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© 2002 International Anesthesia Research Society
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Abstract |
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We studied the influence of age on the neural blockade and hemodynamic changes after the epidural administration of ropivacaine 1.0% in patients undergoing orthopedic, urological, gynecological, or lower abdominal surgery. Fifty-four patients were enrolled in one of three age groups (Group 1: 18–40 yr; Group 2: 41–60 yr; Group 3:
61 yr). After a test dose of 3 mL of prilocaine 1.0% with epinephrine 5 µg/mL, 15 mL of ropivacaine 1.0% was administered epidurally. The level of analgesia and degree of motor blockade were assessed, and hemodynamic variables were recorded at standardized intervals. The upper level of analgesia differed among all groups (medians: Group 1: T8; Group 2: T6; Group 3: T4). Motor blockade was more intense in the oldest compared with the youngest age group. The incidence of bradycardia and hypotension and the maximal decrease in mean arterial blood pressure during the first hour after the epidural injection (median of Group 1: 11 mm Hg; Group 2: 16 mm Hg; Group 3: 29 mm Hg) were more frequent in the oldest age group. We conclude that age influences the clinical profile of ropivacaine 1.0%. The hemodynamic effects in older patients may be caused by the high thoracic spread of analgesia, although a diminished hemodynamic homeostasis may contribute. IMPLICATIONS: Analgesia levels after the epidural administration of 15 mL of ropivacaine 1.0% increase with increasing age. This is associated with an increased incidence of hypotension in the elderly, although an effect of age on the hemodynamic homeostasis may have contributed. It appears that epidural doses should be adjusted for elderly patients.
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Introduction |
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As the elderly population continues to increase, the number of elderly surgical patients will continue to grow. Lumbar epidural anesthesia is often used in elderly patients as part of an anesthetic regimen for orthopedic, urological, gynecological, or lower abdominal surgery. Studies in our institute have shown that elderly patients are more sensitive to epidural anesthesia with bupivacaine (1,2). In these studies, the upper levels of analgesia increased, and the time until maximal caudad spread decreased with increasing age. Furthermore, elderly patients had a faster onset and an enhanced intensity of motor blockade.
Ropivacaine, a recently introduced long-acting local anesthetic, which only contains the S(-)-enantiomer, has proven in clinical studies to provide effective epidural anesthesia in concentrations ranging from 0.5%–1.0% (3). Studies in animals and in humans have shown that, compared with bupivacaine, the systemic toxicity of ropivacaine is reduced (4–6).
Although ropivacaine is frequently used in elderly patients, there are fewer data about the effect of age on the sensory and motor blockade and hemodynamic changes after epidural anesthesia with ropivacaine. The primary objective of this study was to confirm or refute the hypothesis that age affects the upper analgesia levels after the epidural administration of a fixed dose of ropivacaine. In addition, other aspects of neural blockade and hemodynamic changes were studied.
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Methods |
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The protocol of this study was reviewed and approved by the Committee on Medical Ethics of the Leiden University Medical Center. Fifty-five ASA physical status I or II patients who had given their informed consent were enrolled in one of three groups according to their age (Group 1: 18–40 yr; Group 2: 41–60 yr; Group 3:
61 yr). They underwent minor orthopedic, urological, gynecological (excluding obstetrics), or lower abdominal surgery. Patients who had diabetes, had a history of neuromuscular disease or bleeding diathesis, were suffering from clinically significant peripheral arteriosclerosis, or were hypersensitive to amide local anesthetics were excluded. Those who had a history of previous lumbar surgery, radiculopathy, or chronic back pain, weighed more than 110 kg, or were shorter than 150 cm were also excluded. In addition, pregnant women were excluded.
Patients were fasting from midnight until before surgery. Antihypertensive medication was continued on the day of surgery. Patients were premedicated with temazepam 20 mg (<60 yr) or 10 mg (60 yr) orally 45 min before the induction of epidural anesthesia. A rapid IV infusion of 500 mL of saline 0.9% was administered before the induction of epidural anesthesia, and subsequently, an infusion rate of 2 mL · kg-1 · h-1 was maintained. The epidural puncture was performed with the patient in the sitting position at the L3-4 interspace using a midline or paramedian approach. The appropriate lumbar interspace was determined by counting the spines of the vertebrae from both the cranial and caudal directions, and the iliac crest was palpated to confirm the position of the L4 vertebra. After local infiltration of the skin with prilocaine 1.0%, the epidural space was identified with the loss of resistance to the saline technique. Subsequently, with the bevel of a 16-gauge Tuohy epidural needle pointing cephalad, a test dose of 3 mL of prilocaine 1.0% with epinephrine 5 µg/mL was administered. Three minutes later, when there were no signs of inadvertent intravascular or subarachnoid injection and after negative aspiration of cerebrospinal fluid or blood, 15 mL of ropivacaine 1.0% (AstraZeneca, Södertälje, Sweden) was administered slowly at a rate of 1 mL/s. The patient was then placed in the horizontal supine position.
