Evaluation and management of pain in children

Authors:
Julie Hauer, MD
Barbara L Jones, PhD, MSW
Section Editor:
David G Poplack, MD
Deputy Editor:
Carrie Armsby, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 2018. | This topic last updated: May 14, 2018.

INTRODUCTION — Assessment and management of pain are essential components of pediatric care. In children, especially young children, it can be challenging to identify the presence and severity of pain, and
then to treat the pain. The use of assessment tools based upon cognitive ability is important to ensure that children of all ages receive adequate pain control.

Assessment of pain and an overview of pain management in children will be reviewed here. Pain management for specific pediatric clinical settings and conditions are discussed separately:

●Neonatal pain (see "Assessment of neonatal pain" and "Prevention and treatment of neonatal pain")

●Procedural pain management and sedation (see "Procedural sedation in children outside of the operating room" and "Selection of medications for pediatric procedural sedation outside of the operating room",
section on 'Sedation for painful procedures' and "Pharmacologic agents for pediatric procedural sedation outside of the operating room", section on 'Analgesic agents')

●The use of topical anesthetics in children (see "Clinical use of topical anesthetics in children")

●Pain management in children with sickle cell disease (see "Vaso-occlusive pain management in sickle cell disease")

●Chronic abdominal pain (see "Functional abdominal pain in children and adolescents: Management in primary care")

●Pain management following burn injury (see "Paradigm-based treatment approaches for burn pain control")

●Pain in children at the end of life (see "Pediatric palliative care", section on 'Management of end-of-life symptoms')
EVALUATION — The evaluation of pediatric pain includes determining the underlying type, source and location, and severity of pain.

Types of pain — Pain is defined as an unpleasant somatic or visceral sensation associated with actual, potential, or perceived tissue damage. It is classified into nociceptive and neuropathic pain based upon the
underlying pathophysiology. Determining the type of pain helps in identifying the cause of pain, which may guide treatment choices. (See "Assessment of cancer pain", section on 'Inferred pathophysiology (types of
cancer pain)'.)

●Nociceptive pain is caused by stimulation of intact nociceptors as a result of tissue injury and inflammation (figure 1). It is divided into somatic pain with receptors in skin, soft tissue, skeletal muscle, and bone;
and visceral pain with receptors in internal organs, such as the kidney and gastrointestinal tract. Somatic pain is well localized and described as sharp, aching, squeezing, stabbing, or throbbing. Visceral pain is
typically poorly localized, and is often described as dull, crampy, or achy.

●Neuropathic pain is caused by stimulation or abnormal functioning of damaged sensory nerves. It can be caused by compression, transection, infiltration, ischemia, or metabolic injury to the nerves. It is often
described as burning, shooting, electric, or tingling.

Source and location — Details of the primary disease may be helpful in determining the source and type of pain, which may guide management decisions.

●Cancer – Children with cancer may have nociceptive somatic pain (as defined in the preceding section) from bone metastases or tumor, nociceptive visceral pain (eg, from hepatic distention and bowel wall
edema), and neuropathic pain from tumor infiltration of peripheral nerves.

●Developmental impairment – Children with severe developmental impairment have nociceptive pain that may occur acutely from fractures, urinary tract infection, or pancreatitis, or chronically from
gastroesophageal reflex, constipation, positioning, or spasticity. Such children are also at risk for neuropathic pain as a result of visceral hyperalgesia, central neuropathic pain, and development of peripheral
neuropathic pain following surgery [1,2]. (See 'Neurologically impaired children' below.)

●Procedural and postoperative somatic pain.

●Sickle cell disease – Children with sickle cell disease often have acute nociceptive pain (ie, painful crisis) due to vaso-occlusive episodes. (See "Overview of the clinical manifestations of sickle cell disease",
section on 'Acute painful episodes'.)

●Chronic pain – Chronic headaches, abdominal pain, and musculoskeletal pain require a comprehensive assessment; however, often it does not stem from an organic disease process [3]. (See "Headache in
children: Approach to evaluation and general management strategies" and "Chronic abdominal pain in children and adolescents: Approach to the evaluation".)

Localization of pain is also helpful in determining the etiology. There are separate topics that review the evaluation of pain in children for the following specific anatomical sites:
 ●Hip (see "Approach to hip pain in childhood")

●Back (see "Evaluation of the child with back pain")

●Chest (see "Nontraumatic chest pain in children and adolescents: Approach and initial management")

●Joints (see "Evaluation of the child with joint pain and/or swelling")

●Abdomen (see "Causes of acute abdominal pain in children and adolescents" and "Chronic abdominal pain in children and adolescents: Approach to the evaluation")

Assessment of pain severity — The goal of pain assessment is to identify pain, assess severity, and track the response to interventions. Postoperative pain management, for example, can be guided by self-
reporting or with use of a pain assessment tool. Assessment of chronic pain involves identifying the frequency, duration, and severity of pain episodes. Parents and children can be asked to rate the severity of a
typical episode using general categories (mild, moderate, severe) and how pain impacts daily function (attendance at school, play with friends). Pain assessment tools can be used to supplement this information.

In children, assessment of the severity of pain is performed by the following two methods [4]:

●Self-reporting

●Use of behavioral observational scales in patients who are unable to perform self-reporting

Self-reporting — Self-reporting relies upon the cognitive ability of the child to understand that their pain severity can be measured along a continuum [4]. In younger children, evaluation of pediatric pain typically uses
age-based, pain rating scales.

●Younger children (three to eight years of age) – Some children as young as three years of age are capable of quantifying their pain and being able to translate it to a visual representation. In this age group, pain
is quantified by using visual analog pain scales based upon a series of faces showing an increase in distress or pain (figure 2) [5-8]. The reliability of pain assessment increases with age and the cognitive ability
of the child.

●Older children (8 to 11 years of age) – Pain assessment in this age group is generally performed using visual analog tools that rate the intensity of pain on a horizontal or numeric scale (eg, 0 to 10 scale).

