Anesth Analg 2001;93:456-459
© 2001 International Anesthesia Research Society
REGIONAL ANESTHESIA
The Effect of Large-Dose Intrathecal Opioids on the Autonomic Nervous System
Mashallah Goodarzi, MD*, and
Rajalaxmi R. Narasimhan, MD
*Department of Clinical Anesthesia, University of Southern California, Keck School of Medicine; and Saint Jones Hospital, Los Angeles, California
Address correspondence and reprint requests to Mashallah Goodarzi, MD, Department of Anesthesia Mail # 3, Children’s Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027.
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Abstract
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Decreases in blood pressure after the spinal injection of opioids suggest that intrathecal (IT) opioids may have a sympatholytic effect similar to that of local anesthetic drugs. We compared two groups of patients aged 10–16 yr (n = 10 in each group). Group One (IT group) received IT opioids. Group Two (Epidural group) received 0.5% bupivacaine epidurally. The sympathetic effects of IT opioids and epidural bupivacaine were monitored by the changes in toe relative to calf temperature and by the changes in pulse wave gradients with digital plethysmography. Changes in temperature gradients comparing calf to toe and increases in pulse amplitude indicate vasodilatation caused by sympathetic blockade in this model. Calf to toe temperature gradients ( calf-toe) were evaluated by subtracting the two measurements. Pulse wave plethysmography was recorded before and after spinal and epidural injection at intervals of 10 min for 40 min. All patients demonstrated changes in their calf to toe gradients after IT and epidural injections (-3.2 ± 1.6). Systolic blood pressure decreased from a mean of 70 ± 15 mm Hg to 55 ± 10 mm Hg. Pulse wave plethysmography amplitude increased after the intrathecal opioid and epidural bupivacaine injection similarly. We conclude that the increases in pulse wave amplitude and decreases in calf–toe gradients indicate a sympatholytic effect after IT opioids similar to that of local anesthetics.
IMPLICATIONS: The sympatholytic effects of neuraxial opioids were compared with those of local anesthetics. Two groups of patients were assigned to receive a neuraxial opioid or bupivacaine. Our results demonstrate that opioids cause hypotension and peripheral vasodilatation similar to bupivacaine. This finding suggests that neuraxial opioids have a sympatholytic effect comparable to that of local anesthetic drugs.
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Introduction
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Conduction block in nerves can be produced by a variety of chemical compounds. The local anesthetic effects of opioids have been demonstrated in both clinical and laboratory studies. Some opioid compounds are as potent as local anesthetics (1). Intrathecal (IT) sufentanil used for labor analgesia decreases the blood pressure (BP) and causes sensory changes (2). This suggests that IT sufentanil may cause sympathetic blockade because of its local anesthetic effect. The local anesthetic effects of opioids are of particular interest because of their widespread use in epidural and spinal anesthetic techniques. Meperidine has been successfully used for spinal anesthesia with a comparable effect to lidocaine (3). The site of action and mechanism of autonomic block by IT sufentanil is unclear. There are opioid receptors in sensory axons (4). Conduction block in dorsal root axons may result from specific opioid receptor-mediated mechanisms or be the result of nonspecific membrane conduction blocking effects.
Objective evaluation of the autonomic blockade achieved with regional anesthesia in patients under general anesthesia is difficult. The use of digital plethysmography (5,6) and changes in skin temperature can demonstrate sympathetic blockade under general anesthesia (7,8). This study compared the magnitude of the sympathetic blocking effect of IT opioids to that of epidural bupivacaine.
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Methods
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After obtaining approval from the IRB and informed consent from the children’s parents, two groups of adolescents aged 10–16 yr were compared (n = 10 each). Group One (IT group) patients had idiopathic scoliosis and were scheduled for posterior spinal fusion; Group Two (Epidural group) patients were scheduled for major orthopedic surgery, such as open reduction of hip, total hip replacement, or femoral osteotomy. All patients were ASA I or II. None of the patients had any history or signs of autonomic dysfunction, sensory alteration, or cardiovascular disease. Patients were premedicated with 0.5 mg/kg midazolam orally 30 min before induction and were monitored with pulse oximetry, end-tidal CO2, electrocardiogram, arterial line, temperature, and urine output. Room temperature was maintained at 25°C–26°C. Other monitoring included placement of a temperature probe on the great toe and the lateral aspect of the midcalf before the induction of anesthesia. A digital plethysmograph with a recorder (M1020A; Hewlett-Packard, Palo Alto, CA) was attached to the opposite great toe.
Anesthesia was induced with an IV or inhaled anesthetic and maintained with 0.5%–1% isoflurane. After induction and intubation, Group One (IT group) received 10–15 µg/kg preservative-free morphine sulfate mixed with 50 µg sufentanil diluted with 2 mL of preservative-free normal saline IT. Group Two had an epidural catheter placed at L3-4 with a loss of resistance technique and received 2 mg/kg of 0.5% bupivacaine epidurally. End-tidal CO2 was maintained at 30–35 mm Hg, and patient temperature at different sites, BP, and digital wave plethysmography were monitored every 10 min before and after the IT or epidural injection for 40 min.
