Version May 2024
INTRODUCTION — Perioperative pain control is an essential component of the anesthetic plan for infants and children. Inadequately treated pain, even in infants, may have both short-term and long-term deleterious effects [1]. Parents rightfully expect care providers to mitigate their child's experience of pain to the extent that is possible. Establishing an appropriate level of patient and parent expectation that is safely achievable prior to the procedure may help allay anxiety and improve their understanding of contemporary pain management.
This topic will discuss the pharmacologic options, including regional anesthesia, for management of perioperative pain in infants older than one month of age and in children. The general approach to perioperative pain management and evaluation of perioperative pain in children are discussed separately. (See "Approach to the management of acute perioperative pain in infants and children".)
Evaluation and management of pain in neonates, and the effects of untreated pain in neonates, are discussed separately. (See "Management and prevention of pain in neonates" and "Assessment of pain in neonates".)
START WITH NONPHARMACOLOGIC THERAPY — Nonpharmacologic pain control measures should be used for all patients as appropriate. Nonpharmacologic methods of pain control are low risk and may reduce the need for analgesic medication. These therapies are discussed separately. (See "Approach to the management of acute perioperative pain in infants and children", section on 'Start with nonpharmacologic therapy'.)
Most children who have surgery will require medication for pain control in addition to nonpharmacologic analgesia.
REGIONAL ANESTHESIA — Local, neuraxial, and regional analgesia are commonly and increasingly utilized components of the multimodal approach to postoperative pain management in children [2-5]. For many surgical procedures, infiltration of the surgical site with a long-acting local anesthetic (LA; eg, bupivacaine or ropivacaine) by the surgeon can provide effective postoperative analgesia for several hours after surgery. Single injection LA nerve blocks may provide analgesia for 4 to 12 hours, and in some cases through the first postoperative night. For more prolonged analgesia, continuous peripheral nerve blocks or neuraxial analgesia techniques are options. Regional analgesia techniques with LAs may be especially beneficial for children who are at increased risk of respiratory depression with opioids (eg, children with obstructive sleep apnea, some neurologic disorders). Examples of procedures for which regional anesthesia with LAs may be particularly beneficial include the following:
●Open thoracotomy or large subcostal incisions (for improved pulmonary toilet and to allow for early extubation)
●Amputations or limb-salvage procedures (eg, tumor surgery) with risk of developing phantom limb sensations
●Knee surgery that requires continuous range of motion devices or early ambulation and intensive physical therapy
●Major osteotomy (eg, pelvic /femoral osteotomy for congenital hip dislocation)
●Procedures that predispose to bladder, ureteral, or muscle spasm (eg, genitourinary surgery, tendon transfers, or tendon lengthening procedures)
Indications, contraindications, drug choices, and techniques for regional anesthesia and complications are discussed separately (see "Overview of neuraxial anesthesia" and "Overview of peripheral nerve blocks" and "Continuous epidural analgesia for postoperative pain: Technique and management" and "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication"). Technical aspects of regional anesthesia for infants and children are beyond the scope of this topic. General issues regarding regional anesthesia in children are discussed here.
Neuraxial analgesia — Neuraxial techniques commonly used in children include continuous epidural and single injection or continuous caudal epidural techniques. Technical aspects of neuraxial anesthesia techniques are discussed separately (see "Continuous epidural analgesia for postoperative pain: Technique and management"). Issues specific to children are discussed here.
Single injection caudal epidural LA is commonly used for postoperative analgesia for infants and toddlers. A caudal injection of preservative-free LA can provide four to six hours of analgesia for abdominal procedures; in very young infants, a caudal catheter can be placed and advanced to the high lumbar or thoracic region to provide continuous postoperative analgesia [6,7]. Nonopioid adjunctive medications, most typically preservative-free clonidine, may be added to the LA caudal block in order to extend the duration and depth of the block [8,9]. However, we do not routinely use adjuvants, especially in outpatients, because they may be sedating. In contrast with adult epidural analgesia, addition of synthetic opioids (eg, fentanyl) to the LA solution for caudal block has not been shown to improve analgesia in children [10].
We do not administer single shot subarachnoid hydrophilic opioids (eg, morphine, hydromorphone) for postoperative analgesia in children because of the potential for adverse effects (eg, pruritus, urinary retention) and the possibility of delayed respiratory depression, especially if additional systemic opioid is required for breakthrough pain. Adverse effects, complications, and monitoring for patients who have received neuraxial morphine or hydromorphone for postoperative analgesia are discussed separately. (See "Continuous epidural analgesia for postoperative pain: Technique and management".)
Peripheral nerve blocks — Single injection or continuous peripheral nerve blocks and fascial plane blocks are increasingly used for postoperative pain control in children and adults. Techniques, clinical applications, and contraindications for peripheral nerve blocks are discussed separately. (See "Overview of peripheral nerve blocks".)
Efficacy of regional anesthesia — Although it seems intuitively obvious that regional anesthesia might be beneficial for many surgical procedures, improved outcomes from regional anesthesia techniques for postoperative pain management in children, compared with systemic analgesics, remain difficult to prove. In adults, regional analgesia has been well studied, and has been shown to reduce postoperative pain and opioid consumption for a variety of surgical procedures (see "Overview of peripheral nerve blocks" and "Continuous epidural analgesia for postoperative pain: Technique and management"). In contrast, the literature on the efficacy of regional analgesia in children is limited. A 2014 systematic review of the literature identified 73 randomized controlled trials involving various regional anesthesia techniques in children, with small numbers of patients for any given surgical procedure [5]. Several regional anesthesia techniques, for specific procedures, were associated with improved pain outcomes (ie, regional block for inguinal surgery, infraorbital block for cleft lip repair, ring block for circumcision). Significant heterogeneity among studies with respect to block technique and drugs administered precluded a comprehensive meta-analysis. A meta-analysis of seven small trials including approximately 250 children who underwent spine surgery for scoliosis found that postoperative epidural analgesia reduced pain at rest by a small amount (0.8 to 1.5 points on a 0 to 10 scale) compared with systemic analgesia, based on low to moderate quality evidence [11].