●Adolescents – Adolescents can rate their pain using a numerical rating scale without the use of an accessory pain assessment tool (form 1). In this age group, a description of the following components of pain
usually can be obtained from the history:
 •Description: Is the pain sharp, stabbing, dull, burning, or tingling?

•Location and radiation: Where does the pain start and spread to?

•Intensity: How would you rate your pain on a scale of 1 to 10?

•Duration and constancy: Is the pain steady or does it come and go?

•Frequency: How often does the pain occur?

•Factors that worsen or relieve pain: Is there anything that makes the pain better or worse?

Pain-location tools — Several graphic-based pain-location tools have been used to determine the location of pain in children and adolescents including the Adolescent and Pediatric Pain Tool and The Pediatric Pain
Questionnaire. These tools typically use a graphic outline of the body, and the patient is asked to "color" in the areas where he/she is experiencing pain. A systematic review of the literature reported that although the
quality of the studies included was not high, overall there was moderate evidence that these tools reliably located pain in older children (average age of patients: 10 years) [9].

Observational tools — The following observational tools are used to assess pain in infants and children who are unable to self-report. These pain scales are based upon scoring facial expressions, ability to be
consoled, level of interaction, limb and trunk motor responses, and verbal responses [4,10,11].

●Revised Face, Legs, Activity, Cry, Consolability (r-FLACC) tool (table 1) [12,13]: Nonverbal children

●Non-Communicating Children's Pain Checklist-Postoperative Version (NCCPC-PV) [11]: Nonverbal children

●Nursing Assessment of Pain Intensity (NAPI): Newborn to 16 years of age

●Paediatric Pain Profile [14,15]: Nonverbal children

●Individualized Numeric Rating Scale (INRS) [16]

In a study that compared the r-FLACC, NCCPC-PV, and NAPI assessment tools, the r-FLACC received the highest clinical utility score followed by the NAPI [17]. Based upon the limited data, no tool can be
recommended over another. It is important that each center adopt guidelines of routine assessment for the detection of pain and provide staff training in the use of the selected pain assessment tool.
Observational assessment may underestimate pain severity compared with self-reporting. This was illustrated in a study of young children (three to seven years of age) following surgery, in whom pain severity
obtained by observational assessment was lower than that obtained by self-reporting [18].

Behavioral measurement of pain must also be assessed in the context of other sources of distress, such as hunger or anxiety [19].

Nonverbal children with neurologic impairment — Nonverbal children with neurologic impairment (NI) present unique challenges in evaluating the presence and severity of pain as they cannot self-report their
pain. For many such children, pain can remain a frequent, recurrent problem that often remains undertreated without appropriate evaluation.

In this group of children, similar core pain behaviors are consistently identified and can be used to assess and identify pain. However, each child will display a unique set of responses and behaviors. This unique and
variable expression necessitates input from a consistent care provider, often a parent, with knowledge of a child’s typical behavior patterns at baseline and in response to painful and nonpainful (such as hunger)
events.

Specific behaviors that are associated with pain in nonverbal children with NI include:

●Vocalizations (crying, moaning).

●Facial expression (grimacing).

●Inability to be consoled.

●Increased movement, tone and posture (arching, stiffening), and physiologic responses.

●In addition, some children display atypical behaviors such as laughing, becoming withdrawn, increased aggression, or lack of facial expression.

Although pain assessment tools cannot replace the input of a parent or caregiver involved with the child on a daily basis, these tools can supplement the information from the parent/caregiver and assist with
monitoring by assessing severity prior to an intervention to treat pain. The pain assessment tools for nonverbal children with NI include the Revised Face, Legs, Activity, Cry, Consolability (r-FLACC) scale and the
Individualized Numeric Rating Scale (INRS) [12,16]. These scales can be individualized by indicating behaviors specific to each child, with examples provided. This ability to add specific behaviors is an important
feature for children with atypical pain behaviors that are not present in the other tools.

Impact on daily life — Pain can impact participation in school, activities, sports, and relationships. Identifying this impact can then guide goals of management of chronic pain conditions. In chronic pain conditions,
improvement in such areas is more meaningful than routine measurement of pain intensity.
PRINCIPLES OF MANAGEMENT — The main goals of pediatric pain management are to reduce, control, and prevent pain. Management varies depending upon the type, source, severity, and duration of pain. In
some cases, treating the underlying source of pain or other related symptoms, such as distress or anxiety, can relieve the symptom. Even if specific therapy is available to treat the underlying source of pain, it is
important to also provide adequate therapy to relieve any pain and suffering.

General principles — General principles of pain management in children include the following [20-27]:

●Regular pain assessments should be made throughout the course of treatment; self-report should be obtained whenever possible. If the child is not able to self-report, an appropriate validated observational tool
should be used (eg, r-FLACC (table 1)). It is important to base management decisions on an accurate assessment of the child's pain. (See 'Assessment of pain severity' above.)

●Pain management includes both nonpharmacologic and pharmacologic measures. Nonpharmacologic measures (eg, cognitive, behavioral, physical, and supportive therapies) should be provided for children
undergoing painful procedures and/or those who require pharmacologic therapy.

●Oral analgesics should be used when possible to avoid painful routes of administration.

●Side effects of analgesic agents should be anticipated and treated appropriately (eg, pruritus and/or constipation with opioids).

●Adjuvant therapy can be helpful in certain clinical settings (eg, anticonvulsants for neuropathic pain, antidepressants or anxiolytics for coexisting mood disturbances). (See 'Adjuvant agents' below.)

Clinicians who care for children at risk for pain should develop a consistent approach to the management of pediatric pain that is modifiable based upon the clinical setting. Important considerations include [28]:

●The patient's current pain medication regimen

●Prior experience with pain medications, including adverse effects

●Parental experience and fears regarding the use of pain medications

●Previous use of nonpharmacologic interventions

●Child's coping skills

●Social and spiritual factors

WHO two-step strategy — The choice of analgesic medication is dependent upon pain intensity and the child's response to previously administered agents. We agree with two-step approach recommended in the
2012 World Health Organization guidelines [21]:

●Mild pain – Mild pain can generally be adequately treated with acetaminophen and nonsteroidal anti-inflammatory drugs. (See 'Nonopioid analgesics' below.)

