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

Continuous chloroprocaine paravertebral infusions for postoperative analgesia in infants and very young children

Greco C, Boretsky KR. Paediatr Anaesth 2020;30(9):1044-1045
Infants are at increased risk for local anesthetic systemic toxicity. Chloroprocaine may offer a safer alternative to bupivacaine. This study provides more information on the use of 2-chloroprocaine for paravertebral nerve blocks (PVNB) in young children.

This is a retrospective review of the use of 1.5% 2-chloroprocaine for PVNB infusions in infants <18 months undergoing major thoracic and abdominal surgery. PVNB catheters were placed under ultrasound guidance and tunneled subcutaneously. Postoperatively, patients also received intravenous opioids under guidance from a pain service.

There were 91 PVNBs, all unilateral, in 61 patients (mean age 124 [range 1-482] days). An infusion (mean rate of 0.7 [0.5-0.8] mL/kg/h) was maintained for 5.22 (1-13) days. Postoperatively, the mean morphine dose was 0.2 mg/kg/h and fentanyl was 2.1 mcg/kg/h in the first 48 hours. No complications were reported.

2-chloroprocaine can facilitate prolonged peripheral catheter infusion such as PVNB with relatively high infusion rates in infants and young children. The study is limited by the small sample size prohibiting further safety assessments. 

Postoperative pain and psychological outcomes following minimally invasive pectus excavatum repair: a report from the Society for Pediatric Anesthesia Improvement Network

Uhl KM, Wilder RT, Fernandez A, et al. Paediatr Anaesth 2020;30(9):1006-1012
The association of acute and prolonged postoperative pain in children remains poorly understood. The multi-institutional SPAIN collaborative examined perioperative management and outcomes of pediatric patients undergoing MIRPE repair.  After a previously published report of initial in-hospital outcomes this study examined the relationship between acute postoperative pain and the report of pain and psychological symptoms 2 weeks and 3 months postoperatively. 

Eligible patients age 8-30 years scheduled for MIRPE were prospectively enrolled. Patients whose in-hospital data had been collected (N=348) were contacted at 2 weeks (N=158) and 3 months (N=94) to assess maximum daily pain scores. In addition, patients were asked to self-report psychological distress symptoms using the Child PTSD Symptom Scale (CPSS), distinguishing distress, if present, as surgery- or non-surgery-related.

The CPSS survey was completed by 176 of 348 patients (N=82 at 2 weeks, N=18 at 3 months, N=76 at both times). Responders had either received regional anesthesia (43 paravertebral block, 32 epidural, 28 wound catheter, 1 intrathecal) or no regional analgesia (N=72). Surgery-related psychological distress was reported by 65% after 2 weeks and by 30% after 3 months. Patients with high postoperative pain scores had 3 times the odds of surgery-related distress at 2 weeks and 10 times at 3 months. Distress reported at 2 weeks persisted at 3 months in 53%.  Patients reporting such distress at 3 months also had higher pain scores at that time.

MIRPE is associated with significant postoperative pain and can be associated with persistent psychological distress and pain. The study was limited by the participant response rate.

Effect of NSAID use on bone healing in pediatric fractures: a preliminary, prospective, randomized, blinded study

Nuelle JAV, Coe KM, Oliver HA, et al. J Pediatr Orthop 2020;40(8);e683-e689

NSAIDs have been associated with delayed fracture healing. Although non-union is relatively rare in children, orthopedic providers have limited their use of NSAIDs in the pediatric age group, potentially exposing more children to higher doses of opioids as an alternative pain management. This study aimed to examine the effect of NSAIDs on bone healing in the acute phase.

