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254 L. M. W. Webb et al.
Table 2 (continued)
Neuraxial Medication Dosing
Pregabalin PO 25–150 mg QD or BID 1. 25 mg QD or 50–150 mg/day in
2–3 doses. 2. Can increase weekly by
25–150 mg increments to 300–600
divided mg/day. 3. Convert from
gabapentin with 6:1 ratio
(gabapentin:pregabalin).
Dronabinol
(≥ 6 years)
PO 2.5–5 mg/m2/dose Q3–4H 1. Dosing for chemo-induced nausea and
vomiting (CINV)—off-label for pain
control. 2. Single doses 2.5–10 mg.
Nabilone
(≥ 3 years)
PO <18 kg: 0.5 mg
≥ 18–30 kg: 1 mg
>30 kg: 1 mg
BID
BID
TID
1. Dosing for CINV—off-label for pain
control.
Infusion Route Dose (mg/kg/hr) Notes
Ketamine IV 0.025–0.5 1. Infusion dosing based on authors’
hospital guidelines. 2. Consider max
dose of 30 mg/hr.
Dexmedetomidine IV 0.5–2 mcg/kg/hr 1. Requires continuous monitoring. 2.
Watch for bradycardia and
hypotension.
Lidocaine IV 0.5–2 1. Requires continuous monitoring. 2.
Availability of serum lidocaine level
monitoring desirable.
Opioid Route Dose (mg/kg/dose) Frequency Notes: ≥ 50 kg use adult dosing.
(continued)
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Pain Management in Children 255
Table 2 (continued)
Neuraxial Medication Dosing
Oxycodone (IR) PO ≤ 6 months: 0.025–0.05
>6 months and <50 kg: 0.1–0.2
Q6H
Q4–6H
1. Can be immediate release (IR) or
extended (ER). 2. Do not start ER
before patient is on stable IR dosing.
3. Conversion to ER should involve
pain management specialist.
Tramadol
(≥ 12 years)
PO 1–2 Q4–6H 1. Max single dose 100 mg. 2. Max daily
dose 400 mg.
Morphine PO (IR)
IV/SC
Infusion
≤ 6 months: 0.08–0.1
>6 months and <50 kg: 0.15–0.3
≤ 6 months: 0.025–0.05
>6 months and <50 kg: 0.05–0.1
≤ 6 months: 0.008–0.02 mg/kg/hr
>6 months and <50 kg: 0.01–0.04 mg/kg/
hr
Q3–4H
Q3–4H
Q2–4H
Q2–4H
Continuous
Continuous
1. Use caution in patients with sleep
apnea or other respiratory
compromise. 2. Frequency of IV/SC
in infants <3 months Q4–6H. 3.
Dose-reduce in patients with renal
impairment due to active metabolite
build up. 4. Continuous or prolonged
doses require weaning. 5. Conversion
to ER should involve pain
management specialist.
Fentanyl IV
Infusion
Patch
<50 kg: 0.5–1 mcg/kg/dose
<50 kg: 0.5–2.5 mcg/kg/hr
12.5–300 mcg/hr
Q1–2H
Continuous
Q72H
1. Continuous infusion may require
weaning based on duration. 2. Patch
for opioid tolerant on >60 mg MME
daily and initiation should involve
pain management specialist. 3. Patch
should not be titrated more than
Q3–6Days.
(continued)
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256 L. M. W. Webb et al.
Table 2 (continued)
Neuraxial Medication Dosing
Hydromorphone PO
IV
Infusion
>6 months and >10 kg: 0.03–0.06
<50 kg: 0.03–0.08
>6 months and >10 kg: 0.005–0.015
<50 kg: 0.015
>6 months and >10 kg: 0.003–0.005 mg/
kg/hr
<50 kg: 0.003–0.005 mg/kg/hr
Q4H
Q3–4H
Q3–6H
Q3–6H
Continuous
Continuous
1. Usual adult PO dose is 2–4 mg, max 8
mg. 2. Max initial infusion rate in
patients <50 kg is 0.2 mg/hr.
