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Anesth Analg 2003;96:874-880 © 2003 International Anesthesia Research Society
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Abstract |
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Spinal anesthesia has numerous advantages over general anesthesia for patients undergoing lumbar laminectomy and microdisk surgery. In this study, we evaluated the addition of epidural clonidine and/or bupivacaine, injected at the incision site, on postoperative outcome variables in patients undergoing lower spine procedures using spinal anesthesia. One hundred twenty patients having lumbar spine surgery received bupivacaine spinal anesthesia supplemented by 150 µg of epidural clonidine with or without incisional bupivacaine, epidural placebo plus incisional bupivacaine, or placebo with incisional saline. Demographic data, intraoperative hemodynamics, blood loss, pain, nausea, urinary retention, hospital discharge, and other variables were compared by using either analysis of variance or
2 analysis. Demographics were similar. IV fluids, blood loss, incidence of intraoperative bradycardia, and hypotension were not different among groups. Postanesthesia care unit pain scores were lower and demand for analgesics was less in patients who received both the clonidine and subcutaneous bupivacaine. Patients who received epidural clonidine also had improved postoperative hemodynamics. Hospital discharge, urinary retention, and other variables were not different. We conclude that epidural clonidine as a supplement to spinal anesthesia produced no perioperative complications and improved postoperative pain and hemodynamic stability in patients undergoing lower spine procedures. IMPLICATIONS: Spinal anesthesia with supplemental epidural clonidine in combination with incision site subcutaneous bupivacaine was evaluated both intra- and postoperatively and compared with spinal anesthesia alone for lower lumbar spine procedures. Both epidural clonidine and subcutaneous incisional bupivacaine, added to spinal anesthesia for lumbar spine surgery, improves pain relief and reduces the need for postoperative opioids with their associated side effects.
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Introduction |
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Despite the advantages of spinal anesthesia for lumbar spine surgery, no prolonged effect on intermediate (4–24 h) postoperative pain relief has been noted compared with general anesthesia (1). The addition of narcotics to spinal anesthesia is effective in prolonging the analgesic effect, but has also been associated with many unwanted side effects, including respiratory depression, urinary retention, drowsiness, and pruritus (2,3). These same side effects have also been noted with the epidural administration of narcotics (4).
Neuropathic pain, experienced by many patients requiring laminectomy or discectomy, is radiating and burning in nature and responds poorly to opioids whether administered systemically (5) or intraspinally (6). Clonidine has been shown to be effective in reliev-ing neuropathic pain, especially when administered epidurally (7). Patients with chronic back pain caused by arachnoiditis had better pain relief with epidural clonidine compared with morphine (8). In addition, pain associated with deafferentation after spinal injury and pain related to postherpatic neuralgia was also controlled with epidural clonidine (9,10). Because clonidine does not interact with opioid receptors, it has none of the side effects associated with their administration.
This study was designed to determine whether the administration of epidural clonidine, in combination with spinal bupivacaine, would reduce postoperative pain, prolong analgesia, and improve outcome in patients undergoing lower spine procedures. In addition, these patients were also randomized to receive a subcutaneous (SQ) injection of local anesthetic, before surgical incision, to determine whether this preemptive administration of local anesthetic would produce an additional analgesic benefit.
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Methods |
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After approval by the IRB and written informed consent, 120 patients, ASA physical status I–III, undergoing lumbar laminectomy or microdisk procedures, were admitted to the study. Other studies (11,12) comparing the analgesic effect of epidural clonidine have observed demonstrable differences between placebo and clonidine-administered groups with patient numbers of between 10 and 20 per group. Groups of 30 patients each are adequate (80% probability) to determine differences in analgesic effect should they exist between placebo and treatment groups. Patients were excluded from the study if they were pregnant, had a significant cardiac history, bleeding abnormalities, liver disease, or significant renal failure with a serum creatinine >3.0. The same surgeon performed all operations.
