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From the Departments of Child Health and Anesthesiology and the Division of Pediatric Critical Care/Pediatric Anesthesiology, The University of Missouri, Columbia, Missouri
Address correspondence and reprint requests to Joseph D. Tobias, MD, Vice-Chairman, Department of Anesthesiology, Chief, Pediatric Critical Care/Pediatric Anesthesiology, Russell and Mary Shelden Chair in Pediatric Intensive Care Medicine, Professor of Anesthesiology and Child Health, The University of Missouri, Department of Anesthesiology, 3W40H, One Hospital Drive, Columbia, Missouri 65212. Address email to Tobiasj{at}health missouri.edu.
| Abstract |
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| Introduction |
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The potential for neuraxial techniques in pediatric spine surgery is demonstrated by reports of using regional anesthesia as the sole intraoperative anesthetic for major surgical procedures on the spine in both adults and children. Although most experience with regional anesthesia (lumbar epidural or spinal anesthesia) for surgical anesthesia during spine surgery has involved short segment lumbar spine surgery in adults (35), two groups have reported their experience with neuraxial anesthesia to provide intraoperative anesthesia during spine surgery in infants and children (6,7). Dalens et al. (6) describe their experience with "staged segmental scoliosis surgery" (SSSS), a technique that used spinal or epidural anesthesia. Because of associated comorbid features, including respiratory insufficiency in their cohort of 6 patients, the authors deemed the risks of general anesthesia to be prohibitive. All patients had progressive scoliosis requiring PSF that was performed in a staged approach of 35 segments per procedure. A total of 311 operations were performed under epidural or spinal anesthesia for each patient enrolled in this investigation. Despite their success with SSSS, the authors caution against the use of the technique in inexperienced hands. Aronsson et al. (7) provide additional information regarding the use of regional anesthesia to provide surgical anesthesia during orthopedic/spine surgery in infants and children. In their cohort of 22 patients, 8 underwent successful closure of a lumbar myelomeningocele defect under spinal anesthesia.
In addition to the use of neuraxial techniques for intraoperative anesthesia, the literature has provided evidence for the potential efficacy of these techniques to provide postoperative analgesia after spine surgery in adults (810). Joshi et al. (8) compared a lumbar epidural infusion of fentanyl with patient-controlled analgesia (PCA) in a prospective, randomized trial in 20 adults after lumbar laminectomy. Epidural analgesia consisted of a continuous infusion of fentanyl (2 µg/mL) at 410 mL/h administered through an epidural catheter, placed by the surgeon at the completion of the procedure. The catheter tip was placed at the middle of the surgical incision. PCA consisted of morphine, 1 mg every 6 min, as needed. For both groups, IV morphine was available as needed to treat breakthrough pain. Compared with PCA, the epidural group exhibited lower postoperative pain scores and a reduced parenteral morphine requirement during the first 48 h postoperatively. Morphine consumption was 182.4 ± 26.2 mg in the PCA group versus 58.4 ± 16.1 mg in the epidural group. No difference was noted in the adverse effect profile.
We found similar efficacy when using epidural catheters to control postoperative pain in a cohort of 7 adults undergoing short segment lumbar fusion with instrumentation (9). The open label, prospective trial used postoperative epidural infusions. The epidural dosing included an initial intraoperative bolus dose of fentanyl (1 µg/kg) and hydromorphone (5 µg/kg). This was followed postoperatively by a bolus dose of a local anesthetic (0.2 mL/kg of 0.125% ropivacaine) after a normal neurologic examination of the lower extremities was documented. Bolus dosing was followed by a continuous infusion of 0.1% ropivacaine with hydromorphone (10 µg/mL) at 0.2 mL · kg-1 · h-1. A standardized pain scale demonstrated that static preoperative pain exceeded dynamic postoperative pain during the 72-h investigational period.