Systemic arterial blood pressure, measured with an automatic cycling device (Cardiocap, Datex-Ohmeda, Helsinki, Finland), and heart rate, from the electrocardiogram, were recorded at the ward before the epidural administration of ropivacaine, during the induction of epidural anesthesia, and during surgery. They were recorded at 5-min intervals during the first 0.5 h after the induction of anesthesia and thereafter at 15-min intervals until at least 30 min after arrival at the recovery room. Reference values for heart rate and mean arterial blood pressure (MAP) were calculated by averaging the values obtained at the ward before the epidural administration and at its completion. When the coefficient of variation exceeded 20%, or when the ratio of the maximum of the 3 values and the mean value exceeded 1.20, the average of the 2 lowest values were taken as the baseline value. Hypotension was defined as a decrease in systolic blood pressure more than 30% of the preanesthetic value or a systolic blood pressure <90 mm Hg. Hypotension was treated by administering ephedrine 5 mg IV and crystalloid fluids. Bradycardia (<55 bpm) was treated by administering 0.5 mg of atropine IV.
Analgesia was assessed bilaterally in the anterior axillary line by pinprick using a short beveled 25-gauge needle. Analgesia was defined as the inability to detect a sharp pinprick. Results from both sides were averaged. Assessments were made every 5 min during the first 30 min and subsequently every 15 min until complete regression of the sensory blockade. Motor blockade of the lower limb was evaluated by asking the patient to raise the extended leg (flexion of the hip) and to flex the knee and ankle, and it was rated per joint (0 = no blockade, 1 = partial blockade, 2 = complete blockade). The results obtained in both extremities were added, giving a maximum score of 12 (complete motor blockade). Assessments of motor blockade were made immediately after the assessment of the analgesia levels.
Sample sizes were calculated as described by Zar (7). On the basis of a previous study with bupivacaine (2), we assumed a within-groups variance of 3.38 in the upper level of analgesia, the primary outcome variable. A difference of 2 segments in the upper level of analgesia was considered significant. With a two-sided type 1 error of 0.05 and a power of at least 0.80, 18 patients per group (total 54 patients) were required to reveal a difference in the upper level of analgesia of 2 segments between any 2 groups. Frequencies or population percentages were compared using the 
2 test where appropriate. The distribution of analgesia and motor blockade data, and the values of the hemodynamic variables, were tested for normality using the Kolmogorov-Smirnov test (8). Although some variables (times to regression over 2 and 4 segments and times until total recovery from analgesia and motor blockade) met the criteria of a normal distribution, we decided to analyze the data nonparametrically. The Kruskal-Wallis test was used to test whether at least one of the groups had a different distribution. When a significant difference was observed, groups were compared two by two using the Mann-Whitney U-test. Subsequently, the estimate for the mean difference between the two groups and the 95% confidence interval (95% CI) for the median difference were calculated (9). The sequentially rejective Bonferroni-Holm method (10) (i.e., the largest difference between the age groups was required to attain significance at the 0.0167 level, the second largest difference at the 0.025 level, and the smallest difference at the 0.05 level to attain an overall significance level of 0.05) was used to adjust for multiple comparisons in all statistical analyses. All statistics were calculated using the software package SPSS 10.0 (SPSS Inc, Chicago, IL).
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Results |
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Group characteristics and demographic data are presented in Table 1. Fifty-four of 55 patients who received the epidural dose were analyzed. One patient was excluded from analysis because a spinal tap occurred. Of those included, one experienced pain at the site of surgery, which was treated with a single dose of alfentanil 0.5 mg IV, and one received propofol sedation during surgery because of anxiety. Three patients suffered from surgical complications: one patient had a bladder perforation, one acquired the transurethral resection-syndrome, and one had a mild allergic reaction to chlorhexidine. The number of patients in the three study groups differed slightly. Because of the difficulties encountered in the recruitment of younger patients, it was decided to include patients regardless of their age after 50 patients had been recruited. The ratios of men to women were comparable among the groups. In the youngest age group, more patients were ASA I, whereas in the oldest age group, more were ASA II. The patients’ height differed among the age groups (P = 0.04). The median difference between the youngest and oldest age group was 8 cm (95% CI, 2–14). Four patients (one in the middle age group and three in the oldest age group) had well documented hypertension and were treated with ß-antagonist medication.