●Moderate to severe pain – Moderate to severe pain is generally treated with opioid agents, such as morphine, hydromorphone, oxycodone, hydrocodone, fentanyl, and methadone. (See 'Opioids' below.)

Referral — Referral to a pain specialist or palliative care team can be helpful in managing patients with pain that is chronic and/or difficult to control. For hospitalized patients, many institutions have policies in place to
guide referral to inpatient pain teams. For example, pain service consultation is often automatically triggered when epidural or patient-controlled analgesia is used or for postoperative pain management. Other
reasons for referral to pain teams include assessment and management of chronic pain conditions that interfere with attendance in school and participation in activities. Referral to palliative care teams can be
particularly beneficial when pain occurs in the setting of a life-limiting condition. Such teams can assist with pain management, decision making, and psychosocial support. (See "Pediatric palliative care".)

PROCEDURAL PAIN — For children undergoing invasive procedures, adequate pain management is a key component to procedural success. Pain management in this setting may include nonpharmacologic
measures (eg, distraction), topical or local anesthetic therapy (table 2), and/or systemic analgesic agents. Preparing the child prior to the intervention by describing the various steps can help decrease the stress and
anxiety associated with the procedure. The procedure should be performed in a quiet, calm environment with the availability of cognitive-behavioral interventions to reduce distress and anxiety. If the child is
hospitalized, the location of the procedure should be separate from the child's room. The management of pain in children unde rgoing invasive procedures is discussed in greater detail separately. (See "Procedural
sedation in children outside of the operating room" and "Pharmacologic agents for pediatric procedural sedation outside of the operating room", section on 'Analgesic agents'.)

NONPHARMACOLOGIC THERAPY — Nonpharmacologic therapy for pain control includes:

●Physical measures, such as massage, heat and cold stimulation, and acupuncture

●Behavioral measures, such as exercise, operant conditioning, relaxation, biofeedback, desensitization, and art and play therapy

●Cognitive measures, such as distraction, imagery, hypnosis, and psychotherapy

Nonpharmacologic measures are particularly useful in reducing stress and anxiety in children undergoing invasive procedures. In a meta-analysis of 39 randomized clinical trials evaluating various psychological
interventions for needle-related procedural pain in children, distraction and hypnosis significantly reduced pain and stress [29]. (See "Procedural sedation in children outside of the operating room", section on
'Nonpharmacologic interventions'.)
PHARMACOLOGIC THERAPY — Systemic pharmacologic agents used in pediatric pain control in children and infants are reviewed in the following sections. In our center, the use of pharmacologic agents for pain
control is based upon the previously discussed World Health Organization guidelines for pediatric pain management [21]. (See 'WHO two-step strategy' above.)

The management approach may differ according to the type of pain. The approach to pain management in the following conditions is discussed separately:

●Functional abdominal pain (see "Functional abdominal pain in children and adolescents: Management in primary care", section on 'Management of symptoms')

●Headaches (see "Headache in children: Approach to evaluation and general management strategies", section on 'Management')

●Painful crises in sickle cell disease (see "Vaso-occlusive pain management in sickle cell disease")

●Burn pain (see "Paradigm-based treatment approaches for burn pain control")

Nonopioid analgesics — Nonopioid analgesics include acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin use has declined since the 1970s because of its association with Reye's
syndrome.

Nonopioid analgesics are effective for treatment of mild pain; they can also be used in combination with opioids to treat moderate and severe pain.

Acetaminophen — Acetaminophen can be administered orally, rectally, or intravenously (IV). The oral dose of acetaminophen is 10 to 15 mg/kg every four to six hours (not to exceed five doses in 24 hours;
maximum daily dose 75 mg/kg/day[not to exceed 4000 mg/day]). Rectal acetaminophen can be given at doses of10 to 20 mg/kg every four to six hours (not to exceed five doses in 24 hours; maximum daily dose
75 mg/kg/day [not to exceed 4000 mg/day]).

IV acetaminophen dosing is based on age and weight of the patient as follows:

●Infants and children <2 years: 7.5 to 15 mg/kg/dose every 6 hours (maximum daily dose: 60 mg/kg/day)

●Children ≥2 years and adolescents:

•<50 kg: 15 mg/kg/dose every 6 hours or 12.5 mg/kg/dose every 4 hours (maximum single dose 750 mg; maximum daily dose 75 mg/kg/day [not to exceed 3,750 mg/day])

•≥50 kg: 1,000 mg every 6 hours or 650 mg every 4 hours (maximum daily dose 4,000 mg/day)
Dosing errors have been reported with use of IV acetaminophen in children [30]. This issue is discussed in a separate topic review. (See "Clinical manifestations and diagnosis of acetaminophen (paracetamol)
poisoning in children and adolescents", section on 'Iatrogenic IV overdose'.)

NSAIDs — Ibuprofen is the most commonly used NSAID in children. The dose of oral ibuprofen for pain reduction is 4 to 10 mg/kg every six to eight hours (maximum daily dose 40 mg/kg/day). Other commonly used
nonselective NSAIDS include ketoprofen, naproxen, indomethacin, and ketorolac (the latter is given intravenously and is particularly useful in the emergency department and inpatient settings). Selective
cyclooxygenase-2 (COX-2) inhibitors are used less commonly in children.

Because of their anti-inflammatory properties, NSAIDs may be more effective than acetaminophen for pain reduction in inflammatory conditions (eg, systemic juvenile idiopathic arthritis). (See "Systemic juvenile
idiopathic arthritis: Treatment", section on 'Nonsteroidal anti-inflammatory drugs'.)

Adverse events associated with NSAID use, particularly chronic use, include gastrointestinal bleeding and renal toxicity. (See "Nonselective NSAIDs: Overview of adverse effects".)

