Perioperative Pain

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Perioperative pain management should address the preoperative, intraoperative, and postoperative phases for comprehensive intervention and the best attempt to limit the unpleasantness of the surgical pain experience. The management of postoperative pain begins in the preoperative period. The degree of postoperative pain is somewhat influenced by the level of preoperative anticipatory distress (55). Open discussion of expectations of the family and child for the postoperative period should be encouraged. Preoperative visits allow the family and child to meet the anesthesiologist, preview the perioperative care suite, and address anxiety concerning anesthesia and surgery. Child life specialists may conduct tours of the recovery and operative areas. Child life specialists also perform medical role play using dolls, puppets, and games. Thus, the use of child life specialists provides a nonthreatening avenue for patient self-expression (56).

Preoperative preparation helps both the child and the family deal with illness, injury, and treatment.

The concept of wind-up was initially presented by Crile and Katz in 1993. The noxious act of surgery causes injury to C fibers and a heightened response to subsequent stimuli and occurs secondary to central sensitization at the wide dynamic-range neurons of Rexed lamina V (57). McQuay performed a systematic review of the literature and found that intrathecal opioid and epidural local anesthetics administered prior to incision decrease pain scores and need for intravenous opioid for the initial 6 hours postoperatively (58). The evidence to date suggests that wound infiltration before surgical incision does not produce preemptive analgesia in muscle-splitting procedures (59).

Theoretically, preemptive prophylactic intervention should attenuate the occurrence of the wind-up phenomenon. There is conflicting data regarding the efficacy of any one drug class or route of analgesic delivery. The existence of wind-up in the pediatric population has been challenged; thus, the efficacy of preemptive analgesia in children has been questioned (60).

NSAIDs may contribute to preemptive analgesia at two locales. NSAIDs act peripherally as anti-inflammatory agents and may possess a central effect on spinal activity mediated by N-methyl-D-aspartate (61). Timing appears important to the efficacy of preemptive analgesia. Intravenous ketoprofen given 30 minutes prior to incision was effective for breast surgery and reduced opioid consumption by more than 40% for up to10 hours in the immediate postoperative period (61).

Oral premedicants given in the immediate preoperative period have decreased postoperative analgesic requirements. Oral clonidine at 5 Mg/kg has the ability to lower Visual Analog Scale (VAS) scores and intravenous morphine consumption for orthopedic procedures significantly (62). Oral clonidine was effective in lowering VAS and opioid requirements in abdominal procedures for which postoperative pain was managed by neuraxial analgesia but not by parenteral opioids (63). Midazolam, a water-soluble imidazo-benzodiazepine, has no analgesic properties. Yet, when given preoperatively as a sedative, midazolam causes a decrease in postoperative anxiety and analgesic requirements (64).

Intraoperative pain management most often involves general anesthesia and intravenous opioids. Pediatric regional techniques are often performed after the induction of general anesthesia, in contradistinction to awake techniques in adults. Utilization of regional techniques as the primary anesthetic has been reported by Puncuh et al. (65). Children 6 months to 14 years underwent neuraxial anesthesia; however, sedation was required. General anesthesia may cause postoperative apnea in neonates and infants who have preexisting central or peripheral tendencies for apnea. In these cases, local anesthetics with or without epinephrine are used for intrathecal anesthesia in an attempt to avoid respiratory embarrassment.

Adequate pain control in the immediate postoperative period should be obtained as swiftly as possible to decrease postoperative anxiety. Consistent and repeated pain assessment and intervention must be performed in a timely fashion to ensure effective pain relief. Pain assessment should take into account the degree of pain at rest (static pain) and on activity (dynamic pain) to address the changeable aspects of the pain experience.

Breakthrough pain was first defined in 1989 by Portenoy and Hagen in the analysis of cancer pain (66). Today, this term is also applied in cases of nonma-lignant pain (67). The IASP defines breakthrough pain as intermittent exacerbations of pain that can occur spontaneously or in relation to specific activity and pain that increases above the level of pain addressed by the ongoing analgesic; the definition includes incident pain and end-of-dose failure (68). Analgesic boluses can be given a few minutes prior to planned activities in an attempt to lessen incident pain. Breakthrough analgesic doses should be titrated independently from the baseline analgesic. Breakthrough pain must be treated with as-needed doses of analgesics in addition to the usual schedule of administration.

9.1.1. Trauma and Burn-Related Pain

According to a US study, the overall incidence of injuries for children 0-19 years old is 2239 per 10,000. The incidence of injuries from burns is relatively low but of greater severity (69). Approximately 40,000 children are hospitalized annually secondary to burn injuries in the United States. Satisfactory pain relief for these children must be considered while other resuscitative measures are undertaken. A survey by Martinez-Herz et al. of 79 burn centers in North America found that analgesics were used less often for control of pain induced by wound care in pediatric patients than adult cases. Of responders, 17% did not use narcotic analgesia in children, and 8% did not recommend analgesia in any form (70).

