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ACO 310308

REVIEW

CURRENT
OPINION Acute pain management in children: challenges
and recent improvements
Catherine E. Ferland a,b,c,d,e,f, Eduardo Vega a,b,g, and Pablo M. Ingelmo a,b,d,e,f

Purpose of review
The evidence regarding the efficacy of analgesics available to guide postoperative pain treatment in
pediatric patients is limited. Opioid medications are very often an important component of pediatric
postoperative pain treatment but have been associated with perioperative complications. We will focus on
initiatives aiming to provide effective treatment minimizing the use of opioids and preventing the long-term
consequences of pain.
Recent findings
Interpatient variability in postoperative pain is currently managed by applying protocols or by trial and
error, thus often leading to patients being either undertreated or overtreated. Few evidence-based reports
are available to guide the use of opioid medications in children, including the prescription of opioids after
hospital discharge. Using combinations of nonopioid analgesics in a multimodal approach may limit the
need for opioids, thus decreasing the risk of toxicity and dose-related side effects. There is a lack of
adequate research in this field, and more specifically on identifying which patient is at higher risk of poor
postoperative pain management.
Summary
Treatment options have evolved in recent years, including the combinations of multimodal regimens and
regional anesthetic techniques. Using combinations of nonopioid analgesics in a multimodal approach may
limit the need for opioids.
Keywords
children, chronic postsurgical pain, nonopioid analgesics, opioids, postoperative pain

INTRODUCTION there is an actual tendency to reduce or eliminate

An adequate postoperative pain management in
children needs to be a dynamic process embracing
the perioperative period, pain after discharge and
the potential development of persistent postsurgical
pain [1]. Postoperative pain management remains
inadequate in many clinical settings [2,3 ,4]. A
&
recent prospective study by Wilson et al. [5 ] exam-
&
ined the pain profile of patients undergoing general
and urologic surgeries and found that up to 70% of
these patients experienced moderate to severe pain
after surgery.
Opioid medications are very often an essential
component of pediatric postoperative pain treat-
ment. The use of opioids has been associated with
both adequate pain control and perioperative com-
plications. Few reports are available to guide the use
of opioid medications in children, including the
prescription of opioids after hospital discharge.
Hence, there is a need to reinforce the importance
of developing evidence-based opioid guidelines for
treating pain in the pediatric population. Moreover,
the use of opioids to prevent adverse effects [6].
Prediction of pain intensity and the eventual
progression to a chronic pain state has become the
center of interest for intense research efforts.
The current review will describe recent develop-
ments in pediatric postoperative pain. We will focus
on initiatives aiming to provide adequate treatment
minimizing the use of opioids and preventing the
long-term consequences of pain.
a
Department of Anesthesia, McGill University, bChronic Pain Service,
Montreal Children’s Hospital, cResearch Institute of the McGill University
Health Centre, dShriners Hospital for Children-Canada, eAlan Edwards
Centre for Research on Pain, Montreal, Québec, Canada, fSIMPAR
Group, Parma, Italy and gDepartment of Anesthesia, School of Medicine,
Pontifical Catholic University of Chile, Santiago, Chile
Correspondence to Pablo M. Ingelmo, MD, Department of Anesthesia,
Montreal Children’s Hospital, B.04.2427, 1001 Boulevard Decarie, Mon-
treal, QC, Canada H4A3J1. Tel: +1 514 412 4448;
e-mail: pablo.ingelmo@mcgill.ca
Curr Opin Anesthesiol 2018, 31:000–000
DOI:10.1097/ACO.0000000000000579

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Pediatric anesthesia
KEY POINTS
! Considering the variability on pain perception and
pain profile following specific surgical procedures,
postoperative pain has to be assessed and managed as
a dynamic event.
! Regarding the current opioid epidemic, perioperative
caregivers have to face the challenge of improving
postsurgical pain treatment and reducing opioid
prescriptions after surgery.