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Values of the variables of analgesia and motor blockade are shown in Table 2. The upper level of analgesia was different among all groups (P = 0.001), being lowest in the youngest group and highest in the oldest group of patients (Fig. 1). The median difference between the youngest and middle age group was 2 segments (95% CI, 0.5–4), between the middle and oldest group 1.5 segments (95% CI, 0–3), and between the youngest and oldest group 3.5 segments (95% CI, 3–5). The time from maximal cephalad spread of analgesia until the upper level of analgesia had regressed by two segments was different among age groups. Median differences were 52 min (95% CI, 8–98) and 70 min (95% CI, 60–118) when the youngest group was compared with the middle and oldest age groups, respectively. No difference among groups were observed for time to initial onset of analgesia at dermatome level L1-2, time until maximum caudad and cephalad spread, time from maximal cephalad spread until the upper level of analgesia had regressed by four segments, and time until total recovery from analgesia. Maximum degree of motor blockade was different among age groups (P = 0.003). The median difference between the youngest and the oldest age group was 3 (95% CI, 1–4), being less intense in the youngest age group. Time to initial onset of motor blockade and time until a complete recovery from motor blockade were not different among the age groups.
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Hemodynamic data are shown in Table 3. Median reference values for heart rate were not different for the three age groups, nor were the times to reach the minimal value for heart rate or the maximal decrease in heart rate during the first hour after the induction of epidural anesthesia. However, the incidence of bradycardia was more frequent in the oldest age group than in the other two groups (
2 = 8.5; P = 0.01). One patient in the youngest age group suffered from severe bradycardia that was treated by precordial thump and IV atropine. Recovery was uneventful. Median reference values for the MAP were different among the age groups (P < 0.007), being highest in the oldest age group. The median difference between the youngest and oldest group was 10 mm Hg (95% CI, 4–16). The maximal decrease in MAP during the first hour after the induction of epidural analgesia differed among age groups (P < 0.0001), being largest in the oldest group (Fig. 2). The median difference in the maximal decrease of MAP between the middle and oldest group was 15 mm Hg (95% CI, 7–23) and 19 mm Hg (95% CI, 11–28) between the youngest and oldest group. The time until the minimum value of MAP was reached did not differ among the groups. The number of patients suffering from hypotension differed among the groups (2 = 10.2; P = 0.006), being smallest in the youngest group and largest in the oldest group of patients.
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Discussion |
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This study showed that with increasing age the highest level of analgesia increased. In addition, motor blockade was more intense in the oldest compared with the youngest patients. We found no effect of age on the time to maximal caudad spread of analgesia and onset of motor blockade, as was observed in previous studies with bupivacaine (1,2). The maximum decrease of MAP during the first hour after the epidural administration was more profound, and the number of patients that had one or more episodes of hypotension or bradycardia was increased in the oldest group.
Elderly patients exhibit anatomical and physiologic changes that influence the clinical course during epidural anesthesia. An increased sensitivity to local anesthetics, as in older patients, can be attributed to the declining number of myelinated fibers in the dorsal and ventral roots and to the increased permeability, which is caused by the deterioration of myelin sheaths (11). In older patients, the longitudinal spread of the local anesthetic in the epidural space is promoted by sclerosis and calcification of the intervertebral foramina (11–13) and a reduced fatty tissue content of the epidural space (14). This reduction can contribute to a more compliant and less resistant extradural space (14,15). Furthermore, the number of axons in peripheral nerves decreases with advancing age, and the conduction velocity diminishes, particularly in motor nerves (16). The clinical course of epidural anesthesia may be further influenced by a shift of the site of action from a predominantly paravertebral site in the young to a subdural or transdural site in the elderly. This may be partly caused by an increased permeability for local anesthetics of the dura because of an increased size of the arachnoid villi (11). With increasing age, changes in the connective tissue ground substances may result in changes in local distribution, i.e., in the distribution rate of the local anesthetic from the site of injection (the epidural space) to the sites of action (17).
