Effective perioperative pain control in pediatric patients undergoing orthopedic surgery remains a challenge. Developing a successful pain control regimen begins preoperatively with assessment of the patient and discussion with the patient and family regarding expectations. Perioperative pain control regimens are customized based on the type of surgery, patient characteristics, and anticipated severity and duration of the postoperative pain. Recent study focuses on multimodal strategies and regional anesthesia options, allowing for decreased opioid use. This article provides an evidence-based overview of preoperative, intraoperative, and postoperative pain control for the pediatric orthopedic patient.
Key points
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Effective pediatric perioperative pain control in patients undergoing orthopedic surgery is crucial for better outcomes, patient comfort, and satisfaction.
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Inadequate management of postoperative pediatric pain may stem from apprehension about serious complications from analgesic medications.
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Initial perioperative pain planning begins with a multidisciplinary meeting between the patient, patient’s family, surgeon, and anesthesiologist.
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Acute pain control regimens are customized based on type of surgery, surgical site, age of the patient, anticipated severity of postoperative pain, and patient or family expectations.
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Multimodal strategies and regional anesthesia are useful adjuncts to perioperative analgesia.
Introduction
Effective perioperative pain management for the pediatric orthopedic patient continues to be challenging. Avoiding the undertreatment of pediatric pain is critical, because inadequate analgesia may lead to longer hospital stays, patient dissatisfaction and an increased risk of morbidity and mortality. Rabbits and colleagues studied children who underwent inpatient surgery and found a significant deterioration in health-related quality of life at 1-month follow-up in children who suffered severe postoperative pain. Yet, evidence suggests that postoperative pediatric pain may not be adequately treated. For optimal outcomes, perioperative pain management should begin with a surgeon-led multidisciplinary discussion with the patient, their parents, and anesthesiologist regarding expectations before surgery.
Perioperative pain management comprises numerous pharmacologic and nonpharmacologic treatment modalities. Treatment modalities include regional and local anesthesia, dissociative anesthesia, and intravenous sedation (deep and conscious). Nonpharmacologic methods include cognitive behavioral interventions and distraction. Acute postoperative pain management regimens are based on the patient, type of orthopedic surgery performed, and current and anticipated postoperative pain. There is a wide diversity of orthopedic surgeries ranging from traumatic fracture care to elective orthopedic surgeries that require different considerations regarding pain management. This article provides an evidence-based overview of preoperative, intraoperative, and postoperative pain management, as well as their possible complications in pediatric orthopedic surgery.
Introduction
Effective perioperative pain management for the pediatric orthopedic patient continues to be challenging. Avoiding the undertreatment of pediatric pain is critical, because inadequate analgesia may lead to longer hospital stays, patient dissatisfaction and an increased risk of morbidity and mortality. Rabbits and colleagues studied children who underwent inpatient surgery and found a significant deterioration in health-related quality of life at 1-month follow-up in children who suffered severe postoperative pain. Yet, evidence suggests that postoperative pediatric pain may not be adequately treated. For optimal outcomes, perioperative pain management should begin with a surgeon-led multidisciplinary discussion with the patient, their parents, and anesthesiologist regarding expectations before surgery.
Perioperative pain management comprises numerous pharmacologic and nonpharmacologic treatment modalities. Treatment modalities include regional and local anesthesia, dissociative anesthesia, and intravenous sedation (deep and conscious). Nonpharmacologic methods include cognitive behavioral interventions and distraction. Acute postoperative pain management regimens are based on the patient, type of orthopedic surgery performed, and current and anticipated postoperative pain. There is a wide diversity of orthopedic surgeries ranging from traumatic fracture care to elective orthopedic surgeries that require different considerations regarding pain management. This article provides an evidence-based overview of preoperative, intraoperative, and postoperative pain management, as well as their possible complications in pediatric orthopedic surgery.