Before coming to the operating room, all patients received midazolam 2 mg IV. In the operating room, standard monitors were applied and the patient was placed in a seated position. After sterile preparation and draping of the back, 2% lidocaine 3–4 mL was injected SQ into the third or fourth lumbar interspace and an EspocanTM 17-gauge Tuohy combination spinal, epidural needle was advanced until the epidural space was ascertained by loss of resistance. A 27-gauge Sprotte spinal needle was then inserted through the epidural needle until a loss of resistance was noted and free flow of cerebrospinal fluid was visualized after removal of the spinal needle stylet. At this time, 0.75% spinal bupivacaine 1.5 mL (11.25 mg) was injected into the spinal canal. After removal of the spinal needle, 10 mL of 1 of the 4 study solutions was injected into the epidural space. The epidural solutions administered were assigned by computer-generated randomization and patients were divided into four groups. Group 1 patients received 150 µg of epidural clonidine diluted in 10 mL of preservative-free saline. This group also received 
20 mL of 0.5% bupivacaine without epinephrine injected SQ at the site before surgical incision (clon/SQ bup). Group 2 patients were administered 150 µg of epidural clonidine but had 20 mL of saline injected SQ at the incision site (clon/SQ saline). Group 3 patients received 10 mL of preservative-free saline epidurally and were given the 0.5% bupivacaine SQ at the incision site (saline/SQ bup). Group 4 patients received 10 mL of preservative-free saline epidurally and saline injected SQ before surgery at the site of the incision (saline/SQ saline). The patients were next placed supine, and when a stable level of spinal anesthesia was achieved, they were rolled prone and allowed to self-position until comfortable. Oxygen was administered at 2 L/min flow by nasal canula. The patients were sedated with a propofol infusion titrated between 25–50 µg · kg-1 · min-1. This was maintained until the end of surgery at which time it was discontinued and the patient transferred to the postanesthesia care unit (PACU).
Before the study, demographic data, including age, sex, weight, height, and physical status, were collected. Immediately before surgery, baseline heart rate (HR), blood pressure, neurologic status, and hemoglobin concentrations were obtained. Total anesthesia time, surgical time, and total fluids received were recorded. During the course of the surgery, HR or mean arterial blood pressure (MAP) decreases of >20% of baseline were recorded. These variations were treated with atropine 0.4 mg IV or ephedrine 5 mg IV, respectively. HR and MAP increases of >20% were treated with labetalol 5 mg IV and also recorded. Total blood loss was calculated by weighing blood-soaked sponges in combination with blood scavenged from the field minus irrigation.
In the immediate postoperative period, HR and MAP were recorded on admission to the PACU and every 10 min for the first hour. Patients were assessed for pain, sedation, nausea, and vomiting using a Visual Analog Scale. Patients were instructed to place a line at the spot on the scale that best represented their pain, sedation, and nausea in which 0 = none and 10 = maximal effect. Fentanyl 25 µg IV was titrated every 5 min as needed to reduce pain scores to <3. Vomiting was assessed as positive or negative. The number of vomiting episodes was also recorded. If two episodes of vomiting occurred, this was considered severe, and was treated with ondansetron 4 mg IV. If vomiting persisted, trimethobenzamide 200 mg was administered rectally. Time to first rescue analgesia and movement were also recorded.
Over the next 24 h, any incidence of nausea and/or vomiting and severity of pain was assessed and recorded. Once patients were on the ward, meperidine 75–100 mg IM was given every 2 h as needed to keep pain scores <3. All analgesic doses were recorded. The number of hospital days, time to first void, and any incidence of complications (deep venous thrombosis, infections, bleeding, or changes in micturition) were also recorded before discharge from the hospital.
Results were statistically analyzed by using an analysis of variance with Tukey post hoc test for all pairwise comparisons. A P value < 0.05 was considered significant. A least significant difference pairwise multiple comparison test was used for variables comparing the number of patients or number of pain rescue doses and were also reported as significant at P < 0.05. All parametric values were reported as mean ± SEM. A 2 analysis was used to determine differences in the incidences of vomiting, antiemetic therapy, and all other nonparametric variables recorded.
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Results |
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Thirty patients from each group completed the study, but only 29 patients from the saline/SQ saline group were included. The excluded patient from this group was unable to tolerate the prone position while awake. His agitation was uncontrollable after the administration of midazolam and he subsequently received a general anesthetic.
Groups were demographically similar (Table 1). There were no significant differences in the extent of sensory and motor blockade among the groups (Table 2). Also, no difference was noted with regard to total anesthesia time, total surgical time, or amount of local anesthetic used. Data were also similar for the incidence of intraoperative bradycardia and hypotension. Approximately twice as many patients in the saline/SQ bup and saline/SQ saline groups required additional local anesthetic to be administered for intraoperative discomfort compared with patients who received epidural clonidine. Twenty percent of patients in the saline/SQ bup group had intraoperative nausea with much smaller values reported for the other three groups. Individuals who received saline/SQ bup required less fluid compared with the clonidine/SQ bup group, but blood loss was similar in all treatment groups (Table 2).
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Patients who received epidural clonidine had lower MAP in the PACU from admission through 1 to 60 min compared with those who received epidural saline (Table 3). HR was also slower in the PACU in patients who received epidural clonidine. These differences were statistically significant during the 40-, 50-, and 60-min time periods after PACU admission. No differences in postoperative patient sedation were noticed among the groups (Table 4).
