" and "children's recommendations for future pain management". About half of the children reported moderate to severe pain while in the recovery unit and they did not always tell their nurses when they had pain. They also reported experiencing pain in places other than their surgical wounds and stated that nausea and vomiting felt unpleasant and painful. The children indicated that pain medications and the use of nonpharmacological methods helped them cope with their pain and provided several recommendations about how to improve pain management. CONCLUSION: Paediatric postoperative pain management remains suboptimal. The children in our study provided useful information about their pain experiences, how to improve pain management and explained why they did not tell their nurses when they were in pain. RELEVANCE TO CLINICAL PRACTICE: These findings should direct further improvements in paediatric postoperative pain management, such as increased use of pain assessment tools and preparatory information, as well as more appropriate administration of pain medications.

Nurses' Knowledge, Attitudes and Clinical Practice in Pediatric Postoperative Pain Management.

BACKGROUND: Despite readily available evidence to guide practice, children continue to experience moderate to severe pain in hospital postoperatively. Reasons for this may include attitudes of nurses toward pain management and their lack of knowledge in key areas. AIMS: To identify nurses' knowledge and clinical practice of pediatric postoperative pain management and whether there is a link between knowledge and practice. DESIGN AND SETTING: A descriptive cross-sectional study including a questionnaire and observations was conducted in postanesthesia care (recovery) units in six university hospitals in Norway. METHODS: Nurses completed the Pediatric Nurses' Knowledge and Attitudes Survey Regarding Pain Questionnaire-Norwegian Version (PNKAS-N). We observed their clinical practices using a structured observational tool and field notes. RESULTS: Nurses completed the PNKAS-N (n = 193) and were observed (n = 138) giving postoperative care to 266 children (70 hours per unit, 416 hours in total). The mean PNKAS-N score was 29 (standard deviation 4.2) of 40. We identified knowledge deficits, mainly in pharmacologic management, such as in risk of addiction and respiratory depression. We found that, overall, pain was assessed using validated tools in 19% of the children; this fell to 9% in children aged <5 years. More than 66% of children received an inadequate dose of morphine postoperatively. CONCLUSION: Nurses have knowledge deficits about pediatric pain management and do not always use their knowledge in practice, particularly in relation to pain assessment. There is a need to improve nurses' knowledge of pediatric pain management and to test interventions that support the use of that knowledge in practice.

Plasma levels of levobupivacaine during continuous infusion via a wound catheter after major surgery in newborn infants: An observational study.

BACKGROUND: Epidurals may be challenging in neonatal patients due to technical difficulties relating to insertion and the risk of local anaesthesia toxicity. The use of wound catheters with an infusion of local anaesthetic has been shown to be well tolerated in adults and older children. There are few data concerning wound catheter techniques in neonatal patients. OBJECTIVES: The primary aim of this study was to analyse plasma levels of levobupivacaine associated with continuous wound infiltration via a catheter following neonatal surgical procedures. Secondary parameters, including the quality of postoperative analgesia and wound healing, were also noted. DESIGN: A prospective, observational study. SETTING: Paediatric ICU at the Karolinska University Hospital, Stockholm, Sweden, from March 2008 to December 2010. PATIENTS: Twenty newborn infants (median weight 3.48 kg) scheduled for major abdominal or thoracic surgery were included. Exclusion criteria were known or suspected hepatic dysfunction. Before skin closure, a subcutaneous catheter was inserted into the wound followed by a 0.5 mg kg(-1) bolus of levobupivacaine (0.125%, 0.4 ml kg(-1)) through the catheter. A continuous infusion was started 20 to 30 min later at a rate of 0.2 mg kg(-1)h(-1) (0.16 ml kg(-1) h(-1)). MAIN OUTCOME MEASURES: Plasma concentrations of levobupivacaine (total and unbound) at 12, 24, 48 and 72 h postoperatively. Morphine consumption, pain scores and wound healing were also analysed. RESULTS: Median concentrations of unbound and total levobupivacaine at 72 h were 0.018 and 1.305 µg ml(-1), respectively. In 18 out of 20 infants [90%; 95% confidence interval (CI) 68.3 to 98.8], the unbound plasma concentration of levobupivacaine remained relatively stable and below 0.05 µg ml(-1) throughout the 72 h observation period. Pain scores and morphine consumption levels were low. All wounds except one healed within 10 days. CONCLUSION: The studied infusion regimen was associated with plasma levels of levobupivacaine well below those associated with toxicity. Adequate wound healing, low pain scores and a reduced need for opioids were also noted.

Plasma concentrations of levobupivacaine associated with two different intermittent wound infusion regimens following surgical ductus ligation in preterm infants.

