Elliot J. Krane

Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update

The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel alpha(2)-delta ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.

Subclinical Brain Swelling in Children during Treatment of Diabetic Ketoacidosis

Clinically apparent cerebral edema is a rare and often fatal complication of diabetic ketoacidosis. To determine whether subclinical brain swelling occurs more commonly, we obtained cranial CT scans in six children with diabetic ketoacidosis treated with fluid resuscitation and continuous low-dose insulin therapy. Control scans were obtained before hospital discharge. Compared with the scans during convalescence, the early scans of all six children showed a narrowing of the brains ventricular system, compatible with brain swelling. Average changes in diameter were 1.3 +/- 0.1 mm for the third ventricle and 3.7 +/- 0.8 mm for the lateral ventricles (P less than 0.01). In addition, a narrowing of the subarachnoid spaces was subjectively noted during a blind reading of the early scans. Although no single scan was overtly indicative of cerebral edema, the data suggest that subclinical brain swelling may be a common occurrence during treatment of diabetic ketoacidosis in children. Sequential CT scans of the brain may provide a means of evaluating modifications of standard therapy aimed at preventing cerebral edema.

Pediatric Regional Anesthesia Network (PRAN): a multi-institutional study of the use and incidence of complications of pediatric regional anesthesia.

BACKGROUND: Regional anesthesia is increasingly used in pediatric patients to provide postoperative analgesia and to supplement intraoperative anesthesia. The Pediatric Regional Anesthesia Network was formed to obtain highly audited data on practice patterns and complications and to facilitate collaborative research in regional anesthetic techniques in infants and children. METHODS: We constructed a centralized database to collect detailed prospective data on all regional anesthetics performed by anesthesiologists at the participating centers. Data were uploaded via a secure Internet connection to a central server. Data were rigorously audited for accuracy and errors were corrected. All anesthetic records were scrutinized to ensure that every block that was performed was captured in the database. Intraoperative and postoperative complications were tracked until their resolution. Blocks were categorized by type and as single-injection or catheter (continuous) blocks. RESULTS: A total of 14,917 regional blocks, performed on 13,725 patients, were accrued from April 1, 2007 through March 31, 2010. There were no deaths or complications with sequelae lasting >3 months (95% CI 0–2:10,000). Single-injection blocks had fewer adverse events than continuous blocks, although the most frequent events (33% of all events) in the latter group were catheter-related problems. Ninety-five percent of blocks were placed while patients were under general anesthesia. Single-injection caudal blocks were the most frequently performed (40%), but peripheral nerve blocks were also frequently used (35%), possibly driven by the widespread use of ultrasound (83% of upper extremity and 69% of lower extremity blocks). CONCLUSIONS: Regional anesthesia in children as commonly performed in the United States has a very low rate of complications, comparable to that seen in the large multicenter European studies. Ultrasound may be increasing the use of peripheral nerve blocks. Multicenter collaborative networks such as the Pediatric Regional Anesthesia Network can facilitate the collection of detailed prospective data for research and quality improvement.

Postoperative apnea, bradycardia, and oxygen desaturation in formerly premature infants: prospective comparison of spinal and general anesthesia.

Eighteen formerly premature infants scheduled for inguinal herniorrhaphy and who were less than 51 wk postconceptional age were assigned to either the general anesthesia group (GA:atropine, halothane, and nitrous oxide) or the spinal anesthesia group (SA: hyperbaric tetracaine). Twelve-hour, three-channel continuous recordings of respiratory rate (chest wall impedance), electrocardiogram (ECG), and hemoglobin O2 saturation (Spo2) were obtained preoperatively and after surgery. These were analyzed for short (11-15 s) and long (>15 s) apnea spells, periodic breathing, and episodes of hemoglobin oxygen desaturation and bradycardia. Infants in the GA group had lower postoperative minimum Spo2 (68.7% +/- 11.4%) and minimum heart rate (79 bpm +/- 19) than infants in the SA group (80.7% +/- 9.2%, and 109 bpm +/- 30, respectively; P < 0.05) and had lower postoperative minimum Spo2 and minimum heart rate than they had preoperatively (79.0% +/- 13.7%, and 93 bpm +/- 31, respectively; P < 0.05); pre- and postoperative studies in the SA group did not differ. There were no differences in the incidence of postoperative central apnea. We conclude that spinal anesthesia reduces postoperative hemoglobin oxygen desaturation and bradycardia in formerly premature infants undergoing inguinal herniorrhaphy. (Anesth Analg 1995;80:7-13)

