Literature Reviews

By Sabine Kost-Byerly, MD
Former President, Society for Pediatric Pain Medicine
Former Director, Pediatric Pain Management,
Former Director, Multi-disciplinary Pediatric Pain Clinic, Kennedy Krieger Institute
Associate Professor of Anesthesiology and Critical Care Medicine, Emeritus
Johns Hopkins University School of Medicine
Baltimore, Maryland

Acute Pain and Regional Anesthesia

Behavioral Intervention and Disposal of Leftover Opioids: A randomized trial

Voepel-Lewis T, Farley FA, Grant J, et al. Pediatrics 2020;145(1):e20191431  DOI:10.1542/peds.2019-1431

Leftover prescription opioids are frequently kept at home despite the risk of misuse. This study examined whether a behavioral disposal method (Nudge - disposal kit with illustrated instructions) with or without a Scenario-Tailored Opioid Messaging System (STOMP – interactive Web-based program with descriptive pain and risk situations) can change parent’s behavior.  The authors hypothesized that Nudge would provide an easy way for parents to decrease risk thus enhancing response efficacy and that STOMP would enhance the parents’ perception of risk leading to improved disposal behavior.

Parents (N=640) whose children (5-17y) were undergoing short-stay surgery with need for prescribed opioids were prospectively and consecutively recruited. Participants completed a baseline survey and were randomly assigned to four groups: Nudge + routine (N=131), Nudge + STOMP (N=124), Control + STOMP (n-129) or Control + routine (N=133). Outcome measures were prompt opioid disposal as per self-report and photo provided electronically by the parents, the Parents’ Postoperative Pain Measure-Short Form (scored 0-10), and the parental risk perception as assessed by a validated survey (Qualtrics). The parents received electronic surveys on postoperative days seven and 14 and maintained diaries for documentation of opioid administration.

There were no significant differences in the baseline characteristics of the four groups. Several parents (N=61, 11.8%) reported past opioid prescription misuse. Most children took the opioids for <6 days (84%). Leftover opioids were common: >50% of doses (N=99, 19%) and 25-50% (N=148, 28%).  At the final survey (14 days postop) disposal was significantly higher in the intervention groups and highest in the STOMP+Nudge group (38.5%). E-mailed photos confirmed the disposal in 40%. Nudge enhanced timely disposal. Planned retention of the opioid  (N=44, 9%) was significantly lower in the STOMP intervention groups (5.6% vs 12%). Retention was not associated with the number of prescribed or administered doses.  Past parental opioid misuse increased retention plans four-fold whereas higher parental risk perception lowered them. Nudge did not have any independent effect on retention plans.

Interventions such as Nudge, a disposal method, and STOMP, a tool providing risk information, can enhance parental decision-making around prompt opioid disposal and diminish planned retention of opioids.  Comment: please note that even with the intense interventions in this study the prompt opioid disposal rate was at best 38.5% - dismal. Most parents (60%) still had the drugs at home at 14 days postop, even if “only” 9% admitted to concrete plans of retaining the drugs for future (mis)use. We have a long way to go to secure prescription opioids.

Variation Between and Within Hospitals in Single Injection Caudal Local Anesthetic Dose: A report from the Pediatric Regional Anesthesia Network

Taenzer AH, Hoyt M, Krane EJ, et al. Anesth Analg 2020;130(6):1693-1701

Medical practice patterns can vary between providers and institutions. This study explored variations in single dose caudal epidural injection dosing and examined possible causes for such variable practice.

The PRAN database was searched for single injection caudal blocks in children <1 year of age, their local anesthetic (LA) dose, as well as variations in dose within and between institutions. Data was collected prospectively from 2007 to 2015. Local anesthetic doses were converted to bupivacaine equivalent (BE) doses (conversion factor: ropivacaine 1.4, lidocaine 4, chloroprocaine 5). Doses were assessed as mg/kg.

Bupivacaine (B) and ropivacaine (R) were the most commonly LA used (54% R 0.2% and 38% B 0.25%) in the caudal blocks (N=14,367).  Mean volume was 0.93+0.20 mL/kg, mean dose 1.72+ 0.56 mg/kg. Larger children >10 kg received slightly less volume (0.88 mL/kg). High doses (>3 mg/kg) were administered to several of the patients (N=113). The 19 institutions contributed data from 105 to 2763 blocks. The data for BE/kg followed a bimodal distribution whereas the volume was more tightly concentrated around a single value (0.9 mL/kg). BE peaks at institutions were either monomodal or bimodal. The mean BE/kg dose was allied with patient age, weight, LA used, and institution but not number of blocks. Doses varied up to seven-fold and volume up to four-fold.

