Rett's syndrome is a progressive and severely disabling neuromotor disorder that affects women. The classic features of this syndrome include dementia, severe autism, axial hypotonia, spasticity, growth retardation, microcephaly, seizures, muscle wasting, and scoliosis . These patients may show a characteristic abnormal respiratory pattern consisting of episodes of tachypnea and irregular respiration, intermixed with apnea, observed only during wakefulness . These respiratory manifestations might confound the respiratory side effects of opioid analgesics. In addition, these patients may also have a high pain threshold , which may be due to reduced sensitivity to pain resulting from increased beta-endorphin concentrations in the cerebrospinal fluid or impaired abnormal neural transmission and pain processing [4,5]. We describe the use of epidural analgesia after scoliosis surgery in a patient with Rett's syndrome.
A 14-yr-old girl weighing 27 kg was scheduled to undergo a T3-L5 spine stabilization procedure. She had neuromuscular scoliosis secondary to Rett's syndrome, which was diagnosed at the age of 5 yr. Except for epilepsy and an occasionally abnormal respiratory pattern (i.e., changes in respiratory rate), her history, physical examination, and laboratory tests were unremarkable. Previous anesthesia for hip surgery, strabismus correction, and gastric tube placement had been uneventful. Medications at the time of surgery were felbamate and valproic acid.
The intraoperative course was uneventful. At the conclusion of the surgery, but before the closure of the surgical incision, the surgeon placed an epidural catheter (20 gauge, multiple orifices) under direct vision approximately 4 cm into the epidural space at the T10-11 interspace. After the skin was closed, an infusion of bupivacaine 0.1% and hydromorphone (20 [micro sign]g/mL) was started at a rate of 4 mL/h. The patient was transferred to the postanesthesia care unit (PACU), and the trachea was extubated after 15 mins. The patient remained stable in the PACU and was transferred to the intensive care step-down unit with supplemental oxygen. Monitoring included electrocardiograph, hemoglobin oxygen saturation (SaO2), respiratory rate, and blood pressure. The degree of pain was assessed by using a behavioral pain score (graded using facial expression, crying, and movements) because of the patient's lack of communication. In addition, sedation was graded by using a 5-point sedation scale (i.e., wide awake, drowsy, dosing intermittently, asleep or arousable, and unarousable).
On the operative day and the first postoperative day, the patient showed no obvious signs of pain with the epidural infusion maintained at 4 mL/h. A sensory level was not obtainable because of the patient's baseline mental status. On the second postoperative day, the SaO2 decreased to 90%, and the respiratory rate decreased to 6-8 breaths/min. The patient was noted to be more sedated. Due to the changes in the SaO2 and the respiratory rate, the epidural infusion was discontinued. When the patient showed signs of pain, 10 mL of acetaminophen (120 mg/5 mL) with codeine (12 mg/5 mL) elixir was administered through the gastric tube every 4 h.
On the third postoperative day, the respiratory rate decreased to 6-8 breaths/min, and the SaO2 decreased <90%. Naloxone 1 [micro sign]g/kg was administered IV because the respiratory rate and the SaO2 remained low. There were no clinical indications of increased intensity of pain after the administration of naloxone. The respiratory rate and SaO2 improved after a second bolus dose of naloxone, after which a naloxone infusion (10 [micro sign]g [middle dot] kg-1 [middle dot] h-1) was started. In addition, the oral analgesic medications were discontinued. The breathing pattern remained normal during the remainder of the postoperative course. The naloxone infusion was discontinued on the fourth postoperative day, after which the recovery was unremarkable. The patient was discharged home on the sixth postoperative day.
Maguire and Bachman  reported anesthetic implications in a patient with Rett's syndrome undergoing scoliosis surgery. However, they did not discuss postoperative pain management in this patient population. Dearlove and Walker  reported three cases with Rett's syndrome undergoing scoliosis surgery, after which the postoperative course was complicated by pulmonary infections and the need for ventilation for 48-72 hours postoperatively. These authors used an IV morphine infusion (with an initial rate of 25 [micro sign]g [middle dot] kg-1 [middle dot] h-1) and an intrapleural bupivacaine infusion to provide postoperative pain relief.
Although epidural analgesia has been reported to provide superior postoperative pain relief [8,9], placement of an epidural catheter after spine surgery raises the concerns of an increased rate of wound infection and systemic absorption of analgesic medications. Two studies have reported the safety and efficacy of epidural analgesia in patients undergoing spine surgery [10,11]. At the Texas Scottish Rite Hospital for Children at Dallas, approximately 550 children undergoing spine surgery have received epidural analgesia for postoperative pain management.
We used an infusion of bupivacaine and hydromorphone because combinations of local anesthetics and opioid analgesics are superior to either drug alone . Hydromorphone was used because, when many dermatomes are involved, hydrophilic opioids are usually a better choice . Hydromorphone is 3-5 times as potent as morphine when administered epidurally, and it can also be used when cephalad spread of the epidural opioid is required .
One of the most important concerns with the use of epidural opioids is the risk of respiratory depression. However, this can be reduced by avoiding systemic opioids and sedatives and by restricting doses of epidural opioids (e.g., morphine <0.05 mg/kg every 6-12 hours) . The incidence of respiratory depression with epidural analgesia at the Texas Scottish Rite Hospital for Children at Dallas was 2.1% (12 of 550 patients), with only two patients requiring treatment with naloxone. The other concern is the possibility of systemic absorption of local anesthetic resulting in toxic concentrations. It is recommended that the initial epidural bolus of bupivacaine (caudal or lumbar) not exceed 2-2.5 mg/kg and that subsequent infusions of bupivacaine be maintained at no more than 0.4 mg [middle dot] kg-1 [middle dot] h-1 .
The episode of respiratory depression observed in our patient on Postoperative Day 2 may be due to epidurally administered opioid analgesics or breathing impairment associated with Rett's syndrome. The episode on Day 3, however, 12 hours after discontinuation of the epidural infusion and the resumption of normal respiratory function, is unlikely to have been related to epidural medications and, instead, may be related to either the respiratory depressant effects of codeine or to an underlying respiratory impairment.
Breathing impairment in Rett's syndrome is characterized by an inability to maintain normal respiratory patterns during wakefulness, and it represents functional disturbances of the behavioral control of breathing . Several hypotheses have been proposed for the pathophysiology of this respiratory impairment, including an increase in beta-endorphin concentrations [4,5]. The effectiveness of naloxone in maintaining our patient's respiratory rate beyond the duration of the opioids administered either epidurally or orally, without increasing the intensity of pain, may be related to the increased beta-endorphin concentrations in this patient population . It is possible that the use of local anesthetic infusion alone and avoidance of opioids could have prevented the confusion in diagnosis.
In summary, the respiratory impairment associated with Rett's syndrome may confound the respiratory side effects associated with epidurally administered opioids. Therefore, the infusion of low concentrations of local anesthetics alone and avoidance of epidural opioids may be advisable in this patient population. Finally, postoperative respiratory impairment in these patients may be treated with a small-dose naloxone infusion without affecting the intensity of pain.
We thank Dr. Fay Safavi, Director of Anesthesiology and Pain Management, Scottish Rite Hospital for Children at Dallas, and Dr. John Pennant, Associate Professor of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, for reviewing the manuscript.
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