The dose response of caudal morphine in children

The authors compared the duration of analgesia and the frequency of side effects of three doses of caudal epidural morphine in children aged 1.2-7.9 yr. Caudal catheters were inserted in 32 children, randomly assigned to receive 0.033 mg.kg-1, 0.067 mg.kg-1, or 0.10 mg.kg-1 of preservative-free morphine for analgesia after major surgical procedures below the diaphragm. The first dose of caudal morphine was mixed with 0.25 ml.kg-1 of 1% lidocaine to confirm correct caudal catheter placement. By assessment of periodic pain scores and the time intervals between administration of caudal morphine and the recurrence of pain, the authors found that the mean (+/- SD) duration of analgesia was significantly longer after 0.10 mg.kg-1 (13.3 +/- 4.7 h) than after either 0.033 mg.kg-1 or 0.067 mg.kg-1 (10.0 +/- 3.3 and 10.4 +/- 4.2 h, respectively) (P less than 0.02). The frequency of vomiting, pruritus, and urinary retention was similar in each group. Vomiting was less common in patients who had nasogastric drainage than in patients who were fed soon after surgery (P less than 0.05). Delayed respiratory depression occurred in one child after 0.10 mg.kg-1 of caudal morphine. Caudal morphine, 0.033-0.10 mg.kg-1, provided prolonged analgesia in children. The authors recommend 0.033 mg.kg-1 of caudal morphine as an initial dose for children.

Caudal morphine for postoperative analgesia in children: a comparison with caudal bupivacaine and intravenous morphine.

We compared the efficacy, duration, and side effects of preservative-free morphine injected into the caudal space in children, with caudal bupivacaine and with intravenous morphine administration for relief of postoperative pain. Forty-six children, ages 1-16 yr, were randomly assigned to receive intravenous morphine (control group), caudal bupivacaine (0.25%, 1 ml/kg), or caudal morphine (0.5 mg/ml, 0.1 mg/kg). In half the patients given caudal morphine, the morphine was mixed with a dose of lidocaine adequate to produce sacral analgesia, to confirm correct caudal injection of the morphine. Caudal injections were performed at the end of surgery. Time until the first required postoperative intravenous morphine dose was recorded for each patient. The duration of analgesia was significantly greater with caudal morphine (median 12 hr, P less than 0.02) than with caudal bupivacaine (median 5 hr), and both were greater than with intravenous morphine in control patients (median 45 min). Urinary retention, pruritus, and nausea appeared with slightly greater frequency in the caudal morphine group, but no delayed respiratory depression occurred. Caudal morphine (0.5 mg/ml, 0.1 mg/kg) provided 8-24 hr of analgesia in children without a significantly greater incidence of side effects than caudal bupivacaine or intravenous morphine.