Safety of regional anesthesia in children — Regional anesthesia techniques in children are generally very safe. The reported incidence of complications of regional anesthesia/analgesia, performed by or under the direction of experienced practitioners, is very low in children. In a 2012 study on complications in approximately 15,000 regional blocks reported to the Pediatric Regional Anesthesia Network (PRAN), there were no deaths and no complications that lasted more than three months [12]. A 2018 analysis of more than 100,000 blocks from the PRAN, revealed no permanent neurologic deficit and a low incidence of transient deficit (2.4/100,000) or LA toxicity (0.76/100,000) [13]. In a one year prospective multicenter study involving over 30,000 pediatric regional anesthesia procedures reported to the French-Language Society of Paediatric Anaesthesiologists between 2005 and 2006, the rate of complications was 0.12 percent, with no persistent sequelae [4]. In the systematic review described in the previous paragraph, there were no reports of major morbidity related to regional anesthesia in over 5000 pediatric patients [5].
Caregivers and children must be warned that children who have dense blocks may be at risk of burns from warm compresses or other heat source until the block dissipates.
Awake versus asleep block or catheter placement — Unlike routine practice in adults, regional anesthesia procedures are usually performed under general anesthesia in young children, since it may be safer to perform a block in a child who is not moving.
In cooperative teenagers, these procedures may be performed awake or lightly sedated as long as the patient remains cooperative, maintains meaningful contact, and can report signs of mechanical nerve irritation or report symptoms of early local anesthetic systemic toxicity (LAST). However, experts generally agree that asleep block placement is preferable in young children, as infants and children cannot reliably communicate these symptoms when awake, and unexpected movement may contribute to injury. In addition, general anesthesia may make ultrasound guidance or a nerve stimulator easier to utilize in children. Consistent with this approach, a practice advisory from the American Society of Regional Anesthesia recommended that anesthesia or heavy sedation should not be considered a contraindication to regional anesthesia in children [14]. Data from the PRAN database suggest that the rate of complications is similar in children who have blocks placed either asleep or awake [15,16]. A best practice guideline from the European Society for Paediatric Anaesthesiology has endorsed this approach as well [17].
Local anesthetic dosing in children — Infants and young children may be at increased risk of LAST with regional anesthesia techniques, particularly for blocks that target highly vascular sites or require high volumes of LA solutions (eg, intercostal blocks, epidural, caudal, or interfascial plane blocks) (table 1). (See "Local anesthetic systemic toxicity", section on 'Risk factors for LAST'.)
Infants under the age of approximately four months have low serum levels of alpha-1 acid glycoprotein (AAG), which binds amide LAs (ie, lidocaine, bupivacaine, ropivacaine, levobupivacaine). They may also have immature hepatic clearance of these LAs. These two factors increase the free fraction of amide LAs and may increase the risk of LAST. AAG increases with surgical stress but then decreases to basal levels after 48 hours. Maximum infusion rates of amide LAs must be decreased in infants under six months of age and are generally limited to less than 48 hours post-surgery in neonates. In general, the maximum allowable dose of LA should be decreased by at least 30 percent for children (50 percent for bupivacaine) under six months of age [18]. Esters (2-chlorprocaine, procaine, and tetracaine) are metabolized by plasma esterases and few clinically relevant age-related differences are of concern.
When calculating safe doses of LAs for regional anesthesia, all sources of LA must be considered, including infiltration by the surgeon and any topical anesthetic administered. However, published maximum allowable doses of LAs should be viewed as only rough guidelines. Maximum doses that appear in various publications are not evidence based, and don't necessarily take into account the site or technique of LA administration, or other patient factors that increase the risk of toxicity. Several anesthesia societies have created guidelines for LA dosing for pediatric regional anesthesia [17,19]. Recommendations from the European Society for Paediatric Anaesthesiology for doses of LAs for some specific nerve blocks are shown in a table (table 1).
LAST can occur with administration of any LA, by any route of administration. Thus, clinicians should be vigilant for signs of LAST and lipid emulsion should be available for treatment of LAST wherever regional anesthesia is performed. (See "Local anesthetic systemic toxicity", section on 'Management of LAST'.)
Liposomal bupivacaine — Liposomal bupivacaine is a sustained-release formulation of bupivacaine that consists of bupivacaine in an aqueous core encased in multiple phospholipid bilayers. It is approved for several indications in adults; in 2021 the US Food and Drug Administration (FDA) approved the use of liposomal bupivacaine for surgical wound infiltration in children ≥6 years of age. At the present time, we do not use liposomal bupivacaine, due to a paucity of evidence of its efficacy compared with aqueous bupivacaine and high cost. In addition, it is unclear whether LAST associated with liposomal bupivacaine can be effectively treated with lipid emulsion, and if so, whether the dose is the same as would be used to treat aqueous bupivacaine. Finally, liposomal bupivacaine is a white emulsion that can be confused with propofol and may lead to look-alike medication errors [20].
If used, the dose of liposomal bupivacaine is 4 mg/kg up to a maximum of 266 mg, infiltrated into the surgical wound. Liposomal bupivacaine is discussed in detail separately. (See "Clinical use of local anesthetics in anesthesia", section on 'Liposomal bupivacaine'.)
Transdermal lidocaine — We use transdermal lidocaine (patches) for treatment of localized superficial pain (eg, at chest tube insertion sites, lateral chest wall incisions for pectus excavatum repair). Patches may remain in place for up to 12 hours in any 24 hour period [21].
SYSTEMIC ANALGESICS
Multimodal approach — Multimodal analgesia refers to the use of several medications, often started preoperatively, that target multiple loci along the pain pathway. Multimodal therapy attempts to modify the inflammatory response to surgery or decrease the immediate or long-term consequences of tissue injury and the pain that ensues [22]. Such an approach may theoretically improve pain control, limit the dose and adverse effects of any one drug, and reduce opioid requirements. In our practice, the combination of acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs) is the basis for multimodal postoperative analgesia for most patients who are without contraindications (see 'Nonopioid analgesics' below). However, while there are data suggesting efficacy of multimodal analgesic therapy in adults [23-27], an opioid sparing effect remains difficult to prove in children [28].