! An individualized multimodal analgesic program
combining nonopioid analgesics and regional
analgesic techniques may provide adequate
postoperative pain management.
! To provide a tailored pain management more research
is needed to address which patients are at risk to
develop moderate-to-severe postsurgical pain and
chronic postsurgical pain.
POSTOPERATIVE PAIN VARIES
DEPENDING ON THE NOCICEPTIVE
STIMULUS, THE AGE AND THE PREVIOUS
PAIN EXPERIENCE
Predicting the interpatient variability of the pain
intensity and the response to treatment are part of
the daily challenge in clinical practice. The neuro-
physiological mechanisms of postoperative pain
may differ in patients who report similar pain inten-
sity, location, and duration. In real life, we manage
this variability applying protocols or by trial and
error, thus often leading to patients being either
undertreated or overtreated.
The efficacy of oral morphine as a single agent
for postoperative pain after minor outpatient pedi-
atric surgery has been questioned. Children aged 5–
17 years old undergoing minor outpatient orthope-
dic surgery were randomized to receive oral mor-
phine (0.5 mg/kg) or oral ibuprofen (10 mg/kg),
every 6 h as needed. Both interventions decreased
pain with similar efficacy. Children receiving mor-
phine reported more adverse effects (69 vs. 39%),
most commonly drowsiness and nausea. A simplis-
tic reading would suggest that ibuprofen is a better
first-line option after minor orthopedic surgery.
However, in this study, the dose of morphine was
unusually high, 25% of children did not use anal-
gesics, and two-third of them received three or fewer
doses, which may question the need for opioids in
this clinical setting [7]. The one-size-fits-all on pain
prescribing may lead to the wrong dilemma. As
stated by Shilling, it is incorrect to believe that all
surgical patients require opioids [8], as it is also
unfair to generalize that ibuprofen should be the
mainstay of treatment for all types of fractures.
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There is some evidence that postoperative pain
is more severe in older children [9]. The pain
intensity evaluated with behavioral observational
tools increases with age [10]. It is possible then that
younger children may not need as many opioids
than older ones. Children with a mean age of
5 years old and receiving only ibuprofen after
tonsillectomies reported significantly less postop-
erative pain than older patients (mean age 8 years)
receiving just opioids or ibuprofen with narcotics.
Patients taking ibuprofen alone returned to regular
activity and diet sooner than those taking ibupro-
fen with opioids [11].
The prevalence of chronic pain in children
ranges between 20 and 40% worldwide, and 5% of
children and adolescents are severely disabled by
pain [12]. The number of hospital admissions of
patients with chronic pain or due to chronic pain
conditions has increased significantly. Children
with chronic pain often undergo surgery, and effec-
tive perioperative management of their pain can be
challenging [13]. A standard treatment algorithm
may not be helpful for patients with chronic pain
and usually requires an individualized approach.
This may include the use of regional anesthesia
and adjunctive therapies to decrease peripheral
and central sensitization. Such group of children
may benefit from a more aggressive preemptive
analgesic regimen, and may also require signifi-
cantly more analgesics and for a longer time after
surgery [14 ].
&
DO WE PRESCRIBE TOO MUCH OPIOIDS?
Sun et al. [15] suggest that patients receiving opioids
even for a short period are at higher risk of chronic
opioid usage in comparison with patients who have
never used them in the past. Around 11% of high-
school seniors have reported a history of nonmedi-
cal use of opioids, accessed mainly through leftovers
prescribed for family members and previous proce-
dures [16].
Pediatric healthcare providers often prescribe
more opioids than patients routinely need after
discharge. In a sample of 343 pediatric inpatients
(98% postoperative) discharged from a university
children’s hospital, 58% of the opioid doses dis-
pensed were not consumed. The number of doses
prescribed and dispended was the most reliable
predictor of the number of doses remaining. Even
when most families were informed how to dispose of
leftover opioids, only 4% efficiently did so [17 ].
&&
This fact reinforces the idea to provide an adequate
education on the proper methods of opioid disposal
in helping to minimize the availability of unused
postoperative medication [18].