Some investigators, while evaluating the influence of age on the analgesic spread, demonstrated an increased upper level of analgesia with advancing age after a fixed epidural dose of a local anesthetic (1,2,18,19). However, others found that the influence of age on the upper level of analgesia varies with different volumes, and they emphasized the interindividual variability (20–22).
Veering et al. (1,2) studied the influence of age on the clinical profile of bupivacaine 0.5% after epidural administration. They demonstrated that the highest analgesia level and intensity of motor blockade increased with age. Wolff et al. (23) studied 3 groups of mainly elderly patients (mean age: 60–65 years) and found a high cephalad spread (median: T4 in all groups) after a fixed epidural dose of different concentrations of ropivacaine (20 mL of either 0.5%, 0.75%, or 1.0%) and an intense motor blockade with the 1.0% solution.
In contrast to previous studies with bupivacaine (1,2), the time to maximal caudad spread and time to initial onset of motor blockade were not different among age groups in our study. These findings can be explained by the large concentration of the solution used in our study. A large concentration of the local anesthetic solution at the sites of action may have promoted a rapid onset of analgesia at the caudal segments and a rapid onset of motor blockade in all age groups. This could have masked the influence of age on these variables. The reason for choosing a concentration of 1.0% ropivacaine was that it had proved to provide excellent epidural anesthesia for orthopedic surgery.
The difference in height between the youngest and oldest age group corresponds with the increase in average height of the Dutch population (1.3 cm per 10 years during the past 50 years). Because differences in the length of the back are relatively small compared with differences in height, and height is weakly correlated with the number of spinal segments blocked, these differences will not affect the results of this study (24).
Our study demonstrated that the epidural administration of 15 mL of ropivacaine 1.0% was associated with a significant decrease in MAP, particularly in the oldest age group. Nine of the 19 eldest patients experienced a decrease in MAP >30% during the first hour after the epidural induction of anesthesia. The most likely explanation for the hypotension is the high cephalad spread of analgesia because all patients experiencing hypotension had the highest level of analgesia above the T5-dermatome. Nevertheless, a detrimental effect of age on hemodynamic homeostasis could have contributed to the observed hemodynamic changes.
Hypotension is frequent with high levels of epidural anesthesia because of blockade of the preganglionic sympathetic nerve fibers leading to relative hypovolemia and decreased venous return (25). Splanchnic nerve blockade (T6-L1) will result in pooling of the blood in capacitance vessels of the splanchnic bed, contributing to the observed hypotension in patients with high levels of analgesia. In addition, decreased cardiac reserves, structural changes in the arterioles, and changes in the autonomic nervous system with increasing age may contribute to substantial hypotension in elderly patients. Epidural anesthesia extending to high thoracic levels (T1-4) leads to blockade of the preganglionic cardioaccelerator nerve fibers. This may result in reduction of the heart rate. The development of bradycardia after lumbar epidural analgesia extending to low thoracic levels may be the result of decreased cardiac sympathetic tone, decreased venous tone, reflex decrease in heart rate resulting from a decreased degree of pacemaker stretch, or reflex decrease in heart rate mediated via ventricular mechanoreceptors (25).
The hemodynamic effects after the lumbar epidural administration of a local anesthetic in elderly patients has been poorly studied. Wolff et al. (23) found a frequent incidence of hypotension and bradycardia with either 20 mL of ropivacaine 0.75% or 1.0% in elderly patients. A further reduction of the volume of the local anesthetic solution seems to be feasible because in our study the administration of 15 mL was also associated with a frequent incidence of hypotension and bradycardia in older patients.
In conclusion, age influences the clinical profile of ropivacaine 1.0% after an epidural administration. With advancing age, the upper level of analgesia and the intensity of the motor blockade increase. Although this solution provides effective epidural anesthesia, it is associated with a frequent incidence of bradycardia and hypotension, particularly in elderly patients. Whether this is merely a consequence of the high level of anesthesia or an additional effect of age on the hemodynamic effects of epidural anesthesia requires clarification. Further studies are required to determine the optimum dose to provide epidural anesthesia in the elderly patient.
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Acknowledgments |
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Supported financially and ropivacaine was supplied by AstraZeneca, Zoetermeer, The Netherlands.
The authors thank Chantal Sijstermanns, Dorinne Ruijgh, Clarissa Vergunst, Ellen Minkenberg, Koen Deurloo, Maarten Verschuure, and Nils Kock for their valuable clinical assistance.
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Footnotes |
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Presented, in part, at the XVII Annual Congress of the European Society of Regional Anaesthesia, Geneva, Switzerland, September 16–19, 1998.
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References |
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