There are significant practice variations within and between institutions.  Missing surgical data and efficacy data makes interpretation difficult though there may be potential for practice improvement.  The bimodal distribution of the data also needs to be taken into consideration by researchers as they continue to examine the information collected in the PRAN database.

Early experience with erector spinae blocks in children

Holland EL, Bosenberg AT Pediatr Anesth 2020;30(2):96-107 DOI:10.1111/pan13804

The literature for erector spinae blocks in children is limited. This case series (N=164) report aims to address efficacy of the block, as well as feasibility, safety, opioid consumption, and pain scores.

This is a retrospective chart review of patients undergoing erector spinae blocks at a single institution over 20 months. Blocks were performed under anesthesia, using ultrasound, prior to surgery. The authors also performed a Pubmed literature review on the topic.

Patients (N=164; age 2 days-19.4 years, weight 2.3-94.7 kg) received the block within 10 min 79% of the time. Based on changes in heart rate <10% from baseline at incision 70% of the blocks were deemed efficacious. Long-acting opioid were required in 20% intraoperatively. In the PACU, 52% of the patients required opioids (average iv ME 0.07 mg/kg). Infants undergoing gastrostomy surgery (subset) had at least 0.1 mL/kg/dermatome spread with 0.5 mL/kg dose.  The literature review added another 33 publication and an additional 128 children. No complications were described.

Erector spinae blocks can provide effective intraoperative and early postoperative analgesia. Limitations include the retrospective nature of study, single institution, and lacking details in the data available in the literature. Further research needs to address LA spread, duration of action, volume and concentrations required, comparison with other techniques, including continuous catheters.

Racial and Ethnic Differences in Emergency Department Pain Management of Children With Fractures

Goyal MK, Johnson TJ, Chamberlain JM, et al. Pediatrics 2020;145(5):e20193370  DOI:10.1542/peds.2019-3370

With editorial:
Implicit Bias in Pediatrics: An emerging focus in health equity research
Raphael JL, Oyeku SO. Pediatrics 2020;145(5):e20200512 DOI:10.1542/peds.2020-0512

Racial and ethnic disparities have been demonstrated in the ED setting, including in children with some painful conditions. Long-bone fractures are a common painful condition seen in children presenting to EDs. This multicenter study examines whether racial and ethnic differences in process measures and outcomes concerning pain management occur in children with long-bone fractures.

 The retrospective cohort study includes three years of data in the Pediatric Emergency Care Applied Research Network (PECARN) Registry.  PECARN data is collected in an automated process and submitted monthly from seven ED’s (four tertiary care, three affiliated). Eligible patients were <18 years of age, had a long-bone fracture but were neither critically ill nor considered no-urgent (emergency severity index level 2-4). Outcome measures included analgesic administration and pain reduction within 90 min.  Primary exposure was patient’s race and ethnicity. Other variables assessed included patient characteristics, injury severity, and visit characteristics such as ED site and provider type.

 Of the 1.37 million ED visits 2.5% were for long-bone fractures. For patients with at least moderate pain (N=21069) who had their pain re-evaluated within 90 minutes (N=8533, 40.5%, median age 10.0) no racial or ethnic differences were seen for re-assessment of pain score. Although minority children were more likely to receive any analgesic, they were less likely to receive an opioid analgesic. Most children (89.2%) achieved >2 point reduction in pain score within 90 minutes. Whereas minority children were more likely to achieve this reduction they were less likely to achieve minimal or no pain. Racial composition across sites ranged from 0.4 to 94.9% for African Americans and from 3.4 to 44.6% for Hispanic populations.

Ethnic and racial disparities can be seen in process measures and clinical outcomes in children presenting with painful long-bone fractures to the ED.  Further research is required to explore these disparities. Limitations were the retrospective nature of the study and inability to explore other variables due to the setup of the database. 