Methadone PO
IV
≤ 6 months: 0.025–0.05
>6 months and <50 kg: 0.1–0.2
≤ 6 months: 0.025
>6 months and <50 kg: 0.1
Once
Once
Once
Once
1. Can prolong QT interval; baseline
ECG recommended. 2. Many
metabolic interferences—check
interactions with other medications
for dose adjustments. 3. Repeat dosing
useful in opioid tolerant patients using
graded conversions under guidance of
pain management expert; caution in
opioid naïve patients.
Butorphanol
(≥ 18 years)
IM
IV
IN
1–4 mg
0.5–2 mg
1mg
Q3–4H
Q3–4H
Q3–4H
1. Use is off-label in patients <18 years
with defined pediatric regimen.
Naloxone IV/IM/SC/IO
IN
<5 years and ≤ 20 kg: 0.1
≥ 5 years and >20 kg: 2 mg/dose
4–8 mg
Q2–3 min
Q2–3 min
Q2–3 min
1. Table dosing is for opioid overdose. 2.
Reversal of respiratory depression:
0.001–0.005 mg/kg/dose, up to 2 mg/
dose, Q2 min. 3. Pruritus: infusion at
0.25–2 mcg/kg/hr; higher doses may
reverse pain control.
(continued)
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Pain Management in Children 257
Table 2 (continued)
Neuraxial Medication Dosing
Naltrexone
(low-dose) [82]
PO 1–5 mg QD 1. Low-dose naltrexone (LDN) defined
by <5 mg daily. 2. Use of LDN in
chronic pain supported by emerging
data.
Nalbuphine IV/IM/SC 0.05–0.2 Q3–6H 1. Max single dose 20 mg. 2. Max daily
dose 160 mg.
Buprenorphine IM/IV
Transdermal
2–12 years: 2–6 mcg/kg/dose
>12: 0.3 mg
≥ 18 years: start 5 mcg/hr
Q4–8H
Q6–8H
Q7D
1. IV administration should be via slow
push. 2. IV/IM doses are for acute
pain. 3. Transdermal patch is off-label
in pediatrics; titration is beyond scope
of this chapter.
PCA/NCA/CCA
(dosing for patients <50 kg)
Basal
(mg/kg/hr)
Demand
(mg/kg/dose)
Lockout
(minutes)
Notes
Morphine 0–0.03 0.01–0.03 6–8 1. Demand dose is delivered by nurse or
caregiver for NCA/CCA. 2. Lockout
on NCA/CCA is usually 30 minutes.
3. For children and adolescents ≥ 50
kg, use adult PCA dosing guidelines.
4. Clinician boluses can be
administered and are usually twice the
demand dose with lockout averaging
1–2 hours.
Fentanyl 0–0.5 mcg/
kg/hr
0.2–0.5 mcg/kg/dose 5–15
Hydromorphone 0–0.004 0.003–0.004 6–10
§
Increased: with epinephrine in neonates and with clonidine in both neonates and adolescents [64].
‡
Lipophilic opioids may improve CA density but do not increase analgesic duration [45].
¥
Especially with higher dose opioids (intrathecal fentanyl >1 mcg/kg or morphine >5 mcg/kg) [64].
* Maximum dose: fentanyl SAB = 25–50 mcg; fentanyl CA=50 mcg; morphine SAB=250 mcg [81].
¤
Maximum dose: for single shot or loading PNC depends on patient weight, age, and number of blocks.
š
NSAIDs may require dose reduction for renal impairment.
°Ketorolac dosing varies significantly with age/weight.
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258 L. M. W. Webb et al.
effect and are not always sufficient when used by themselves [16]. Special consid-
erations should be made when using NSAIDs in infants less than six months of age,
as well as those patients with concerns for kidney dysfunction, given the increased
risk of developing acute kidney injury [16]. Topical NSAIDs, like diclofenac, may
be an option for those in whom systemic administration is contraindicated or in the
treatment of musculoskeletal pain.
Antidepressants including selective serotonin and combined serotonin and nore-
pinephrine reuptake inhibitors (SSRIs and SNRIs) and tricyclics are becoming a
core treatment of neuropathic and other chronic pain states. Mood stabilizers—for
example duloxetine, which is an SNRI—can therefore be utilized to decrease the
reuptake of serotonin and norepinephrine, leading to improved pain pathway inhibi-
tion and pain control [17]. Furthermore, these medications are useful for managing
anxiety and depression, which frequently coincide and interplay with chronic pain
states [17].