This was a randomized, controlled, single-blinded study in skeletally immature patients (males<16 years, females<14 years) with long bone fractures. The NSAID group (N=49) received 4-10 mg/kg/dose (max 800 mg) up to 3.2 g/day. Ketorolac 0.5 mg/kg iv/im q6h was available for inpatients and ED patients. The control group (N=46) received acetaminophen 10-15 mg/kg/dose (max 1 g) up to 4 g/day. Breakthrough pain was managed with oxycodone and/or fentanyl in both groups. Caregivers were asked to record pain scores for 72 hours and medication use for 3 weeks post injury. Outcome measures included radiographically documented healing of fracture at 4 time points (1-2, 6, and 10-12 weeks, 6 months) post injury and persistent pain.

Most enrolled patients (95/102) completed 6- month follow-ups. Both groups achieved fracture healing without apparent differences or delays (3 months: 98% in  control group, 100% in NSAID group; 6 months: all). There were no significant differences in the use of acetaminophen versus NSAIDS (average 4 days) or in opioid breakthrough need (2 days). 

NSAIDs did not delay fracture healing in skeletal immature children in this single center study. Limitations of the study include a higher incident (not statistically significant) of diaphyseal fractures in the NSAID group, which may heal faster, and a focus on oral ibuprofen.  (The authors’ sample size calculations, based on limited available literature and prior in-house experience, may also have resulted in a sample size too small to find rare complications.)

High parental anxiety increases narcotic use in adolescent patients following spinal fusion

Sarkisova N, Andras L, Yang J et al. J Pediatr Orthop 2020;40(9):e794-797
Parental perceptions and behaviors may influence their children’s postoperative recovery.  This study aimed to explore high parental anxiety and prolonged postoperative opioid use in adolescents.

Patients aged 11-20 years (N=58; female 49, male 9) with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal fusion (PSF) surgery were prospectively enrolled. At a pre-surgery clinic visit, parents completed the State-Trait Anxiety Inventory (STAI) and patients the Spence Children’s Anxiety Scale (SCAS). At the first postoperative visit, patients and parents rated the child’s pain and completed a survey about stress levels and medication use in the prior 24 hours.

Patients (mean age 15 [range10-20] years) with a mean curve of 57 (44-103) degrees had 11 (6-14) levels fused. They went home on postoperative day 3 (2-6) and returned to clinic 2-3 weeks after surgery. There were no complications. Prior to surgery, high state and trait (general) anxiety scores were noted respectively for 36% and 29% of the parents. At the postoperative clinic visit, 28% of patients were still using opioid analgesics. Patients, whose parents had high general trait anxiety scores, were twice as likely to still be taking opioids (8/17[47%] vs 8/41[20%]). Patients with high anxiety scores themselves (10/58; 17%) did not demonstrate a prolonged opioid use. Patients and parents rated pain similarly. Parents, whose children were still taking opioids, rated the experience as more stressful.

Patient anxiety did not seem to impact postoperative opioid use after PSF whereas parental anxiety did. Identifying and counseling anxious parents may be helpful when trying to limit adolescent postoperative opioid use (and potentially also in household diversion). Short-term follow-up and a single center population limit this study. 

Incidence of and factors associated with prolonged and persistent postoperative opioid use in children 0-18 years of age

Ward A, De Souza E, Miller D. et al. Anesth Analg 2020:131(4):1237-1248
Information concerning the risk of prolonged opioid use after surgery in previously opioid-naïve children remains limited.  This study aimed to assess the incidence of prolonged opioid use after surgery (POUS, >=1 prescription filled in 90-180 days after surgery), persistent postoperative opioid use (PPOU, >=60 days of opioid prescriptions filled in the 90-365 days after surgery) and to identify associated factors for increased and decreased odds of such use in the pediatric age group.

The authors accessed de-identified medical and pharmacy claims for the years 2003 to 2017 from a national insurance provider maintained Optum Clinformatics Data Mart database, focusing on the 20 most common surgical procedures in 4 age groups (0-<2, 2-<6, 6-<12, and 12-18 years) of opioid-naïve children. A baseline reference sample was constructed by a random 25% sample of patients not undergoing surgery in each age group. Outcome measures were POUS and PPOU. In addition to demographic variables, chronic pain, cancer, substance use disorders, and mood or personality disorders were examined.