A 2017 systematic review of the literature on analgesic efficacy of systemic nonopioid analgesics found evidence of clinical analgesic efficacy (ie, reduction in postoperative pain and opioid consumption) for acetaminophen, NSAIDs, dexamethasone, ketamine, clonidine, and dexmedetomidine, but insufficient or no available data on the benefits of other medications [29]. Opioid sparing effects have been difficult to demonstrate partly because of variability in dose and intervals of administration, drug combinations, variety of surgical procedures, age and patient population, follow-up duration, and outcome measures in existing studies.
Pharmacologic differences between children and adults — Pharmacokinetics and pharmacodynamics of many medications change as a child matures, due to age related differences in volume of distribution, enzyme function and metabolism, and drug clearance. In addition, the effects of centrally acting drugs may reflect maturation of neural tissue and the functioning of the blood brain barrier and transport mechanisms [30-35]. Comprehensive review of pharmacology in children is beyond the scope of this topic.
Oral administration whenever possible — Systemic analgesics should be administered to children orally whenever possible, and the subcutaneous and intramuscular route specifically avoided because of the pain and fear associated with injections.
Nonopioid analgesics
Acetaminophen — We suggest perioperative acetaminophen for postoperative analgesia for children who are without severe liver disease. We administer preoperative oral acetaminophen for most patients, and often continue postoperative, regularly scheduled acetaminophen for up to 72 hours, depending on the procedure. Multiple studies have found that even a single preoperative or intraoperative dose decreases postoperative pain and/or opioid consumption for a variety of minor and major surgical procedures, as long as an adequate blood level is achieved [29,36,37].
Published maximum allowable doses of acetaminophen vary; the primary concern with high doses is the risk of hepatotoxicity. We administer acetaminophen 15 mg/kg orally or intravenously 30 minutes before the procedure, and postoperatively every six hours, maximum dose 3.25 g per day. Doses of acetaminophen should be reduced for patients with hepatic or renal dysfunction. We avoid administration of combined opioid/acetaminophen oral preparations (eg, oxycodone-acetaminophen or hydrocodone-acetaminophen), as the maximum recommended dose of acetaminophen may be exceeded with dosing every four hours or if additional doses of acetaminophen are given for other indications (table 2).
Route of administration — The oral route of administration of acetaminophen is preferred; the intravenous (IV) route can be used in the patient who is nil per os (NPO; nothing by mouth) or vomiting. Oral, IV, and rectal administration may be equally effective, however, consistent blood levels are difficult to achieve via the rectal route. We avoid rectal administration of any drug in the awake patient, if possible, because of patient comfort and because of absorption issues. The rate of absorption and bioavailability of rectal acetaminophen are highly variable and depend on whether the drug is absorbed directly into the portal system (upper rectum) or systemic vasculature (middle and lower rectum) [38,39], and whether the suppository is trapped in stool or expelled.
Rectal dosing is never used in the neutropenic child because of the risk of bacteremia.
Nonsteroidal antiinflammatory drugs — We administer intraoperative and postoperative NSAIDs for patients who are expected to have moderate to severe postoperative pain, in consultation with the surgeon and if there is not an elevated risk of bleeding. Doses of NSAIDS are shown in a table (table 2). NSAIDs may reduce postoperative pain and opioid consumption after a variety of surgical procedures in children, though the degree of benefit remains unclear [40-42].
●In a 2012 meta-analysis of 27 randomized controlled trials including approximately 1000 pediatric surgical patients, intraoperative or postoperative administration of nonselective NSAIDs decreased postoperative opioid requirement and postoperative nausea and vomiting (PONV) [40]. However, meta-analysis identified marked heterogeneity among studies and a high risk of publication bias.
●A 2018 systematic review of 13 randomized controlled trials that evaluated the analgesic efficacy of ketorolac found only very low quality data and insufficient evidence to confirm or refute a beneficial analgesic effect, and insufficient data to perform a meta-analysis [41].
Adverse effects of NSAIDs in children — NSAIDs may be associated with renal injury, platelet dysfunction, gastrointestinal toxicity, and possibly poor bone healing, although the latter remains highly speculative (see "Nonselective NSAIDs: Overview of adverse effects"). We avoid NSAIDs or reduce doses in patients with the following conditions:
●Age <6 months
●Renal dysfunction, or those taking potentially nephrotoxic medications
●Hypoperfused states (eg, hypovolemia, cardiac dysfunction)
●Coagulopathy, intrinsic or caused by medications
●History of gastrointestinal hemorrhage or inflammatory bowel disease
Ketorolac use in the very young remains controversial; safety and beneficial analgesic effects have not been confirmed. The limited available literature consisting of mostly small, retrospective studies offers little consensus on the risk of bleeding or renal dysfunction in young infants [43-46]. Glomerular and tubular maturation continues through 18 to 24 months of age, yet several studies have reported no increase in renal dysfunction after administration of ketorolac to young infants [43-47]. Although ketorolac has been prescribed in infants including post cardiac surgery [43-46], unless reasons are compelling, we usually avoid administration of ketorolac under six months of age.
Intravenous ibuprofen is approved by the US Food and Drug Administration (FDA) for use in children >6 months of age. In 2023, the FDA expanded the pediatric approval to include children >3 months to <6 months of age, for use as a single, one-time-only dose for the acute treatment of pain or fever [48].
Concerns regarding the safety of NSAIDs in neonates are discussed separately. (See "Management and prevention of pain in neonates", section on 'Nonsteroidal anti-inflammatory drugs (not recommended)'.)
The appropriateness and timing of NSAID administration should be discussed with the surgeon especially if the procedure entails a high risk of bleeding, or for procedures in which bleeding may be critical (eg, neurosurgery, vascular surgery, retroperitoneal surgery). We also discuss NSAID administration with the surgeon for patients who undergo tonsillectomy (although we specifically avoid ketorolac in this group), complex spinal surgery, or pleurodesis. The perioperative administration of NSAIDs for analgesia after tonsillectomy is discussed separately. (See "Anesthesia for tonsillectomy with or without adenoidectomy in children", section on 'Nonopioid analgesics' and "Tonsillectomy (with or without adenoidectomy) in children: Postoperative care and complications", section on 'First-line analgesic therapy'.)
