Opioids In Children Research Articles

Single-dose Intraoperative Methadone for Pain Management in Pediatric Tonsillectomy: A Randomized Double-blind Clinical Trial.

More than 500,000 elective tonsillectomies are performed in U.S. children annually. Pain after pediatric tonsillectomy is common, often severe, and undertreated. There is no consensus on the optimal management of perioperative tonsillectomy pain. Methadone, with an elimination half-life of 1 to 2 days, has a longer duration of effect than short-duration opioids such as fentanyl. The primary objective of this study was to investigate the intraoperative use of methadone for pediatric tonsillectomy. It tested the hypothesis that methadone would result in less postoperative opioid use compared with short-duration opioids in children after tonsillectomy. This double-blind, randomized, parallel group trial in children (3 to 17 yr) undergoing tonsillectomy compared single-dose intravenous methadone (0.1 mg/kg then 0.15 mg/kg age-ideal body weight, in a dose escalation paradigm) versus as-needed short-duration opioid (fentanyl) controls. Opioid use, pain, and side effects were assessed in-hospital and 7 days postoperatively via electronic surveys. The primary outcome was total 7-day opioid use in oral morphine equivalents per kilogram (kg). Secondary outcomes were opioid use in the postanesthesia care unit, daily pain scores, and total number of 7-day opioid doses used. Data analysis included 60 children (20/group), age 5.9 ± 3.7 yr (mean ± SD; median, 4; range, 3 to 17). Total 7-day opioid use (oral morphine equivalents per kg median [interquartile range]) was 1.5 [1.2, 2.1] in controls, 0.9 [0.1, 1.4] after methadone 0.1 mg/kg (P = 0.045), and 0.5 [0, 1.4] after methadone 0.15 mg/kg (P = 0.023). Postanesthesia care unit opioid use (oral morphine equivalents per kg) in controls was 0.15 [0.1, 0.3], 0.04 [0, 0.1] after methadone 0.1 mg/kg (P = 0.061). and 0.0 [0, 0.1] after methadone 0.15 mg/kg (P = 0.021). Postoperative pain scores were not different between groups. No serious opioid-related adverse events occurred. This small initial study in children undergoing tonsillectomy found that single-dose intraoperative methadone at 0.15 mg/kg age ideal body weight was opioid-sparing compared with intermittent fentanyl.

Opioid Utilization after Cardiac Surgery in the Pediatric Medicaid-Insured Population

To determine the variation of outpatient opioid prescribing across the US in postoperative pediatric cardiac patients. Retrospective, cross-sectional study using a concatenated database of Medicaid claims between from 2016 through 2018 of children 0-17years, discharged after cardiac surgery and receiving an opioid prescription within 30days. Filled prescriptions were identified and converted to morphine milligram equivalents (MME). Use, duration, and dose were analyzed by sex, race, ethnicity, residence urbanicity, and region. Among 17 186 Medicaid-enrolled children after cardiac surgery, 2129 received opioids within 30days of discharge. Females received lower doses than males (coefficient -0.17, P=.022). Hispanic individuals were less likely to receive opioids (coefficient 0.53, P<.05, 95% CI: 0.38-0.71) and for shorter periods (coefficient 0.83, P<.001). Midwest (MW) (OR 0.61, 95% P-values < 0.05, 95% CI: 0.46-0.80) and Northeast (NE) (OR 0.43, 95% P-values < 0.05, 95% CI: 0.30-0.61) regions were less likely to receive opioids but used higher doses compared with the Southeast (SE) (MW coefficient 0.41, Southwest (SW) coefficient 0.18, NE coefficient 0.32, West (W) coefficient 0.19, P<.05). There were significant variations in opioid prescribing after cardiac surgery by race, ethnicity, sex, and region. National guidelines for outpatient use of opioids in children after cardiac surgery may help limit practice variation and reduce potential harms in outpatient opioid usage.

Analysis of Factors Affecting Postoperative Opioid Requirement in Pediatric Patients Undergoing Pectus Excavatum Repair with Multimodal Analgesic Management.