Gabapentinoids, which include gabapentin and pregabalin, have a long-standing
history in the treatment of chronic and neuropathic pain in adults and can be used
to successfully treat pain in children. Neuropathic and chronic pain in children can
be associated with or caused by numerous etiologies not limited to injury, surgery,
phantom limb pain, cancer and chemotherapy, and chronic illnesses [18]. Gabapenti-
noids are some of the most frequently used medications for pain control in these pain
states [18].
The use of cannabis and its derivatives for pain management, and other indications,
has exploded in recent years, particularly with increased legalization of medical and
recreational use [19, 20]. While the adult literature supports several indications,
including management of a variety of pain syndromes [19, 21], data supporting the
use of cannabinoids in the pediatric population has been limited mostly to treatment
of chemotherapy-induced nausea and vomiting (CINV) and seizures/epilepsy [19,
20]. Presently, nabilone and dronabinol are the only regulated synthetic cannabinoids
available [19, 20], and both have dosing guidelines (Table 2) for pediatric patients.
There are case reports of cannabis s uccessfully treating pain conditions in pediatric
patients [20], but there is a paucity of evidence detailing efficacy and safety [19, 20].
However, there is strong evidence for the importance of the endocannabinoid
system in brain development, with the perinatal and adolescent periods being partic-
ularly vulnerable; the sequelae of pediatric marijuana exposure during these periods
is linked with far-reaching effects on neurocognition, psychiatric disease, addiction,
and even epigenetics [19, 20, 22, 23]. Because cannabinoid metabolism is complex,
with significant inhibitory effects on the cytochrome P450 pathway, drug interactions
are another important consideration in their use [19, 21]. Further studies are needed
to elucidate whether there is a role for cannabis in the treatment of pediatric pain and
provide guidelines for safe administration.
Nonopioid intravenous infusions, such as ketamine (an NMDA-receptor antag-
onist), dexmedetomidine (an alpha-agonist), and lidocaine (a local anesthetic with
NMDA-receptor antagonism) are effective in the pediatric population [24]. Despite
ketamine’s common use in the pediatric population, consideration should be paid
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Pain Management in Children 259
to conflicting evidence about neurotoxicity versus neuroprotection in brain develop-
ment of young patients, especially under the age of three years [25]. Dexmedeto-
midine is recently purported to have properties protective of the brain and other
organs, which perhaps increases its utility in pediatric pain management [26, 27].
Infusions in pediatric patients require weight-based dosing (Table 2) to avoid under-
or overdosing.
Opioid Medications
Opioid medications are a mainstay of pain treatment in pediatric patients because
of efficacy and relative safety, but opioid administration is not without risk and
controversy [5, 13, 14]. Pediatric opioid dosing (Table 2) is usually weight- and/
or age-based and administration can be considerably different in pediatric patients
compared to adults. Patient-controlled analgesia (PCA) use is prevalent with the
inclusion of nurse- and caregiver-controlled analgesia (NCA and CCA) utilized for
patients without the developmental or neurocognitive abilities to self-administer anal-
gesic doses [13, 28–31]. Continuous opioid infusions are commonly used in pediatric
pain management, despite evidence contrary to that in adults, showing non-superior
pain control and increased adverse events [13, 30, 31]. Continuous cardiorespiratory
monitoring is mandatory while administering intravenous opioids [30, 31]. Capnog-
raphy may enhance the safety of administration of opioid medications but presents
challenges in pediatric patients [32].
While most opioid formulations are safe to administer to children, there are special
considerations for pediatric patients [5]. Route of administration—oral, intravenous,
intranasal, transdermal, subcutaneous, intrathecal, and rectal—is impacted by phar-
macodynamics, pharmacokinetics, and even pharmacogenetics [5]. Naloxone should
be dispensed to high-risk pediatric patients in case of accidental overdose [14].