●Scoliosis surgery – Perioperative administration of NSAIDs for analgesia after scoliosis surgery and some other orthopedic procedures is controversial, due to the possible risk of poor postoperative bone healing [49]. We do not routinely avoid NSAIDs after scoliosis surgery, and believe the benefits outweigh the potential risks for most patients. However, we usually avoid the use of NSAIDS in patients with higher baseline risk of poor bone healing (eg, patients with connective tissue disorders, osteopenia, prior failed spinal fusion), and patients with distal long bone fractures that have a high intrinsic risk of nonunion.
Several single institution retrospective studies have reported that perioperative ketorolac administration was not associated with an increase in pseudoarthrosis after spinal fusion for scoliosis in adolescents [50-52]. The literature on nonunion after long bone fractures and spinal fusion in adults is inconclusive and is discussed separately. (See "Nonselective NSAIDs: Overview of adverse effects", section on 'Healing of musculoskeletal injury'.)
●Pleurodesis – For most patients who undergo pleurodesis, we administer NSAIDs after the first postoperative day, if bleeding is not an issue. The use of NSAIDs for analgesia after pleurodesis is controversial, due to concern that the antiinflammatory effect may reduce the efficacy of the procedure. Most pleurodesis procedures in pediatrics are performed for spontaneous pneumothorax and success depends on adhesion of the parietal to the visceral pleura. Animal studies have suggested that NSAIDs may inhibit adhesion formation after pleurodesis [53,54] and may increase the recurrence rate of pneumothorax. Evidence in humans is limited; small single institution retrospective studies of pediatric patients who underwent pleurodesis have found similar rates of recurrence of pneumothorax in patients who received ketorolac and those who did not [55,56]. In one of these studies, patients who received ketorolac received less postoperative opioid, had less PONV, and were less likely to be using opioids at discharge [56].
Other nonopioid adjunctive medication — We administer perioperative adjunctive medications (ie, gabapentin, ketamine, dexamethasone, dexmedetomidine) for opioid-sparing analgesia selectively and based primarily on the demonstrable beneficial effects of these medications in adults. The literature on the pediatric use of these medications and others that may be used in adults is limited.
●Gabapentin – We frequently administer a single dose of gabapentin 15 to 20 mg/kg orally (maximum dose 600 mg) two hours prior to induction for children who undergo major surgical procedures (eg, scoliosis repair, pectus excavatum repair) that are associated with significant postoperative inflammatory pain and that may have an additional neuropathic pain component. We limit the dose to 600 mg to avoid delayed emergence from anesthesia and excessive immediate postoperative sedation. We usually do not continue gabapentin postoperatively, due to the risk of respiratory depression when combined with opioids [57]. In our experience, postoperative gabapentin may also cause excessive somnolence and the inability to participate in physical rehabilitation. (See "Nonopioid pharmacotherapy for acute pain in adults", section on 'Gabapentinoids'.)
Literature on the analgesia and opioid sparing effects of gabapentin in children is sparse and inconclusive, and the optimal dose and timing has not been determined [58,59].
●Ketamine – We routinely administer ketamine postoperatively for analgesia in children who undergo amputation and for children who are at high risk of neuropathic pain. We also administer ketamine selectively for children who are opioid tolerant, or as an opioid-sparing agent in children who have persistent opioid-related adverse effects. We administer ketamine postoperatively as an analgesic adjuvant at "ultra-low" dose ranges of 0.025 to 0.05 mg/kg/hour up to 0.1 mg/kg/hour IV. Adverse effects are rare at these doses but may include vivid dreams, hallucinations, and hypertension. Ketamine may be contraindicated in some neurologic conditions such as elevations in intraocular or intracranial pressure. Institutional and state policies may limit the use of ketamine to closely monitored settings and preclude use on general pediatric floors.
We do not routinely administer ketamine intraoperatively as an analgesic adjunct in children. In adults, ketamine is commonly used both intraoperatively as well as postoperatively for analgesia after surgery that results in moderate to severe pain (see "Nonopioid pharmacotherapy for acute pain in adults", section on 'Ketamine'). The available evidence on the intraoperative administration of ketamine in children is limited and does not confirm either analgesic efficacy or opioid-sparing effects after the first few postoperative hours [60-62]. In a 2016 meta-analysis of 11 randomized controlled trials involving intraoperative and/or postoperative IV ketamine in children undergoing a variety of surgical procedures, ketamine did not exhibit an opioid-sparing effect in the first 24 hours after surgery [60]. The number of included studies may have been insufficient to draw firm conclusions on the analgesic effects of intraoperative ketamine.
●Dexamethasone – We administer dexamethasone selectively, for combined effects of analgesia and prophylaxis for PONV. We use dexamethasone for patients who undergo procedures with a high incidence of PONV (eg, strabismus surgery, tonsillectomy), and for patients who have a history of PONV or in whom vomiting might jeopardize the surgical repair (eg, pectus excavatum repair). We administer dexamethasone after induction of anesthesia (0.5 mg/kg IV, maximum dose 10 mg).
Perioperative dexamethasone for tonsillectomy is discussed separately. (See "Anesthesia for tonsillectomy with or without adenoidectomy in children", section on 'Dexamethasone'.)
●Dexmedetomidine – We administer a single dose of dexmedetomidine 0.5 to 1 mcg/kg IV for a wide variety of patients primarily for prophylaxis for emergence delirium. Dexmedetomidine is a selective presynaptic alpha adrenoreceptor agonist with sedative and possible analgesic properties. Dexmedetomidine is often administered as part of a multimodal opioid-sparing strategy (see "Nonopioid pharmacotherapy for acute pain in adults", section on 'Alpha-2 receptor agonists'). Studies of the use of dexmedetomidine in children suggest a reduction in postoperative pain and opioid consumption for some surgical procedures, though the optimal dosing is unclear [63,64]. (See "Emergence delirium and agitation in children", section on 'Prevention'.)
●Intravenous lidocaine – We do not typically use IV lidocaine to treat postoperative pain, though others do. IV lidocaine is often used intraoperatively as a single bolus dose to blunt the hemodynamic perturbations associated with induction and intubation. It may also be used as a continuous infusion intraoperatively as an opioid-sparing adjuvant and has been used for children who underwent abdominal surgery, spinal surgery, and tonsillectomy, with inconsistent effects on postoperative opioid consumption and pain scores [65-68]. (See "Nonopioid pharmacotherapy for acute pain in adults", section on 'Intravenous lidocaine'.)