Opioids — Opioids are generally used in children with moderate or severe pain, or pain that is refractory to nonopioid analgesics. They are most commonly used for pain relief following surgery or associated with
specific conditions, such as sickle cell disease or cancer. (See "Management of acute perioperative pain" and "Vaso-occlusive pain management in sickle cell disease", section on 'Acute pain
management' and "Cancer pain management: General principles and risk management for patients receiving opioids".)

Opioids reduce pain by interacting with one or more of the opiate receptors in the central nervous system (table 3).

Opioid prescribing precautions — Opioid prescription requires individual expertise and systems that adequately monitor safe use so as to minimize the risks of addiction and withdrawal. When pain is expected to
be short term, such as following surgery, the duration of treatment with opioids should be limited. Other considerations include informing a family to store opioids in a safe location, ideally in a locked cabinet, to reduce
the risk of accidental overdose by other children and discourage diversion of opioids for illicit use.

Chronic pain is ideally managed by a team with expertise in all modalities of management, including nonpharmacologic and nonopioid medications, so as to minimize chronic use of opioids. When opioids are used,
contracts can be drafted and signed by parents stating that they will request the medication from a single provider. The need for such steps should not be a barrier to opioid use in individuals receiving palliative care
for life-limiting conditions. (See "Use of opioids in the management of chronic non-cancer pain", section on 'Opioid agreement/consent form'.)

Choice of opioid — The choice of opioid is based upon the intensity and duration of pain, the preferred mode of administration, the associated adverse effects, prior experience (if available), and the preference of
the patient and family. For children with acute pain who are opioid naive, short-acting agents are generally preferred over long-acting or extended-release preparations. Oral agents are used for pain of moderate
severity if the patient is able to tolerate oral medication. Intravenous opioids may be warranted for severe acute pain. For chronic severe pain, a sustained-release preparation (eg, OxyContin or transdermal fentanyl)
or agents with a long half-life (eg, oral methadone) are generally used. (See 'Initial dosing' below.)
Specific agents — A comprehensive discussion of all opioids used in the management of pain in children is beyond the scope of this topic. Commonly used agents are listed below; the initial doses and route of
administrations are presented in the table (table 4) [4,28,31]. Additional information is available in Lexicomp.

●Morphine is the most commonly used opioid in children with moderate to severe pain because of its demonstrated efficacy and relative safety [28]. Morphine is available in oral, sublingual, subcutaneous,
intravenous, rectal, and intrathecal preparations.

●Hydromorphone has similar properties to morphine but is more lipid soluble, which may increase its potency. It also has slightly more rapid onset. Anecdotally, hydromorphone is often perceived as causing
fewer side effects (eg, pruritus, gastrointestinal upset) compared with morphine; however, data supporting these advantages are generally lacking.

●Oxycodone has similar properties to morphine, but is more potent and has a slightly longer half-life.

●Hydrocodone has similar potency as morphine. It is often prescribed in combination with acetaminophen (hydrocodone-acetaminophen). If this preparation is used, caregivers should be instructed not to give
the child other acetaminophen-containing medications as this can lead to acetaminophen overdose and hepatotoxicity. (See "Clinical manifestations and diagnosis of acetaminophen (paracetamol) poisoning in
children and adolescents", section on 'Inappropriate dosing by a caregiver'.)

●Fentanyl has some unique properties that make it a useful opioid in pediatric pain control. Intravenous fentanyl has a shorter onset and duration of action than morphine, which makes it particularly useful in
children undergoing invasive procedures who require conscious sedation and analgesia. (See "Pharmacologic agents for pediatric procedural sedation outside of the operating room", section on 'Analgesic
agents'.)

In addition, fentanyl is the only opioid that is available in a transdermal form. The fentanyl patch has a long duration of action, which provides consistent and prolonged analgesia for children with chronic severe
pain who are unable to take oral medications. Fentanyl patches cannot be used as the initial opioid for pain because of its long onset of action, and cannot be used for acute or escalating pain because its long
half-life makes it difficult to titrate drug dose.

●Methadone requires less frequent administration compared with other opioids. Methadone is also available as an elixir that can be used as an extended analgesic agent in children who are unable to swallow
pills. However, titration of methadone is complicated because of its rapid distribution (half-life between two and three hours) followed by its slow variable elimination (half-life between 4.2 to 130 hours) that may
result in drug accumulation and toxicity two to five days after initiation or an increase in dose [32].

Agents not recommended — We suggest avoiding codeine and tramadol in children <12 years because of variability in metabolism that can alter the level of active drug the child is exposed to, resulting in fatal
overdoses in extreme cases [33-36]. In children ≥12 years, caution should be used in prescribing these drugs, particularly in obese patients and those with obstructive sleep apnea or severe lung disease, which may
increase the risk of serious breathing problems. These drugs should not be used for management of postoperative pain following tonsillectomy and/or adenoidectomy (T&A) in children of any age. (See "Tonsillectomy
(with or without adenoidectomy) in children: Postoperative care and complications", section on 'Pain'.)

In 2017, the US Food and Drug Administration (FDA) issued warnings and contraindications for the use of codeine and tramadol for pain management in all children <12 years old [36]. Similar warnings regarding
codeine have been issued by other agencies, including Health Canada [37] and European Medicines Agency (EMA) [38].

Metabolism of codeine and tramadol is genetically determined by the highly polymorphic enzyme P450 2D6 (CYP2D6) pathway. These drugs are ineffective in some children due to genetic polymorphisms
in CYP2D6 that cause poor metabolism of the drug [39]. Of even greater concern, a small portion of children may have increased conversion to active metabolites (extensive and ultrarapid-metabolizer phenotypes),
which can lead to overdose [33,34,40-42].

There have been more pediatric fatalities reported in association with codeine than with tramadol. The 2017 FDA statement cited data from the adverse event reporting system from 1969 to 2015 during which time
there were 64 cases reported worldwide of respiratory depression associated with codeine use in children, including 24 deaths [36]. During the same period, there were nine reported cases of respiratory depression
associated with tramadol use in children, including three deaths. All three fatalities occurred outside the US and involved tramadol oral drops, a formulation not available in the United States.

