Literature Reviews

By Sabine Kost-Byerly, MD
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

Remembering the Pain of Surgery One Year Later: A Longitudinal Examination of Anxiety in Children’s Pain Memory Development

Noel M. Rosenbloom B, Pavlova M et al. Pain 2019;160(8):1729-39  DOI: 10.1097/j.pain.0000000000001582

Progression from acute to chronic pain is poorly understood.  Recall of pain can be more severe than the pain originally experienced. High levels of anxiety may contribute to such negatively-biased pain memories and development of chronic pain. This study examined the effect of anxiety on the development of children’s pain memory over time.  It is part of a larger study, yet unpublished, examining risk factors for chronic postoperative pain in children.

A prospective study included 237 children (aged eight to 18 yrs, female n=140, white 60%) undergoing major orthopedic or general surgery.  Assessment consisted of a preoperative questionnaire (past and current pain experiences, medications use, psychological and emotional functioning), examination of intraoperative anesthesia management and in-hospital postoperative pain experience, and follow-up at six and 12 months postoperatively. Measures included NRS-I (intensity), NRS-M (movement), NRS-U (unpleasantness), CASI (Childhood Anxiety Sensitivity Index), PCS-C (Pain Catastrophizing Scale-Children), and CPASS (Child Pain Anxiety Symptoms Scale).

Many children had prior surgeries (61%) and ongoing pain issues (62%), although only 8% were taking analgesics prior to surgery. Hospital length of stay LOS was 4.7 (range one to 36) days. Boys and girls had comparable pain experiences with pain at baseline 2/10, postoperative in-hospital pain 4/10, at 6 months 2.4/10, and at 12 months 2.8/10. Incidence of chronic postsurgical pain at surgery site (>3/10) was 35% and 38% at six and 12 months respectively.  Patient pain recall at 12 months post-surgery was higher for all NRS measures than actual initially reported scores. Higher anxiety and pain catastrophizing scores in the perioperative phase were positively correlated with negatively biased recall at 12 months follow-up, which in turn was tied to higher reported pain scores at follow-up.

Anxiety sensitivity and pain catastrophizing at baseline were predictive of children’s recall of pain intensity one year postoperatively.

Transversus Abdominal Plane Block in Children: Efficacy and Safety: A Randomized Clinical Study and Pharmacokinetic Profile

Sola C, Menacé C, Bringuier S, et al. Anesth Analg 2019;128(6):1234-1241
DOI: 10.1213/ANE.0000000000003736

The transversus abdominal plane (TAP) block is a commonly used regional anesthetic procedure providing analgesia for abdominal procedures.  The safest and most efficacious regimen for ultrasound-guided TAP blocks remains to be defined. This study assessed the pharmacokinetic profile and analgesia achieved after low volume/high concentration (LVHC) versus high volume/low concentration (HVLC) levobupivacaine.

In a prospective randomized study in 70 children undergoing outpatient inguinal surgery,  Levobupivacaine (LB) 0.4 mg/kg was either administered as 0.2 mL/kg of 0.2% LB (HVLC) or as 0.1 mL/kg of 0.4% LB (LVHC). Pharmacokinetic profile study was performed. Primary outcome measure was need for postoperative opioid analgesic rescue.

Most of the 70 patients (71%) included in the final analysis did not require any additional analgesia. The difference in the number of children in the LVCH group (35%) versus the one in the HVLC group (23%) needing analgesic rescue was not statistically significant.  Mean pain scores between groups were similar at discharge. The pharmacokinetic profiles were comparable; the highest total and free LB concentrations (average peak 22 minutes post-injection) remained well below toxic thresholds.

There was no difference in the quality of postoperative analgesia of 0.4 mg/kg of LB when administered as HVLC or LVHC.

Fentanyl Versus Remifentanil-based TIVA for Pediatric Scoliosis Repair: Does it Matter?

Kars MS, Villacres Mori B, Ahn S, et al. Reg Anesth Pain Med 2019;44(6):627-631
DOI: 10.1136/rapm-2018-100217

Acute opioid tolerance and opioid-induced hyperalgesia (OIH) can be a concern in painful major surgery such as adolescent idiopathic scoliosis (AIS) repair.  This study aimed to assess whether fentanyl-based TIVA would be more advantageous than remifentanil-based TIVA in diminishing such undesirable effects.

A retrospective study comprised of patients with AIS undergoing posterior spinal fusion within a 3.5-year period, receiving remifentanil 0.05 to 0.5 μg/kg/min (N=37) during the first 18 months and fentanyl 0.5 to 2 μg/kg/hour (N=25) in the latter two years as part of a standardized TIVA protocol for AIS surgery. Primary outcome was 24h-postoperative opioid consumption (continuous plus demand morphine or hydromorphone PCA). Secondary outcomes were mean 24-48h postoperative pain score (VAS), time to extubation, assisted ambulation, length of stay, and postoperative N&V.