Methadone is safe and efficacious in children; it requires monitoring due to the risk
of QT prolongation and metabolic effects with drug interactions [13]. Codeine has a
black box warning for pediatric administration due to the potential for fatal overdose
in rapid metabolizers [5, 33]; further, its unreliable metabolism makes it an undesir-
able choice [5, 13]. Tramadol should not be administered to children under the age
of twelve due to similar concerns about ultrarapid metabolizers and overdose [5, 33].
Use of meperidine is not recommended in infants and children due to its side effect
profile and the availability of safer alternatives [5]. Transdermal patches have also
been used with success in children and may be a consideration when other routes
of administration are challenging [5, 34]. Mixed agonist-antagonists (nalbuphine,
butorphanol, and buprenorphine) and pure antagonists (naltrexone) have also been
used to treat a variety of pain conditions [5, 34].
Consideration must be given to common complications of opioid therapy
including constipation, nausea/vomiting, pruritis, respiratory depression, urinary
retention, and sedation, in addition to tolerance, dependence, and withdrawal [13].
Naloxone can be used to treat many opioid-related side effects, including overdose
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260 L. M. W. Webb et al.
[14]. Nalbuphine is effective for pain control with fewer side effects [5, 35] and is
used to treat opioid-induced side effects, with particular efficacy in treating opioid-
induced pruritis and urinary retention [35, 36]. The risk of opioid exposure leading
to abuse increases significantly in adolescence and early adulthood. Therefore, prac-
tices that promote opioid stewardship, such as proper prescribing and disposal of
opioids, are vital to curbing the opioid epidemic [13, 14]. While they are not without
complications and side effects, opioids remain a commonly used, safe, and effica-
cious treatment for pediatric pain, when administered properly and thoughtfully with
appropriate patient education [13, 14].
Opioid dosing conversion tables, whether in pediatrics or adults, should be used as
a rough guide, considering that tables are largely based on single dose studies in the
adult population and without consideration for each medication’s steady state concen-
tration. One should always complete the math associated with opioid conversions,
including a dose reduction when needed for incomplete cross-tolerance. Assessment
of the patient’s condition and clinical judgement should ultimately determine the final
dose calculation and desired regimen. An example of an online automated opioid
conversion calculator can be found at https://globalrph.com/medcalcs/opioid-pain-
management-converter-advanced/.
6 Interventional Pain Therapy: Regional Anesthesia,
Complications, and Imaging
Regional Anesthesia
Though frequently questioned, the safety and efficacy of pediatric nerve block perfor-
mance, even in anesthetized children, has been demonstrated by several large studies
[37–40]. However, pediatric local anesthetic dosing should be weight-based (Table 2)
and further decreased in infants less than six months old, who have decreased levels of
protein, specifically alpha-1-acid glycoprotein. Because local anesthetics are highly
protein-bound, more unbound (active) local anesthetic is present in young infants,
requiring decreased dosing compared even to older children [41]. While techniques
for performance of neuraxial, especially thoracic and lumbar epidural, and periph-
eral nerve blockade in the pediatric population are similar to adults, anatomic and
physiologic considerations differ in pediatrics.
Awareness of anatomic landmark differences is paramount when performing
neuraxial anesthesia in neonates and children. The adult spinal cord and dural sac
commonly terminate around L1/2 and S2, respectively, whereas spinal cord and
dural termination in infants is around L3 and S3/4, respectively [42]. In addition, the
distance to the epidural space is very small compared to adults, typically about 1mm
per kg in infants older than six months [43].
The infant neuraxis differs from adults physiologically in that infants have nearly
twice the volume of cerebrospinal fluid and have increased spinal cord blood flow
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Pain Management in Children 261
with higher uptake of drugs from the subarachnoid space [41]. As such, spinal
blockade in infants has a shorter duration of action with requirement for increased
local anesthetic dose [41]. See Table 2 for weight-based spinal dosing.
Caudal epidural anesthesia (CEA) remains one of the most commonly performed
nerve blocks in children. CEA has typically been performed via a landmark-based
approach with identification of the sacral cornua guiding access to the epidural
space through the sacral hiatus. Ultrasound use for CEA has been shown to increase
the accuracy of block placement and likely increase block success [44]. Dosing
of CEA is based on level of desired coverage, with 0.5 ml/kg covering the sacral
dermatomes, 1ml/kg covering the lumbar dermatomes, and 1.25 ml/kg covering
thoracic dermatomes [45]. In the setting of CEA, local anesthetics frequently require
dilution to achieve higher dermatomal spread and avoid exceeding weight-based
dosing limits. The maximum dosing for CEA is less than 25 ml, restricting its use
for thoracic coverage in older children [46].
