Half-Yearly Journal Review of Regional Anesthesia and Pain Medicine Literature

Dr. CasiasBy Timothy Casias, MD
Seattle Children’s Hospital
Seattle, WA

Hello, this article provides a brief synopsis of some of the research articles related to pediatric regional anesthesia and pain medicine that were published from January 1, 2016 through June 30, 2016.

The Analgesic Sparing Effect of Ketamine for Postoperative Pain Management after Pediatric Surgery on the Body Surface
A small study published by Urabe, et. al, from Japan in April 2016, consisting of 58 patients, evaluated the effects of ketamine on the amount of postoperative pain control.  It is known that ketamine is an NMDA antagonist and can provide analgesia as well.  This study investigated the analgesic effect of ketamine for postoperative pain in children undergoing surgery on the body surface.  Fifty-eight patients were divided into two groups, either ketamine or control, and post-operative analgesia was extracted from charts.  The ketamine group received an IV bolus of ketamine (1 mg/kg) prior to surgical incision.  There were no significant differences of usage and frequency of supplementary analgesic usage among groups. 

Comment:  There are many different ideas for how to decrease usage of IV opioids in both the peri-operative and post-operative period.  This small study does not show a difference in the analgesic effects when ketamine was added as a single bolus prior to incision in what appears to be more superficial surgeries.  However, more studies should be done that evaluate a bigger cohort of children and also focus on more procedures that result in moderate to severe postoperative pain.

Urabe, T, Nakanuno R, Hayase K, Sasada S, Iwamitsu R, Senami M. Masui. 2016 Apr;65(4):348-51.

Use of Cryoanalgesia During a Nuss Procedure
A case report by Kim, et. al, in March in the Journal of Thoracic Cardiovascular Surgery discusses how they performed thoracoscopic transthoracic cryoanalgesia during the Nuss procedure.  Typically these patients receive either an epidural or patient-controlled analgesia for post operative pain.  However, cryotherapy, which was introduced in the 1970s can potentially produce analgesia that can last for several weeks.  Here they describe a technique in which a cryoprobe is inserted during the thoracoscopy.  The rigid thorascope transverses across the anterior mediastinum (after dissection) and the cryoprobe tip is placed perpendicular to the intercostal nerve.  The nerve is treated at negative 60 degrees Celcius for two minutes.  This provided analgesia for about 1 month, which is equivalent to time needed for the intercostal nerve axonal regeneration.

Comment:  Even though this is a surgical technique of analgesia, this is something that can perhaps be achieved by the surgeons while they are already in the thoracic space for the Nuss procedure, and thus provide a longer lasting pain relief for the patient under direct visualization of the nerve through the scope.  However, longer term effects of cryotherapy and its implication for larger numbers remains to be investigated.

Kim, S, Idowu, O, Palmer, B, Lee SH, J Thorac Cardiovasc Surg. 2016 Mar;151(3):887-8.

Prevention and Management of Procedural Pain in the Neonate: An Update
A new policy statement published by the AAP in February 2016 discusses prevention and management of procedural pain in the neonate.  This is an important aspect not only because it is ethical, but also because neonates are subject to many repeated painful procedures.  Neonates are at a greater risk of neurodevelopmental impairment because of a multitude of factors such as preterm birth, multiple painful stimuli in the NICU as well as underlying disease processes.  Nociceptive pathways are active and functional as early as 25 weeks of gestation, and may elicit a generalized or exaggerated response to noxious stimuli.  Even though there are major gaps in knowledge regarding pain processing, assessment and treatment among this patient population, there are many safe and effective therapies that are underused for routine minor, yet painful procedures.

Non-pharmacologic treatment strategies include swaddling combined with positioning, facilitated tucking, nonnutritive sucking, breastfeeding, sensorial stimulation, and massage.  Pharmacologic treatment strategies include sucrose and glucose, opioids, benzodiazepines, acetaminophen, and topical anesthetic agents. 

Repetitive pain in the NICU has been associated with adverse neurodevelopmental, behavioral, and cognitive outcomes.  The group also recommends working on the significant gaps in research, especially looking at the pharmacologic treatments for pain prevention and management by asking for a call on more research to address these gaps in knowledge.