Given the above-mentioned studies demonstrating the use of regional anesthetic techniques to provide surgical anesthesia in adults and children for spine surgery as well as the evidence regarding the efficacy and safety of regional anesthesia techniques in providing postoperative analgesia in adults after lumbar spine surgery, neuraxial techniques may be warranted for children after major spine surgery. The remainder of this manuscript will review previous reports regarding the use of neuraxial techniques to provide analgesia after spine surgery in the pediatric population. As the available information regarding these techniques is reviewed, several problematic variables are evident. There are variations in 1) the dose of the medications used; 2) the route of delivery (intrathecal [IT] or epidural); 3) the mode of delivery (single dose, intermittent bolus dosing, or continuous infusion); 4) the number of catheters used (one versus two); 5) the medications infused (opioids, local anesthetics, or both); 6) the opioid used (morphine, fentanyl, hydromorphone); 7) analgesic regimen of the control group (intermittent "as needed" morphine or PCA); 8) the type of surgery (short segment lumbar fusion, short segment laminectomy for dorsal rhizotomy [DR], PSF, and ASF); and 9) the surgical approach (open versus thoracoscopic). With advances in surgical technique, the anterior approach has become much more commonplace (11). The Kaneda system allows an anterior approach for thoracic scoliosis with fusion and instrumentation at 46 levels thereby avoiding the need for a long segment posterior fusion. In our practice, this technique has replaced procedures formerly performed posteriorly or through an anterior-posterior approach.
The spinal surgery population also represents a very diverse group of patients with various disease processes including idiopathic scoliosis, neuromuscular conditions, and cerebral palsy. The latter group may have associated developmental delays that affect the assessment of pain. All of these factors need to be considered as the various reports regarding regional anesthetic techniques for postoperative analgesia are reviewed.
| Analgesia After Spine Surgery: Intrathecal Opioids |
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Goodarzi (14) evaluated the efficacy of lumbar IT morphine (0.02 mg/kg) plus IT sufentanil (50 µg) placed before the start of the surgical procedure during PSF. The study cohort included 80 pediatric patients, 40 of whom received IT morphine/sufentanil and 40 of whom received IV sufentanil (13 µg/kg). The intraoperative blood loss expressed as the percentage of the blood volume was less in the IT morphine/sufentanil group when compared with the control group (27.4% ± 42.8% versus 53.5% ± 33.5% of the blood volume, P < 0.02). The IT patients required postoperative analgesia at 14.5 h postoperatively (range, 036 h) compared with the immediate need in the control group. Additionally, postoperative mobilization was better tolerated in the IT morphine patients. Although the PaCO2 levels were higher in the IT group, no respiratory depression was noted.
Gall et al. (15) evaluated the efficacy of 2 doses of IT morphine (2 or 5 µg/kg) versus saline in 30 children ranging in age from 9 to 19 yr undergoing PSF. Intraoperative blood loss was significantly less in the 5 µg/kg group (14 ± 10 mL/kg) than in the 2 µg/kg group (34 ± 19 mL/kg) and the control group (41 ± 23 mL/kg). The first 24 h of morphine consumption by PCA was 49 ± 17, 19 ± 10, and 12 ± 12 mg in the saline, 2 µg/kg, and 5 µg/kg IT morphine groups respectively, P < 0.0001. The time to first analgesic use was 0.2 ± 0.1, 4.0 ± 1.3, and 9.0 ± 4.6 h in the 3 groups respectively (P = 0.0009). Median pain scores at rest were in the 020 mm range during the first 24 h postoperatively in the 2 and 5 µg/kg IT morphine groups and the values were statistically significant from the saline control group at 2, 4, and 14 h postoperatively. Although there was a trend toward lower pain scores in the 5 µg/kg IT morphine group, pain scores during coughing were not different among the 3 groups. Adverse events including end-tidal carbon dioxide more than 55 mm Hg, respiratory rate <12 breaths/minute, sedation score more than 2, nausea, vomiting, and pruritus were not different among the 3 groups.
Dovsal Rhizotomy
Two reports outline the use of IT morphine after DR surgery (16,17). Dews et al. (16) randomized 27 children to receive 10, 20, or 30 µg/kg of IT morphine after DR. The time to the first requirement for supplemental IV morphine was not different among the 3 groups; however, during the first 6 h postoperatively, the total morphine use was less in the patients who received 30 µg/kg of IT morphine (79.1 ± 74, 189.6 ± 126, and 38.6 ± 47 µg in the patients who received 10, 20, and 30 µg/kg of IT morphine respectively; P < 0.05 when comparing 30 µg/kg patients versus the other 2 groups). After the initial 6 h postoperatively, the only difference was that the patients who received 20 µg/kg of IT morphine required statistically more morphine than either the 10 µg/kg or 30 µg/kg group. The authors were puzzled by these results and could offer no conclusive reason for this finding. No difference in adverse effects, including nausea/vomiting, respiratory depression, or pruritus, was noticed among the 3 groups.