Preoperative considerations
Effective pain management begins preoperatively with a thorough assessment of the expectations of both the patient and the patient’s family, and the expected level and duration of postoperative pain. The child and parents need to have information regarding the specific surgical procedure, expected severity of pain, and the available nonpharmacological and pharmacologic treatments available provided to them in a clear and simple manner. This discussion ideally takes into account the patient’s and family’s level of education and is undertaken in their native language.
Premedication
Preoperative premedication reduces patient anxiety, lessens the stress of separation from parents before surgery, and aids in the induction of general anesthesia. Midazolam is the most frequently used drug for pediatric premedication. Midazolam is a short-acting benzodiazepine with a fast onset administered via multiple routes but preferred in its oral form. Oral midazolam (0.5–0.7 mg/kg) provides effective preoperative premedication without a significant risk of respiratory adverse effects. Midazolam is commonly administered 15 to 20 minutes before planned induction. Although midazolam has several beneficial effects, it also has several possible adverse effects, such as excessive sedation, amnesia, restlessness, and cognitive impairment.
Nonpharmacologic Interventions
Nonpharmacologic interventions, which include distractions and relaxation techniques, may help ease the patient’s preoperative anxiety regarding the impending surgery and pain. Child life specialists are available at many institutions to provide support through play therapy, music therapy, and other methods. Use of these interventions in the holding area or in the operating room just before induction has been noted to decrease anxiety and improve pain control and patient cooperation. The presence of the parents at induction is another potential strategy but is variably permitted based on institutional preferences. According to Kain and colleagues, children older than 4 years old, those with parents with low anxiety levels, or children with a low baseline level of activity benefit from parental presence during induction.
Intraoperative considerations
Intraoperative pain considerations are an integral aspect of the intraoperative management plan for the pediatric patient. There are numerous opportunities to positively affect the postoperative course: from anesthetic medication options to regional blocks. The ultimate goal is to provide adequate analgesia for treatment, and minimize physical discomfort and negative psychological impact while ensuring the safety and welfare of the child.
General Anesthetics
The new Food and Drug Administration (FDA) warning from December 4, 2016 regarding general anesthetics will certainly cause some parental concerns and questions. The warning states general anesthesia and sedation drugs used in children younger than 3 years of age undergoing anesthesia for more than 3 hours or repeated use of anesthetics “may affect the development of children’s brains.” The FDA has also issued a labeling change for 11 common general anesthetic and sedative agents that bind to gamma-aminobutyric acid (GABA) or N-methyl-D-aspartate acid (NMDA) receptors, including all anesthetic gases, such as sevoflurane, and intravenous agents, such as propofol, ketamine, barbiturates, and benzodiazepines. Despite this warning, the current literature remains difficult to interpret due to confounding factors. Children who require multiple procedures at this young age often have other sources of anoxic or inflammatory insult to the developing brain that may have caused injury before receiving anesthesia. Recent study has sought to fill the voids in the literature. Davidson and colleagues recently demonstrated that less than an hour of exposure to sevoflurane was not associated with poorer neurodevelopmental outcomes in a randomized controlled trial of infants younger than 60 weeks. Sun and colleagues had similar conclusions in the Pediatric Anesthesia and Neurodevelopment Assessment (PANDA) study, a sibling-matched cohort study of children younger than 36 months. The anesthetic group was exposed to various combinations of inhaled and intravenous anesthetics, including propofol, thiopental, ketamine, and midazolam. There was no difference in IQ scores between siblings when assessed at ages 8 to 15 years. Given this new FDA warning, Andropoulos and Greene recommend an extensive preoperative discussion between parents, surgeons, other physicians, and anesthesiologists about duration of anesthesia, any plans for multiple general anesthetic exposures for multiple procedures, and the risks and benefits of possibly delaying the procedure until after 3 years of age.
Although rare, in the late postoperative period pediatric patients may display maladaptive behavioral changes days, weeks, or even months after surgery. These behaviors include bed wetting, sleep disturbances, temper tantrums, and attention-seeking behavior. A study by Fortier and colleagues found that the presence of preoperative anxiety, sevoflurane-based anesthesia, younger age, emergence delirium, and a lower birth order were found to be risk factors for the development of postoperative maladaptive behavior.