The 62 patients (11-20 years, 70% female) were not uniformly distributed throughout the two groups.  Analysis needed to adjust for more males, older age, and less acetaminophen use in the remifentanil group.  The fentanyl group had higher opioid use during the first and the second 24 hours postoperatively; their pain scores were higher as well.

Intraoperative fentanyl infusion within a standardized TIVA protocol was associated with postoperative higher pain scores and opioid needs than a remifentanil infusion.

The retrospective nature (with potentially unknown variables pre- and post-intervention) and the small size of the study limit the conclusions to be drawn.  A future RCT (likely multi-center due to size requirement) and additional optimal adjuvant medication assessment may be needed.

Decreased Opioid Prescribing in Children Using an Enhanced Recovery Protocol

Baxter KJ, Short HL, Wetzel M, et al. J Pediatr Surg 2109;54(6):1104-1107  DOI: 10.1016/j.jpedsurg.2019.02.044

Enhanced Recovery Protocols (ERP) are associated with decrease in-hospital use of opioids and length of stay (LOS). This study examined opioid prescribing at discharge.

A retrospective study examined postoperative opioid prescription data in patients (N=99, 1-18 years) for three years each pre- and post-ERP implementation for elective colorectal surgeries. ERP called for regional anesthesia intraop, followed by postop analgesia with acetaminophen (10 mg/kg q6h), ketorolac (0.5 mg/kg q6h x 12), gabapentin (10 mg/kg q8h), and morphine (0.05 mg/kg q4 h prn). Primary outcome was the opioid prescription (drug, dose, number of doses) at discharge. Discharge management was not standardized. Secondary outcomes were in-hospital opioid use, length of stay (LOS), need for prescription refills post-discharge.

Of the 99 patients (median age 16, female N=51, IBD N=88, total colectomy or ileocecectomy N=65) slightly more (57%) were treated post-ERP start. LOS decreased from four to three days. Significantly fewer patients received in-hospital opioids post-ERP initiation (intraop 46% vs. 100%, postop 59% vs. 95%). Median morphine equivalents (ME) significantly decreased for patients receiving opioids in-hospital. At discharge, fewer patients received prescriptions for opioids (31% vs. 70%) although the number of doses and the ME prescribed were similar, as were complication and readmission rates.

ERP in pediatric patients may be associated with decreased opioid use throughout the perioperative period. Limitations of the study include single center data, small sample size, and missing postoperative pain scores. (The author did not address actual post-discharge opioid use and leftover medications. They also mentioned that they “have continued to refine the process and make improvements through monthly…ERP reviews”, potentially introducing unknown variables along the way, always a problem in these retrospective pre- and post-intervention studies).

Trends in Opioid Prescribing for Adolescents and Young Adults in Ambulatory Care Settings

Hudgins JD, Porter JJ, Monuteaux MC, et al. Pediatrics 2019;143(6) pii: e20181578
DOI: 10.1542/peds.2018-1578

Adolescents and young adults are at risk of opioid misuse after exposure associated with medical treatment. This study aimed to assess opioid prescribing in young patients receiving care in emergency departments (ED) and outpatient clinics in order to further enlighten the epidemiology of opioid prescribing in this population.

A retrospective analysis examined data collected in the National Hospital Ambulatory Medical Care Survey (NHAMCS) and National Ambulatory Medical Care Survey (NAMCS) over 11 years from 2005 until 2015. Included patients were adolescents (13-17 years) and young adults (18-22 years).

Data analyzed included 78,430 visits that extrapolated to 197 million ED and 801 million outpatient visits in the weighted sample. Rate of opioid prescribing was 14.9% for ED (29 million) and 2.8% for ambulatory visits (22 million). The rate of opioid prescriptions increased from 2.9% of the adolescent to 7.5% of the young adult visits. Opioid prescriptions were between four to six times more common in patients seen in the ED, with the highest rate seen at 17.9% of the young adult visits. Highest rates for diagnosis in the ED were dental disorders (59.7%) and clavicle fractures (47%). Most common opioid prescribed was hydrocodone. Over time there was a small decrease in opioid prescriptions written for both age groups in the ED but none for either group in ambulatory settings. Family practice and orthopedic practices had the highest total number of visits with opioid prescriptions; the highest rates were seen in general and orthopedic practices. Low rates were seen in pediatrics and psychiatry.

Adolescents and young adults commonly receive opioid prescriptions in ED and ambulatory care settings increasing their risk for future opioid misuse. The total volume of prescriptions written in these settings is significant. Opioid prescribing patterns need to be further defined. Recent policies and guidelines seem to have had variable impact on prescribers. Targeted interventions and education may be needed.

Patient-controlled Analgesia for Children with Life-limiting Conditions in the Community: Results of a Prospective Observational Study

Henderson EM, Rajapakse D, Kelly P, et al.  J Pain Symptom Manage 2019;57(5):e1-e4  DOI: 10.1016/j.jpainsymman.2019.02.015

Patient-controlled analgesia (PCA) is an alternative to continuous parenteral infusions with breakthrough analgesia in pediatric palliative care.  This study aimed to assess use of PCA in children with life-limiting conditions highlighting barriers to its practice.