There were 23,820 surgeries (S) in 14,684 patients (P) in age group 0-<2 years,  56,057 S in 42,467 P aged 2-<6 years, 55,045 S in 47,545 P aged 6-<12 years, and 88,464 S in 68,692 P aged 12-18 years. Increased rates of POUS were associated with myringotomy (in age group 0-<2y), adenoidectomy and/or tonsillectomy (2-<6y, 6-<12y, 12-18y), laparoscopic appendectomy (6-<12y, 12-18y), tympanoplasty with typanomeatal flap (6-<12y), septoplasty and closed reduction of nasal fracture (12-18y) knee athroscopic chondroplasty or partial synovectomy (12-18y), shoulder arthroscopic capsulorrhaphy (12-18y), and removal of deep fixation device (12-18y). Age, history of mood/personality disorders, and chronic pain were positively associated with POUS. Male gender, Asian race, year of surgery and removal of completely impacted tooth were negatively associated with it. The OR for PPOU in 12-18 year-olds was 2.2 [95% CI 1.5-33] but there were few patients with PPOU in the younger age groups.

POUS was positively associated with increased age, more surgeries and more variables in the older age groups. The negative association with the year of surgery may suggest a greater awareness of the risk of perioperative opioid use in recent years.

Chronic Pain and Palliative Care

Parent cognitive, behavioral, and affective factors and their relation to child pain and functioning in pediatric chronic pain: a systematic review and meta-analysis

Donnelly TJ, Palermo TM, Newton-John TRO Pain 2020;161(7):1401-1419
A better understanding of how parental cognitive, behavioral, and emotional factors are related to a child’s chronic pain and functioning may inform appropriate psychological interventions.  This study tried to identify parent factors presented in the literature and quantify the association between those factors and child pain and disability.

A systematic review of electronic databases identified 54 relevant studies. Meta-analyses addressed associations between parent pain catastrophizing, protective behavior, anxiety and depression with child pain, disability, school and emotional functioning.

The 54 studies (45 from US) included 8819 patients with a median age of 13.8 (range <1-18) years. Participants were mostly white, female (68%), and had mothers as the involved parent (87.5%). Most studies were conducted in outpatient clinics (N=49) and the majority involved heterogeneous chronic pain (N=31) or rheumatological (N=13) conditions. Higher parent pain catastrophizing had a small association with child disability and depression and a weak association with child pain intensity. Increased parent protective behavior was moderately associated with increased child disability and decreased school attendance and weakly with child pain intensity and depression. Parent depression moderately correlated with child depression.

Parent factors seem to be associated with child pain and functioning. The available studies do not allow further detailed assessment of the parent-child dyad or the family environment as variables.

Racial and ethnic differences in communication and care for children with advanced cancer

Mack JW, Uno H, Twist CJ, et al.  J Pain Symptom Manage 2020(4):782-789
Racial and ethnic disparities in end-of-life care have been shown in adults with advanced cancer, but data for children is limited. This study aimed to examine whether there are differences in communication and care based on race and ethnicity in children with advanced cancer.

This was a prospective cohort study at 9 pediatric cancer centers with enrollment of 95 parents (42% minorities) of patients (mean age 6 years) with neuroblastoma and poor prognosis. Questions in a survey included: discussion of prognosis, likelihood of cure, intent of treatment, goals of care. Medical records were reviewed for care delivered.

While only 26% of parents understood the poor prognosis (chance of cure <25%), minority parents were even less to do so (OR=0.19; 95% CI=0.06=0.63). They also were less aware that the current cancer-directed therapy was unlikely to be curative (OR 0.07, 95% CI-0.02-027). Minority children were more likely to receive high-intensity medical care. Parents’ goals of care (primarily improvement in quality of life) and their prioritization did not differ between ethnic and racial groups.

Understanding of prognosis is limited in all racial and ethnic groups but minorities are more severely affected. Minority children with advanced disease received more intense medical interventions. It is unclear how or if this management relates to the parental understanding of the child’s prognosis and/or differences in care team communication with parents. This study is limited by its small size and focus on patients with a particular cancer diagnosis.