Children with pectus excavatum are treated with surgical repair in a procedure known as minimally invasive repair of pectus excavatum (MIRPE). MIRPE causes considerable postoperative pain, resulting in the administration of a substantial dose of opioids. This study aimed to identify perioperative factors that influence the requirement for opioids in children undergoing MIRPE. Retrospective data from children who underwent MIRPE were analyzed. A multimodal analgesic protocol was implemented with a continuous wound infiltration system and administration of non-opioid analgesics. Intravenous opioid analgesics were administered if the pain score was greater than 4. The cumulative opioid use was assessed by calculating the morphine equivalent dose at 6, 24, and 48 h after surgery. Perioperative factors affecting the postoperative opioid use were identified with multiple linear regression analyses. This study included 527 children aged 3-6 years, with a mean age of 3.9 years. Symmetrically depressed chest walls, a lower Haller index, and a lower revised depression index were found to be associated with decreased postoperative opioids. Boys required higher opioid doses than girls. Longer pectus bars (10 inches versus 9 inches) were associated with increased opioid use. Severity indices, gender, and the length of pectus bars influence postoperative opioid requirement in children undergoing MIRPE surgery with multimodal analgesia.

Risk of exposure to prescription opioids in children and adolescents with autism spectrum disorder: A nationwide longitudinal study.

Whether children and adolescents with autism spectrum disorder (ASD) are more likely to be exposed to prescription opioids than others remains unknown. The Taiwan National Health Insurance Research Database was employed, and 14,849 children and adolescents with ASD and 148,490 age- and sex-matched non-ASD controls were enrolled between 2001 and 2009 and followed up till the end of 2011. Those exposed to prescription opioids during the follow-up period were identified. Patients with ASD were more likely to be exposed to prescription opioids (hazard ratio [HR]: 4.95, 95% confidence interval [CI]: 4.50-5.45), including intravenous or intramuscular opioids (HR: 5.80, 95% CI: 5.23-6.43) and oral or transcutaneous opioids (HR: 2.32, 95% CI: 1.87-2.89), than were non-ASD controls. Furthermore, the ASD cohort had the increased likelihood of cumulative exposure of >14 days (HR: 6.19, 95% CI: 4.91-7.79) and >30 days (HR: 7.17, 95% CI: 5.19-9.90) to prescription opioids compared with the control cohort. ASD was a risk factor for exposure to prescription opioids. Close monitoring of prescription opioid use is necessary for at-risk children and adolescents with ASD, such as those having with or chronic pain. We found that patients with ASD were more likely to be exposed to prescription opioids, including intravenous or intramuscular opioids and oral or transcutaneous opioids, than were non-ASD controls. We suggest that close monitoring of prescription opioid use is necessary for at-risk children and adolescents with ASD, such as those having with or chronic pain.

Pupil response to painful stimuli during inhalation anaesthesia without opioids in children.

Pupil dilation reflex measured by a pupillometer is known to be a useful parameter for assessing the response to perioperative noxious stimuli. In children, pupillometer can reflect changes after painful stimuli during anaesthesia or guide anaesthesia to reduce opioid consumption. However, to date, there are no data regarding pupil response during inhalation anaesthesia with analgesia by intravenous acetaminophen in children. We planned a prospective, single-armed study of children aged between 3 and 12 years who underwent surgery under general anaesthesia. Anaesthesia was maintained by 1 minimum alveolar concentration (MAC) of sevoflurane, and 15 mg/kg of acetaminophen was administered. Patients' left eye was examined using a pupillometer after induction, before and after skin incision and train-of-four stimulus. Pupil diameter and other pupillometric parameters were recorded. Increase in heart rate by 15% was regarded as insufficient analgesia to skin incision and indicative powers of pupillometric parameters for insufficient analgesia were examined by receiver-operating characteristics. A total of 33 patients were included. Enlarged pupil, large increase in pupil diameter and low neurological pupil index (NPi) after skin incision were good indicators of insufficient analgesia for skin incision. Children with insufficient analgesia showed abnormal NPi value. However, increase in pupil diameter and decrease in NPi were observed even in patients without increase in the heart rate after the skin incision. We suggest dilation of the pupil and decrease in NPi can indicate response to noxious stimuli in children. Regardless of sufficiency of analgesia, pupil dilation and decrease in NPi were observed after skin incision in children under general anaesthesia with 1 MAC of sevoflurane and intravenous acetaminophen.