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DO WE ALWAYS NEED OPIOIDS IN POST
ANESTHESIA CARE UNIT?
It is difficult to differentiate emergence delirium and
pain in the clinical practice. Emergence delirium
starts almost always during awakening and resolves
within 15 min. When a child is unable to make ‘eye
contact’ and is ‘unaware of the surroundings’ is
more likely having emergence delirium rather than
pain. The association of ‘abnormal facial expres-
sion’, ‘crying’, and ‘inconsolability’ during the first
15 min after awakening better describes a child in
pain. The practical problem is that almost half of
children with emergence delirium will also have
pain behavior during the early phases of awakening
[19]. Therefore, the caregiver in the recovery room
may struggle with the decision of giving a dose of
opioid to treat pain, consoled the child or provide a
dose of propofol to treat emergence delirium.
The association of no eye contact and unaware-
ness of surroundings in children with pain behavior
censored with a behavioral scale decreases signifi-
cantly every 5 min. In the case of an unclear cause of
the unsettling behavior, to console the child for
5 min may be the appropriate intervention. If the
child is inconsolable, makes eye contact and seems
oriented, pain may likely be the diagnosis and
should be treated accordingly [20].
Other causes than pain and emergence delirium,
like thirst, could be responsible for unsettling behav-
ior after anesthesia and may lead to an inappropriate
use of opioid in the recovery room. Children aged
6 months to 4 years old were offered apple juice
10 ml/kg before an opioid administration if the Face
Legs Activity Cry Consolability score was at least 4.
The use of apple juice before analgesics reduced by
more than half the proportion of children who
required opioids or who vomited [21].
THEN, IS IT POSSIBLE TO TREAT PAIN
WITHOUT OPIOIDS?
Treatment options for postoperative pain have
evolved in recent years, including the combinations
of multimodal analgesic regimens and regional
anesthetic techniques. Using combinations of non-
opioid analgesics in a multimodal approach may
limit the need for opioids, thus decreasing the risk
of toxicity and dose-related side effects [22].
Many institutions and societies have modified
their guidelines after the recent restrictions on the
use of codeine in children. A recent analysis of the
French guidelines shown that pain management
after tonsillectomy needs to be improved [23].
NSAIDs in combination with acetaminophen seem
at least as useful as the combination acetaminophen
and tramadol with no difference in hemorrhage
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Acute pain management in children Ferland et al.
rates requiring readmission and further surgical
intervention [24]. However, despite adequate medi-
cal prescriptions, pain intensity after tonsillectomy
remains high during the first 6 postoperative days.
The Swedish national guidelines for the treat-
ment of pain after adenotonsillectomy recommend
preoperative or intraoperative administration of
betamethasone, clonidine, and acetaminophen.
Postoperative pain treatment at home includes
the combination of acetaminophen, NSAIDs, and
oral clonidine rather than opioids as rescue analge-
sia [25]. Two years after the launch of the guidelines,
none of the departments included in a national
survey were prescribing codeine or tramadol. The
general opinion among physicians was that the
guidelines impacted the postoperative recovery pos-
itively, including pain, nausea, return to regular
food intake, and constipation [26].
The intraperitoneal instillation of local anes-
thetics during laparoscopic surgery has been
reported less often in children than in adults. Two
studies in pediatric population reported no compli-
cations or toxicity from the local anesthetic while
reducing pain scores, opioid use, and the need for
rescue analgesia [27].
The intraperitoneal nebulization of local anes-
thetics through micro vibration-based aerosol
humidification devices combines the analgesic ben-
efits of gas conditioning (humidification) and local
anesthetic instillation. This method has shown high
efficacy in the control of postoperative pain and the
reduction of postoperative morphine consumption
when compared with both placebo and peritoneal
instillation in different clinical scenarios in adults
[28,29]. The intraperitoneal nebulization of ropiva-
caine has recently been associated with significant
postoperative pain reduction and with improve-
ments in recovery of toddlers undergoing laparo-
scopic herniorrhaphy [30].