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In the first 30 min after PACU admission, peak pain scores were significantly increased in the saline/SQ saline group compared with all other groups (Table 4). After 40 min in the PACU, those patients receiving epidural clonidine continued to have lower pain scores compared with patients who did not receive clonidine. The number of patients requiring a rescue dose of fentanyl to control postoperative pain was significantly decreased in all groups when compared with those who received only epidural saline with SQ saline at the incision site. In addition, compared with those patients who received epidural saline, the time interval before patients required a rescue analgesic for postoperative pain was longer in the patients who were given clonidine (Table 4). The amount of fentanyl administered was also significantly reduced in patients receiving both epidural clonidine plus SQ bupivacaine. Patients who received epidural clonidine also had a longer motor block after spinal anesthesia (Table 4).
In the intermediate recovery period after discharge from the PACU, no difference in pain scores was noted among the groups. However, there was a decrease in the number of rescue doses of meperidine in those individuals who received SQ bupivacaine compared with those who had no SQ injection of local anesthetic (Table 5). No differences were noted among the groups in postoperative discharge day, nausea, vomiting, urinary retention, or other complications.
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Discussion |
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A decrease in surgical time, reduced intraoperative hypertensive episodes, decreased blood loss, and less intraoperative pain and nausea are among the many reported advantages of spinal anesthesia compared with general anesthesia for patients undergoing lumbar laminectomy and microdisk surgery (1,2). Neuropathic pain that occurs from spine pathology is radiating and burning in nature. In many instances, it is not well controlled with opioids, whether administered systemically or intrathecally. Clonidine, however, has been shown to be beneficial in patients with neuropathically mediated pain (13) and is effective in pain symptoms related to spine pathology (8,9). It produces analgesia by mimicking the activation of descending noradrenergic pathways. Clonidine is effective in reducing neuropathic pain, especially in situations in which opioids may not be well tolerated or are ineffective (13). Neuropathic pain associated with radiculopathy or other spinal cord pathologies may involve the sympathetic nervous system (14). Sympathetic hyperactivity may be reduced from the administration of epidural clonidine through three mechanisms of action. Clonidine may inhibit nociceptive neurotransmitter release in the dorsal horn and sympathetic outflow in the spinal cord intermediolateral column (15). In addition, it may inhibit norepinephrine release from sympathetic terminals in the periphery (16). Lastly, epidural clonidine may also be reabsorbed into the systemic circulation where it reaches the
2 adrenoreceptors of the dorsal horn and provides analgesia by increasing the antinociceptive threshold of the spinal cord which activates the descending noradrenergic pathway to inhibit small-diameter afferent-induced substance P release (17) This is the first study to observe the effects of a combination bupivacaine spinal anesthetic with epidural clonidine in patients undergoing lumbar spine surgery with neuropathic pain. Several studies have demonstrated that the epidural and spinal administration of clonidine reduces postoperative MAP (7,18). We also noted better hemodynamic control in our patients with reduced MAP and decreased HR in the PACU when patients received epidural clonidine. No differences were noted in the incidence of intraoperative hypotension between patients who received epidural clonidine and those who did not. This suggests that the vasodilatation produced by the spinal anesthetic far outweighed the effect of clonidine which did not seem to have an additional hypotensive effect when combined with spinal anesthesia. Clonidine reduces blood pressure by inhibiting preganglionic sympathetic neural activity in the spinal cord. It can also reach the brainstem via systemic redistribution or cephalad spread in the cerebrospinal fluid, further contributing to decreased blood pressure. These same mechanisms may also be responsible for the noted decreases in HR after the administration of epidural clonidine.
Patients undergoing lumbar laminectomy experience severe pain during the postoperative period. Several studies have evaluated the use of intermittent epidural morphine for postoperative analgesia after lumbar laminectomy and found this technique superior to IM or IV patient-controlled analgesia dosing (20,21). Another study evaluated the effect of continuous epidural fentanyl infusions for control of postoperative pain and found a rapid onset of analgesia with a decrease in the incidence of respiratory depression, pruritus, nausea, and vomiting compared with patients who received epidural morphine (22). Although continuous epidural fentanyl after lumbar laminectomy provided better analgesia and fewer side effects than epidural morphine, it still produced side effects that were similar to patients who received IV patient-controlled analgesia therapy. In addition, no data are available concerning complications that may occur with an indwelling catheter in close proximity to a fresh surgical site.