Variability in discharge opioid prescribing practices for children: a historical cohort study.

Legitimate opioid prescriptions can increase the risk of misuse, addiction, and overdose of opioids in children and adolescents. This study aimed to describe the prescribing patterns of discharge opioid analgesics following inpatient visits and to determine patient and prescriber characteristics that are associated with prolonged opioid prescription. In a historical cohort study, we identified patients discharged from hospital with an opioid analgesic prescription in a tertiary pediatric hospital from 1 January 2016 to 30 June 2017. The primary outcome was the duration of opioid prescription in number of days. We assessed the association between patient and prescriber characteristics and an opioid prescription duration > five days using a generalized estimating equation to account for clustering due to repeated admissions of the same patient. During the 18-month study period, 15.4% of all admitted patients (3,787/24,571) were given a total of 3,870 opioid prescriptions at discharge. The median [interquartile range] prescribed duration of outpatient opioid therapy was 3.75 [3.00-5.00] days. Seventy-seven percent of the opioid prescriptions were for five days or less. Generalized estimating equation analysis revealed that hospital stay > four days, oxycodone prescription, and prescription by clinical fellows and the orthopedics service were all independently associated with a discharge opioid prescription of > five days. Most discharge opioids for children were prescribed for less than five days, consistent with current guidelines for adults. Nevertheless, the dosage and duration of opioids prescribed at discharge varied widely.

Mortality by opioid poisoning in children and teenagers and opioid prescriptions

BackgroundNo comparisons between mortality from opioids in children and teenagers and opioid prescription patterns have been made in England.AimTo investigate if an association exists between mortality rates from opioid poisoning in persons aged 19 years old and under and community opioid prescription in England.MethodsA retrospective analysis was undertaken for 2016 to 2019, comparing community opioid prescriptions and mortality rates from opioid poisoning.ResultsThe number of opioid prescriptions decreased over the study period (− 2.4%, p < 0.001). Most deaths due to opioid poisoning in children and teenagers were seen in those under one year old and those aged between 15 and 19 years old (Kruskal-Wallis: p = 0.12; Dunn’s test: p = 0.01). Deaths in all age ranges did not change significantly (Poisson Regression Analysis: p > 0.05).ConclusionDespite the reduction in community opioid prescriptions, there was no decrease in the number of deaths in children and teenagers due to opioid poisoning.

94 Short-term use of therapeutic opioids for children and future opioid use disorders: A systematic review and qualitative study of decision-maker information needs

Abstract Primary Subject area Emergency Medicine - Paediatric Background Healthcare visits, hospitalizations, and deaths due to opioid-related harms continue to rise for children, despite an overall decline in opioid prescriptions. Decision-makers (including patients and families, clinicians, and policy-makers) require high quality syntheses to inform decisions regarding opioid use. Previous research has found that how systematic review (SR) results are presented may influence uptake by decision-makers. Evidence summaries are appealing to decision-makers as they provide key messages in a succinct manner. Objectives 1) To conduct an SR examining the association between short-term therapeutic exposure to opioids in children and development of opioid use disorder, and 2) To gain perspectives from policy decision-makers on the usability and presentation of results through the form of an evidence summary. Design/Methods We conducted an SR following methods recommended by Cochrane. A medical librarian conducted a comprehensive search and two authors were involved in study selection, data extraction and quality assessment. Studies were eligible if they reported primary research in English or French, and study participants had therapeutic exposure to opioids before age 18 years. Results were described narratively. Decision makers were recruited through purposive and snowball sampling methods, and they participated in interviews to discuss an evidence summary based on the SR. Interviews were transcribed and data were analyzed using content analysis. Ethics approval was obtained for the qualitative study. Results Nineteen American studies involving 47,191,990 participants were included. One study demonstrated that short-term therapeutic exposure may be associated with opioid abuse. Four others showed an association without specifying duration of exposure. Fourteen studies provided information on prevalence or incidence of opioid misuse following therapeutic exposure, median 27.8% [interquartile range 21.4% – 30.7%]; notably, 12 of them did not specify duration of therapeutic exposure. Identified risk factors were contradictory and remain unclear. Decision makers had mixed preferences for the presentation of evidence, depending on their degree of involvement in research versus practice. A majority preferred having methods and key characteristics of studies included in the first page of the evidence summary. They noted that the summary should not be text-heavy and details should be appended. Conclusion A number of studies suggest there is an association between lifetime therapeutic opioid use (unknown duration) and future nonmedical opioid use; however, there is limited evidence to determine whether short-term exposure is specifically associated with these outcomes. Policy and decision-makers prefer a succinct evidence summary for this SR, with study-specific details provided as an appendix. PROSPERO Registration: 122681.