Specific anesthetic agents affecting postoperative pain
Although the anesthesiologist has the ultimate decision regarding choice of anesthetic agents, it is important for the surgeon to be familiar with the medications used, especially in regard to their possible effects on postoperative pain control. General anesthesia is usually administered with various combinations of drugs, including ketamine, propofol, barbiturates, benzodiazepines, opioids, dexmedetomidine, and inhaled agents. A more detailed discussion of the drugs known to have an effect on analgesia perioperatively follows.
Ketamine
Ketamine is a phencyclidine-derived agent that blocks NMDA receptors, providing a dissociative anesthesia that combines sedation, analgesia, and amnesia. It has become a popular means of sedation in the pediatric population and has been shown to be both safe and efficacious in more than 11,000 pediatric subjects. Common side effects include dose-dependent respiratory depression, emergence reactions, nausea, emesis, and clumsiness. Meta-analysis of 35 randomized blinded controlled studies demonstrated use of ketamine intraoperatively decreases pain intensity and analgesic requirement in the postoperative care unit (PACU) but failed to have any further effect on pain intensity and opioid requirement more than 6 hours postoperatively. Prolonged low-dose intravenous infusion of ketamine failed to demonstrate any difference in postoperative opioid use, pain scores, adverse effects of opioids, or length of hospital stay compared with placebo.
Alpha-2 agonists
Clonidine acts as an alpha-2 receptor stimulator, likely working on receptors centrally in the spine and locus coerulus. It has been shown to prolong time to first rescue analgesia postoperatively, enhance efficacy of postoperative sedation and analgesia, and reduce propofol requirements for intraoperative sedation. When used in conjunction with bupivacaine intrathecally, clonidine prolongs the duration of both sensory and motor blocks. Transdermal clonidine has also been used in multimodal strategies (see later discussion).
Dexmedetomidine is another alpha-2 receptor agonist that acts centrally on the brainstem by inhibiting release of norepinephrine. It has become a common means of sedation in the intensive care unit but recently has been used as a procedural anesthetic agent as well. Patient’s receiving dexmedetomidine require 50% less morphine compared with placebo, and it provides cooperative sedation and easy transition from sleep to waking, important factors in the pediatric patient to minimize psychological trauma from undergoing surgery. It is also among the only drugs used for sedation and anesthesia that does not cause neurodegeneration in animal models, which may increase its popularity given the new FDA warning.
Propofol
Propofol is a short-acting intravenous agent commonly used for induction and maintenance of anesthesia in the pediatric population. The drug acts on the GABA receptors, causing central nervous system depression, although its mechanism is not completely understood. Propofol is known to cause pain at the intravenous site during administration, therefore patients are often premedicated with local anesthetic, opioids, or ketamine. Adverse effects also include postoperative nausea and vomiting, and emergence delirium and apnea, although these are less common with propofol use than with inhaled agents. Propofol’s effect on analgesia in the pediatric and adult population is still controversial, with many conflicting results; thus further study is warranted.
Inhaled agents
Inhaled agents, such as sevoflurane and desflurane, are also commonly used in the pediatric population for induction and maintenance of anesthesia. They alter activity of neuronal ion channels, including nicotinic acetylcholine, GABA, and glutamate receptors, providing rapid induction and rapid emergence. Malignant hyperthermia, dose-dependent hypotension, nausea vomiting, and apnea are among the inhaled agents’ adverse effects.
Emergence agitation or delirium is another dreaded reaction common in the pediatric patient, especially after the use of inhaled agents. It is a rare motor agitation state that can occur shortly after emergence from anesthesia that has been associated with significant preoperative anxiety. During this state, the patient is confused, unaware of his or her surroundings, inconsolable, agitated, kicking, holding their head back, and has an absence of eye contact. Typically, treatment is supportive unless the patient is at risk for self-injury. If the symptoms are severe, medical intervention may be required with intravenous sedatives, opioids, or propofol. Pharmacologic interventions that have been found to aid in the prevention of emergence delirium include administration of ketamine, propofol (continuously or at the completion of surgery), and intraoperative fentanyl.