The widespread knowledge of ultrasound-
guided procedures has increased the use of regional
anesthesia as part of multimodal analgesia protocols
[31 ]. Ultrasound-guided peripheral nerve blocks
&
enhance the quality of the analgesia allowing reduc-
tion or prevention of opioid use [32,33 ]. Regarding
&
neuraxial procedures, many drugs have been used
through the epidural route aiming at reducing the
total dose of the local anesthetic or increasing the
duration of its analgesic effect. Clonidine (1–2 mg/
kg) significantly prolongs the length of the analgesia
and decreases the use of breakthrough pain medica-
tion after caudal anesthesia [34]. Dexmedetomidine
(1 mg/kg), an eight times more selective for the a-2
adrenergic receptor than clonidine, produced a sim-
ilar increase in the analgesic times [35]. Nonetheless,
doses higher than 1 mg/kg have been associated with
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Pediatric anesthesia
respiratory depression, bradycardia, and hypoten-
sion [36–38].
The analgesic effects of magnesium are medi-
ated through a noncompetitive antagonist effect on
N-methyl-D-aspartate receptors and regulation of
the calcium influx into neurons. When added to
caudal anesthesia, magnesium increases the depth
and extension of the local anesthetic effect and
reduces the incidence of unsettled behavior after
anesthesia [39,40].
CAN WE PREDICT WHICH PATIENT IS AT
RISK OF DEVELOPING INTENSE PAIN OR
CHRONIC POSTSURGICAL PAIN?
Chronic postsurgical pain (CPSP) is defined as pain
developed or increased in intensity after surgery,
lasting at least 3 months with a significant negative
impact on the quality of life. This pain is related to
the surgical anatomical or referred area (e.g., derma-
tome) and can be either a continuation of acute
postsurgical pain or be developed after an asymp-
tomatic period [41,42 ]. The prevalence of CPSP in
&&
children across different clinical settings is 20% at
12 months after surgery. The severity of acute post-
operative pain (visual analog scale > 30 mm) in the
first 24 h after surgery is one of the main risk factors
of having CPSP [43 ,44].
&
Despite the promises of genetics unveiling sev-
eral links between gene polymorphisms and post-
operative pain, the best available predictors of CPSP
remain the clinical risk factors [42 ,45].
&&
Surgery-induced peripheral neural activation and
central neuroplastic changes may determine postop-
erative pain intensity. Quantitative sensory testing
(QST) is a method that can provide relevant informa-
tion on the pain threshold and pain tolerance. It can
give strong hints on central pain mechanisms and
can also evaluate the efficiency of the descending
inhibitory pain response through a conditioned pain
modulation paradigm. A recent systematic review
including 30 studies on preoperative QST predicting
pain after surgery in adults did not find a consistent
association between preoperative detection and pain
thresholds and postoperative pain intensity [46 ].
&&
However, QST variables related to the central mech-
anisms were more frequently associated with postop-
erative pain intensity. Additional work needs to be
accomplished to translate the information provided
by the QST in a clinically relevant benefit for the
postoperative pain management [47].
Central noradrenergic inhibitory centers may
participate in the development and maintenance
of allodynia and hyperalgesia after a nerve lesion
[48]. Therefore, quantifying the biomarkers concen-
trations involved in the endogenous excitatory
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afferent mechanisms or the reduced efficacy of the
endogenous inhibitory efferent mechanisms could
help in predicting postoperative pain outcomes.
Ferland et al. [49] found that the preoperative
plasma and cerebrospinal fluid concentrations of
norepinephrine were associated with the intensity
of pain 6 weeks after spinal surgery in adolescents.
The preoperative concentrations of norepinephrine
levels in cerebrospinal fluid were significantly higher
in patients reporting moderate-to-severe pain in
the immediate postoperative period and 6 weeks
after surgery.