Quantitative Pupillometry as a Predictor of Pediatric Postoperative Opioid-Induced Respiratory Depression.

Safe postoperative pain relief with opioids is an unmet critical medical need in children. There is a lack of objective, noninvasive bedside tool to assess central nervous system (CNS) effects of intraoperative opioids. Proactive identification of children at risk for postoperative respiratory depression (RD) will help tailor analgesic therapy and significantly improve the safety of opioids in children. Quantitative pupillometry (QP) is a noninvasive, objective, and real-time tool for monitoring CNS effect-time relationship of opioids. This exploratory study aimed to determine the association of QP measures with postoperative RD, as well as to identify the best intraoperative QP measures predictive of postoperative RD in children. After approval from the institutional review board and informed parental consent, in this prospective, observational study of 220 children undergoing tonsillectomy, QP measures were collected at 5 time points: awake preoperative baseline before anesthesia induction (at the time of enrollment [T1]), immediately after anesthesia induction before morphine administration (T2), 3 minutes after intraoperative morphine administration (T3), at the end of surgery (T4), and postoperatively when awake in postanesthesia recovery unit (PACU) (T5). Intraoperative use of opioid and incidence of postoperative RD were collected. Analyses were aimed at exploring correlations of QP measures with the incidence of RD and, if found significant, to develop a predictive model for postoperative RD. Perioperative QP measures of percentage pupil constriction (CONQ, P = .027), minimum pupillary diameter (MIN, P = .027), and maximum pupillary diameter (MAX, P = .034) differed significantly among children with and without postoperative RD. A predictive model including the minimum pupillary diameter 3 minutes after morphine administration (MIN3), minimum pupillary diameter normalized to baseline (MIN31), and percentage pupillary constriction after surgery (T4) standardized to baseline (T1) (CONQ41), along with the weight-based morphine dose performed the best to predict postoperative RD in children (area under the curve [AUC], 0.76). A model based on pre- and intraoperative pupillometry measures including CONQ, MIN, along with weight-based morphine dose-predicted postoperative RD in our cohort of children undergoing tonsillectomy. More studies with a larger sample size are required to validate this finding.

Efficacy of intravenous lidocaine infusions for pain relief in children undergoing laparoscopic appendectomy: a randomized controlled trial