Other Publications of Note

Comparison of regional analgesia techniques for pleurodesis pain in pediatric patients
Xie J, Mooney DP, Cravero J Paediatr Anaesth 2020;30(10):1102-1108
A retrospective case series from a single institution including 66 patients (23 thoracic epidurals, 34 paravertebral blocks, 9 no block).

Effect of mental rotational skills training on ultrasound-guided regional anaesthesia task performance by novice operators: a rater-blinded, randomized, controlled trial
Hewson DW, Knudsen R, Shanmuganathan S, et al. Br J Anaesth 2020;125(2):168-174  doi:
Study exploring the effect of a training intervention, the mental manipulation and rotation of three-dimensional models, on the performance of ultrasound-guided needling tasks.

Postoperative pain control modalities for pectus excavatum repair: a prospective observational study of cryoablation compared to results of a randomized trial of epidural vs. patient-controlled analgesia
Dekonenko C, Dorman RM, Duran Y et al. J Pediatr Surg 2020;55(8):1444-1447
Data from 35 patients involved in a prospective observational study of cryoablation was integrated with data of 65 patients from a prior, never published, trial with 2 arms (If a first study does not show the desired statistically significant differences, add another arm sometime later and now report significance and even get it published).

Risk of postdural puncture headache in adolescents and adults
DelPizzo K, Luu T, FDields KG, et al.  Anesth Analg 2020;131(1):273-279
A prospective observational study assessing the risk of postdural puncture headache in 12-45 year-old patients after ambulatory lower extremity surgery under combined spinal-epidural surgery (Higher risk noted in adolescents).

Hydromorphone population pharmacokinetics in pediatric surgical patients
Balyan R, Dong M, Pilipenko V et al. Paediatr Anaesth 2020;30(10):1091-1101
A prospective study in children undergoing major elective surgery describing hydromorphone population pharmacokinetics and associated simulation.

Emergency Department provider survey regarding acute sickle cell pain management
Martin OY, Thompson S, Carroll A, et al. J Pediatr Hematol Oncol 2020;42(6):375-380  doi:
A study presenting the results of a survey administered to ED providers at a single institution.

Pain outcomes following mastectomy or bilateral breast reduction for transgender and non-transgender patients who received pectoralis nerve blocks
Verdecchia N, Grunwaldt L, Visoiu M. Paediatr Anaesth 2020;30(9):1049-150
A short report from a single pediatric institution examining reported pain and postoperative opioid use after breast surgery in 67 transgender and 33 female patients (no patient ages were provided).

The time course of pain after tonsillectomy
Tan L, Carachi P, Anderson BJ. Paediatr Anaesth 2020;30(9)
A short report of an audit of analgesic use and pain scores over 7 days post day-stay surgery in a cohort of 94 children at a single institution.

Caregiver anxiety and the association with acute pain in children undergoing elective ambulatory surgery in a lower-middle-income country setting
Knoetze R, lachman A, Moxley K, et al.  Paediatr Anaesth 2020;30(9):990-997
A cross-sectional, descriptive study involving 76 children aged 4-12 years and their caregivers in Cape Town, South Africa.

Effects of obstructive sleep apnea and obesity on morphine pharmacokinetics in children
Dalesio NM, Lee CK, Hendrix CW, et al. Anesth Analg 2020;131(3):876-884
A study of the pharmacokinetics of a single 0.5 mg/kg of morphine in 3 groups of 5-12 year-old children: controls, and with obese or non-obese OSA syndrome.

Physicians prescribe more opioids than needed to treat pain in children after outpatient urological procedures; an observational cohort study
Hunsberger JB, Hsu A, Yaster M, et al. Anesth Analg 2020;131(3):866-875
Study involving parent interviews at 48h and 10-14 days post outpatient surgery assessing pain, opioid use and opioid disposal.