NO DOUBT, WE NEED ADDITIONAL
RESEARCH
The evidence regarding the efficacy of analgesics
available to guide postoperative pain treatment in
pediatric patients is limited. The use of perioperative
acetaminophen, NSAIDs, dexamethasone, ketamine,
clonidine, and dexmedetomidine may decrease post-
operative pain and opioid consumption in some
pediatric surgical populations. However, we do
not have enough information to conclude the peri-
operative use of gabapentin, magnesium, dextro-
methorphan, lidocaine, amantadine, pregabalin,
and esmolol [50 ,51].
&
Approximately 80% in the United States and
over 50% in Europe of drugs given to children are
prescribed ‘off-label’, because they have not received
approval for their use in younger age groups [52]. For
example, there are no drugs with a pediatric label as
an analgesic approved by the food and drugs admin-
istration (FDA) for children less than 6 months of
age. Only ibuprofen has a pediatric label for children
6–24 months. For children older than 24 months,
only acetaminophen, a combination of hydroco-
done and acetaminophen, and transdermal fentanyl
have pediatric labeling. Naproxen, intravenous
buprenorphine, fentanyl citrate injection, and
extended-release oxycodone have been approved
for older children and adolescents [53]. Clinical
trials are needed to evaluate the safety and efficacy
of analgesics across all pediatric age spans to avoid
inappropriate extrapolation of adult data to chil-
dren. The Analgesic, Anesthetic, and Addiction
Clinical Trial Translations, Innovations, Opportuni-
ties, and Networks (www.acttion.org) Pediatric
Pain Research Consortium has recently provided
recommendations on specific trial designs for acute
pain in children. This consensus effort embraced
the guidance from the US FDA and the European
Medicines Agency on analgesic trials for children.
They also defined pain models and methodologies
in different clinical settings for neonates, infants,
toddlers, children, and adolescents [54 ].
&&
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ACO 310308
CONCLUSION
An optimal perioperative pain management is essen-
tial to enhance recovery after surgery. However, peri-
operative pain management continues to be a
challenge and very often with suboptimal results.
Among the explanations is the variability in percep-
tion of pain, the scarcity of procedural specific pain
treatment guidelines, the extrapolation from adult
data and the lack of tools to efficiently predict which
patient is at risk of moderate-to-severe postoperative
pain and CPSP. Considering the opioid epidemic and
the impact of chronic pain in this susceptible popu-
lation, the progress in these research fields will hope-
fully help healthcare providers to build a tailored pain
treatment with a focus on a reduction of opioid use
and risk of developing CPSP.
Acknowledgements
None.
Financial support and sponsorship
The current work was supported by an unrestricted grant
from The Montreal Children Foundation for the Chronic
Pain Service of the Montreal Children’s Hospital.
Conflicts of interest
P.M.I. is member of the Editorial Board of Pediatric
Anesthesia. The remaining authors have no conflict of
interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Walker SM. Pain after surgery in children: clinical recommendations. Curr
Opin Anaesthesiol 2015; 28:570–576.
2. Cai Y, Lopata L, Roh A, et al. Factors influencing postoperative pain following
discharge in pediatric ambulatory surgery patients. J Clin Anesth 2017;
39:100–104.
3. Wilson CA, Sommerfield D, Drake-Brockman TF, et al. Pain after discharge
& following head and neck surgery in children. Paediatr Anaesth 2016;
26:992–1001.
Practical view of the real-life problems of pain after discharge in children under-
going ophtalmoly and ear, nose throat surgery.
4. Emons MI, Petzke F, Stamer UM, et al. Current practice of acute pain
management in children – a national follow-up survey in Germany. Paediatr
Anaesth 2016; 26:883–890.
5. Wilson CA, Sommerfield D, Drake-Brockman TFE, et al. A prospective audit of
& pain profiles following general and urological surgery in children. Paediatr
Anaesth 2017; 27:1155–1164.
Description of the problems associated with the postoperative pain after sub-
umbilical surgery in children.