Determining which children are ultrarapid-metabolizers is difficult, making routine testing impractical. With any opioid, there is an increased chance of an overdose in overweight/obese children if dosing is based upon
total body weight rather than lean mass, since there is a lower distribution of morphine to fatty tissue.

Initial dosing — The opioid dose and interval are adjusted to obtain pain relief and avoid unacceptable side effects. The required dose varies with the severity of the pain, type of pain, and preexisting opioid
tolerance.

When initiating opioid therapy for frequent or constant pain, short-acting agents are scheduled typically every four hours (table 4). After five or six half-lives (eg, 24 to 48 hours), a basal daily requirement is calculated
based upon the previous 24-hour opioid requirement, and a long-acting opioid preparation can be substituted for persistent pain management. An additional short-acting opioid is used for breakthrough pain at a dose
that is 10 percent of the 24-hour opioid requirement.

Based upon the child's response, the opioid dose may be increased by 25 to 50 percent per day until adequate analgesia is obtained or intolerable side effects occur. If pain remains severe, it may be necessary to
increase the daily dose by 50 to 100 percent.

For most opioid agents, there is no fixed upper limit for effective daily dose. If there are more than three breakthrough doses in a 24-hour period, the initial scheduled daily dose and breakthrough doses should be
added up and recalculated as a new scheduled daily and breakthrough dosing schedule for the next 24-hour period.
In children with altered mental status or compromised breathing, opioids are started at the lowest initial dose and titrated in the same standardized manner.

Escalating pain — Escalating pain can occur, especially in children with chronic untreatable conditions, such as cancer. Pain control guidelines for escalating pain include the following [43]:

●Administer breakthrough doses (10 to 20 percent of 24-hour opioid scheduled dose) of a short-acting opioid agent, which is given intravenously every 15 minutes until pain is relieved.

●Increase the opioid bolus by 30 to 50 percent every third dose if the pain continues.

●Once adequate pain control is achieved, recalculate a new 24-hour opioid dose based upon the previous 24-hour daily dose and breakthrough doses.

●Consider adding an adjuvant or coanalgesic nonopioid agent. (See 'Nonopioid analgesics' above and 'Adjuvant agents' below.)

●If the patient has significant adverse effects with adequate pain control, change to a new opioid, and reduce the new dose of opioid by 25 to 50 percent.

●If the patient has significant adverse effects without adequate pain control, change opioid agents without reducing the equianalgesic dose. (See 'Opioid equivalence dosing' below.)

Patient-controlled analgesia — Patient-controlled analgesia (PCA) is an option for adolescent and mature preadolescent children who are able to reliably assess their pain. For children who are not developmentally
appropriate for PCA (eg, because of young age or developmental disability), nursing-controlled analgesia (NCA) with close monitoring is an option [44-46]. (See "Cancer pain management with opioids: Optimizing
analgesia", section on 'Patient-controlled analgesia' and "Management of acute perioperative pain", section on 'Patient-controlled analgesia'.)

Opioid equivalence dosing — When changing opioid agents, it is important to be familiar with equivalent analgesic dosing of the different opioids so that the desired analgesic effect can be maintained (table 4).
Opioid doses generally are expressed in parenteral morphine equivalents. The unit opioid dose generally used is 10 mg of parenteral morphine, and doses of other drugs for oral or parenteral administration are listed
in equianalgesic amounts.

When opioids are changed, the dose of the calculated equivalent analgesic dose of the new drug should be lowered by 25 to 50 percent and increased as needed. This avoids overmedication, which occurs due to
differences in the structure of the different opioids and their affinity for the opiate receptors (ie, cross-tolerance).

Adverse effects — When treating pain with opioids, it is important to anticipate and manage their adverse effects to assure continued use. The following adverse effects of opioids and their management are
discussed in greater detail separately. (See "Prevention and management of side effects in patients receiving opioids for chronic pain".)

●Nausea and vomiting

 ●Constipation

●Sedation and cognitive dysfunction

●Respiratory depression

●Myoclonus and hyperalgesia

●Pruritus

Renal and hepatic impairment — In patients with renal or hepatic impairment, side effects can occur more readily due to accumulation of metabolites, especially with meperidine, morphine, and tramadol.

In patients with impaired renal function, fentanyl and methadone are considered the safest opioids; oxycodone and hydromorphone should be used with caution; and morphine should be avoided [47,48]. In addition,
dose adjustment is required in children. (See "Cancer pain management with opioids: Optimizing analgesia", section on 'Use in renal failure'.)

Adjuvant agents — Adjuvant therapy can be used in any child with pain, regardless of the intensity. It can enhance analgesic efficacy, treat concurrent symptoms, and/or provide independent analgesic activity for
specific types of pain. Adjuvant therapy is particularly helpful for neuropathic pain and chronic pain, including in children with cancer or with severe neurologic impairment. Consultation with a pain specialist or
palliative care team can assist with use of these medications.

Adjuvant therapy in children includes the following classes of drugs, which are discussed in greater detail separately. (See "Cancer pain management: Adjuvant analgesics (coanalgesics)".)

●Antidepressants for neuropathic pain (tricyclic antidepressants)

●Anticonvulsants for neuropathic pain (gabapentin, carbamazepine)

●Glucocorticoids for hepatic distention and cerebral edema

●Bisphosphonates for bone pain due to tumor

●Radiation therapy for bone pain due to tumor

Neurologically impaired children — Pain is a frequent and significant problem for neurologically impaired children that is often underrecognized and undertreated [49]. Sources of nociceptive pain may include
gastroesophageal reflux, urinary tract infection, bone fracture, hip dislocation/subluxation, dystonia, constipation, acute pancreatitis, and gallstones. In nonverbal children with neurologic impairment who present with
apparent pain, an assessment for these causes is appropriate. If no treatable cause is identified, an empirical trial of gabapentin therapy can be initiated. Gabapentin can be beneficial in these children because it
targets visceral hyperalgesia and central neuropathic pain [1,2]. Other medications that can improve comfort in such children include tricyclic antidepressants, clonidine, and opioids [2,50]. Given the complexities of
assessing pain in children with neurologic impairment and the need for ongoing adjustments in the care plan, often over many years, referral to a pediatric palliative care team is generally warranted.