Optimal administration doses and duration have not been established. IV lidocaine regimens reported in pediatric studies include a bolus of 1 to 1.5 mg/kg IV, followed by infusion at 1.5 to 2 mg/kg/hour. The infusion is typically discontinued at the end of surgery, but in some studies has been continued into the postoperative period [65].
Adverse effects of IV lidocaine at the doses used clinically are rare [65]. Importantly, lidocaine should only be used outside the operating room in an appropriately monitored and staffed intensive care setting by individuals well versed in the signs and symptoms of toxicity and its treatment. It requires an awake patient so that early signs of toxicity can be readily determined. In addition to conventional resuscitative measures, 20 percent intralipid must be immediately available to treat local anesthetic systemic toxicity if necessary. (See "Local anesthetic systemic toxicity", section on 'Lipid rescue'.)
●Medications for treatment of muscle spasm – We administer skeletal muscle relaxants postoperatively as needed after procedures that are associated with muscle or bladder spasm (eg, genitourinary reconstruction, scoliosis surgery, tendon releases or transfers). Our drug of choice is diazepam, which has been used extensively in children. Methocarbamol is an alternative for children >16 years of age.
The combination of these drugs, which are central nervous system and respiratory depressants, raises serious concerns when combined with opioids. Patients who require such combinations should be closely monitored for respiratory depression, excessive somnolence, or upper airway obstruction, especially during initiation of therapy. (See 'Dosing precautions' below.)
•Diazepam – We prefer to administer diazepam by the oral route, if possible, at a dose of one-third to one-half of the usual recommended dose for anxiety. We administer 0.03 to 0.05 mg/kg of diazepam every six hours either around-the-clock or as needed, separating the dosing of opioid and benzodiazepine by at least two hours to avoid the risk of excessive sedation.
•Methocarbamol – Methocarbamol is often administered to children >4 years of age for postoperative muscle spasm. It is metabolized by the liver and excreted by the kidney. The IV form contains polyethylene glycol and should not be administered to patients with renal insufficiency. The dose is 10 mg/kg orally or IV, either as needed or scheduled, for a maximum of 48 to 72 hours.
•Others – We generally avoid the presynaptic alpha-agonist tizanidine in the immediate postoperative period because of its tendency to contribute to hypotension. We do not recommend the cyclic antidepressant cyclobenzaprine because of its drug interactions and significant adverse effect profile.
Opioids — Opioids may be indicated for moderate to severe postoperative pain when alternative methods are unlikely to provide adequate analgesia. The safe use of systemic opioids requires modification of doses for high-risk patients and monitoring for respiratory depression and side effects.
Dosing precautions — Opioid administration should start with low doses, and increased in small incremental amounts as necessary, based on patient response. Opioid dosing must be prompt but iterative, especially in the early phases of postoperative care until an effective dose is established, and should take into account patient risk factors such as prematurity, age, history of apnea, and other underlying disease.
The following considerations apply to administration of oral or IV opioids.
●Avoid opioid infusion – We generally avoid the routine use of continuous opioid infusions, including by patient-controlled anesthesia (PCA). If we do utilize a continuous infusion, the rate of infusion is at the lowest effective dose and we rely on clinician boluses for breakthrough pain.
If opioids are administered by continuous infusion, systems should be in place to monitor and respond to adverse events, including:
•Strict institutional guidelines for clinical and electronic patient monitoring
•Low patient-to-nursing ratios
•Frequent nursing assessment
•Rapid alert and medical response by experts in pediatric airway management
●Avoid other respiratory depressants – Administration of sedatives or respiratory depressants (eg, benzodiazepines for muscle spasm, antihistamines for pruritus) concomitantly with opioids increases the risk of respiratory depression or airway obstruction and should generally be avoided or given in reduced dose.
●High-risk patients – Children with significant pre-existing neurologic impairment are often on medications for control of seizures and spasticity. They may be at increased risk of excessive sedation, airway compromise, and pulmonary aspiration if systemic opioids and antispasmodics are utilized at standard doses [69-72]. If opioids are necessary for these patients, the opioid doses may need to be reduced, and if possible, they should be initially titrated to effect in a carefully monitored setting. Consideration should be given to regional anesthesia techniques to minimize or eliminate the need for additional central nervous system or respiratory depressants.
Regularly scheduled versus as needed dosing — When prescribing oral opioids for use after discharge, we prescribe them on an as needed basis. For hospitalized patients, regularly scheduled dosing of analgesics, including opioids, is occasionally required for very painful procedures, especially on the first postoperative night, to assure timely administration. Around the clock opioid dosing is not offered routinely for children with certain neurologic disorders; developmental delay that may affect central respiratory control or that may interfere with maintenance of airway patency; a history of apnea; or ex-premature infants.
When ordered on a scheduled basis, we often include the proviso to hold opioids for sleep, sedation, or decreased respiratory rate (for age) in the postoperative orders and we allow the parent or patient (if old enough) to refuse. Before the child goes to sleep for the night, we occasionally ask permission to awaken the child if necessary to administer oral analgesics if we have reason to believe that significant pain will result if a dose is missed.
Monitoring during opioid administration — Inpatient monitoring for patients who receive IV opioids should include the frequent expert clinical assessment of respiratory rate, depth and pattern, level of sedation, and oxygen saturation via pulse oximetry. Many institutions require frequent "focused clinical evaluations" in addition to standard every four hours vital signs for any patient who is receiving IV opioids by PCA.