BACKGROUND: Administration of local anesthetics by a surgically placed wound catheter has recently been shown to reduce the need for postoperative morphine administration in extremely preterm infants undergoing ductus ligation. The primary aim of this randomized safety study was to define the plasma levels of levobupivacaine (LB) following two different intermittent infusion regimens. METHODS: Eighteen preterm infants 23-27 gestational weeks, median birthweight 721 g scheduled for ductus ligation were included in the study. All patients were anesthetized according to a standardized protocol based on high-dose fentanyl (25-50 µg·kg(-1) ). Before skin closure, a subcutaneous catheter was inserted into the wound. The patients were randomized to receive one of the two intermittent infusion regimens: Group BII: Initial bolus plus early start of the intermittent infusion or Group DII: No bolus plus delayed start (8 h) of the intermittent infusion. Blood samples for determination of LB plasma concentrations were obtained on six occasions during the 24-h postoperative observation period, as well as hourly postoperative pain assessments using the Echelle Douleur Inconfort Noveau (EDIN) pain scale. RESULTS: Plasma concentrations of LB ranged from 0.094 to 1.682 µg·ml(-1) and 0 to 0.549 µg·ml(-1) in group BII and DII, respectively. Both regimens were associated with low postoperative EDIN pain scores (24 h median of 0 and 1 in group BII and DII, respectively). No signs of systemic local anesthetic toxicity were noted. CONCLUSIONS: The two studied intermittent infusion regimens were associated with plasma levels below potentially toxic levels and were both associated with adequate postoperative pain scores.

Pain in children--are we accomplishing the optimal pain treatment?

Morphine, paracetamol and local anesthetics have for a long time been the foremost used analgesics in the pediatric patient by tradition but not always enough effective and associated with side effects. The purpose with this article is to propose alternative approaches in pain management, not always supported up by substantial scientific work but from a combination of science and clinical experience in the field. The scientific literature has been reviewed in parts regarding different aspects of pain assessment and analgesics used for treatment of diverse pain conditions with focus on procedural and acute pain. Clinical experience has been added to form the suggested improvements in accomplishing an improved pain management in pediatric patients. The aim with pain management in children should be a tailored analgesic medication with an individual acceptable pain level and optimal degree of mobilization with as little side effects as possible. Simple techniques of pain control are as effective as and complex techniques in pediatrics but the technique used is not of the highest importance in achieving a good pain management. Increased interest and improved education of the doctors prescribing analgesics is important in accomplishing a better pain management. The optimal treatment with analgesics is depending on the analysis of pain origin and analgesics used should be adjusted thereafter. A multimodal treatment regime is advocated for optimal analgesic effect.

Aspects of pharmacokinetics and pharmacodynamics of sufentanil in pediatric practice.

Sufentanil is a potent synthetic opioid. Like other opioids, sufentanil creates a stable hemodynamic environment in cardiovascularly compromised pediatric patients. Clearance, expressed as per kilogram, is increased in children compared to adults. The P450 CYP3A4 enzyme is responsible for the major metabolic N-dealkylation pathway. Enzyme activity is reduced in neonates but the maturation of sufentanil clearance is not described. The free active fraction is affected by age because of the reduced α(1) -acid glycoprotein plasma concentrations in neonates. Intranasal administration of sufentanil is a possible option for premedication, procedural sedation and analgesia in children, as this option has been found to be safe and effective. Studies concerning the pharmacokinetics and dynamics of sufentanil administered as a bolus or continuous infusion in children are few.

Effect of oral naloxone hydrochloride on gastrointestinal transit in premature infants treated with morphine.

BACKGROUND: Opioids are common drugs for pain treatment in preterm newborn infants, in spite of several adverse effects. Constipation is a frequent problem when opioids are used in both adults and neonates. Although several studies indicate that the oral administration of naloxone hydrochloride (NH) improves intestinal motility during opioid therapy, there is still a lack of evidence in newborns. AIM: The aim of this study was to assess the efficacy of NH against reduced intestinal motility during opioid treatment. METHODS: A retrospective cohort study was performed. We analysed the medical records of fifteen infants (Group 1) treated with continuous morphine (MO) infusion and fourteen infants (Group 2) treated with both oral NH (3 microg/kg 4 times daily) and MO. RESULTS: There was no statistically significant difference in the total MO dose. Infants treated both with NH and MO had a tendency to improve their mean stool frequency/day. A statistically significant improvement was observed in the mean total food intake (mL/kg/day) of the infants treated with NH (p = 0.014). No difference in the mean food retention between the two groups was observed. CONCLUSION: Orally administrated NH seems to improve intestinal motility resulting in increased food intake/day and improved stool frequency/day in premature newborn infants treated with MO. Further studies are needed to corroborate these findings.

Perception of pain following rectal administration of morphine in children: a comparison of a gel and a solution.

BACKGROUND: Rectal administration of morphine is one possible route of delivery in children. The aim of this study was to determine the pain experience during rectal administration of two different morphine preparations. METHODS: The acceptance of the pain of rectal administration of morphine for premedication was studied in 120 children. Children were randomized to receive either morphine solution in saline (0.2 mg.kg(-1), 1 mg.ml(-1)) or morphine gel (0.2 mg.kg(-1), 1 mg.ml(-1)) with an adjusted pH for rectal use in a double-blind fashion. Children were stratified into three groups according to age (1-2, 3-6, and 7-10 years). Pain was assessed with the Children's Hospital of Eastern Ontario Pain Scale, the McGrath Facial Affective Scale, or the visual analogue scale, depending on the age group. RESULTS: The overall pain scores in all age groups were low. Children aged 1-2 years (P < 0.01) and 3-6 years (P < 0.05) had significantly less pain when morphine was administered as a gel than a solution. The difference in pain experience between the two forms was not significant in the age group of 7-10 years. CONCLUSION: The results indicate that most of the children tolerated rectal administration of morphine well in terms of pain experience, in both gel and solution form. The morphine gel, intended for rectal use appears to be the preparation of choice in children aged 1-6 years.