Intrathecal Injection
Spinal injections can be performed after induction of general anesthesia before incision or injected directly into the dura during spinal fusion. The injection can provide up to 24 hours of pain control following lower extremity surgery. Patients can experience all the adverse effects of intravenous morphine use: nausea, pruritus, urinary retention, and most notably respiratory depression, which can occur up to 24 hours after injection. The hydrophilic nature of morphine and hydromorphone allow them to migrate cephalad and act on the brainstem, increasing risk of dose-dependent adverse reactions. Respiratory monitoring and avoidance of respiratory depressants are recommended. Intrathecal injection with opioids may also reduce blood transfusion requirements, by inducing hypotension during posterior spinal fusion (PSF). In a study of 187 children using low-dose intrathecal morphine (ITM) during a variety of procedures, 81% did not require opioid rescue medications in the first 8 hours postoperatively and 37% had sustained pain relief 24 hours after intrathecal injection. The ideal dosing is unclear but in a study comparing a low dose (5 mcg/kg) with a high dose (15 mcg/kg) and a control group; the low-dose group demonstrated less blood loss, sufficient analgesia, and side effects similar to the control group ( Table 1 ).
| Study | Route | Medication or Dosing |
|---|---|---|
| Erdogan et al, 2016 a | Epidural | Patient-controlled: morphine 0.2 mg/mL, 0.25 mL/kg morphine bolus and 0.25 mL/kg morphine on demand and no infusion Continuous infusion: morphine 0.2 mg/mL, morphine loading set 0.1 mL/kg, followed by a 0.05 mL/kg/h continuous infusion of morphine, and a 0.025 mL/kg bolus dose of morphine |
| Sucato et al, 2005 | Epidural | Hydromorphone 20 mcg/mL and 0.1% bupivacaine at 0.1–0.2 mL/kg/h |
| Van Boerum et al, 2000 | Epidural | Bupivacaine 0.1% with morphine 0.05 mg/kg/h, additional doses of 0.03 mg/kg/h given by patient-controlled demand |
| Hong et al, 2017 b | Epidural or intrathecal | Epidural: bolus with hydromorphone 5 mcg/kg (max 200 mcg) and 1 mcg/kg fentanyl (max 50 mcg), followed by a continuous infusion of 40–60 mcg/h, and patient-controlled bolus doses of 5 mcg Intrathecal: morphine 12 mcg/kg (max 1000 mcg) |
| Milbrandt et al, 2009 c | Epidural or intrathecal | Epidural: hydromorphone 10–20 mcg/kg followed by a continuous infusion of hydromorphone 20 mcg/mL bupivacaine 0.1% at an initial rate of 0.1–0.2 mL/kg/h Intrathecal: morphine extended-release 7 mcg/kg and PCA |
| Ravish et al, 2012 d | Epidural and intrathecal | Morphine 3–5 mcg/kg followed by ropivacaine 0.1% with or without fentanyl 2 mcg/mL at anesthesia pain service discretion |
| Cao et al, 2011 e | Intrathecal | Bupivacaine: 0.5% bupivacaine 0.2–0.4 mg/kg Intrathecal clonidine: 0.5% bupivacaine 0.2–0.4 mg/kg and 1 mcg/kg clonidine IT Intravenous clonidine: 0.5% bupivacaine 0.2–0.4 mg/kg and 1 mcg/kg clonidine IV |
| Eschertzhuber et al, 2008 f | Intrathecal | Low dose: morphine 5 mcg/kg and 1 mcg/kg sufentanil High dose: morphine 15 mcg/kg and 1 mcg/kg sufentanil |
| Gall et al, 2001 | Intrathecal | Morphine 2 mcg/kg or Morphine 5 mcg/kg and morphine PCA |
| Ganesh et al, 2007 | Intrathecal | Morphine 4–5 mcg/kg |
| Goodarzi, 1998 | Intrathecal | Morphine 20 mcg/kg and 50 mcg sufentanil |
a Equivalent results in both groups with lower morphine consumption in PCA group.
b IT morphine group transitioned to oral pain medications sooner with shorter length of stay.
c IT provided equal pain relief for first 24 hours with less adverse effects.
d Lower pain scores compared with PCA.
e IT clonidine prolonged sensory and motor blocks; both IT and IV clonidine reduced postoperative pain.