Epidural clonidine enhanced immediate postoperative outcome by reducing pain, the number of patients receiving rescue doses of fentanyl, the amount of rescue fentanyl given, and an increase in the time to first rescue dose of analgesic. Clonidine prolongs sensory and motor block associated with intrathecal bupivacaine (23). Several studies have reported that the addition of epidural clonidine increased both sensory and motor block from intrathecal local anesthetics by approximately 31% (14). Clonidine blocks conduction of C and A 
fibers and increases potassium conductance, intensifying the neural block of local anesthetics (24). It may also cause local vasoconstriction in the clinical setting, reducing removal of local anesthetic. Our results agree with these findings. Patients who received epidural clonidine in conjunction with spinal bupivacaine required their first analgesic 3.7 ± 0.5 hours after surgery. This is in complete agreement with the other studies previously mentioned in which the average time of sensory block was 3.7 hours (14). Although clonidine prolonged motor block in our patients, this increase was not clinically significant and did not require a prolonged PACU admission. This is in agreement with the findings of Carabine et al. (11) who also found prolonged analgesia with minimal motor effects after epidural clonidine. That group also noted hypotension in the postoperative period, which was reported as clinically nonsignificant. We noted a relatively significant reduction in MAP in both groups who received epidural clonidine compared with those who received epidural saline. In addition, a mild reduction in HR was also noted in the clonidine-treated groups, suggesting an effect on sympathetic output produced by the drug rather than a prolongation in the effect of the spinal anesthetic.
Bonhomme et al. (25) recently evaluated the effect of epidural small-dose morphine in combination with clonidine for postoperative analgesia after lumbar disk surgery. They reported reduced pain with movement after surgery using small-dose clonidine and morphine, which was not manifest when a combination of bupivacaine and clonidine was used. Their patients experienced a frequent incidence of difficulty in initiating micturition (30%–45%) not seen in our population. This may be related to the fact that their patients received a general anesthetic in which both IV and epidural narcotics were given. Our patients received a spinal anesthetic with no intraoperative narcotics. Thus, spinal anesthesia with combina-tion epidural clonidine provided good postoperative analgesia with less of the side effects noted with combination general and epidural anesthesia. Urinary retention has not been noted with neuroaxial clonidine administration and, in fact, it may actually hasten the time to first micturition after spinal anesthesia (26). Our results show no difference in micturition problems among the groups which may reflect the opioid rescue doses used for postoperative pain.
Those patients receiving local SQ bupivacaine at the incision site in addition to epidural clonidine reported lower pain scores and had slower HRs in the PACU than those who did not receive the injection. In addition, the amount of rescue fentanyl to treat postoperative pain was minimal in the group that received both epidural clonidine and SQ bupivacaine compared with clonidine or SQ bupivacaine alone, suggesting a cumulative analgesic effect with combination therapy. Over time, however, it seems that patients who received SQ bupivacaine had a more prolonged analgesic effect compared with those who received epidural clonidine which may reflect the analgesic half-life of epidural clonidine (approximately 180 min) compared with the depot effect of SQ bupivacaine, which lasted approximately 13 hours after lumbar laminectomy when a 0.375% concentration was administered (27). Our results agree well with other studies that demonstrate that the administration of epidural clonidine produced 2–6 hours of analgesia with no increase in duration beyond a 400-µg dose (14). This duration of action is similar to that of epidural fentanyl and reflects clonidine’s lipid solubility.
There were no statistical differences in the number of patients experiencing nausea or vomiting in either the PACU or during the 24-hour postsurgical period. In addition, there seemed to be no sedative effect of epidural clonidine as demonstrated by no difference in Steward recovery scores among the groups. This is one of the noted advantages of administering epidural clonidine compared with other forms of analgesia.
This study demonstrates that the administration of epidural clonidine to spinal anesthesia for patients undergoing microdisk or lumbar laminectomy surgery produced better postoperative pain control and hemodynamic stability. Also, those patients receiving local bupivacaine in addition to epidural clonidine reported prolonged postoperative analgesia. There were no significant increases in the frequency of postoperative nausea or vomiting in the patients receiving epidural clonidine and no difference in intraoperative hemodynamic variables. Thus, epidural clonidine provided an important short-term analgesic benefit with minimal side effects.
In conclusion, spinal anesthesia produces good perioperative and superb intraoperative conditions for lower spine surgical procedures (1). Epidural cloni-dine as a supplement to spinal anesthesia improves immediate postoperative outcomes in the PACU by providing a stable hemodynamic profile while reducing pain and the need for narcotics with their negative side effects. Although the effect of epidural clonidine is short lived, the addition of SQ bupivacaine further improves the postoperative outcomes of these patients by prolonging pain relief and reducing the need for additional analgesia. We recommend this combination anesthetic as a superior technique compared with spinal anesthesia alone for improving outcomes after lower lumbar spine surgery.
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References |
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