●Monitoring for sedation – In children who receive opioids, sedation almost always precedes clinically significant advancing respiratory depression. We utilize a modified Pasero Opioid Induced Sedation Scale (m-POSS), and attempt to maintain a score of 1 or 2 (either awake and alert or slightly drowsy but easily aroused by voice or light touch) [73]. The m-POSS includes five possible scores and actions, as follows:
•S – Sleep, easy to arouse: No action necessary
•1 – Awake and alert: No action necessary
•2 – Slightly drowsy, easily aroused: No action necessary
•3 – Frequently drowsy, arousable, drifts off to sleep during conversation: monitor respiratory status and sedation level closely until sedation level is stable at <3; consider reducing opioid dose
•4 – Somnolent, minimal or no response to verbal or physical stimulation: stop opioid; consider administering naloxone; notify prescriber or anesthesiologist; monitor respiratory status and sedation level closely until sedation level is stable at <3 and respiratory status is satisfactory
●Monitoring for respiratory depression – In addition to clinical assessment, we monitor oxygen saturation in all children on PCA whether or not a continuous infusion is utilized. Importantly, oxygen administration may improve peripheral arterial oxygen saturation (SpO2) while masking signs of hypoventilation. Intensified monitoring should be utilized in all infants (whose respiratory control mechanisms may be immature) and any child who has significant central nervous system or cardiorespiratory comorbidity, obstructive/central sleep apnea, or who requires supplemental oxygen to maintain oxygen saturation while receiving IV opioids postoperatively.
End tidal carbon dioxide (CO2) monitors or transcutaneous CO2 trend monitoring may be helpful if tolerated by the patient, but does not supplant direct clinician vigilance [74,75]. (See "Carbon dioxide monitoring (capnography)".)
Prevention and treatment of opioid-related side effects — Opioids are associated with nausea, pruritus, and constipation. Options for prevention and treatment of side effects and pediatric doses are shown in a table (table 3). All children who receive opioids and who are able to take oral medications should also receive prophylaxis for opioid-induced constipation, if not contraindicated by the surgery (eg, gastrointestinal [GI] surgery). We administer senna and docusate for children who are able to tolerate oral medication during opioid therapy (table 4).
Isolated pruritus associated with opioid administration, particularly in a facial distribution, is not primarily histamine-mediated and may be effectively treated with low doses of an opioid antagonist or agonist-antagonist, thereby avoiding the potential sedation and respiratory depression associated with antihistamines. Options include nalbuphine 0.1 mg/kg IV to a maximum of 5 mg over 20 minutes every six hours or naloxone 0.25 mcg/kg/hour IV [76,77]. Urinary retention associated with opioids can be treated with bladder catheterization, or similar doses of nalbuphine or naloxone may be tried [78,79].
Parenteral opioids — Opioids provide swift and potent analgesia when administered parenterally. In children, parenteral opioids are almost exclusively administered intravenously, with the intramuscular route specifically avoided. Patient fear of a shot and its attendant discomfort is thought to contribute to a child's silent suffering.
Bolus IV injections (ie, IV push or by infusion over 15 minutes) are often used for moderate pain, with doses carefully titrated to analgesic requirements but with the avoidance of excessive sedation, respiratory depression, and hemodynamic instability. However, commonly used opioids, such as morphine or hydromorphone, given by such intermittent techniques, often result in somnolence for 45 minutes to one hour and generally do not maintain therapeutic analgesic levels for more than two to three hours. Bolus doses are often not repeated in a timely manner.
PCA is useful in children who can cooperate with and understand instructions for use of the PCA pump. This technique allows self-dosing with opioids up to a predetermined limit with a lockout interval set by the clinician. (See 'Patient-controlled analgesia in children' below.)
The most commonly used parenteral opioids in children are morphine, hydromorphone and less often fentanyl. IV opioid doses shown in the table are general suggestions that must be tailored to the individual patient (table 5). PCA doses are discussed below. (See 'Patient-controlled analgesia in children' below.)
●Morphine – Morphine is the prototypical opioid and is widely used for postoperative pain management in children. The onset of analgesia is rapid, with the peak effect occurring within 10 to 20 minutes after an IV dose, with analgesic duration of approximately two to four hours [80]. The pharmacokinetics of morphine in children is similar to adults, but in neonates and young infants, protein binding is reduced and half-life is increased [81]. Neonates may be at increased risk of opioid induced respiratory depression, but by the age of three to six months, analgesic effects and respiratory depression are similar to adults with equivalent plasma concentrations of morphine [82].
Rapid bolus administration of morphine can release histamine, and may cause hypotension. Morphine is metabolized by the liver and active metabolites are cleared by the kidneys; doses should be reduced in patients with hepatic or renal impairment, or reduced cardiac output.
Dosing for acute pain in opioid naïve patients is shown in a table (table 5).
●Hydromorphone – Hydromorphone is a semisynthetic opioid agonist that has a slightly more rapid onset of analgesia compared with morphine, with peak effect in as little as 10 minutes after an IV dose [83]. Scant data are available on hydromorphone pharmacology in children. One small study in children suggested that hydromorphone is approximately 5 times as potent as morphine [84]. We prefer morphine rather than hydromorphone for small children (ie, <20 kg), since small volume administration errors can result in significant pharmacologic effects with hydromorphone.
Hydromorphone tends to be more sedating at equianalgesic doses than morphine but may be less likely to cause nausea, vomiting, or pruritus [84-88]. Hydromorphone is metabolized by the liver and an active metabolite is cleared by the kidney. Based on experience in adults, doses should be reduced in children with renal or hepatic insufficiency. Dosing for acute pain is shown in a table (table 5).
●Fentanyl – Fentanyl is a synthetic opioid 70 to 100 times more potent than morphine, with more rapid onset of action (two minutes) and time to peak effect (three to five minutes) than morphine [83,89]. Fentanyl may be associated with bradycardia; however systemic blood pressure is usually maintained because of minimal histamine release.
Although fentanyl is considered a drug with a short half-life, it does exhibit context sensitivity; repetitive doses will result in an increase in plasma half-life and longer lasting effect. Tolerance may develop rapidly to fentanyl (over 48 to 72 hours) requiring higher doses to achieve the same clinical effect. Fentanyl may be used for initial rapid pain control in a monitored setting, but is not recommended for subsequent pain control outside of the intensive care unit. Doses for acute pain control are shown in a table (table 5).
●Avoid meperidine – We do not use meperidine in children. Meperidine is metabolized to normeperidine, which may accumulate and cause seizures with repetitive dosing [90]. Meperidine has no clinical advantages over other opioids used for analgesia. In addition, there are multiple drug interactions that the practitioner should be aware before prescribing this drug. For specific interactions, use the drug interactions program included with UpToDate. Dexmedetomidine has largely replaced low dose meperidine for control of postoperative shivering in children.