Epidural Therapy
Local anesthetics and/or opioids can be injected into the epidural space at a caudal or lumbar level (see Table 1 ). These are good analgesic options for thoracic, pelvic, and lower extremity surgery. The use of epidural analgesia carries the risk for postoperative nausea, dizziness, hypotension, motor weakness, respiratory depression, and development of an epidural hematoma. Respiratory depression has been demonstrated in 10% to 12% of cases ; although in a recent study by Ravish and colleagues, lower rates of respiratory depression (7.8%) were seen with lower dose infusions (3–5 mcg/kg of 0.1% ropivacaine ± fentanyl) and addition of ITM. One of the major side effects with use of local anesthetic is motor blockade, making it inappropriate for use in patients with postoperative concerns for neurologic compromise or compartment syndrome.
Epidural therapy can be given as a single injection or continuous infusion. Continuous infusion can be used for inpatient procedures and remains in place for several days, allowing alteration of volume and concentration of infusion for optimal pain control. A pain consultation service ideally monitors patients frequently for adequacy of pain control and adverse reactions. There are concerns regarding catheter placement and leakage, which can affect efficacy and adverse reactions. Turner and colleagues examined catheter placement in subjects undergoing PSFs by injecting 14 subjects with iohexol contrast in the catheter before obtaining a postoperative chest radiograph. Nine subjects had satisfactory analgesia postoperatively, 7 of which had contrast medium seen in the spinal canal on radiograph. In all 5 subjects (36%) who had inadequate analgesia, there was no contrast visualized within the spinal canal or paravertebral gutter space. Patient-controlled intermittent bolus of epidural infusion is another way to maximize efficacy and minimize adverse reactions. In a recent prospective randomized, double-blind study, there was lower cumulative morphine consumption and less adverse reactions in the patient-controlled group, with no difference in pain scores compared with continuous infusion. The addition of baclofen to epidural infusion has not been proven to provide any analgesic benefit.
Peripheral Nerve Blocks
From 1996 to 2006, the number of orthopedic procedures being performed with a combination of peripheral nerve block and general anesthesia increased from 1.2% to 43%. Ultrasound-guided techniques have expanded their use and allowed for smaller amounts of anesthetic, limiting risk of toxicity. There are several benefits to nerve blocks, including decreased opioid requirements, earlier postoperative return of gastrointestinal function, and attenuation of the stress response caused by surgical procedures. Targeting the innervation of the surgical site allows less use of opioids and avoidance of their systemic effects, making nerve blocks an integral tool for pediatric procedures.
Studies have shown nerve blocks to be safe without lasting neurologic injuries and overall incidence of complications of 0.9 in 1000 regional blocks. Most complications involve failure to place an effective block or inadequate analgesia postoperatively. Serious complications, such as hematoma formation, peripheral nerve injury, and local anesthetic toxicity, are rare. Local anesthetics, however, carry a risk of cardiotoxicity secondary to binding myocardial sodium channels, making appropriate dosing crucial. The precise placement of blocks in children is often done with sedation or after induction of general anesthesia, both of which are proven to be safe techniques.
The smaller caliber of peripheral nerves in children makes them more susceptible to the pharmacologic actions of anesthetic drugs. Blocks can be performed with either a single injection or catheter infusion. Anghelescu and colleagues retrospectively reviewed 179 cases of peripheral nerve block catheters and found only 2 cases of infection, both associated with femoral catheters and catheters in place more than 9 days; therefore, catheter infusion is a good option for procedures with greater expected postoperative pain duration.