6. Centers for Disease Control and Prevention. Drug overdose deaths in the
United States continue to increase in 2016. Opioid OverdoseOpioid. Avail-
able at: https://www.cdc.gov/drugoverdose/epidemic/index.html.
7. Poonai N, Datoo N, Ali S, et al. Oral morphine versus ibuprofen administered
at home for postoperative orthopedic pain in children: a randomized con-
trolled trial. CMAJ 2017; 189:E1252–E1258.
8. Shilling A. Can it be done-opioid-free recovery?: Commentary on an article by
Gijs T.T. Helmerhorst, MD, et al.: ‘Pain relief after operative treatment of an
extremity fracture: a noninferiority randomized controlled trial’. J Bone Joint
Surg Am 2017; 99:e123.
0952-7907 Copyright ! 2018 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Acute pain management in children Ferland et al.
9. Elinder K, Söderman AC, Stalfors J, et al. Factors influencing morbidity after
paediatric tonsillectomy: a study of 18,712 patients in the National Tonsil
Surgery Register in Sweden. Eur Arch Otorhinolaryngol 2016;
273:2249–2256.
10. Avian A, Messerer B, W€ unsch G, et al. Postoperative paediatric pain pre-
valence: a retrospective analysis in a university teaching hospital. Int J Nurs
Stud 2016; 62:36–43.
11. Sowder JC, Gale CM, Henrichsen JL, et al. Primary caregiver perception of
pain control following pediatric adenotonsillectomy: a cross-sectional survey.
Otolaryngol Head Neck Surg 2016; 155:869–875.
12. King S, Chambers CT, Huguet A, et al. The epidemiology of chronic pain in
children and adolescents revisited: a systematic review. Pain 2011;
152:2729–2738.
13. Coffelt TA, Bauer BD, Carroll AE. Inpatient characteristics of the child
admitted with chronic pain. Pediatrics 2013; 132:e422–e429.
14. Brooks MR, Golianu B. Perioperative management in children with chronic
& pain. Paediatr Anaesth 2016; 26:794–806.
A comprehensive review of the problems associated with the postoperative pain
control of children with chronic pain.
15. Sun EC, Darnall BD, Baker LC, et al. Incidence of and risk factors for chronic
opioid use among opioid-naive patients in the postoperative period. JAMA
Intern Med 2016; 176:1286–1293.
16. McCabe SE, West BT, Boyd CJ. Leftover prescription opioids and nonme-
dical use among high school seniors: a multicohort national study. J Adolesc
Health 2013; 52:480–485.
17. Monitto CL, Hsu A, Gao S, et al. Opioid Prescribing for the treatment of acute
&& pain in children on hospital discharge. Anesth Analg 2017; 125:2113–2122.
Excellent analysis of the overprescription of opiods after pediatric surgical pro-
cedures.
18. Grant DR, Schoenleber SJ, McCarthy AM, et al. Are we prescribing our
patients too much pain medication? Best predictors of narcotic usage after
spinal surgery for scoliosis. J Bone Joint Surg Am 2016; 98:1555–1562.
19. Somaini M, et al. Emergence delirium, pain or both? A challenge for clinicians.
Paediatr Anaesth 2015; 25:524–529.
20. Somaini M, Sahillioğlu E, Marzorati C, et al. Emergence delirium or pain after
anaesthesia – how to distinguish between the two in young children: a
retrospective analysis of observational studies. Br J Anaesth 2016;
116:377–383.
21. Chauvin C, Schalber-Geyer AS, Lefebvre F, et al. Early postoperative oral fluid
intake in paediatric day case surgery influences the need for opioids and
postoperative vomiting: a controlled randomized trialdagger. Br J Anaesth
2017; 118:407–414.
22. Kaye AD, Cornett EM, Helander E, et al. An update on nonopioids: intravenous
or oral analgesics for perioperative pain management. Anesthesiol Clin 2017;
35:e55–e71.