Judicious administration of opioids is indicated because oversedation may result when standard dosing is used in the face of a reduced volume of distribution. Initially, release of catecholamines after burn injury preserves the blood pressure and heart rate despite the decrease in cardiac output. Subsequently, massive fluid shifts caused by the loss of endothelial integrity result in significant hypo-volemia and hemoconcentration. The decline in cardiac output is secondary to the fluid shifts and reduction in venous return. Further decrease in cardiac output occurs despite adequate fluid resuscitation; the decreased output is a result of direct myocardial depression from interleukins, tumor necrosis factor, and oxygen-free radicals (71).

By classification, full-thickness burns involve the destruction of nerve endings at the site of the injury and result in lack of sensation. Contiguous areas are sensitized and painful. Concurrently, in the region of full-thickness burn, some nerve endings are spared, and pain can still be generated (72). Other pain generators include nerve regeneration with associated paresthesia and neuroma formation and nerve entrapment by scar or contractures. The phenomenon of hyperalgesia associated with partial full-thickness thermal injury is characterized by a decrease in the pain threshold and the development of spontaneous pain. This is likely to be mediated by increased sensitization of the A-5 fiber afferents at the site of burn injury (73).

After the burn insult, the activated nerve terminals release the neuropeptides substance P and calcitonin gene-related peptide, which results in vasodilatation. Injured cells also release inflammatory mediators that cause nociceptor activation, which subsequently causes peripheral sensitization in the immediate region of injury (primary hyperalgesia) (74).

There are two types of acute burn-related pain. Procedural pain is associated with events involving wound care, such as dressing changes and whirlpool baths. Background pain refers to the unpleasant sensation occurring at rest. Underestimation of this latter type of pain could cause the child to suffer more from anxiety and may increase pain intensity experienced during subsequent procedures (75).

Regular assessment of pain is key to managing burn pain. Most burn centers in North America use methods like behavioral observation, monitoring of physical parameters, and parental reports to measure the level of pain. VAS and verbal assessment provide easy grading of pain severity (76). The child's perceptions, level of cognition, and coping behaviors should be regularly assessed and addressed during this period. Accurate measurement of their discomfort is imperative for the development of a proper strategic treatment plan (77).

Aggressive pain management with opioids has been shown to attenuate the development of posttraumatic stress disorder (19). However, analgesic requirements may change after the first 24 hours of burn care because of decreased protein levels and increased bioavailability of free drugs. Because of the shifts in drug availability and physiological instability, administration of opioids requires close observation and frequent pain assessment (77). The treatment plan should address background pain and provide additional dosing for the intense, brief pain associated with procedures. A comprehensive long-term plan for possible chronic pain should be developed before discharge from the hospital. Acute Medical Pain

Many children who require hospital admission first present to the emergency department. The administration of opioid analgesics in patients with acute abdominal pain is frequently limited because of fear of masking symptoms. A survey of 700 board certified or board-eligible pediatric surgeons and emergency medicine physicians revealed that surgeons with more than 10 years of experience were less likely to give analgesics than emergency medicine physicians of comparable experience. The rationale for administering analgesics was based on the literature by 3% of surgeons and 23% of emergency physicians. The majority of emergency physicians who withheld analgesics (64 of 74) stated that disapproval by the surgeon was their main reason for withholding analgesia (78). The use of sonography and computed tomography scan can speed diagnosis such that pain intervention can be readily given without fear of masking symptoms. The many causes of acute abdominal pain are beyond the scope of this chapter. Opioids should be used with caution, however, because diagnostic radiology is not universally utilized, and current evidence is limited.

Johnston et al. (79) conducted a survey of pain intensity on admission and discharge from the emergency room. Highest pain intensities were caused by musculoskeletal pain in adults, but children experienced headaches as the worst pain. In addition, children who were present with only their mothers had less improvement than those who were accompanied by fathers only or both parents. Chronic and Recurrent Pain

Hospital admission for new-onset headache requires work-up for organic disease. Occipital neuralgia with pain over the distribution of the lesser occipital nerve is common in children with achondroplasia secondary to stenosis of the foramen magnum (80).

Children with chronic pain syndromes are often admitted for acute or abortive treatment of unbearable pain, such as in intractable migraine. These acute pain episodes in the presence of chronic pain syndromes require knowledge of the chronic pain philosophies and treatment trends, as well as the armamentarium to address the patient in extreme pain. Abortive migraine treatment includes oral preparations of NSAIDs, caffeine, and isometheptene. Nausea and vomiting may require administration of intravenous antiemetics. The use of opioids or bultabital compounds is acceptable as second-line therapy, but the trend is toward using the triptan preparations (80) instead of narcotics. The use of ergotamines and steroids is reserved for refractory cases.