Intravenous lidocaine, a potent local anesthetic with analgesic and anti-inflammatory properties, has been shown to be an effective adjunct that reduces intra- and postoperative opioid consumption and facilitates pain management in adults. While it shows promise for use in the pediatric population, limited evidence is available.ObjectivesTo determine if general anesthesia with intraoperative intravenous lidocaine infusion versus general anesthesia without intravenous lidocaine infusion in children undergoing laparoscopic appendectomy decreased opioid requirements intra- and postoperatively.DesignA single-center parallel single-masked randomized controlled study. A computer-generated blocked randomization list was used to allocate participants. The study was conducted between March 2019 and January 2020. Setting: Pediatric teaching hospital in Poland.ParticipantsSeventy-four patients aged between 18 months and 18 years undergoing laparoscopic appendectomy. Seventy-one patients fulfilled the study requirements.InterventionIntravenous lidocaine bolus of 1.5 mg/kg over 5 min before induction of anesthesia followed by lidocaine infusion at 1.5 mg/kg/h intraoperatively. The infusion was discontinued before the patients’ transfer to the postanesthesia care unit (PACU).Primary outcome measureThe primary outcome measure was total nalbuphine requirement in milligrams during the first 24 h after surgery.Secondary outcome measuresThe secondary outcome measures were intraoperative fentanyl consumption, intraoperative sevoflurane consumption, time to the first rescue analgesic request, incidence of postoperative nausea and vomiting during the first 24 h after surgery, frequency of side effects of lidocaine.ResultsChildren (n = 74) aged 5–17 randomly allocated to receive intraoperative lidocaine infusion (n = 37) or no intervention (n = 37). Seventy-one were included in the analysis (35 in the study group and 36 in the control group). There was no difference in the cumulative dose of nalbuphine in the first 24 h after removal of the endotracheal tube between groups [median of 0.1061 (IQR: 0.0962–0.2222) mg/kg in the lidocaine group, compared to the control group median of 0.1325 (IQR: 0.0899–0.22020) mg/kg, p = 0.63].Intraoperative fentanyl consumption was lower in the lidocaine group [median of 5.091 (IQR: 4.848–5.714) μg/kg] than in the control group [median of 5.969 (IQR: 5.000–6.748), p = 0.03].Taking into account the additional doses administered based on clinical indications, the reduction in the requirement for fentanyl in the lidocaine group was even greater [median of 0.0 (IQR: 0.0–0.952) vs 0.99 (IQR: 0.0–1.809) μg/kg, p = 0.01].No difference was observed in the sevoflurane consumption between the two groups [median of 32.5 ml (IQR 25.0–43.0) in the lidocaine group vs median of 35.0 ml (IQR: 23.5–46.0) in the control group, p = 0.56].The time to first analgesic request in the lidocaine group was prolonged [median of 55 (IQR: 40–110) min in the lidocaine group vs median of 40.5 (IQR: 28–65) min in the control group, p = 0.05].There was no difference in the frequency of PONV between the two groups (48.57% in the lidocaine group vs 61.11% in the control group, p = 0.29).No lidocaine related incidence of anaphylaxis, systemic toxicity, circulatory disturbances or neurological impairment was reported, during anesthesia or postoperative period.ConclusionsIntraoperative systemic lidocaine administration reduced the intraoperative requirement for opioids in children undergoing laparoscopic appendectomy. This effect was time limited, and hence did not affect opioid consumption in the first 24 h following discontinuation of lidocaine infusion.Trial registrationNCT03886896.

Reducing post-operative opioids in children undergoing outpatient urologic surgery: A quality improvement initiative

Opioid prescriptions have been implicated as one of the proximate causes of the national opioid epidemic. Children and adolescents and their families are at risk for increased opioid exposure through prescriptions after surgery. In pediatric urologic surgery, indications for postoperative opioids can vary widely and a focus on opioid stewardship is important to reduce potential harms. To measure the efficacy of a quality improvement initiative aimed to reduce post-operative opioids for pain management in a large pediatric surgical cohort. Patients undergoing ambulatory pediatric urologic surgery at a tertiary children's hospital between July 2016 to June 2019 were analyzed. Structured physician peer-to-peer comparisons, electronic health record redesign and a standardized pain management protocol were implemented. Rate of opioid prescriptions per month, utilization of non-opioid analgesia, unplanned encounters in the emergency department and/or office during implementation were aggregated. Opioid doses and prescribed opioid days before and after protocol implementation were analyzed. A subcohort, from October-December 2018 was administered a patient-reported outcome questionnaire focused on pain management and return to baseline activity. A total of 6684 consecutive outpatient urologic cases were included (median age=3.3 years old (IQR 0.9-9.2) and 92.3% male). Comparing 6 months pre-intervention and the post-intervention latest 6 month intervals, opioid prescription rate decreased from 43.9% to 2.3% (p<0.001). Additionally, non-opioid analgesia with ketorolac increased from 30.7% to 50.6% (p<0.001). Concurrently, no differences in the rate of office visits within 5 days, overall ED visits, ED visits for pain or for bleeding within 30 days after implementation were identified. Between October to December 2018, 373 cases were performed and a Patient-Reported Outcome (PRO) questionnaire was completed for 128 of those patients (34%). Families reported a low patient pain score of 3.7 (SD 2.4) and a rapid postoperative recovery time of a median 2 (IQR 1-4) days to full resumption of pre-operative level of activity. High satisfaction with opioid reduction in post-operative pain management was reported (median score of 10 (IQR 8-10)). Opioid prescriptions and utilization may be minimized without increasing unplanned encounters or adversely affecting quality of life. The QI framework utilized in this process can be implemented to reduce opioid exposure in other surgical patient populations.