23. Constant I, Ayari Khalfallah S, Brunaud A, et al. How to replace codeine after
tonsillectomy in children under 12 years of age? Guidelines of the French
Oto-Rhino-Laryngology – Head and Neck Surgery Society (SFORL). Eur Ann
Otorhinolaryngol Head Neck Dis 2014; 131:233–238.
24. Walrave Y, Maschi C, Bailleux S, et al. Pain after tonsillectomy: effectiveness
of current guidelines? Eur Arch Otorhinolaryngol 2018; 275:281–286.
25. Ericsson E, Brattwall M, Lundeberg S. Swedish guidelines for the treatment of
pain in tonsil surgery in pediatric patients up to 18 years. Int J Pediatr
Otorhinolaryngol 2015; 79:443–450.
26. Alm F, Jaensson M, Lundeberg S, et al. Adherence to Swedish guidelines for
pain treatment in relation to pediatric tonsil surgery: a survey of the multi-
disciplinary team. Int J Pediatr Otorhinolaryngol 2017; 101:123–131.
27. Hamill JK, Rahiri JL, Liley A, et al. Intraperitoneal local anesthetic in pediatric
surgery: a systematic review. Eur J Pediatr Surg 2016; 26:469–475.
28. Allegri M, Ornaghi M, Ferland CE, et al. Peritoneal nebulization of ropivacaine
during laparoscopic cholecystectomy: dose finding and pharmacokinetic
study. Pain Res Manag 2017; 2017:4260702.
29. Scalia Catenacci S, Lovisari F, Peng S, et al. Postoperative analgesia after
laparoscopic ovarian cyst resection: double-blind multicenter randomized
control trial comparing intraperitoneal nebulization and peritoneal instillation
of ropivacaine. J Minim Invasive Gynecol 2015; 22:759–766.
30. Tian X, Yang P, Su T, et al. Intraperitoneal ropivacaine and early postoperative
pain and postsurgical outcomes after laparoscopic herniorrhaphy in toddlers:
a randomized clinical trial. Paediatr Anaesth 2016; 26:891–898.
31. Wick EC, Grant MC, Wu CL. Postoperative multimodal analgesia pain
& management with nonopioid analgesics and techniques: a review. JAMA
Surg 2017; 152:691–697.
Interesting review on the use of multimodal opioid-free analgesia.
32. Lam DK, Corry GN, Tsui BC. Evidence for the use of ultrasound imaging in
pediatric regional anesthesia: a systematic review. Reg Anesth Pain Med
2016; 41:229–241.
33. Guay J, Suresh S, Kopp S. The use of ultrasound guidance for perioperative
& neuraxial and peripheral nerve blocks in children: a Cochrane review. Anesth
Analg 2017; 124:948–958.
Systematic review on the efficacy and safety of regional anesthesia in children.
34. Schnabel A, Poepping DM, Pogatzki-Zahn EM, Zahn PK. Efficacy and safety
of clonidine as additive for caudal regional anesthesia: a quantitative sys-
tematic review of randomized controlled trials. Paediatr Anaesth 2011;
21:1219–1230.
www.co-anesthesiology.com 5
CE: Swati; ACO/310308; Total nos of Pages: 6;
ACO 310308
Pediatric anesthesia
35. Lonnqvist PA, Ecoffey C, Bosenberg A, et al. The European society of regional
anesthesia and pain therapy and the American society of regional anesthesia
and pain medicine joint committee practice advisory on controversial topics in
pediatric regional anesthesia I and II: what do they tell us? Curr Opin
Anaesthesiol 2017; 30:613–620.
36. Al-Zaben KR, Qudaisat IY, Abu-Halaweh SA, et al. Comparison of caudal
bupivacaine alone with bupivacaine plus two doses of dexmedetomidine for
postoperative analgesia in pediatric patients undergoing infra-umbilical sur-
gery: a randomized controlled double-blinded study. Paediatr Anaesth 2015;
25:883–890.
37. Goyal V, Kubre J, Radhakrishnan K. Dexmedetomidine as an adjuvant to
bupivacaine in caudal analgesia in children. Anesth Essays Res 2016;
10:227–232.