Cystic fibrosis can be associated with headaches and facial pain caused by sinusitis or coughing paroxysms (81,82). Migraine and tension headaches are the most common types of pediatric headaches. By age 15 years, 5.3% of children have migraines, 15.7% have frequent nonmigrainous headaches, and 54% have infrequent nonmigrainous headaches. More than 82% of children by late adolescence experienced some type of headache (83). Sickle Cell-Related Pain

The vaso-occlusive crisis (VOC) of sickle cell disease is heralded by pain that may be localized or diffuse (84,85). Sickle cell disease was first described in 1910 by Herrick (84). This was the first molecular disease defined and was described by Linus Pauling (85). It was Sydenstricker who first used the word crisis to describe the abdominal pains and jaundice that occurs during the VOC event. Ingram in 1956 examined the electrophoretic properties of normal and sickled hemoglobin and discovered the substitution of glutamic acid for valine at the sixth position of the hemoglobin chain, which led to a change in ionic charge from neutral to phobic. Deoxygenation leads to crystal formation, tactoids, and stacking of red blood cells, such that sludging in the microvascu-lature occurs and results in ischemia and organ infarction. Hemolysis results in jaundice (86,87).

More than 2 million African Americans and Hispanic Americans are affected by sickle cell disease. Other peoples affected include those of Arab, Indian, and Asiatic descent or of descent from wherever there was malarial spread from equatorial Africa. Generally, patients present with abdominal pain, back pain, or extremity pain, especially of the legs. Any one or a combination of these regions may be affected during a VOC (88). Shapiro and coworkers in the 1990s described the event as a painful episode to deemphasize the emotional component in an effort to improve coping (89). Despite an attempt to control the behavioral facet by deemphasizing the anxiety, it has been shown that many patients objectively test positive for anxiety and a sense of helplessness.

Most patients with sickle cell disease have few crises that require hospital-ization. Approximately only one-fourth of patients with sickle cell disease have frequent crises. Many VOC episodes are handled at home or in day hospitals, which supports the fact that early, effective intervention can curtail most uncomplicated crises (90). However, when a patient fails at-home care, strong analgesics are indicated. Of patients who present to the emergency departments, 50% do so for painful events. Approximately 30% present with febrile events, and 20% come in for combined pain and fever (91). Patients often require large doses of opioids but obtain minimal relief. In addition, pain scores are not inversely related to the amount of opioid administration (92). Because opioids do not have a ceiling effect on analgesia, increased doses are given in an effort to decimate the pain. Often, the sedation from the opioids can be severe, resulting in inadequate ventilation, hypoxia, and worsening of the crisis pathophysiology. Acute chest syndrome, a complicated VOC presentation, has been associated with high-dose exposure to systemic opioids (93). Acute Cancer-Related Pain

A review by Docherty found that children and adolescents with cancer focused primarily on symptoms of pain and fatigue (94). Pain caused by disease occurs in fewer than 50% of cases at the time of diagnosis in pediatric oncological disease. However, children with cancer experience multiple types of pain during their course of care. Procedure-related pain because of venipunctures, bone marrow biopsies, and aspirates or lumbar punctures is common. Surgical causes of procedure-related pain include resection of solid tumors and staged procedures requiring repeated operations and placement of central intravascular access ports with subsequent removal. Some chemotherapy regimens (e.g., granulocyte-colony stimulating factor and vinca alkaloids) provoke neuropathic pain at a later time (95). Organic platinum compounds such as oxaliplatin can cause pain at the onset of infusion (96).

Oral mucositis results from the cytotoxic effects of chemotherapy and radiation therapy. Apoptosis of the oral epithelium occurs, and overgrowth of bacteria, fungi, and viruses in combination with the release of cytokines results in oral ulcers and a characteristic burning pain (97). Resolution of the symptoms is temporally related to the recovery of the neutrophil count from the cytotoxic nadir (98).

Wolfe and colleagues (99) found that 89% of parents felt that their children experienced "a lot" or "a great deal" from at least one symptom at the end-of-life. Pain was the most common symptom, yet only 27% of families found symptom-specific interventions to be successful in managing the pain. Parental distress can be great and is inversely proportional to the time elapsed after diagnosis (100).

Death distress is usually more profound in young patients and appears to be inversely correlated to spiritual "groundedness" (101). Differing spiritual beliefs between the caregiver and the adolescent patient can be a cause of worsening distress. Health professionals are encouraged to be familiar and nonjudgmental of spiritual or religious beliefs of their patients (102).

The principles of cancer pain management are now well established. The Cancer Pain Relief Program of the World Health Organization developed an analgesic ladder for the management of pain of increasing intensity (103). For mild pain, the recommendations start with NSAIDs. This drug class must be used with caution in those patients receiving steroids as part of their oncological management. NSAIDs are also contraindicated for patients who have renal insufficiency, intravascular volume depletion as seen with intractable vomiting, congestive heart failure, or peptic ulcer disease. A ceiling effect may occur, and increasing doses will lead to side effects without additional benefits. Unlike NSAIDs, opioids have no ceiling effect.

In the World Health Organization ladder, moderate pain is treated with traditionally weak opioids. Agents, such as codeine, oxycodone, hydrocodone, and meperidine, are used. Mixed agonists-antagonists are incorrectly considered protective against respiratory depression but may have greater side effects. These mixed agonists also have a ceiling effect. For severe pain, traditionally strong opioids are used. Unless contraindicated, morphine is generally considered the agent of choice. Other strong opioids include methadone, hydromorphone, levorphanol, and oxymorphone (103).

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