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REGIONAL ANESTHESIA

The Effects of Age on the Median Effective Concentration of Ropivacaine for Motor Blockade After Epidural Anesthesia with Ropivacaine

Department of Anesthesiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China

Address correspondence and reprint requests to Yuhong Li, PhD, Department of Anesthesiology, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003 Hangzhou, People’s Republic of China. Address e-mail to yuh_li2002{at}hotmail.com.

	Abstract

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Minimal local analgesic concentrations have been defined as the median effective concentration (EC₅₀). In this study, we sought to examine the effect of age on motor blockade and determine the motor block EC₅₀ of elderly patients after epidural administration of ropivacaine in patients undergoing urological or minor lower limb surgery. ASA physical status I–II patients were enrolled in 1 of 2 age groups (Group 1: 70 yr; Group 2: <70 yr). Each received a 15-mL bolus of epidural ropivacaine without epinephrine. The first patient in each group received 0.425%. Up-down sequential allocation was used to determine subsequent concentrations at a testing interval of 0.025%. Effective motor blockade was defined as a modified Bromage score >0 within 30 min. The motor blockade EC₅₀ of ropivacaine was 0.383% (95% confidence interval, 0.358%–0. 409%) in group 1 and 0.536% (95% confidence interval, 0.512%–0.556%) in group 2 (P < 0.01). We conclude that age is a determinant of motor blockade EC₅₀ of ropivacaine with epidural administration.

	Introduction

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Lumber epidural anesthesia is often used in elderly patients as part of an anesthetic regimen for transurethral urological or lower limb surgery. In patients with an average age of 73 yr, epidural bupivacaine produces a shorter onset, a higher sensory level of blockade, and longer duration of anesthesia compared with younger volunteers, average age 25 yr (1). The terminal half-life increased and the total plasma clearance of bupivacaine decreased with increased age (2). During epidural blockade, the use of ropivacaine in patients older than 61 yr resulted in more intense motor blockade and a higher upper level of analgesia than in patients 18–40 yr (3).

The character of anesthesia, analgesia, and motor blockade after epidural administration is dependent on the volume, concentration, and dose of local anesthetic administrated. Ropivacaine is a long-acting local anesthetic that only contains the pure S (-)-enantiomer. This formulation is very promising for elderly patients because of its reduced central nervous system and cardiotoxic potential and its decreased propensity for motor block, while retaining the differential blockade properties (4,5).

The minimal local analgesic concentration (MLAC) has been defined as the median effective concentration (EC₅₀) for epidural analgesia in the first stage of labor (6–8). When the MLAC methodology is used to determine the EC₅₀ for motor blockade for epidural analgesia, we can define this as the motor block minimal local analgesic concentration (MMLAC). MMLAC studies have reported that the overall EC₅₀ for motor blockade during epidural anesthesia in lower limb surgery was 0.414% (95% confidence interval [CI], 0.411%–0.416%) (9). There is no gender effect in motor blockade EC₅₀ of epidural ropivacaine (9). However, the effect of age on motor blockade EC₅₀ of epidural ropivacaine has not been studied. Our aim was to use the MMLAC methodology to determine the motor blockade EC₅₀ for epidural anesthesia in elderly patients and to investigate whether age affects motor blockade EC₅₀ of epidural ropivacaine.

	Methods

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After obtaining approval from the hospital’s Human Investigation Committee and written informed consent from the patients, 80 ASA physical status I–II patients were enrolled into one of two groups according to age (Group 1: 70 yr; Group 2: <70 yr). All patients underwent transurethral urological or minor lower limb surgery. Patients with a history of diabetes, neuromuscular disease or bleeding diathesis, clinically significant peripheral arteriosclerosis, or hypersensitivity to amide local anesthetics, previous lumbar surgery, radiculopathy, or chronic back pain and pregnant women were excluded.

Participants were allocated to one of two groups in a double-blind, prospective study design. The anesthesiologist performing the procedure and subsequent assessment was blinded as to the concentration. All patients were premedicated with diazepam 5 mg (<70 yr) or 2.5 mg (70 yr) orally 30 min before the induction of epidural anesthesia. After IV prehydration with 500 mL of lactated Ringer’s solution, patients were placed in the flexed lateral position. The epidural space was identified with the loss of resistance to air technique at the L_2–3 or L_3–4 level. Every puncture was performed with a 16-gauge Tuohy epidural needle. A multiorifice epidural catheter was advanced 3 cm in a cephalad direction into the epidural space. For the purpose of this study, the test dose was omitted. After negative aspiration for cerebrospinal fluid or blood, 15 mL of ropivacaine (Naropin®; AstraZeneca, Sodertalje, Sweden) without epinephrine was administered slowly at a rate of 1 mL/s through the catheter. The patient was then placed in the horizontal supine position.

The concentration of ropivacaine administered to a particular patient was determined by the response of the previous patient, using an up-down sequential allocation technique. The testing interval was 0.025% weight/vol. The first patient in each group received 0.425% weight/vol ropivacaine based on prior pilot data (9).