Comment:  This policy statement discusses both pharmacologic and nonpharmacologic treatment therapies that exist in literature with level of evidence for their efficacy in the neonatal population and further encourages clinicians and researchers to address the gaps in knowledge. 

Pediatrics. 2016 Feb;137(2):e20154271.

Blood Bupivacaine Concentrations After Transversus Abdominal Plan Block and Neonates: A Prospective Observational Study
A small prospective, observational study by Suresh, et.al, in March examines the blood concentrations of bupivacaine after a transversus abdominis plane (TAP) block.  Although the use of TAP blocks to minimize postsurgical pain has been demonstrated in neonates, there is limited safety data available for this population.  It is unknown what plasma levels of local anesthetics are safe in neonates after TAP blocks.  In this study, ten neonates were included and after general anesthesia was induced they received an ultrasound-guided TAP block with 0.125% bupivacaine for a total volume of 1 mL/kg.  Dried blood spot samples were obtained and analyzed at 0, 5, 15, 30, 60, 120 minutes, 4, and 24 hours after the TAP block.  This showed that the highest blood concentration that was measured occurred at the 30 minute interval and was 0.26 mg/mL, which is significantly lower than potentially toxic plasma levels (1.5 – 2.0 mg/mL).  None of the patients demonstrated any potential signs of local anesthetic toxicity. 

Comment:  This study shows that in the neonatal population, TAP blocks can be safely performed using 0.125% bupivacaine at 1 mL/kg without having high plasma levels.  This might be a good alternative for abdominal surgeries when an epidural is not an appropriate option.

Suresh, S, De Oliveria, GS Jr.  Anesth Analg. 2016 Mar;122(3):814-7.

An Analysis of 34,218 Pediatric Outpatient Controlled Substance Prescriptions
There has been much discussion over the last year about controlled substance prescriptions and this was even referenced in our last newsletter.  This study by George, et.al, in March examines a large database of controlled substance discharge prescriptions (34,218) written by the providers at their institution from January 1, 2007 to February 14, 2014 for demographic information (age, formulation, and amount of drug dispensed).  They specifically were evaluating the role of a computerized system in reducing a previously reported 82% error rate in handwritten discharge controlled substance prescriptions.  In addition, they randomly regenerated 2% (700) of prescriptions based on stored data and analyzed them for errors using previously established error criteria.  Patients in the database averaged 9 years of age and 36.7 kg.  The most commonly prescribed opioid was oxycodone (73%) and was prescribed as a single agent uncombined with acetaminophen.  Codeine was prescribed 7% of the times and was combined with acetaminophen.  The number of oxycodone tablets averaged 51, with the range being 1-1080 tablets). 

Of the subset of the randomized prescriptions, all drugs were legible and used best prescribing practice.  3.6 had incorrect weights compared with the most recent in the chart.  Their findings reported that the computerized prescription writer eliminated most but not all of the errors common to handwritten prescriptions.  Oxycodone is the most common prescribed opioid and is dispensed in large quantities.

Comment:  This article demonstrates an improved, prescription mechanism using a computer ordering system compared to the hand written prescriptions minimizing the prescriptions errors. However, this article also helps to bring home the point that there are a significant amount of prescriptions that are written for controlled substances and some of them send children home with a large quantity of opioids.  More research and policies should be put in place to try to ensure that the opioid that gets sent home with the patient is appropriate for the amount of pain that one should expect and for appropriate storage and disposal of unused opioid medications.

George, JA, Park, PS, Hunsberger, J, Shay JE, Lehmann, CU, White, ED, Lee, BH, Yaster, M. Anesth Analg. 2016 Mar;122(3):807-1

Practice Patterns and Adverse Events of Nitrous Oxide Sedation and Analgesia: A Report from the Pediatric Sedation Research Consortium
A moderate sized study by Tsze, et. al, published in Pediatrics in February was done examining the use of nitrous oxide outside the operating room in various settings by a diverse range of providers.  This data was prospectively collected by the Pediatric Sedation Research Consortium, which was then retrospectively analyzed for children who received nitrous oxide as the primary sedative.  A total of 1634 nitrous oxide administrations were identified and the majority was performed in sedation units, mostly by advanced practice nurses or physician assistants.  The most common adjunct medication was midazolam.