The prevalence of phantom sensation and pain in pediatric amputees

Phantom sensations and pain occur with an unknown frequency in children. We hypothesized that such experiences are common among children, and occur more often than is recognized by health-care personnel. Children and adolescents, ages 5-19 years, who had undergone limb amputation in the past 10 years, served as subjects for this retrospective study. Subjects were divided into three major groups depending upon the indication for amputation: congenital deformity (CD), trauma/infection (TI), and cancer (Ca). Surveys assessing phantom sensations and phantom pain were mailed to children and their parents/guardians. The incidence of phantom sensations was 100% in each group, and phantom pain occurred in the overwhelming majority. Both types of phantom phenomena began within days of surgery for almost all patients. Seventy-five percent of children and adolescents who had experienced phantom pain also had preoperative limb pain. At the time of the study, phantom pain had resolved in only 35% of the subjects. Phantom pain was documented in the medical records of only 40% of those answering positively to questions regarding phantom pain on the questionnaire. We conclude that phantom pain occurs commonly in children and adolescents. The association of preoperative pain in the diseased extremity and the later occurrence of phantom pain suggests that preoperative regional anesthesia may prevent phantom pain.

Delayed Respiratory Depression in a Child after Caudal Epidural Morphine

The treatment of acute and chronic pain in adults with intrathecal or epidural narcotics is presently a widely accepted modality (1) and has been shown to be superior to conventional narcotic administration in several controlled studies (2-5). More recently, the use of epidural and intrathecal narcotics has been extended to children (6-8) and has also been demonstrated in this population to result in superior analgesia without an unacceptable frequency of side effects (9,lO). Respiratory depression, the most consequential side effect ascribed to spinal narcotics (11/12), is thought to result from rostra1 conduction of opioid dissolved in cerebrospinal fluid (CSF) to the brain stem with subsequent depression of medullary centers of respiration (1,13). Although well recognized as a risk in adult patients, it has not until now been reported in a child.

The OOPS procedure (Operation on Placental Support): In utero airway management of the fetus with prenatally diagnosed tracheal obstruction

Tracheal obstruction of the newborn caused by cervical masses such as teratomas and cystic hygromas can result in a profound hypoxic insult and even death, owing to an inability to establish an adequate airway after birth. Prenatal sonographic diagnosis of these congenital anomalies permits (1) anticipation of an airway problem at the time of delivery and (2) formulation of an algorithm for airway management while oxygen delivery to the baby is maintained through the placental circulation. This is the report of a fetus in whom a large anterior cervical cystic hygroma was detected by prenatal ultrasonography. A multidisciplinary management team was assembled, and an algorithm for airway management was developed. Elective cesarean delivery of the fetal head and thorax, under conditions of uterine tocolysis, permitted a controlled evaluation of the airway and endotracheal intubation while oxygen supply to the infant was maintained through the placenta. The baby remained intubated, and 2 days later underwent subtotal excision of the cervical cystic hygroma. Pharmacological maintenance of the feto-placental circulation after hysterotomy is an invaluable adjunct to airway management of the neonate with prenatally diagnosed tracheal obstruction.

A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. I. Emergence and recovery profiles

Pyloric stenosis is sometimes associated with hemodynamic instability and postoperative apnea. In this multicenter study we examined the hemodynamic response and recovery profile of remifentanil and compared it with that of halothane in infants undergoing pyloromyotomy. After atropine, propofol, and succinylcholine administration and tracheal intubation, patients were randomized (2:1 ratio) to receive either remifentanil with nitrous oxide and oxygen or halothane with nitrous oxide and oxygen as the maintenance anesthetic. Pre- and postoperative pneumograms were done and evaluated by an observer blinded to the study. Intraoperative hemodynamic data and postanesthesia care unit (PACU) discharge times, PACU recovery scores, pain medications, and adverse events (vomiting, bradycardia, dysrhythmia, and hypoxemia) were recorded by the study’s research nurse. There were no significant differences in patient age or weight between the two groups. There were no significant differences in hemodynamic values between the two groups at the various intraoperative stress points. The extubation times, PACU discharge times, pain medications, and adverse events were similar for both groups. No patient anesthetized with remifentanil who had a normal preoperative pneumogram had an abnormal postoperative pneumogram, whereas three patients with a normal preoperative pneumogram who were anesthetized with halothane had abnormal pneumograms after.