38. Sridhar RB, Kalappa S, Nagappa S. Nonopioid (dexmedetomidine, dexa-
methasone, magnesium) adjuvant to ropivacaine caudal anesthesia in pedia-
tric patients undergoing infraumbilical surgeries: a comparative study. Anesth
Essays Res 2017; 11:636–641.
39. El-Agamy A, El-Kateb AMM. Addition of magnesium sulfate to caudal block for
preventing emergence agitation in sevoflurane-based anesthesia in children.
Ain-Shams J Anaesthesiol 2015; 8:217.
40. Kim EM, Kim MS, Han SJ, et al. Magnesium as an adjuvant for caudal
analgesia in children. Paediatr Anaesth 2014; 24:1231–1238.
41. Treede RD, Rief W, Barke A, et al. A classification of chronic pain for ICD-11.
Pain ; 156:1003–7.
42. Lavand’homme P. ‘Why me?’ The problem of chronic pain after surgery. Br J
&& Pain 2017; 11:162–165.
Outstanding review on chronic postsurgical pain (CPSP).
43. Rabbitts JA, Fisher E, Rosenbloom BN, Palermo TM, et al. Prevalence and
& predictors of chronic postsurgical pain in children: a systematic review and
meta-analysis. J Pain 2017; 18:605–614.
Undated Meta-analysis on the predictors of CPSP in children and adolescents.
44. Batoz H, Semjen F, Bordes-Demolis M, et al. Chronic postsurgical pain in
children: prevalence and risk factors. A prospective observational study. Br J
Anaesth 2016; 117:489–496.
6 www.co-anesthesiology.com
Copyright © 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
45. Voepel-Lewis T, Caird MS, Tait AR, et al. A high preoperative pain and
symptom profile predicts worse pain outcomes for children after spine fusion
surgery. Anesth Analg 2017; 124:1594–1602.
46. Sangesland A, Storen C, Vaegter HB. Are preoperative experimental pain
&& assessments correlated with clinical pain outcomes after surgery? A sys-
tematic review. Scand J Pain 2017; 15:44–52.
Valuable analysis of the relationship between experimental evaluation of pain and
clinical outcomes in postoperative pain.
47. Werner MU, Jensen EK, Stubhaug A. Preoperative quantitative sensory
testing (QST) predicting postoperative pain: Image or mirage? Scand J Pain
2017; 15:91–92.
48. Taylor BK, Westlund KN. The noradrenergic locus coeruleus as a chronic pain
generator. J Neurosci Res 2017; 95:1336–1346.
49. Ferland CE, Parent AJ, Saran N, et al. Preoperative norepinephrine levels in
cerebrospinal fluid and plasma correlate with pain intensity after pediatric
spine surgery. Spine Deform 2017; 5:325–333.
50. Zhu A, Benzon HA, Anderson TA. Evidence for the efficacy of systemic opioid-
& sparing analgesics in pediatric surgical populations: a systematic review.
Anesth Analg 2017; 125:1569–1587.
Systematic review on the available evidence of the efficacy of pharmacological
treatment of acute pain in children.
51. Boric K, Dosenovic S, Jelicic Kadic A, et al. Interventions for postoperative
pain in children: an overview of systematic reviews. Paediatr Anaesth 2017;
27:893–904.
52. Food and Drug Administration. Drug research and children. Available at: https://
www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm143565.htm.
53. Food and Drug Administration. New pediatric labeling information database.
Available at: https://www.accessdata.fda.gov/scripts/sda/sdNavigation.cfm?
sd=labelingdatabase.
54. TWalco GA, Kopecky EA, Weisman SJ, et al. Clinical trial designs and models
&& for analgesic medications for acute pain in neonates, infants, toddlers, children,
and adolescents: ACTTION recommendations. Pain 2018; 159:193–205.
Outstanding review describing the clinical models for pharmacological research in
acute pain in children.
Volume 31 ! Number 00 ! Month 2018