A prospective observational study included patients considered for PCA by a multidisciplinary tertiary palliative care team. Inclusion criteria were rapidly escalating pain, opioid-naïve or minimal opioid use, steady opioid background requirement but with breakthrough pain, or opioid requirement and end of life.  PCA was provided under the supervision of hospital tertiary palliative care services but community-based nursing teams managed the day-to-day needs of the patient including PCA pumps. Parents or community nurses provided daily assessments of pain (FLACC, NRS), pain characteristics, PCA and other medication use, and other interventions in managing pain.

Just 11/40 patients considered by the team over a 16-month period were thought to be suitable for PCA. Exclusions were due to pain not being the primary symptom (N=11), managed by other means (N=8), or primarily neuropathic in nature (N=2). Death occurred (N=3) or nursing support in the community was insufficient (N=8).  Of the 11 patients offered PCA, four declined. Thus, seven patients (age six to 17 years; six malignant, one non-malignant disease) used PCA up to 35 days. Background infusions varied between none up to 0.65 mg/kg/h and demand doses were between 0.02 to 1 mg/kg with the highest doses seen in the child remaining on PCA for 35 days. Two patients asked for removal of PCA due to mobility issues and pain at the SQ infusion site. Pain score and bolus use only correlated one to two weeks before death but not later.

Lack of community nursing support limits pain management with PCA in the community. Pain assessment in palliative care patients needs to go beyond pain intensity measurements but include function and mobility, a biopsychosocial model. 

Other Publications of Note

Regional Anesthesia for Sternotomy and Bypass – Beyond the Epidural
Raj N. Paediatr Anaesth 2019;29(5):519-529 DOI: 10.1111/pan.13626.
Educational review.

The Migration of Caudally Threated Thoracic Epidural Catheters in Neonates and Infants.
Simpao AF, Gálvez JA, Wartman EC et al. Anesth Analg 2019;129(2):477-481
DOI: 10.1213/ANE.0000000000003311
Retrospective single institution study demonstrating frequent postoperative migration of caudally inserted threated catheters, especially in smaller and younger infants.

Opioid Sensitivity in Children With and Without Obstructive Sleep Apnea
Montana MC, Juriga L, Sharma A, et al. Anesthesiology 2019;130(6):936-945
DOI: 10.1097/ALN.0000000000002664
A fixed-rate infusion of fentanyl led to similar concentration-miosis relations in children with and without OSA. There was no change in ventilator drive in either group with the particular infusion leaving the question of increased opioid sensitivity in children with OSA unanswered.

Outpatient Prescription Opioid Use in Pediatric Medicaid Enrollees with Special Health Care Needs
Feinstein JA, Rodean J, Hall M, et al. Pediatrics 2019;143(6). Pii: e20182199
DOI: 10.1542/peds.2018-2199
Opioid prescriptions are not unusual for pediatric patients with special health care needs, especially for those who are aged >10 years, have multiple chronic conditions, or polypharmacy. Most prescriptions (75%) are associated with outpatient status.

The Effect of Drug Disposal Bag Provision on Proper Disposal of Unused Opioids by Families of Pediatric Surgical Patients: A Randomized Clinical Trial.
Lawrence AE, Carsel AJ, Leonhart KL, et al. JAMA Pediatr 2019 Jun 24:e191695
DOI: 10.1001/jamapediatrics.2019.1695
Provision of a drug disposal bag containing activated charcoal and detailed instructions concerning postoperative opioid use, storage and disposal increased the likelihood of excess opioid disposal.

The Role of Narrative in The Development of Children’s Pain Memories: Influences of Father- and Mother-Child Reminiscing on Children’s Recall of Pain
Noel M, Pavlova M, Lund T, et al. Pain 2019;160(8):1866-1875  
DOI: 10.1097/j.pain.0000000000001565
More elaborative parental reminiscing style and greater use of emotional words predicted more accurate/positively biased pain memories whereas greater parental use of pain words predicted more negatively biased pain memories

Endogenous Pain Modulation in Children with Functional Abdominal Pain Disorders
Pas R, Rheel E, Van Oosterwijck S, et al. Pain 2019;160(8):1883-1890
DOI: 10.1097/j.pain.0000000000001566
Young children with FAPD demonstrated secondary hyperalgesia and decreased functioning of endogenous analgesia.

Cognitive Behavioral Therapy for Persistent Severe Fatigue in Childhood Cancer Survivors: A Pilot Study
Boonstra A, Gielissen M, van Dulmen-den Broeder E, et al. J Pediatr Hematol Oncol 2019;41(4);313-318   DOI: 10.1097/MPH.0000000000001345
Childhood cancer survivors with severe fatigue can experience significant improvement with CBT.

Grief Reaction and Coping Strategies of Trainee Doctors Working in Paediatric Intensive Care
Ffrench-O’Carroll R, Feeley T, Crowe S, et al. BJA 2019;123(1):74-80
Some trainee doctors in the PICU experience significant grief and emotional reactions after pediatric deaths. They see a lack of professional support and debriefs.

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