Medical use and misuse of prescription opioids in US 12th grade youth: school-level correlates
McCabe SE, Schulenberg J, McCabe V, et al. Pediatrics 2020;146(4):e 20200387
Presentation of data from the Monitoring the Future study from 2002 to 2017.

Adolescent opioid misuse attributable to adverse childhood experiences
Swedo EA, Sumner SA, De Fijeter S, et al. J Pediatr 2020;224:102-109
A cross-sectional survey assessing self-reported lifetime exposure to adverse childhood experiences and recent opioid misuse in middle and high school students in Ohio in 2018. 

Attentional biases in pediatric chronic pain: an eye-tracking study assessing the nature of the bias and its relation to attentional control
Soltani S, van Ryckegham DML, Vervoort T, et al. Pain 2020;161(10):2263-2273
Laboratory study assessing eye-tracking in response to visually and emotionally stimulating pictures in 168 youth with and without chronic pain.

Pain-related behavior and abnormal cutaneous innervation in a murine model of classic Ehlers-Danlos syndrome
Syx D, Miller RE, Obeidat AM, et al. Pain 2020;161(10):2274-2283
Basic science study exploring possible EDS-related pain mechanisms.

The prevalence of hypermobility in children with irritable bowel syndrome and functional abdominal pain is similar to that in healthy children
Shulman RJ, Self MM, Czyzewski DI, et al. J Pediatr 2020;222:134-140
Assessment of 109 patients with prospective 2-week diaries and child- and parent-reported measures of anxiety, depression, and somatization.

Adverse drug effects related to multiday ketamine infusions; multicenter study
Mendelson AM, Kohan L, Okai J, et al. Reg Anesth Pain Med 2020;45:679-680
Research letter describing adverse drug effects including hallucinations and liver enzyme elevations in 115 adult patients undergoing inpatient continuous 5-day ketamine infusions for chronic pain.

Thirty-five years of acute pain services: where do we go from here?
Stamer UM, Liguori GA, Rawal Narinder. Anesth Analg 2020;131(2):650-656
Special article examining the evolution of pain services from postoperative to perioperative care delivery models and changing outcomes parameters.

How should we approach parental refusals of opioids on behalf of children in the perioperative setting? A practical approach based on ethical theory.
Moreno-Galvan A, Marron JM, Marsiglio AM.  Paediatr Anaesth 2020:30(8):852-858
Special Interest Article

Sedation, analgesia, and neuromuscular blockade: an assessment of practices from 2009 to 2016 in a national sample of 66,443 pediatric patients cared for in the ICU
Patel A, Trujillo-Rivera E, Faruqe F, et al. Pediatr Crit Care Med 2020;21(9):e599-e609 
A retrospective analysis based on data from a national database involving 161 ICUs with pediatric admissions between 2009 and 2016.

Hospital or home? Where should children die and how do we make that a reality?
Johnston EE, Martinez I, Currie E, et al. J pain Symptom Manage 2020(1):106-115
Systematic review of literature concerning preferred location of death of children in North America.

A methodologic approach to conducting a statewide community needs assessment of pediatric palliative care and hospice resources
Brock KE, Aleen KE, Barton C, et al. J Pain Symptom Manage 2020;60(3):531-538
Presentation of a mixed-method descriptive design with multiple stages using the state of Georgia as an example.

Patterns of hospice and home-based palliative care in children: an Ohio Pediatric Palliative Care and End-of Life Network study
Grossehme DH, Humphrey L, Friebert S, et al.  J Pediatr 2020;225:152-156
A retrospective cohort study describing demographics and clinical characteristics of 209 patients referred to pediatric hospice and home-based palliative care programs in Ohio in 2016.

Mapping pediatric palliative care development in the WHO-European region: children living in low-to-middle-income countries are less likely to access it
Arias-Casais N, Garralda E, Pons JJ, et al.  J Pain Symptom Manage 2020;60(4):746-753  doi:
Study presenting results based on a survey, open-ended interview and rating process involving 51 of 54 European countries.

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