Similar findings were reported by Harris et al. (17) when comparing the analgesic efficacy of IT morphine after DR in 50 patients. The authors noticed no difference in the quality of analgesia when comparing small dose (715 µg/kg), moderate dose 1625 µg/kg), and large dose (2635 µg/kg) IT morphine therapy. When considering all patients, the duration of analgesia ranged from 3 to 48 h (mean, 12.2 ± 9.5 h). Although the incidence of adverse effects was not different among the 3 groups, nausea and vomiting occurred in 42% of the patients. Naloxone was required in 2 patients, one for apnea in the operating room and another for somnolence.
| Analgesia After Spine Surgery: Epidural Analgesia |
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Single-Catheter, Intermittent Dosing of Epidural Morphine after PSF or DR
Amaranth et al. (18) retrospectively reviewed their experience with epidural morphine after PSF in 35 adolescents who ranged in age from 11 to 17 yr (Table 2). Seventeen patients had an epidural catheter placed at the L1-2 level before closure of the wound. Intermittent doses of morphine (3050 µg/kg) were administered once or twice daily to provide postoperative pain relief. For both groups, supplemental doses of either IV or IM morphine were available as needed to provide pain relief. Opioid consumption was significantly less in the epidural morphine group on postoperative days 1 and 2. Morphine consumption during day 1 was 27.0 ± 11.6 mg in the control group versus 16.4 ± 13.6 mg in the epidural morphine group (P < 0.05).
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Single-Catheter, Intermittent Dosing of Epidural Morphine, DR
Two studies have evaluated intermittent dosing of either epidural morphine or epidural morphine with butorphanol after DR (20,21). Sparkes et al. (20) reported their experience with epidural morphine in 28 consecutive patients after DR. Postoperative analgesia was provided by intermittent doses of epidural morphine (0.05 mg/kg) with 16 of the 28 patients also receiving bupivacaine. The epidural catheters were left in place for 72 h. Analgesia was successful in all patients without the need for IV opioids. After epidural morphine, the duration of analgesia was 11.44 ± 3.10 h (range, 6.518 h). One catheter was removed for possible intrathecal migration and one was dislodged during patient transport. Pruritus and nausea/vomiting were noted in 10 patients (38%).
Lawhorn et al. (21) randomized 14 children to receive either epidural morphine (80 µg/kg) or epidural morphine (80 µg/kg) with epidural butorphanol 40 µg/kg administered via an indwelling epidural catheter after DR. The catheter was placed at the completion of the surgical procedure and dosed every 1824 h during the postoperative period. As-needed supplemental analgesia was provided by PCA morphine. There were statistically significant decreases (morphine group versus morphine-butorphanol group) in the incidence of pruritus (57% versus 0%; P < 0.03), nausea and vomiting (85.7% versus 14.2%; P < 0.03), mean time to sustain oxygen saturation more than 90% without supplemental oxygen (10.79 h versus 0.79 h; P < 0.03), and time to first use of supplemental opioids (40.86 versus 224.86 min; P < 0.045). Both groups experienced adequate analgesia with average pain scores of 2.64 ± 0.43 and 1.67 ± 0.34.
Single Catheter, Continuous Infusion, Epidural Morphine, DR
Malviya et al. (22) randomized 27 children to receive either a continuous epidural infusion of morphine or a continuous infusion of IV morphine after selective DR. The surgical technique involved complete laminectomies at L3-5 and partial laminectomies at L2 and S1. The epidural group had a catheter placed at the completion of the procedure. The catheter was dosed with morphine (30 µg/kg) diluted to a volume of 0.15 mL/kg. This was followed by a continuous infusion of epidural morphine at 3 µg · kg-1 · h-1. The IV opioid group received intraoperative morphine (0.050.1 mg/kg) followed by morphine administered using nurse-controlled PCA with 0.02 mg of morphine every 10 min as needed with no basal infusion rate. The epidural group had better pain control and fewer muscle spasms and tolerated activity better than the IV group.