SUMMARY AND RECOMMENDATIONS

●The evaluation of pediatric pain includes determining the underlying type of pain (nociceptive versus neuropathic pain), source and location of pain, and the severity of pain. (See 'Evaluation' above.)

●Assessment of the severity of pediatric pain is based upon the child's cognitive ability. Self-reporting is used in children who are able to understand and report their pain severity along a continuum (eg, visual
analog scales, FACES scale (figure 2)). In infants and children who are unable to perform self-reporting, behavioral observational scales are used (eg, revised Face, Legs, Activity, Cry, Consolability [r-FLACC]
tool (table 1)). Pain assessment in nonverbal children with neurologic impairment is challenging because they are unable to self -report. However, observational tools based on behavioral response including input
from daily caregivers (eg, parents) are helpful in the assessment of pain in this group of children. (See 'Assessment of pain severity' above.)

●The goal of pediatric pain management is to reduce, control, or prevent pain in children. Pain management varies depending upon the type, source, severity, and duration of pain. General principles of pain
management in children include the following (see 'Principles of management' above):

•Regular pain assessments should be made throughout the course of treatment. (See 'Assessment of pain severity' above.)

•Pain management includes both nonpharmacologic and pharmacologic measures. Nonpharmacologic therapy (eg, cognitive, behavioral, physical, and supportive therapies) should be provided for children
undergoing painful procedures and/or those who require pharmacologic therapy. (See 'Nonpharmacologic therapy' above.)

•Mild pain can generally be adequately treated with acetaminophen and nonsteroidal anti-inflammatory drugs. (See 'Nonopioid analgesics' above.)

•Moderate to severe pain is generally treated with opioid agents (eg, morphine, hydromorphone, oxycodone, hydrocodone, fentanyl, methadone). The choice of opioid is dependent upon the intensity and
duration of pain, preferred mode of administration, associated adverse effects, previous experience (if available), and preference of the patient and family (table 4). (See 'Opioids' above.)

•Oral analgesics should be used when possible to avoid painful routes of administration.

•Side effects of analgesic agents should be anticipated and treated appropriately (eg, pruritus and/or constipation with opioids).
 •Adjuvant therapy can be helpful in certain clinical settings (eg, anticonvulsants for neuropathic pain, antidepressants or anxiolytics for coexisting mood disturbances). (See 'Adjuvant agents' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Joanne Wolfe, MD, who contributed to an earlier version of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

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19. Berde C, Wolfe J. Pain, anxiety, distress, and suffering: interrelated, but not interchangeable. J Pediatr 2003; 142:361.
20. McGrath PA. Development of the World Health Organization Guidelines on Cancer Pain Relief and Palliative Care in Children. J Pain Symptom Manage 1996; 12:87.
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23. Fein JA, Zempsky WT, Cravero JP, et al. Relief of pain and anxiety in pediatric patients in emergency medical systems. Pediatrics 2012; 130:e1391.
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26. Taddio A, Appleton M, Bortolussi R, et al. Reducing the pain of childhood vaccination: an evidence-based clinical practice guideline. CMAJ 2010; 182:E843.
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44. Czarnecki ML, Salamon KS, Jastrowski Mano KE, et al. A preliminary report of parent/nurse-controlled analgesia (PNCA) in infants and preschoolers. Clin J Pain 2011; 27:102.
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46. Monitto CL, Greenberg RS, Kost-Byerly S, et al. The safety and efficacy of parent-/nurse-controlled analgesia in patients less than six years of age. Anesth Analg 2000; 91:573.
47. Murphy EJ. Acute pain management pharmacology for the patient with concurrent renal or hepatic disease. Anaesth Intensive Care 2005; 33:311.
48. Dean M. Opioids in renal failure and dialysis patients. J Pain Symptom Manage 2004; 28:497.
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Topic 6254 Version 30.0

GRAPHICS

Nociceptor sensitization following tissue injury

Nociceptor sensitization is partly mediated by the release of toxic substances (potassium, prostaglandin, bradykinins, and substance P) from damaged tissue. Those toxic substances excite nociceptors and increase their sensitivity
to pain (hyperalgesia). Substance P, released by an axon reflex, induces vasodilation and mast-cell degranulation leading to histamine and serotonin release. These inflammatory agents sensitize damaged tissue and surrounding
nociceptors even further prolonging the hypersensitivity state (secondary hyperalgesia).

K+: potassium; PG: prostaglandin; BK: bradykinin; SP: substance P; 5HT: serotonin.

Redrawn from: Sosnowski M, Lebrun P, Fodderie L. Anesth Clin North Am 1992; 10:211.
Graphic 63962 Version 7.0

Wong-Baker FACES pain rating scale

Explain to the child that each face is for a person who feels happy because he has no pain (hurt) or sad because he has some or a lot of pain. Face 0 is very happy because he doesn't hurt at all. Face 1 hurts just a little bit. Face 2
hurts a little more. Face 3 hurts even more. Face 4 hurts a whole lot. Face 5 hurts as much as you can imagine, although you don't have to be crying to feel this bad. Ask the child to choose the face that best describes how he is
feeling. Rating scale is recommended for persons age three years and older. Point to each face using the words to describe the pain intensity. Ask the child to choose the face that best describes own pain and record the
appropriate number.