Patient-controlled analgesia in children — PCA is a widely used modality of IV opioid administration in children who are capable of understanding and controlling the PCA pump, usually children over seven or eight years of age [91,92]. The PCA pump is programmed to allow the patient to self-administer small doses of opioid with a fixed lockout interval. PCA reduces delay in patient access to pain medication, provides the patient a sense of control over pain, and may result in a lower total dose of opioid compared with as needed or around the clock bolus opioid administration [93]. In a randomized trial including 82 children and adolescents who underwent major orthopedic surgery, PCA provided equivalent analgesia without an increase in opioid-related side effects, compared with intramuscular morphine [91]. PCA doses for children are shown in a table (table 6).
●PCA settings – Similar to IV opioid infusions unrelated to PCA, the use of a continuous background infusion for PCA is not routinely recommended, and should be limited to carefully selected patients who are opioid tolerant and/or receiving care in a properly monitored unit. If the demand dose alone provides inadequate relief, we allow several supplemental clinician-administered (usually nurse-administered) bolus doses that are based on strict limits and clinical evaluation criteria. We usually set the patient-activated demand dose lockout interval to at least 10 minutes and the minimum time period between clinician boluses set at 15 to 20 minutes. Further details regarding PCA pump settings are shown in a table. (table 6)
●Dose adjustments – Dose adjustments are based on patient use pattern which can be obtained by review of the pump history. Patients who press the button in a staccato fashion are either highly anxious or need additional education about the pump's functionality. The same may be true for patients who rarely use the button and are yet in apparent pain.
The PCA usage pattern history, the patient's pain intensity, and underlying medical/surgical condition should be evaluated within several hours of initiating PCA.
•If the one hour demand dose total approaches the amount allowed by the lockout interval, we increase the demand dose by approximately 20 percent.
•An increase in demand dose may also be indicated if frequent clinician boluses have been required.
•If the patient cannot sleep or obtain relief because of the need for frequent self-administered doses, we consider a night-basal infusion (with intensified monitoring required).
If conventional dosing does not relieve pain adequately, the patient should be evaluated for underlying pathology, especially for patients who cannot effectively communicate.
●Avoid authorized agent PCA control – Unauthorized use of the demand dose button by caregivers must be strongly discouraged. We suggest avoiding authorized agent controlled analgesia (AACA), which was formerly called "parent- or guardian-authorized analgesia," except in the rarest circumstances. As an alternative, clinician boluses can be administered by health care providers who can assess pain and vital sign changes before and after a dose. If AACA is considered, we agree with nursing organizations that recommend institutional protocols and formal education programs for authorized agents [94,95].
Transition of analgesics to the oral route occurs as soon as the patient is reliably able to take liquids comfortably. We also usually wait until the patient is mobilized successfully before stopping the PCA to allow for the rapid administration of opioid if needed as the patient increases movement.
Oral opioids — Similar to other systemic analgesics, oral administration of opioids is preferred when appropriate, once pain is controlled with IV opioids in the recovery room. It is often appropriate to switch to oral opioids as soon as possible after non-GI surgery and for patients in whom GI motility is not impaired and nausea or vomiting is well controlled. Surgical procedures amenable to oral agents include extremity fractures, some oromaxillary procedures (eg, third molar extraction) and more superficial procedures (eg, abdominal wall hernia repair and tissue expander placement). (See 'Oral administration whenever possible' above.)
We suggest using immediate-release (IR) opioids, rather than extended-release (ER) formulations, for acute pain in opioid naïve children. IR opioids are easier and safer to titrate on and off than ER opioids. (See "Use of opioids for postoperative pain control", section on 'Choice of opioid'.)
●Oxycodone – Oxycodone is the oral opioid most commonly prescribed by the author for moderate-to-severe postoperative pain. In our experience, oxycodone causes less nausea and vomiting than hydromorphone or morphine. It is available as a tablet or as a solution (1 mg/mL). Dosing for hydromorphone is shown in a table (table 7).
●Morphine – We tend to avoid oral morphine for most children because it may be associated with a high incidence of nausea and vomiting. Doses of IR oral morphine are shown in a table (table 7).
●Hydrocodone – Although it is commonly prescribed by others, we do not prescribe hydrocodone for children, because it is only available in the United States in combination with acetaminophen or ibuprofen. The hydrocodone-acetaminophen combination could result in acetaminophen toxicity if administered every four hours or if administered with other sources of acetaminophen (see 'Acetaminophen' above). The hydrocodone-ibuprofen tablet is available at a dose of hydrocodone too high for many children. We avoid the use of combination drugs, preferring to administer each component separately (table 7).
●Methadone – We use methadone for inpatients with acute, severe, or refractory postoperative pain. Because of its multiple pharmacologic targets, it is an especially effective analgesic for both inflammatory nociceptive and neuropathic pain. Additionally, there is evidence that it may mitigate the development of opioid tolerance [96]. It is the only long-acting opioid that may be prescribed for young children since it is available in liquid form. Methadone should only be prescribed by clinicians experienced with its use because of its complex pharmacology, multiple drug interactions, and long, variable half-life. We routinely obtain a baseline electrocardiogram before prescribing it since it can prolong the QT interval, and we are especially cautious about combining methadone with other drugs that may prolong the QT interval or use similar cytochrome P450 metabolic pathways.
We may choose to administer methadone intraoperatively for procedures that are known to be exquisitely painful, such as pectus excavatum repair, sternotomy, thoracotomy, and selected major orthopedic procedures. It is administered as a single intraoperative dose of 0.2 mg/kg, usually at the beginning of the case. Studies indicate that total postoperative opioid consumption in morphine milligram equivalents may be reduced for as long as 36 hours postoperatively [97,98].
For severe refractory postoperative pain, we may administer low-dose methadone along with either oral IR opioids every 4 hours as needed, or a demand-dose PCA (without a continuous infusion). For such a regimen we usually administer methadone 0.1 mg/kg orally per day, divided into doses administered every 8 or 12 hours. Patients should be monitored closely, as methadone dose reduction may be required after three or four days. We aim to wean methadone by one dose per day after the first 48 to 72 hours to transition to IR opioid along with an NSAID and acetaminophen for discharge. Several other safe strategies have been published for methadone administration in the acute perioperative setting [97,99].