Continuous neuraxial and peripheral nerve infusions can be used in pediatric
patients, keeping in mind that these patients are more sensitive to local anesthetics
and have age-dependent metabolism and clearance [4]. Studies of continuous local
infusions of ropivacaine and bupivacaine in the pediatric population have shown
that infusion rates to a maximum dose of 0.5 mg/kg/hour can be safely used [47].
A typical starting dose for these infusions is 0.2 mg/kg/hour and slow titration, and
careful monitoring for signs of local anesthetic systemic toxicity (LAST), maximizes
the ability to safely achieve pain control. Ropivacaine has been shown to be safer
in pediatrics, when compared to bupivacaine, given its decreased cardiotoxicity and
decreased plasma accumulation during an infusion [48, 49]. Consider chloroprocaine
infusions for infants less than six months of age or less than eight kg in weight, as
immature renal and hepatic function can lead to decreased clearance of amide local
anesthetics and decreased volume of local anesthetic at therapeutic doses may not
allow for adequate spread within the epidural space to provide coverage. See epidural
adjuvant dosing in Table 2.
Growing demand for improved outpatient pain control that minimizes opioids and
other medications has enhanced the popularity of ambulatory nerve catheter infu-
sions. Multiple factors require consideration when running home catheter programs:
(a) patient selection (healthy, cooperative); (b) reliable families who express comfort
with managing the catheter and its requirements; and (c) the establishment of a home
catheter service with resources, protocols, and personnel to manage outpatients with
infusions. Complications are typically minor, such as leaking or early dislodgement,
and education is essential in the success of these catheters [50].
Regional Anesthesia Complications
Though the incidence of complications in pediatric regional anesthesia is rare, as
evidenced by the large studies mentioned above, they do occur. Special considerations
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262 L. M. W. Webb et al.
apply to complications including local anesthetic systemic toxicity (LAST), catheter
dislodgement, neurologic complications, and postdural puncture headache.
One of the rare, yet most serious complications of regional and neuraxial anes-
thesia in children is LAST. Children have both a relatively increased cardiac output
and systemic uptake of local anesthetics, putting them at increased risk for toxi-
city [8]. Since anesthesiologists perform much of pediatric regional and neuraxial
anesthesia/analgesia while the patient is under general anesthesia, patients do not
exhibit the typical symptoms of LAST (headache, somnolence, vertigo, perioral or
lingual paresthesia). Rather the clinician must watch for signs of toxicity including
muscle rigidity, unexplained hypoxemia, tachycardia, dysrhythmias, or cardiovas-
cular collapse [8]. Because early warning signs may be masked by general anesthesia,
cardiovascular collapse may be the presenting sign [51]. Monitoring with an electro-
cardiogram (ECG) is essential, as peaked T wavesare one of the earlier signs of LAST;
further, T wave change on ECG (not heart or blood pressure change like adults) is the
most sensitive marker for positivetest dose in children [52]. A test dose should contain
0.5 mcg/kg epinephrine, up to 15 mcg ( adult dose). Management must be quick and
cognitive aids such as the Society for Pediatric Anesthesia’s Pedi Crisis (https://ped
sanesthesia.org/pedi-crisis-app/) can help ensure complete and effective manage-
ment. To treat LAST, administer intralipid 20% as a bolus (1.5 ml/kg intravenous
over one minute, repeat every three to five minutes until hemodynamically stable),
followed by an intralipid infusion for at least ten minutes after the patient is hemo-
dynamically stable (0.25 mL/kg/min, increase as needed to 0.5 mL/kg/min). Ensure
that epinephrine dosing is decreased (1 microgram/kg intravenous/intraosseous as
needed) compared to the cardiac arrest dose. Treat seizures with midazolam (0.05-
0.1 mg/kg intravenous), not propofol, which will worsen hemodynamic collapse.