Prescribing of Nonsteroidal Anti-inflammatory Drugs, Tramadol, and Opioids in Children: Patterns of Its Utilization.

ABSTRACTBackground:Analgesic is commonly used in children but little is known about its patterns of utilization. This study explored the patterns of analgesic prescribing in children.Materials and Methods:This cross-sectional study used prescription databases of tertiary hospital settings in Malaysia from 2010 to 2016. Prescriptions for nine NSAIDs (diclofenac, ketoprofen, etoricoxib, celecoxib, ibuprofen, indomethacin, mefenamic acid, meloxicam, and naproxen), tramadol, and five other opioids (morphine, oxycodone, fentanyl, buprenorphine, and dihydrocodeine) prescribed for children aged <18 years were included. Number of annual patients and prescriptions were measured and analyzed using Stata v15.Results:During a 7-year study period, a total of 5040 analgesic prescriptions of the nine NSAIDs, tramadol, and five other opioids were prescribed for 2460 pediatric patients (81.8% NSAIDs patients, 17.9% tramadol patients, and 0.3% opioid patients). Ibuprofen was the primary analgesic in young children less than 12 years old (≤2 years old [y.o.] [75%], 3–5 y.o. [85%], and 6–12 y.o. [56.3%]). However, there was a wide range of analgesics used in older children (>12 y.o.) with the majority for naproxen (13–15 y.o. (28.2%) and 16–17 y.o. (28.2%). Other frequently prescribed analgesics for older children included ibuprofen (20.6%) and diclofenac (18.2%) for 12–15 y.o. and diclofenac (26.7%) and tramadol (17.6%) for 16–17 y.o.Conclusion:Ibuprofen was the primary analgesic for children less than 12 y.o., whereas there was a wide range of analgesics prescribed for children age >12 y.o. including naproxen, diclofenac, and tramadol.

Knowledge, attitudes and practices of Canadian pediatric emergency physicians regarding short-term opioid use: a descriptive, cross-sectional survey.

In the midst of the current opioid crisis, physicians are caught between balancing children's optimal pain management and the risks of opioid therapy. This study describes pediatric emergency physicians' practice patterns for prescribing, knowledge and attitudes regarding, and perceived barriers to and facilitators of short-term use of opioids. We created a survey tool using published methodology guidelines and distributed it from October to December 2017 to all physicians in the Pediatric Emergency Research Canada database using Dillman's tailored design method for mixed-mode surveys. We performed bivariable binomial logistic regressions to ascertain the effects of clinically significant variables (e.g., training, age, sex, degree of worry regarding severe adverse events) on use of opioids as a first-line treatment for moderate pain in the emergency department, and prescription of opioids for moderate or severe pain for at-home use in children. Of the 224 physicians in the database, 136 (60.7%) completed the survey (60/111 [54.1%] women; median age 44 yr). Of the 136, 74 (54.4%) had subspecialty training. Intranasally administered fentanyl was the most commonly selected opioid for first-line treatment of moderate (47 respondents [34.6%]) and severe (82 [60.3%]) pain due to musculoskeletal injury. On a scale of 0 (not worried) to 100 (extremely worried), physicians' median score for worry regarding physical dependence was 6.0 (25th percentile 0.0, 75th percentile 16.0), for worry regarding addiction 10.0 (25th percentile 2.0, 75th percentile 20.0) and for worry regarding diversion of opioids 24.5 (25th percentile 14.0, 75th percentile 52.0). On a scale of 0 (not at all) to 100 (extremely), the median score for influence of the opioid crisis on willingness to prescribe opioids was 22.0 (25th percentile 8.0, 75th percentile 49.0). The top 3 reported barriers to prescribing opioids were parental reluctance (57 [41.9%]), lack of clear guidelines for pediatric opioid use (35 [25.7%]) and concern about adverse effects (33 [24.3%]). Binomial logistic regression did not identify any statistically significant variables affecting use of opioids in the emergency department or prescribed for use at home. Emergency department physicians appeared minimally concerned about physical dependence, addiction risk and the current opioid crisis when prescribing opioids to children. Evidence-based development of guidelines and protocols for use of opioids in children may improve physicians' ability to manage pain in children responsibly and adequately.