The Effect of Intraoperative Methadone During Pediatric Cardiac Surgery on Postoperative Opioid Requirements

Barnett AM, Machovec KA, Ames WA, et al. Pediatr Anesth  DOI:10.1111/pan13903

Children undergoing cardiac surgery have complex pain management needs as intraoperative analgesia is often followed by postoperative opioid infusions and sedation, prolonged weaning and extended hospital stays. This study explored whether the intraoperative sole use of intravenous methadone would improve efficacy of analgesia and improve the side effect profile.

This before- and after-intervention study is a retrospective chart review of all pediatric (<18y) patients undergoing cardiac surgery under cardiopulmonary bypass within a 14-month period, seven months each pre- and post-practice change to methadone. Prior to the change, patients received fentanyl boluses and infusions in addition to anesthesia maintenance with sevoflurane and dexmedetomidine infusions. During the second half of the period opioids were replaced by up to 0.4 mg/kg of intravenous methadone. The authors assessed a neonatal group (N=44, 21 pre-, 23 post-intervention) and an older group (N=154, 69 pre, 85 post).

In the neonatal patients, the post-intervention group had lower needs for intraoperative but not postoperative opioids and dexmedetomidine although the authors noted that the groups were somewhat dissimilar with the post group being smaller and having higher ASA scores.  In the older group, which had comparable demographics, intraoperative requirements for opioids were lower (0.7 vs. 2 MME/kg) as were midazolam (0.06 vs. 0.1 mg/kg) and dexmedetomidine (1 vs. 3 mcg/kg). The reduced need for opioids continued for the first 24 hours and for sedatives for the entire seven-day postoperative period. There was no difference in pain scores.

Intraoperative use of the long-acting opioid methadone may result in a decreased need for postoperative opioids and sedatives in children undergoing cardiac surgery. This single institution study is limited by its retrospective nature. The design of a comparison with historical patients after an intervention is prone to miss variables affecting the outcome.

Chronic Pain and Palliative Care

Parent Physical and Mental Health Contributions to Interpersonal Fear Avoidance Processes in Pediatric Chronic Pain

Birnie KA, Heathcote LC, Bhandari RP, et al. Pain 2020;161(6):1191-1201  DOI: 10.1097/j.pain.0000000000001820
With editorial:

Fear, Boldness, and Caution: Parent effects on how children manage chronic pain.
Gauntlett-Gilbert J, Jordan A Pain 2020;161(6):1127-1398 10.1097/j.pain.0000000000001821

Chronic pain in children affects and is affected by family health and dynamics. Even though there has been increasing interest in the intergenerational risk and transmission of physical and mental illnesses few studies have examined parent and family factors in children’s development, coping, and functioning with chronic pain. This study aimed to assess an integrative model of parents’ mental and physical health with interpersonal fear avoidance in pediatric chronic pain. The authors hypothesized that poorer parent health would be associated with more parent pain catastrophizing, protective behaviors, and child catastrophizing resulting in greater pain interference.  What moderators examined were child age and parent self-report of pain.

Participants included all eligible pediatric patients (N=448, 8-18y) and parent dyad presenting to university-based interdisciplinary outpatient pain clinic. Data was collected electronically prior to the initial intake assessment over a three-year period. Outcome measures included basic demographics for parent and child, the Pain Catastrophizing Scale for Children (PCS-C), the CAT version of the PROMIS pediatric pain interference domain, the PROMIS global health domain (parent), the Pain Catastrophizing Scale for Parents (PCS-P), the Adult Responses to Children’s Symptoms (ARCS) with a pain-specific stem.

Children (N=340 age 13-18y, N=108 age 8-12, mean age 14.6, 73% female, 61% white) reported mean pain duration of 30 months. Older child age was related to greater child pain interference and worse parent physical health. Parents (mean age 46, range 24-74, mainly mothers, married, and white) frequently (44%) reported personal pain problems, most often in multiple locations or widespread, had other medical issues (36%) and psychological difficulties (26%). Parents with pain problems had poorer physical and mental health. Children of parents with pain problems reported greater pain interference themselves.

Poorer parent health is associated with greater child pain interference through interpersonal fear avoidance mechanisms. The study contributes to the concept of pain as a family issue.

Impact of Specialized Pediatric Palliative Care: A systematic review

Marcua KL, Santos G, Ciapponi A, et al. J Pain Symptom Manage 2020;59(2):339-364  DOI: 10.1016/j.jpainsymman.2019.08.005.