Avoid tramadol and codeine — We suggest avoiding codeine and tramadol in children <12 years of age, for postoperative pain after tonsillectomy in children of any age, and for children with renal insufficiency or who are prone to upper airway obstruction. Codeine and tramadol are metabolized by the highly polymorphic enzyme CYP2D6. For both drugs, children who are either extensive or ultrarapid metabolizers of these drugs are at risk for overdose of active metabolites. Conversely, the drugs may be ineffective in children who have genetic polymorphisms that cause poor metabolism. These issues are discussed in detail separately. (See "Pain in children: Approach to pain assessment and overview of management principles", section on 'Agents not recommended' and "Tonsillectomy (with or without adenoidectomy) in children: Postoperative care and complications", section on 'Pain not responsive to other measures'.)
Postdischarge analgesia with opioids — We follow a multimodal opioid sparing strategy for postdischarge analgesia, which includes nonpharmacologic methods of analgesia in addition to acetaminophen and NSAIDs and add opioids only as necessary. For same-day surgery patients, we administer the first oral dose of opioid several hours before discharge; for those who have been inpatients, we prefer to switch to IR oral medications at least 24 hours before discharge in order to observe the effect.
For patients who will require opioids after discharge, we prescribe up to a five- to seven-day course of immediate-acting opioids, depending on the expected severity and duration of acute pain [100,101]. Postdischarge opioids are prescribed on an as-needed basis. We emphasize that the primary analgesics are acetaminophen and ibuprofen at home (regularly scheduled every six hours each, given sequentially on an alternating basis such that the patient receives either acetaminophen or ibuprofen every three hours for the first 24 to 48 hours, then as needed). The patient is advised that opioid may be given at least one-half hour prior to strenuous movement or for incidental pain if needed. We assume most patients will require an average of four doses of opioid per 24-hour period for the first several days, tapered thereafter, and limit the amount dispensed based on the type of surgery. Instruction is given on proper disposal of unused opioid upon recovery.
Patients who will be discharged with opioid prescriptions should be screened for risk factors for opioid misuse, and a Prescription Drug Monitoring Program (PDMP) database should be checked prior to prescription. Excessive prescription of opioids should be avoided, and patients and caregivers should be instructed on safe storage and disposal of opioids. Availability of naloxone should be discussed with patients and caregivers. Opioid prescribing after discharge is discussed in detail separately. (See "Management of acute pain in opioid naïve adults in the ambulatory setting", section on 'Opioids'.)
Long-acting opioids have limited or no role in the treatment of acute procedural or postoperative pain and should not be routinely prescribed after discharge. If opioids are required for more than 7 to 10 days postoperatively, a consultation with a pediatric pain treatment specialist may be required.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute pain management".)
SUMMARY AND RECOMMENDATIONS
●Nonpharmacologic pain control – Nonpharmacologic pain control measures should be used for all patients as appropriate. They are low risk and may reduce the need for analgesic medication. (See 'Start with nonpharmacologic therapy' above.)
●Regional anesthesia
•Regional anesthesia techniques (ie, neuraxial block, peripheral nerve block, local anesthetic [LA] infiltration, transdermal lidocaine) may be particularly beneficial for patients who undergo very painful procedures, or who are at increased risk of respiratory depression with opioids. (See 'Regional anesthesia' above.)
•Regional anesthesia procedures are usually performed under general anesthesia in young children, since it may be safer to perform a block in a child who is not moving. (See 'Awake versus asleep block or catheter placement' above.)
•Infants and young children may be at increased risk of local anesthetic systemic toxicity (LAST) with regional anesthesia techniques, particularly for blocks that target highly vascular sites or require high volumes of LA solutions (eg, intercostal blocks, epidural, caudal, or interfascial plane blocks). Lipid emulsion should be available for treatment of LAST wherever regional anesthesia is performed (table 1). (See 'Local anesthetic dosing in children' above.)
●Nonopioid analgesics
•We administer nonopioid analgesics (ie, acetaminophen and nonsteroidal antiinflammatory drugs [NSAIDs]) as the basis for multimodal analgesia for most patients without contraindications to them, and add other medications as necessary. We suggest perioperative administration of acetaminophen for pain control for children without severe liver disease (Grade 2C). We administer intraoperative and postoperative NSAIDs for patients who are expected to have moderate to severe postoperative pain, in consultation with the surgeon, and if there is not an elevated risk of bleeding (table 2). (See 'Nonopioid analgesics' above.)
•We administer perioperative adjunctive medications (ie, gabapentin, ketamine, dexamethasone, dexmedetomidine, diazepam) for opioid-sparing analgesia selectively. (See 'Other nonopioid adjunctive medication' above.)
●Opioids
•Opioids may be indicated for moderate to severe postoperative pain when alternative methods are unlikely to provide adequate analgesia. Patients who receive systemic opioids should be monitored for respiratory depression, sedation, and side effects (table 5 and table 3). Doses should be modified for high-risk patients. Does of opioids should be modified for high-risk patients. (See 'Dosing precautions' above.)
•We avoid continuous intravenous (IV) opioid infusion, including as part of patient-controlled analgesia (PCA), and avoid the simultaneous administration of other respiratory depressants. (See 'Dosing precautions' above.)
•PCA may be appropriate for children who are capable of understanding and controlling the PCA pump, usually children over seven or eight years of age (table 6). (See 'Patient-controlled analgesia in children' above.)
•Oral administration of opioids is preferred when appropriate, once pain is controlled with IV opioids in the recovery room. We use short-acting oral opioids, rather than long-acting preparations, for acute pain control in opioid naïve patients. (See 'Oral opioids' above.)
●Postdischarge analgesia – We follow a multimodal opioid-sparing strategy for postdischarge analgesia, which includes nonpharmacologic methods of analgesia in addition to acetaminophen and NSAIDs, and add opioids only as necessary. Patients who are discharged with opioid prescriptions should be screened for risk factors for opioid misuse. Patients and their caregivers should be instructed on safe storage and disposal of opioids. Availability of naloxone should be strongly recommended. (See 'Postdischarge analgesia with opioids' above.)
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