Single Catheter, Continuous Infusion, PSF
Arms et al. (23) collected prospective data regarding epidural analgesia in 12 pediatric patients with an average age of 13 yr after PSF. The epidural catheter was inserted by the surgeon before wound closure (Table 3). Variability was demonstrated in the location of the distal tip of the catheter. It was located at T5-6 in 1 patient, T6-7 in 5 patients, T7-8 in 4 patients, T8-9 in 1 patient, and T11-12 in 1 patient. One patient received an intraoperative bolus and the other 11 were dosed postoperatively in the Pediatric Intensive Care Unit. The bolus included 3050 µg/kg of morphine with 510 mL of 0.1%0.25% bupivacaine. The bolus was followed by a continuous infusion of bupivacaine with morphine supplemented by nurse-controlled analgesia or PCA. The total hourly doses of epidural medications varied from 410 mL/h of 0.0625%0.125% bupivacaine and 510 µg · kg-1 · h-1 of morphine. Postoperative analgesia was judged satisfactory in all patients with average pain scores on a 0 to 10 scale at rest and with movement of 3.3/3.8, 3.6/5.1, 2.7/4.2, 2.6/3.7, and 0/2 on days 1 through 5, respectively. One patient with Duchenne muscular dystrophy developed atelectasis and respiratory failure requiring reintubation. This was thought to be unrelated to the epidural infusion.
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Cassady et al. (25) compared the efficacy of thoracic epidural analgesia (continuous infusion of bupivacaine and fentanyl) with IV PCA in 33 patients ranging in age from 11 to 18 yr. They noted no difference in the analgesia between the two groups as assessed using a visual analog scale. The epidural group had a faster return of bowel sounds. Twenty percent of patients receiving epidural analgesia had return of bowel sounds on the day of surgery, compared with 0% in the IV PCA group. On the first morning after surgery, bowel sounds were present in 80% of the epidural patients compared with 43.75% of the IV PCA patients.
Additional data are presented by Turner et al. (26) using an epidural infusion of fentanyl/bupivacaine after PSF in 14 patients ranging in age from 12 to 22 yr. After catheter placement, location was evaluated with dye injection. In 5 patients, no dye was noted in the epidural space and no analgesia was obtained. In 7 patients, dye was seen in the epidural space, and in 2 patients, dye was seen in the paravertebral gutters. These 9 patients had adequate analgesia. The authors concluded that correctly placed catheters provided effective analgesia.
Single Catheter, Continuous Infusion, ASF
In the previously mentioned study of Shaw et al. (24), a percutaneous epidural catheter was placed in 5 patients undergoing ASF. Although this practice is feasible, we have subsequently reported another option in adolescents undergoing ASF using the Kaneda anterior spinal fusion system. The technique involves the intraoperative placement of the catheter into the epidural space through the vertebral foramen (27). Placement of the Kaneda system involves resection of the rib head that allows access to the vertebral foramen as well as a view of the posterior longitudinal ligament and epidural space. Our report included 10 patients ranging in age from 12 to 17 yr (27). After placement, the catheter was dosed intraoperatively with hydromorphone 5 µg/kg and fentanyl 1 µg/kg. Postoperatively, when the patient was awake and a normal neurologic examination had been demonstrated, the catheter was dosed with 0.2 mL/kg of 0.2% ropivacaine. This was followed by a continuous infusion of 0.1% ropivacaine + hydromorphone 10 µg/mL at 0.2 mL · kg-1 · h-1. Adequate analgesia was achieved in all 10 patients. The means of the individual patients median daily pain scores were 2.3, 2.3, 2.2, 1.8, and 1.7 for postoperative days 1 to 5, respectively.