There was a low prevalence of adverse events (6.5%), with vomiting being the most common event at 2.4%.  Serious adverse events were very rare and only occurred in 0.2% of the population studied.  These events were airway obstruction in 2 children and oxygen desaturation in 1 child.  The odds of emesis increased when opioids were also administered and when NPO time was less than 2 hours for clear fluids.  NPO for a full meal less than 6 hours did not increase the odds of vomiting and there were no aspiration events. 

Comment:  This study shows that nitrous oxide given outside of the operating room is associated with a low prevalence of adverse events.  In this population, sedation was administered by non-anesthesiologists, on most sedation services. 

Tsze, DS, Mallory, MD, Cravero, JP, J Pediatr. 2016 Feb;169:260-5.e2.

Postoperative Pain Management in Children of Hispanic Origin: A Descriptive Cohort Study
Brown, et. al, in a publication in February in Anesthesia and Analgesia evaluated 105 Hispanic families post tonsillectomy and adenoidectomy to evaluate the postoperative pain patterns.  This study had children aged 2 to 15 years old and participating parents completed baseline and demographic packets.  Recorded postoperative pain ratings and administration of analgesics at home for 1 week were collected during home visits.  The results showed a high incidence of significant pain in the first 24 hours at home (70%), yet 32% of children received 0 to 1 dose of analgesia.  Overall, 21% of children received 4 or less total doses of pain medication over the entire week after surgery. 

Comment:  This study highlights the probable role that cultural components play in assessment of pain and its treatment.  Even with good follow-up and education, some cultural groups might not use pain medication as prescribed. 

Brown, R, Fortier, MA, Zolghadr S, Gulur P, Jenkins, BN, Kain, ZN, Anesth Analg. 2016 Feb;122(2):497-502.

 Can Perioperative Acupuncture Reduce the Pain and Vomiting Experienced after Tonsillectomy?  A Meta-analysis.
Cho, et. al, published their findings in March in Laryngoscope evaluating whether perioperative acupuncture can reduce pain and vomiting after tonsillectomy.  The authors independently searched MEDLINE, SCOPUS, and Cochrane databases until June 2015 to find studies that examined the effects acupuncture after tonsillectomy.  They found twelve studies comprising a total of 1,025 participants.  They found that the pain scores reported by patients during the first 48 hours and the postoperative need for analgesics were significantly lower in the acupuncture group versus the control group.  In addition, the incidence of postoperative nausea and vomiting was also significantly lower in the acupuncture group than in the control group.  No major adverse events were noted.  However, due to high levels of heterogeneity in several of the measured parameters, they believe that acupuncture was not evaluated sufficiently.

Comment:  Over the last couple of decades acupuncture has gained more acceptance in Western medicine.  There are many studies that have demonstrated some improvements in clinical outcomes by using acupuncture, but larger studies need to be done.  In addition, not all hospital have resources to provide acupuncture services readily in the operating room.

Cho, HK, Park, IJ, Jeong, YM, Lee, YJ, Hwang, SH, Laryngoscope. 2016 Mar;126(3):608-15

The Relationship Between Parent Trait Anxiety and Parent-reported Pain, Solicituous Behaviors, and Quality of Life Impairment in Children with Cancer
Link and Fortier in January published a small study in the Journal of Pediatric Hematology and Oncology about the relationship between parent anxiety and pain/quality of life impairment in children.  Pain related disability has been shown to be associated with parental psychological distress.  A total of 353 parents of children treated for cancer completed measure of anxiety, behavioral responses to children’s pain, and of their child’s quality of life and pain.  Children aged 8-18 also computed measures of their own pain.  They found that parental anxiety was significantly associated with parent rating of child’s pain severity and quality of life.  Regression analysis revealed that parental anxiety significantly predicted solicitous behaviors, pain frequency, and child quality of life.  These findings suggest that parental anxiety plays a significant role in the parent’s perception of their child’s pain and quality of life.  There was no significant relationship between parent trait anxiety and child reported pain severity.
Comment:  This study demonstrates that there is a relationship between the parental anxiety and how much pain they perceive their child to be in.  However, this relationship does not correlate with how much pain the child actually reports.  Further research needs to be conducted to investigate the effects of measures to decrease parental anxiety in order to optimize successful pain management in this patient population

Link, CJ, Fortier, MA, J Pediatr Hematol Oncol. 2016 Jan;38(1):58-62.

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