Factors Associated With Frequent Opioid Use in Children With Acute Recurrent and Chronic Pancreatitis.

The aim of the study was to understand the association of frequent opioid use with disease phenotype and pain pattern and burden in children and adolescents with acute recurrent (ARP) or chronic pancreatitis (CP). Cross-sectional study of children <19 years with ARP or CP, at enrollment into the INSPPIRE cohort. We categorized patients as opioid "frequent use" (daily/weekly) or "nonfrequent use" (monthly or less, or no opioids), based on patient and parent self-report. Of 427 children with ARP or CP, 17% reported frequent opioid use. More children with CP (65%) reported frequent opioid use than with ARP (41%, P = 0.0002). In multivariate analysis, frequent opioid use was associated with older age at diagnosis (odds ratio [OR] 1.67 per 5 years, 95% confidence interval [CI] 1.13-2.47, P = 0.01), exocrine insufficiency (OR 2.44, 95% CI 1.13-5.24, P = 0.02), constant/severe pain (OR 4.14, 95% CI 2.06-8.34, P < 0.0001), and higher average pain impact score across all 6 functional domains (OR 1.62 per 1-point increase, 95% CI 1.28-2.06, P < 0.0001). Children with frequent opioid use also reported more missed school days, hospitalizations, and emergency room visits in the past year than children with no frequent use (P < 0.0002 for each). Participants in the US West and Midwest accounted for 83% of frequent opioid users but only 56% of the total cohort. In children with CP or ARP, frequent opioid use is associated with constant pain, more healthcare use, and higher levels of pain interference with functioning. Longitudinal and prospective research is needed to identify risk factors for frequent opioid use and to evaluate nonopioid interventions for reducing pain and disability in these children.

Impact of Intravenous, Perioperative-Administrated Lidocaine on Postoperative Serum Levels of Endogenous Opioids in Children.

Endogenous opioids are neuropeptides involved in pain-relieving processes. In the periphery, they are synthesised and stored in cells of the immune system. In the current study, we describe the influence of perioperative, intravenous (i.v.) lidocaine infusion in children on postoperative, serum endogenous opioid concentrations in children. Forty-four children undergoing major spinal surgery were enrolled in the cohort study. They were divided into two groups: group A (n = 21) generally anesthetised with fentanyl, propofol, rocuronium, a mixture of oxygen/air/sevoflurane and with analgetics and co-analgetics: morphine, acetaminophen, metamizole, gabapentin, dexamethason and group B (n = 23) where, in addition to the above-described general anesthesia, patients were given i.v. lidocaine as a co-analgesic. We also recruited 20 healthy age- and gender-matched children (group C). We measured endogenous opioid levels in serum using immunoenzymatic methods. We evaluated postoperative pain intensity using a numerical or visual pain scale and demand for morphine. The levels of measured endogenous opioids were similar in the control and in the studied groups before surgery. We noted that group B patients had lower pain intensity when compared to group A subjects. In group B, the elevated serum concentrations of β-endorphin, enkephalin and dynorphin in the postoperative period were reported. We also observed that the levels of endogenous opioids negatively correlated with morphine requirements and positively correlated with lidocaine concentration. Multidrug pain management including lidocaine seems to be more efficient than models without lidocaine. The endogenous opioid system should be considered as a novel target for pain relief therapy in children.

Evaluation of a Non-Parenteral Opioid Analgesia Protocol for Acute Sickle Cell Pain Episodes in Children.