Double Catheter, Continuous Infusion, PSF
In our initial experience with epidural catheters for analgesia after PSF, several patients complained of pain at the top or bottom of the incision. Given anecdotal experience in adults (28,29), we evaluated the potential efficacy of a two epidural catheter system to provide analgesia after PSF (30). The double epidural catheter technique was evaluated in 14 patients ranging in age from 5 to 17 years (30). Before wound closure, two epidural catheters were placed. Under fluoroscopy, the tip of the upper catheter was positioned at T1-4 and the tip of the lower catheter was positioned at L1-4. The catheters were first dosed with a solution that contained 1 µg/kg of fentanyl and 5 µg/kg of hydromorphone diluted in 0.3 mL/kg of preservative-free saline. The solution was divided and 0.2 mL/kg injected into the lower catheter and 0.1 mL/kg was injected into the upper catheter. After completion of the surgical procedure and demonstration that the patients neurologic examination had returned to baseline, the catheters were dosed with local anesthetic solution. This included 0.2% ropivacaine (0.2 mL/kg into the lower catheter and 0.1 mL/kg into the upper catheter) and a continuous infusion was started. The continuous infusion, which consisted of 0.1% ropivacaine plus hydromorphone 10 µg/mL, was infused at 0.1 mL · kg-1 · h-1 into the upper catheter and 0.2 mL · kg-1 · h-1 into the lower catheter. IV diazepam was used as needed to control muscle spasms. IV ketorolac was used for mild to moderate pain. The efficacy of analgesia was assessed using a visual analog pain score (0 to 10). Effective analgesia was provided for the 14 patients without adverse effects. The average and (range) of the patients median pain scores from days 1 to 5 were 1.5 ± 1.6 (04), 1.6 ± 1.5 (04), 1.4 ± 1.3 (03), 1.1 ± 1.1 (03), and 0.9 ± 0.9 (02) respectively. The average (range) of the patients maximum pain scores from days 1 to 5 were 3.5 ± 2.3 (07), 4.0 ± 1.6 (26), 3.1 ± 1.7 (16), 2.4 ± 1.5 (04), and 2.2 ± 1.4 (04), respectively. The patients required 03 doses of diazepam on days 1 and 2 and 02 doses on days 3 through 5.
Similar efficacy using a double-catheter technique was subsequently demonstrated by Ekatodramis et al. (31) in 23 adolescents. At the completion of the surgical procedure, the cephalad catheter was positioned at T4-6 and the lower catheter was positioned at T10-L1. Once a normal postoperative neurologic examination was documented, the epidural infusion was started. This included an initial bolus of 0.0625% bupivacaine (8 mL for patients weighing more than 50 kg and 5 mL for those weighing <50 kg). This was followed by a continuous infusion of 0.0625% bupivacaine with fentanyl 2 µg/mL and clonidine 3 µg/mL at 10 mL/h. The efficacy of analgesia was assessed using a visual analog scale (0 to 100). Complete analgesia at rest was obtained in all of the patients. During mobilization and respiratory physiotherapy, analgesia remained adequate in 19 of the 23 patients. Four of the patients required IV morphine for pain scores more than 30.
| Potential Adverse Effects of Regional Anesthetic Techniques |
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The literature contains isolated reports of neurologic deficits that may have been contributed to by the epidural analgesic techniques. Hered et al. (32) reported a 12-yr-old girl who developed a persistent Horners syndrome after PSF, whereas Prunell (33) described lower extremity paralysis after PSF in an 11-yr-old patient. In the first patient, the Horners syndrome was still present 6 mo after the surgical procedure. The authors offered several plausible explanations for its etiology, including direct surgical trauma to the thoracic sympathetic fibers of the spinal cord during the procedure, compression of the sympathetic fibers from an isolated hemorrhage, direct trauma to the paravertebral sympathetic chain, or a toxic effect from the epidural. Although previous reports have documented transient Horners syndrome with epidural anesthesia, none resulted in a permanent deficit. In the report of Purnell (33), the epidural catheter was dosed intraoperatively with 20 mL of 0.25% bupivacaine, and when the patient awoke she was unable to move her lower extremities. There was no change over the ensuing 2 h, and the child was returned to the operating room and the spinal instrumentation was removed. Motor and sensory function gradually returned and was back to baseline 9.5 h after dosing of the epidural catheter. As in the other case, no definitive cause of the problem was identified, but the authors offered the possibilities of spinal cord compression, ischemia, or problems related to the epidural anesthesia.
The majority of the studies reviewed in this manuscript suggest that normal neurologic function should be demonstrated before the use of local anesthetics. Postoperative weakness or neurologic changes should not be attributed to the epidural catheter but should immediately be evaluated because of the potential for epidural bleeding with spinal cord compromise after these surgical procedures. Should the neurologic findings be erroneously attributed to the use of local anesthetic in the epidural solution, there may be a delay in the diagnosis of potentially reversible surgical conditions. The use of dilute solutions of local anesthetics should eliminate the potential for sensory or motor changes from the local anesthetic.
An additional issue with neuraxial techniques of analgesia relates to their potential effect on intraoperative monitoring techniques such as somatosensory evoked potentials. Schubert et al. (34) and Goodarzi et al. (35) have demonstrated no effect on the amplitude or latency of somatosensory evoked potentials after the administration of IT morphine. Loughman et al. (36) demonstrated that the administration of epidural bupivacaine in concentrations of 0.5% and 0.75%, but not 0.25%, interfered with somatosensory evoked potential monitoring.