Regional considerations
There are numerous regional anesthetic techniques that can be used to help alleviate postoperative pain. It is important for the surgeon to be familiar with the anatomy and pharmacology of the anesthetics to effectively administer the block and/or discuss the appropriate block to be used for a procedure with the anesthesiologist.
Upper extremity
The axillary or brachial plexus block is a safe and effective means of anesthesia and analgesia for procedures below the elbow. The target of the block is the axillary sheath containing the axillary artery and vein, and the radial, median, and ulnar nerves. The musculocutaneous nerve runs outside the sheath and may not be affected by the block, which accounts for the unreliability of this block above the elbow. In addition to the above-mentioned complications, Horner syndrome has been reported, although these complications are rare with axillary blocks.
Lower extremity
The lower extremity may require multiple nerve blocks to anesthetize all areas affected by the procedure. The femoral nerve innervates the dermatomes over the anterior thigh and knee, as well as most of the femur. The knee joint receives innervation from articular branches of the femoral, common peroneal, and saphenous nerves. Femoral nerve blocks are indicated for surgery on the anterior thigh, knee arthroscopy, and anterior cruciate ligament (ACL) reconstruction. The adductor block is growing in popularity because it has less risk of motor block to the adductor and quadriceps muscle, and allows for early mobilization. It is used for procedures on the distal anterior thigh and knee arthroscopy. The saphenous branch of the femoral nerve is anesthetized with this technique. The sciatic nerve block is a good option for knee surgeries as well; especially those involving the posterior thigh, including ACL repairs with hamstring autograft.
Local Anesthesia
The hematoma block is often used in outpatient fracture management and has been shown to be an effective means of perioperative analgesia. Herrera and colleagues retrospectively studied pain control in subjects who received hematoma block with 0.25% bupivacaine after elastic nailing of femoral fractures. The time to first opioid administration was significantly greater in the hematoma group compared with no block. Bulut and colleagues performed a double-blind randomized controlled trial with 20 subjects who received 0.5% bupivacaine via subfascial catheters postoperatively and a control group infused with normal saline. There was a substantial decrease in postoperative pain in the local anesthetic group at 4 to 48 hours. The use of local anesthetic infusion catheters has also been examined in lower extremity surgery for cerebral palsy subjects in a prospective randomized controlled trial. A catheter was tunneled into the incision site and delivered using an infusion device, which provided a steady infusion of anesthetic for 48 hours. Parents reported significantly lower pain scores in the infusion group.
The authors’ limited experience with continuous infusion of local anesthetic is that pain control is improved when done in conjunction with opioids; extravasation of the anesthetic may cause skin irritation or chemical burns.
Postoperative considerations
Postoperative pain control has been the focus of recent literature in the pediatric population. Adequate pain control in this population can be difficult due to inadequacies assessing pain, but there are numerous tools that can help make the postoperative experience less traumatic.
Nonopioid Analgesia
Acetaminophen
Acetaminophen is a commonly used medication for pain control in children. It is a weak inhibitor of cyclooxygenase-1 and cyclooxygenase-2 in peripheral tissues, accounting for its lack of anti-inflammatory effect and stronger analgesic and antipyretic properties. Acetaminophen is often preferentially used over ibuprofen in pediatric patients because of the lower risk of side effects, especially Reye syndrome. Acetaminophen’s major adverse effects include kidney and/or liver toxicity, especially in patients with prior kidney or liver disease. There has been some concern regarding its link to increased asthma exacerbations but a recent study of 300 children with mild persistent asthma demonstrated no difference in asthma control or incidence of asthma exacerbations compared with ibuprofen. Acetaminophen can be administered orally, rectally or intravenously, and is safe at all ages with weight-based dosing (15 mg/kg/dose) ( Table 2 ). Intravenous acetaminophen has become a popular option for perioperative use. It has been shown to improve early pain scores but has no effect on opioid consumption postoperatively in pediatric and adolescent spine patients.
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