We evaluated a protocol comprising intranasal diamorphine (IND) combined with oral short and modified-release morphine for children at the emergency department (ED) with acute painful episodes of sickle cell disease (SCD). In a retrospective audit of 83 episodes in 38 children, the mean time between arrival in the treatment area and the administration of IND was 10 min (range <5 min to 1.39 h). IND was administered in <5 min in 43 (51.6%), and in <20 min in 75 (90.4%) episodes. Persisting pain, requiring background analgesia with modified-release oral morphine, was required in 25 (30.1%) episodes. Inadequate control of pain requiring a switch to intravenous morphine PCA was required in eight episodes in four patients. Acute chest syndrome (ACS) developed in four of 83 episodes (4.8%, 95% CI 0.2–9.4%) and in four of 38 children (10.5%, 95% CI 0.7–20.5%). In conclusion, this protocol enabled the rapid administration of strong opioid analgesia in an ED setting, and may reduce the short and long-term adverse effects associated with parenteral opioids in children. There was no evidence of an increased incidence of ACS associated with use of oral morphine.

Doctors and Nurses’ Knowledge and Attitudes Towards Pediatric Pain Management: An Exploratory Survey in a Children's Hospital

Despite the existence of protocols for effective pain control, pediatric pain is still high, due to scarce knowledge of its treatment, especially regarding opioids. This study aimed to evaluate doctors and nurses’ knowledge of pain treatment and the use of opioids in children, before and after the implementation of Law 38/2010, that represented an important step in guaranteeing patients’ rights to gain access to appropriate services for pain control and palliative care in Italy and in establishing the obligation of specific training programs in this matter for health professionals. An ad hoc questionnaire was developed and administered before (investigation A) and after (investigation B) the issuance of the Law. In B both doctors and nurses showed a slight but significant increase in correct answers and a reduction in incorrect ones, mainly concerning the category Myths and Prejudices. In both investigations doctors and nurses showed adequate general knowledge, yet there were some gaps regarding the specific knowledge of opioid drugs. Most of the participants were not familiar with the Law and its provisions.Investigation B showed an improvement in health professionals’ knowledge, perhaps due to a hospital environment that followed the provisions of Law 38/2010. Nevertheless, the establishment of training courses according to the Law is needed to improve the knowledge of opioids, as well as to dispel deeply rooted myths and prejudices on pediatric pain.

Intranasal therapy with opioids for children and adolescents with cancer: results from clinical studies.

Opioids are essential for the treatment of pain, which is a serious symptom for children and adolescents affected by cancer. Intranasal opioids may be very useful for the treatment of breakthrough pain in children and adolescents with cancer, for their little invasiveness, ease of administration, rapid onset of action, and high bioavailability. Intranasal drug delivery may be influenced by anatomical and physiological factors (nasal mucosa absorption area, mucociliary clearance, enzymatic activity, anatomical anomalies, chronic or inflammatory alterations of nasal mucosa), drug-related factors (molecular weight, solubility), and delivery device. Fentanyl is a lipophilic opioid commonly proposed for intranasal use among pediatric patients, but no studies have been conducted yet about intranasal use of other available opioids for management of pediatric cancer pain. In this review, we analyze several elements which may influence absorption of intranasal opioids in children and adolescents, with a focus on pharmacokinetics and therapeutic aspects of each opioid currently available for intranasal use.

The Society for Pediatric Anesthesia recommendations for the use of opioids in children during the perioperative period.

SummaryOpioids have long held a prominent role in the management of perioperative pain in adults and children. Published reports concerning the appropriate, and inappropriate, use of these medications in pediatric patients have appeared in various publications over the last 50 years. For this document, the Society for Pediatric Anesthesia appointed a taskforce to evaluate the available literature and formulate recommendations with respect to the most salient aspects of perioperative opioid administration in children. The recommendations are graded based on the strength of the available evidence, with consensus of the experts applied for those issues where evidence is not available. The goal of the recommendations was to address the most important issues concerning opioid administration to children after surgery, including appropriate assessment of pain, monitoring of patients on opioid therapy, opioid dosing considerations, side effects of opioid treatment, strategies for opioid delivery, and assessment of analgesic efficacy. Regular updates are planned with a re‐release of guidelines every 2 years.

Serum levels of endogenous opioids in children during multimodal anesthesia

Serum levels of endogenous opioids in children during multimodal anesthesia