Neuraxial opioids, particularly morphine, can result in rostral spread resulting in delayed respiratory depression. The study of Blackman et al. (13), which included 33 patients who received IT morphine, noted early respiratory depression in 3 patients and late respiratory depression in 5 patients. However, these investigators diluted the IT morphine in 10 mL of fluid, which may have encouraged cephalad spread. In the other reports, no other problems were noted except for occasionally high PaCO2 values when compared with control groups. Additional adverse effects with neuraxial opioids include pruritus, nausea, and vomiting. These problems may be more common with neuraxial morphine (37), with an incidence as high as 30%60% in some studies. These problems led to our use of hydromorphone and fentanyl with a dual epidural catheter technique to limit the need for hydrophilic opioids to achieve greater dermatomal spread. Other investigators have shown that a combination of epidural morphine and butorphanol may effectively eliminate the problems of pruritus, nausea, and vomiting and improve the analgesic efficacy of the epidural technique (21).
Perhaps the greatest concern of neuraxial techniques after spine surgery is the potential risk of infection related to the epidural catheter. Despite the increasing experience in the literature with neuraxial techniques after spine surgery, there are no reports of infectious complications related to the regional anesthetic technique. Clinical experience has demonstrated the efficacy of prolonged use of tunnelled catheters (38).
| Summary |
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The reports in the literature regarding IT/epidural analgesia for spine surgery are limited in many instances by the lack of a control group; however, in most cases, prospective studies demonstrate a reproducible benefit of neuraxial techniques. When considering the use of IT morphine, the literature is reproducible with improvements in postoperative analgesia with a decreased need for IV opioids. Additionally, the studies of Goodarzi (14) as well as Gall et al. (15) demonstrate decreased intraoperative blood loss. Although the dose used by Goodarzi was as large as 20 µg/kg, Gall et al. (15) demonstrated improvements in the postoperative pain course as well as decreased intraoperative blood loss with a lumbar IT morphine dose of 5 µg/kg. This approach seems to be an effective technique with an acceptable adverse effect profile. The major disadvantage is the limited duration of action of 1824 h at best.
When considering epidural analgesia, several studies using various combinations of local anesthetics and opioids demonstrate the efficacy of the technique, but there are limited studies to demonstrate its superiority over conventional PCA. Although Amaranth et al. (18) demonstrated decreased opioid requirements in patients who received epidural morphine; the only prospective, randomized trial that has been performed demonstrated no difference in analgesic efficacy between epidural analgesia and IV PCA (25). The study did demonstrate a more rapid return of gastrointestinal function in the epidural group. The lack of analgesic benefit noted in the study of Cassady et al. (25) may have resulted from the use of a lipophilic opioid, fentanyl, to cover several dermatomes (1012 for most procedures). We continue to use the regimen outlined in our previous study (30) for patients undergoing PSF. A dual epidural catheter technique is used to allow the use of lipophilic opioids and thereby avoiding the adverse effects of hydrophilic opioids.
The evaluation of the efficacy of regional anesthetic techniques is clouded by the problems mentioned previously, including the dose of the medications used, the route of delivery (IT or epidural), the mode of delivery (single dose, intermittent bolus dosing, or continuous infusion), the number of catheters used (one versus two), the medications infused (opioids, local anesthetics, clonidine), the opioid used (morphine, fentanyl, hydromorphone), analgesic regimen of the control group (intermittent "as-needed" morphine or PCA), the type of surgery (short segment lumbar fusion, short segment laminectomy for DR, PSF, and ASF), and the surgical approach (open versus thoracoscopic).
Future studies may help determine the optimal anesthetic technique for these procedures. Potential cost issues related to maintenance of the epidural infusion versus potential cost savings in hospital or ICU stay must be considered. These evaluations should use the current standard of analgesia (IV PCA) as the control group. Given the recent evidence regarding the benefits of acetaminophen in postoperative pain, it may be appropriate to include it in the analgesic regimen of the control group. The new cyclooxygenase 2 inhibitors, if they lack effects on new bone formation, may also be effective adjuncts for the parenteral group. Recent information regarding epidural clonidine and the spine surgery study of Ekatodramis et al. (31), demonstrate that it may offer additional advantages to epidural local anesthetics and opioids. When considering such studies, potential cost issues related to maintenance of the epidural infusion versus potential cost savings in hospital or ICU stay must be considered.
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