Statistical analysis consisted of Student’s t-tests for comparison of demographic data and repeated-measures analysis of variance for individual comparison to compare changes in temperature and BP over time. A P value <0.05 was considered significant.
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Results
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Demographic data for age and weight were comparable between the groups (Table 1). Mean age and weight for the IT group were 14 ± 3 yr and 46 ± 9 kg, and for the Epidural group they were 13 ± 6 yr and 39 ± 6 kg, respectively. The mean temperature gradient difference between calf and toe before induction was 3.1°C ± 1.1°C in both the Epidural and IT groups.
After the induction of anesthesia, the temperature gradients (calf - toe) decreased to -1.2°C ± 1.7°C in both groups and decreased significantly to -3.2°C ± 1.6°C after the injection of IT opioids or epidural bupivacaine (Fig. 1 and 2). Changes in the core temperature were comparable between the groups. Systolic BP decreased significantly in both IT and Epidural groups by 23 ± 14 mm Hg and 28 ± 18 mm Hg after the injection, respectively.
Hypotension (mean, 55–60 mm Hg) persisted in the IT opioids group during the scoliosis surgery, whereas the Epidural group required another dose of bupivacaine within 2–3 h to achieve the same BP. The pulse wave amplitude increased within 10 min after both blocks and attained peak amplitude at 20 min (Figs. 3, 4)
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Figure 3. Amplitude change in pulse wave plethysmography after the induction of general anesthesia and epidural bupivacaine injection.
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Figure 4. Amplitude change in pulse wave plethysmography after the induction of general anesthesia and injection of intrathecal opioids (ITO).
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Discussion
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IT opioids are effective for perioperative or postoperative pain management. Neuraxial opioids act on the opioid receptors in the spinal cord, and theoretically they should not block the autonomic and motor fibers or cause hypotension.
Cohen et al. (9) reported changes in sensation to pinprick and temperature after 10 µg of IT sufentanil for labor anesthesia. They also reported hypotension in some patients despite 500 mL of fluid loading of balanced salt solution before IT injection. Other studies have reported transient sensory changes with IT sufentanil, fentanyl, or meperidine, as well as a 14% incidence of hypotension after IT injection of alfentanil during labor. The explanation for these findings was that an IT opioid may exert a weak local anesthetic effect (10,11).
In support of this action, morphine blocks the action potentials in internally perfused squid giant axons by inhibiting changes in sodium conductance (12). Kosterlitz and Wallis (13) reported that both meperidine and methadone had significant local anesthetic effects on mammalian peripheral nerve fibers. Morphine also produced a dose-dependent reduction in compound action potential amplitude (14). Gissen et al. (15) described the effect of large concentrations of fentanyl (95 and 189 µM) and sufentanil (86 and 173 µM) on isolated rabbit vagus nerves maintained at 20°C–22°C. They reported a significant reduction in the amplitude of the A-fiber component of the compound action potential during exposure to the larger concentrations of both sufentanil (to approximately 34% of control) and fentanyl (to approximately 29% of control). Smaller reductions were noted when the nerve sheath was left intact.
This study demonstrated changes in temperature indices, plethysmography, and the occurrence of hypotension after the administration of IT opioids or epidural bupivacaine. Taken together, these studies suggest that neuraxial opioids have a local anesthetic effect in larger concentrations, whereas at smaller concentrations they may produce only segmental sensory block.
In this study, the administration of IT opioids and 0.5% epidural bupivacaine caused comparable hypotension and bradycardia within a few minutes of injection in both groups. The changes in calf-toe and plethysmography in our study showed that the IT opioid effect on axonal block under general anesthesia was similar to that of local anesthetics.
The differences between clinical and experimental observations are difficult to explain. The effect of small-dose IT opioids could be predominantly mediated via spinal cord opioid µ receptors rather than by a local anesthetic effect of conduction blockade. These findings suggest that IT opioids may have local anesthetic activity on nerve conduction. The site of action and the mechanism of IT opioids on sensory changes and BP remains unknown. It is possible that conduction block in dorsal root axons may be the result of specific opioid-receptor mechanisms or of nonspecific membrane conduction blocking effects. We used a large concentration of IT opioids that caused hypotension and peripheral vasodilatation. If these changes were because of an IT opioid effect on µ receptors in the spinal cord, as has been hypothesized, then the decreases in BP may have been caused by opioid-induced pain relief. This seems unlikely because our patients were under general anesthesia without pain or stress.
In comparing the effects of IT opioids with those of epidural bupivacaine, both groups showed comparable results. Even though there was uncertainty in separating analgesic effects from sensory changes in other studies, it can be hypothesized that large concentrations of IT opioids can have local anesthetic effects, as shown in laboratory studies. Whether the decrease in BP results from a sympathectomy caused by local anesthetic action or from pain relief remains controversial.
In conclusion, our findings demonstrate that large concentrations of IT opioids cause hypotension and peripheral vasodilatation, similar to epidural bupivacaine. These results strongly suggest that these changes result from a sympathectomy effect of neuraxial opioids comparable to local anesthetic drugs(16–19).
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Acknowledgments
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The authors thank Dr. Randal Wetzel for his guidance in preparing this manuscript.
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References
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Accepted for publication April 3, 2001.
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Abstract
Introduction