Additionally, avoid vasopressin, calcium channel blockers, and beta blockers. LAST
may recur four to six hours after the initial event, so patient monitoring must continue
through this period [53].
An additional complication that occurs in pediatric regional and neuraxial anal-
gesia is catheter dislodgement, which is a leading factor in epidural analgesic failure
[54]. Unlike in adult patients, replacing an epidural or regional catheter in chil-
dren may require general anesthesia or deep sedation, making the replacement of a
dislodged catheter very challenging and potentially forcing a change in pain manage-
ment modality.Catheters in pediatric patients have the propensity to leak, and leakage
or sweating can cause the dressing to loosen or fall off, risking exposure of the inser-
tion site. Measures like the use of Dermabond® at the insertion site and Mastisol®
Liquid Adhesive to help secure the transparent occlusive dressing (Tegaderm™) are
helpful to prevent displacement of the dressings and decrease leaking [55]. Using
consistent securement, including subcutaneous tunneling and/or suturing where
appropriate, and education may decrease rates of catheter dislodgement [55, 56].
Neurologic complications in pediatric patients are rare. A recent review of over
100,000 blocks by the Pediatric Regional Anesthesia Network (PRAN) found a rate
of 2.4 in 10,000 cases [40]. Most of the complications were sensory and resolved
within weeks to months, with no permanent deficits noted [40]. If a patient develops
sensory or motor deficits after regional or neuraxial anesthesia, it is essential to ensure
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Pain Management in Children 263
rapid assessment (history and physical exam), diagnosis, and treatment. For periph-
eral nerve injuries, consultation with neurology and early imaging are essential when
motor deficits are present [57, 58]. Neurophysiologic tests including electromyog-
raphy and nerve conduction studies can help to localize the site of nerve injury,
though it may not be possible to distinguish whether the injury resulted from anes-
thesia or surgery [58]. These studies also offer prognostic information depending on
the degree of injury. Most injuries improve with physical therapy [57].
In pediatric patients, post-dural puncture headaches (PDPH) may occur as a
complication of neuraxial anesthesia/analgesia or as a complication of diagnostic
lumbar puncture, especially when performed with a large gauge cutting needle.
PDPH in children exhibits similar symptoms to adults [59]. The majority of PDPH
resolve within a week with conservative management and symptomatic treatment
with medications (methylxanthines, gabapentin, cosyntropin, and/or hydrocortisone)
and minor interventions (greater occipital nerve blocks and sphenopalatine blocks)
[60–63].
Conservative therapy (as above) should be considered first line for pediatric
patients with PDPH, but epidural blood patch (EBP) may be required when conser-
vative therapy fails. Children may not tolerate or be eligible for an EBP, since general
anesthesia or deep sedation are often required for pediatric patients to tolerate the
invasive procedure; thus, it is utilized less commonly in children compared to adults.
Performance of an EBP is the same as in adults with the f ollowing caveats: a. if
awake, the injection should cease if the child describes pressure or discomfort in
the back; b. if anesthetized, no more than 0.3 ml/kg or 20 mL of blood should be
injected [64]. Two hospitals in Finland described their experience in performing 42
EBPs in 41 children over a ten-year period. Five patients were aged 3–12 years and
the remaining 36 patients were aged 13–18 years. The initial success rate of EBP
was 90%, with permanent relief in 85%. There was no correlation with the volume
of blood injected and the efficacy of EBP [64].
Imaging in Children
A discussion of pediatric regional anesthesia is not complete without considering
risks and benefits of imaging modalities in children. The use of ultrasound (US) is now
a mainstay of acute pain and regional anesthesia clinical practice, and it is critical to
pediatric anesthesia for its role in improving safety and providing diagnostic imaging.
US enhances safety in the following ways: a. avoids radiation exposure to vulnerable
patients, many of whom may require further medical radiation exposure in their lives;
b. enhances safety margin for patients receiving regional anesthesia, most of whom
are under general anesthesia where typical safety warnings—like paresthesia—are
masked; and c. allows for targeted placement of local anesthetic in a population where
volume is limited by lower toxic doses and landmark techniques carry increased risk
due to anatomical variations based on changes in patient age and size [65, 66]. US
is increasingly utilized in aiding pediatric neuraxial anesthesia, especially caudal
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