Reproduced with permission from: Wong DL, Hockenberry-Eaton M, Wilson D, et al. Wong's Essentials of Pediatric Nursing, 6th ed. Mosby, St. Louis, 2001. p.301. Copyright © 2001 Elsevier.
Graphic 51021 Version 4.0
Monthly pain scale

Graphic 50711 Version 5.0

 Revised FLACC pain score

Scoring
Categories
0 1 2

F No particular expression or smile Occasional grimace or frown, withdrawn, disinterested; appears sad or worried Frequent to constant frown, clenched jaw, quivering chin; distressed-looking face: expression of fright or panic
Face

L Normal position or relaxed Uneasy, restless, tense; occasional tremors Kicking, or legs drawn up; marked increase in spasticity, constant tremors or jerking
Legs

A Lying quietly, normal position, Squirming, shifting back and forth, tense; mildly agitated (eg, head back and forth, aggression); shallow and Arched, rigid, or jerking; severe agitation, head banging; shivering (not rigors); breath-holding, gasping or sharp
Activity moves easily splinting respirations, intermittent sighs intake of breath; severe splinting

C No cry (awake or asleep) Moans or whimpers, occasional complaint; occasional verbal outburst or grunt Crying steadily, screams or sobs, frequent complaints; repeated outbursts, constant grunting
Cry

C Content, relaxed Reassured by occasional touching, hugging, or being talked to, distractable Difficult to console or comfort; pushing away caregiver, resisting care or comfort measures
Consolability

This pain score can be used to assess pain from burns and other etiologies for preverbal children.

 Each of the five categories (F) Face; (L) Legs; (A) Activity; (C) Cry; (C) Consolability is scored from 0-2, which results in a total score between zero and ten.
 Patients who are awake: Observe for at least 1-2 minutes. Observe legs and body uncovered. Reposition patient or observe activity, assess body for tenseness and tone. Initiate consoling interventions if needed.
 Patients who are asleep: Observe for at least 2 minutes or longer. Observe body and legs uncovered. If possible reposition the patient. Touch the body and assess for tenseness and tone.
 The revised FLACC can be used for children with cognitive disability. The additional descriptors (in italics) are included with the original FLACC. The nurse can review the descriptors within each category with parents. Ask them if
there are additional behaviors that are better indicators of pain in their child. Add these behaviors to the tool in the appropriate category.

Reproduced with permission. Copyright © 2002 The Regents of the University of Michigan.
Graphic 81819 Version 2.0

Common topical local anesthetic preparations for use prior to venipuncture or venous cannulation in children

Onset of Duration of Depth of

Agent Dose action action anesthesia Precautions, adverse effects, and comments*¶
(minutes) (minutes) (mm)

Lidocaine administration via a 2 to 2.5 mg (0.2 to 0.25 mL of buffered 1% lidocaine solution) delivered using compressed 1 to 3 60 5 to 8  Ensure that the device is not applied directly over a vein during administration.
needle-free delivery system (J-tip) CO2.

Liposomal lidocaine (LMX4, LMX5) LMX4 (liposomal lidocaine 4%): 30 60 to 120 See lidocaine-  Available over-the-counter.
Δ
 Age <4 years: 1 g applied to puncture site (6.25 cm2 of skin). prilocaine

 Age ≥4 years: 1 to 2.5 g applied to puncture site (6.25 cm2 of skin).

Supplied as 5 g, 15 g, and 30 g tube.

Tetracaine (amethocaine) gel Tetracaine 4%: 30 to 45 250 to 360 See lidocaine-  Do not use in infants younger than one month of age.
(Ametop, Angel)  Age ≥1 month: Apply 1 g of gel to puncture site (6.25 cm2 of skin) under an occlusive prilocaineΔ
 Capillary dilation with skin redness is typical and transient.
dressing.

Supplied as 1.5 g tubes designed to deliver 1 g when squeezed.

Self-heating lidocaine and tetracaine 70 mg lidocaine and 70 mg tetracaine per patch: 20 to 30 90 up to 8  Do not use in patients with para-aminobenzoic acid hypersensitivity.
patch (Synera)
Lidocaine-prilocaine (eutectic
mixture of local anesthetics
[EMLA], Oraqix, Lidopril, Priloxx)
 Apply one patch to intact skin for 20 to 30 minutes and promptly remove. After one failed
attempt, one additional patch may be applied in children. Simultaneous application of
more than one patch is not recommended in children ≤12 years.
Typical dose for venipuncture or venous cannulation:
 Age ≥3 months and weight ≥5 kg: Apply 1 to 2 g of EMLA cream over no more than 10
cm2 of skin under an occlusive dressing at the puncture site.
Dosing based on patient weight:
 <5 kg: Apply up to 1 g per 10 cm2 area under an occlusive dressing 60 minutes prior to
procedure. Maximum dosing for a 24-hour period: Maximum total dose (for all sites
combined): 1 g; maximum application area: 10 cm2; maximum application time: 1 hour.
 ≥5 kg to ≤10 kg: Apply 1 to 2 g per 10 cm2 area under an occlusive dressing for at least
60 minutes prior to procedure. Maximum dosing for a 24-hour period: Maximum total
dose (for all sites combined): 2 g; maximum application area: 20 cm2; maximum
application time: 4 hours.
 >10 kg to ≤ 20 kg: Apply 1 to 2 g per 10 cm2 area under an occlusive dressing for at least
60 minutes prior to procedure. Maximum dosing for a 24-hour period: Maximum total
 The heating element contains iron. Thus, the patch must be removed before some
diagnostic procedures, especially magnetic resonance imaging.
 Prolonged application of the patch to intact skin or application to broken skin or
mucous membranes may result in serious local anesthetic toxicity.
 Approximately 90% of the drug dose remains in the patch after use. Fold the
medicated side of the patch over on itself before discarding.
 Transient skin erythema and swelling at the application site is common with routine
use.
60 60 to 120 3 at 60 min  Do not use in children with methemoglobinemia.
5 at 120 min
 May cause methemoglobinemia with excessive application or in infants younger than
6 at 180 to 240
12 months of age with predisposition to methemoglobinemia (eg, G6PD deficiency or
min
taking methemoglobin-inducing medication).
 Use with caution in children with atopic dermatitis (potential for increased absorption)
or hepatic impairment (decreased breakdown of absorbed medication) because of
increased risk of local anesthetic toxicity. Rarely associated with contact dermatitis.
 dose (for all sites combined): 10 g; maximum application area: 100 cm2; maximum
application time: 4 hours.