Specialized pediatric palliative care (SPPC) is not as common and available as palliative care for adults. This study tried to address the impact of SPPC concerning its effects on outcomes in patients, caregivers, and at the systems level.

The authors undertook a systematic review following Cochrane methods. Electronic data sources were searched for time of January 1996 to June 2018. Studies included, RCTs, cohort, case-control, as well as before-after studies with SPPC as the intervention.

The qualitative synthesis included 24 studies (one RCT, 16 cohort and seven before-after studies). The studies were heterogenic and many (13/24) were small with <100 patients. Whereas a few studies (5/24) examined SPPC on a population base, most of them (19/24) described the impact of a single institution’s program. Described interventions in the studies were not sufficiently detailed to allow for a comparison. “Usual care” was a common control group.  Risk of selection bias was high in almost half of the studies.

The study provided a systematic review of SPPC in the scientific literature but due to the heterogeneity of the studies a meta-analysis was not feasible. Conclusions remain limited. Further high-quality research in the field is needed.

Practice Improvement

Reducing Postoperative Pain in Children Undergoing Strabismus Surgery: From bundle implementation to clinical decision support tools

Ali U, Tsang M, Campbell F, et al. Pediatr Anesth 2020;30(4):415-423  DOI:10.1111/pan13811

Pediatric patients undergoing strabismus surgery can experience significant postoperative pain. The aim of this quality improvement (QI) project was to reduce the incidence of moderate to severe pain by 25% over a 12-month period.

The project by a multidisciplinary QI team is based on iterative Plan-Do-Study-Act cycles and the Institute for Healthcare Improvement model. A retrospective medical record review (N=100) provided baseline data. Interventions included a) a perioperative bundle (preoperative acetaminophen, intraoperative dexamethasone and ketorolac, long acting opioid, two anti-emetics), b) staff reminders, c) presentation of data at departmental rounds, and finally d) a clinical electronic decision aide.  Outcome measures were postoperative pain scores in the PACU, bundle compliance, and PACU length of stay (LOS).

Within the 4.25 years of data collection data for 1127 patients was included. Clinical practice was heterogeneic for bundle measures at baseline.  The incidence of moderate to severe pain was gradually reduced from a baseline of 47.3% to 21%. Mean bundle adherence increased to 79%.  Changes were sustained. There was no change in the LOS in the PACU.

Although the authors did not achieve their goal of a 25% reduction in the incidence of moderate to severe pain, they felt they had made meaningful progress in their care. QI projects can homogenize practice and enhance outcomes. Limitations include the retrospective nature of the baseline patient dataset.

Other Publications of Note

Managing Patients with Chronic pain During COVID-19 Outbreak: Considerations for the rapid introduction of remotely supported (eHealth) pain management services
Eccleston C, Blyth FM, Dear BF, et al. Pain 2020;161(5):889-893  DOI: 10.1097/j.pain.0000000000001885
The authors review opportunities and challenges of eHealth for the management of patients with chronic pain during the COVID-19 pandemic.

Pediatric Perioperative Outcomes: Protocol for a systematic literature review and identification of a core outcome set for infants, children, and young people requiring anesthesia and surgery
Razavi C, Walker SM, Moonesinghe SR, et al. Paediatr Anesth 2020;30(4):392-400  DOI:10.1111/pan13825
The authors present the first step in the development of outcome measures for infants, children, and young people: formation of the international Pediatric Perioperative Outcomes Group, description of methodologies, and systematic literature reviews.

Addressing the Challenge of Pain Education in Low-Resource Countries: Essential pain management in Papua New Guinea
Marun GN, Morriss WW, Lim JS, et al. Anesth Analg 2020;130(6):1608-1615
DOI: 10.1213/ANE.0000000000004742 
Poorly treated pain is a global health care problem. Papua New Guinea is a low-resource country in the South-West Pacific with considerable health care challenges, including a high burden of painful disease. The Essential Pain Management program is to improve pain knowledge, teach a simple system for managing pain, and address local pain management barriers.

One Step Closer to Effective Pain Management Around the World?
Livingston PL, Nyirigira G. Anest Analg 2020;130(6):1605-1607 DOI: 10.1213/ANE.0000000000004787
The article describes the introduction and first eight years of an educational program on Essential Pain Management in a low-resource country.