 >20 kg: Apply 1 to 2 g per 10 cm2 area under an occlusive dressing for at least 60
minutes. Maximum dosing for a 24-hour period: Maximum total dose (for all sites
combined): 20 g; maximum application area: 200 cm2; maximum application time: 4
hours.

Supplied as 5 g and 30 g tube.

* Local anesthetic toxicity (arrhythmias, seizures, coma, and death) may occur if these agents are applied to large areas of the skin for prolonged periods of time or applied to broken skin, rashes, or areas of skin irritation. For more information

refer to UpToDate graphics and topics on local anesthetic toxicity.

¶ Immediate-type allergy (including anaphylaxis) to local anesthetics is rare. However, contact dermatitis to topical anesthetics can occur. Avoid topical use in children with a history of blistering skin lesions or localized eczema following past

application. For further discussion of the assessment and management of immediate and delayed hypersensitivity due to local anesthetics, refer to UpToDate topics on allergic reactions to local anesthetics.

Δ Both liposomal lidocaine and tetracaine gel provide more complete anesthesia than lidocaine-prilocaine, but the depth of anesthesia appears to be similar.

Dosing:

1. Eichenfield LF, Funk A, Fallon-Friedlander S, Cunningham BB. A clinical study to evaluate the efficacy of ELA-Max (4% liposomal lidocaine) as compared with eutectic mixture of local anesthetics cream for pain reduction of venipuncture in

children. Pediatrics. 2002;109(6):1093-1099.

2. Fein JA, Zempsky WT, Cravero JP; Committee on Pediatric Emergency Medicine and Section on Anesthesiology and Pain Medicine; American Academy of Pediatrics. Relief of pain and anxiety in pediatric patients in emergency medical

systems. Pediatrics. 2012;130(5):e1391-e1405.

3. Koh JL, Harrison D, Myers R, Dembinski R, Turner H, McGraw T. A randomized, double-blind comparison study of EMAL and ELA-Max for topical anesthesia in children undergoing intravenous insertion. Paediatr Anesth. 2004;14(12):977-982.

4. Luhmann J, Hurt S, Shootman M, Kennedy R. A comparison of buffered lidocaine versus ELA-Max before peripheral intravenous catheter insertions in children. Pediatrics. 2004;133(3 pt 1):e217-e220.

5. Ametop (Tetracaine 4 percent) gel. Alliance Pharmaceuticals Ltd, United Kingdom, 9/3/2018.

6. Synera Prescribing Information. Galen US Inc., Souderton, PA; March 2014.

Depth of analgesia:

1. Wahlgren C, Quiding H. Depth of cutaneous analgesia after application of a eutectic mixture of the local anesthetics lidocaine and prilocaine (EMLA cream). J Am Acad Dermatol 2000; 42:584.

2. Bjerring P, Arendt-Nielsen L. Depth and duration of skin analgesia to needle insertion after topical application of EMLA cream. Br J Anaesth 1990; 64:173.

3. Synera Prescribing Information. Galen US Inc., Souderton, PA; March 2014.

4. FAQ. J-TIP Needle-Free Injection System website. http://www.jtip.com/faq.html. Accessed March 19, 2015.
Graphic 117407 Version 6.0

Opiate receptor activity

Opiate receptor Pharmacologic effect

mu (µ) Analgesia, miosis, respiratory depression, euphoria, physical dependence, suppression of opiate withdrawal

kappa (k) Spinal analgesia, does not suppress opiate withdrawal

sigma (σ) Dysphoria, hallucinations, respiratory and vasomotor stimulation

delta (Δ) Unclear

Graphic 52205 Version 2.0
 Opioid analgesics commonly used in children

Equianalgesic dose*

Drug Oral IV
Oral dose and frequency¶ IV dose and frequency¶

(mg) (mg)

MorphineΔ 30 10 0.3 mg/kg every three to four hours 0.05 to 0.1 mg/kg every two to four hours

Hydromorphone 7.5 1.5 0.03 to 0.06 mg/kg every three to four hours 0.015 mg/kg every two to four hours

Oxycodone◊ 20 N/A 0.1 to 0.2 mg/kg every four to six hours N/A

Hydrocodone◊ 30 N/A 0.1 to 0.2 mg/kg every four to six hours N/A

Fentanyl N/A 0.1 (100 mcg) N/A 0.5 to 1 mcg/kg every one to two hours

Methadone § § 0.1 mg/kg every 4 to 8 hours 0.05 to 0.1 mg/kg every 4 to 8 hours

N/A: not available.

* Approximate equianalgesic dose for estimation when changing opioid agents.

¶ Doses are for individuals >6 months old with a maximum weight of 50 kg. Suggested dose ranges are for management of acute pain. Oral doses refer to immediate release products.

Δ Dose adjustment for renal insufficiency may be required. Not recommended in severe renal insufficiency.

◊ If a combined opioid-acetaminophen product is prescribed, caregivers should be instructed not to give the child other acetaminophen-containing medications as this can lead to acetaminophen overdose and hepatotoxicity.

§ Due to gradual drug accumulation at tissue sites, the dose and frequency of methadone differs for initial compared with repeated use; dose and interval given is usual after repe ated use; methadone should be initiated and titrated by a

clinician experienced with its use.

Adapted from: Gutstein HB, Akil H. Opioid analgesics. In: Goodman & Gilmans pharmacological basis of therapeutics, 11th ed, McGraw-Hill, New York 2006.
Graphic 79047 Version 9.0
Contributor Disclosures
Julie Hauer, MDNothing to discloseBarbara L Jones, PhD, MSWNothing to discloseDavid G Poplack, MDNothing to discloseCarrie Armsby, MD, MPHNothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

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