Youth Perspectives of Prescription Pain Medication in the Opioid Crisis.
Harbaugh CM, Vu JV, DeJonckheere M, et al.  J Pediatr 2020, 221(6):159-164  DOI:10.1016/j.jped.2020.02.003
Youths are aware of the opioid crisis, but they perceive less risk of prescription pain medication prescribed by a doctor, than from other sources. Policies should aim education to youth in clinical as well as nonclinical settings, emphasizing the risks of addiction and overdose with all opioids.

Giving Youth the Real Facts About the Opioid Crisis
Goodman, DM. J Pediatr 2020,221(6):1-3
Results of an open-ended text messaging survey of 745 respondents recruited via social media on prescription pain medications: exposure and access, perceived safety, and associations with the word “opioid”.

Postoperative Pain Control Following Minimally Invasive Correction of Pectus Excavatum in Pediatric Patients: A systematic review
Archer V, Robeninson T, Kattail D, et al.  J Pediatr Surg 2020;55(5):805-810  DOI: 10.1016/j.jpedsurg.2020.01.023
The authors present a systematic review and comparison of nine RCTs after a search of several databases. The studies did not lend themselves to a meta-analysis.

The effectiveness of Epidural Blood Patch in Patients With Cerebral Palsy Treated With Intrathecal Baclofen Implantation
Imerci A, Rogers K, Dixit D, et al. Pediatr Anesth 2020;30(2):153-160  DOI:10.1111/pan13791
Case series of 29 epidural blood patches in 26 patients.

Thoracic Caudal Epidural Catheter Localization Using Ultrasound Guidance
Bachman SA, Taenzer AH. Pediatr Anesth 2020;30(2):194-195  DOI:10.1111/pan13796
Case report with ultrasound and schematic drawing.

First National Survey on Opioids Prescribing Practices of Canadian Pediatric Surgeons
Zani-Ruttenstock E, Sozer A, O’Neill Trudeau M, et al.  J Pediatr Surg 2020:55(5):954-958  DOI: 10.1016/j.jpedsurg.2020.01.034.
This first national survey on opioid prescribing methods across Canada. There seems to be inadequate education for surgeons and families about opioid use.

Placebo Effect in Children: The role of expectation and learning
Gniß S, Kappesser J, Hermann C.  Pain 2020;161(6):1191-1201
This is a prospective study with an interesting and complex design to allow assessment of placebo effect in children and young adults.

Musculoskletal Pain in Six-year-old Children: The Generation R study
Vasn den Heuvel MM, Jansen PW, Bindels PJE, et al. Pain 2020;161(6):1278-1285  DOI: 10.1097/j.pain.0000000000001797
Examination of the prevalence of musculoskeletal pain and associations with physical and psychosocial factors in an ongoing population-based prospective cohort study in the Netherlands

Hypnosis for Pain in Pediatric Oncology: Relevant and effective or an intervention of the past?
Heidelberg RE, Alschuler KN, Ramsey WA, et al. Pain 2020;161(5):901-915  DOI: 10.1097/j.pain.0000000000001790
The advancement in medical treament have increased cure and long-term survival rates in pediatric
oncology often come at the cost of significant pain and symptom burden during treatment. Hypnosis can have a positive impact for pain management in pediatric oncology patients.

Avoid or Engage? Outcomes of Graded Exposure in Youth With Chronic Pain Using Sequential Replicated Single-case Randomized Design
Simmons EL, Vlaeyen JW, Declercq L, et al. Pain 2020;161(3):520-531   DOI: 10.1097/j.pain.0000000000001735
The authors evaluated the effectiveness of individually tailored graded in vivo exposure treatment for youth with chronic pain using a sequential replicated single-case experimental phase design with multiple measures.

Home Intranasal Dexmedetomidine for Refractory Dystonia in Pediatric Palliative Care
De Zen L, Della Paolera S, Del Rizzo I, et al. J Pain Symtom Manage 2020;59(6)e3-e5 
DOI: 10.1016/j.jpainsymman.2020.02.022.
Case report.

Defining the Boundaries of Palliative Care in Pediatric Oncology
Cuviello A, Raisanen JC, Donahue PK, et al. J Pain Symtom Manage 2020;59(5):1033-1042  DOI: 10.1016/j.jpainsymman.2019.11.022.
Mixed-methods study.

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