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 for the first 30 min. Motor strength was assessed in both legs using the modified Bromage scale (0 = able to perform a full straight leg raise over the bed for 5 s, 1 = unable to perform the leg raise but can flex the leg on the knee articulation, 2 = unable to flex the knee but can flex the ankle articulation, 3 = complete motor blockade). The maximum motor blockade 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. A Bromage score of 0 was considered ineffective. Any other response on either leg was effective. Outcomes for motor blockade were defined as follows:

Effective: Bromage score >0 at 30 min of injection on either leg. A result defined as effective directed a 0.025% weight/vol decrease for the next patient enrolled to that group.

Ineffective: Bromage score unchanged at 0 within 30 min of injection on both legs. A result defined as ineffective directed a 0.025% weight/vol increase for the next patient enrolled to that group.

After the evaluation at 30 min, the study was complete and the epidural was dosed according to the criteria of the attending anesthesiologist.

Systemic arterial blood pressure, measured with an automatic cycling device (Cardiocap; Datex-Ohmeda, Helsinki, Finland), and heart rate, from the electrocardiogram, were recorded throughout the study at 5-min intervals. Hypotension was defined as a decrease in systolic blood pressure by more than 30% of the preanesthetic value or a systolic blood pressure <90 mm Hg. Hypotension was treated by administering ephedrine 6 mg IV and crystalloid fluids. Bradycardia (<55 bpm) was treated by administering 0.5 mg of atropine IV.

Demographic data were presented as a median (range) and count (n) as appropriate. Medians (ranges) were analyzed by using the Mann-Whitney U-test, and counts or proportions were analyzed by using the Fisher’s exact test. The median effective concentrations were estimated from the up-down sequences by using the method of Dixon and Massey (10–12). The following software packages were used to perform analyses: Excel 2000 (Microsoft, Redmond, WA) and SPSS 11.0 (SPSS Inc., Chicago, IL). Statistical significance was defined for overall error at the 0.05 level. All P values were two sided. Sample-size estimation was based on the standard deviation (sd 0.08%). Power was set at 0.9 with a minimal difference of 0.1% in potency to be significant.

	Results

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Seventy patients were enrolled in the study (Table 1). The number of patients in the two study groups differed slightly because of the difficulties encountered in the recruitment of elderly patients. In group 2 more patients were classified as ASA I, whereas in group 1 more were classified as ASA II (P < 0.01).

Table 2 demonstrates the sensory and motor blockade data of the two age groups. There were no significant differences between the age groups in the upper level achieved for pinprick sensation or onset time of motor blockade. However, the maximum degree of motor blockade in effective subjects was greater in the elderly group (P = 0.008).

Figure 1 shows the sequences of effective and ineffective motor blockade. Using the formula of Dixon and Massey (10–12), EC₅₀ of ropivacaine for motor blockade in elderly patients was 0.383% (95% CI, 0.358%–0.409%) and in young patients was 0.536% (95% CI, 0.512%–0.556%) (P < 0.001).

View larger version (25K): [in this window] [in a new window]   Figure 1. The motor median effective local analgesic concentrations (EC50) of ropivacaine of patient in two age groups as determined by technique of up-down sequential allocation. Error bars represent 95% confidence interval. (Group 1: 70 yr; Group 2: <70 yr)

Hemodynamic data are shown in Table 3. Median baseline values for heart rate were not different for the two age groups, nor were the times to reach the minimal value for heart rate or the maximal decrease in heart rate or the incidence of bradycardia during the 30 min after the induction of epidural anesthesia. Median baseline values for systolic and diastolic blood pressure were different between the age groups (P = 0.0001 and P = 0.013), with values being higher in the older age group. The maximal decrease in mean arterial blood pressure (MAP) during 30 min after the induction of epidural anesthesia, the time to maximum decrease in MAP, or the number of patients suffering from hypotension did not differ between the groups.

	Discussion

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This is the first study to specifically assess EC₅₀ for motor blockade in elderly patients receiving epidural anesthesia with ropivacaine. The MLAC study design is a very useful tool because it allows the estimation of the EC₅₀ of epidurally administered local anesthesia, which produces a defined outcome (EC₅₀) (10–14). We have shown that the MMLAC of ropivacaine in younger patients is 50% larger than in the elderly patients.

A modified Bromage scale was used to evaluate the lower extremity. In our study, we wanted to detect subtle diminutions in muscle strength and evaluate maximum motor block. To improve sensitivity, we also asked the patients to perform a knee and ankle bend and scored according to the degree of motor block.

In this study, we chose the up-down sequential allocation technique rather than random allocation because of the ease with which it estimates EC₅₀ of a sample. This technique has also been applied to determine dose-response pharmacodynamics for inhaled and IV anesthetics (15–17). Further, this technique can be more efficient (30%–80% reduction) in the sample size required than other methods that allocate to a predetermined fixed testing level (10,11,18). Using this up-down sequential allocation technique, the concentration of ropivacaine received by a particular patient was determined by the response of the previous patient. If we had used the random allocation method to perform this study, the larger dose of epidural anesthetics may have resulted in a higher upper level of anesthesia and potentially more intense hemodynamic change (3).

This study showed that with increasing age the EC₅₀ of ropivacaine for motor blockade decreased. Likewise, over varying concentrations epidurally, the degree of motor blockade was more intense in the older compared with the younger patients. However, it is surprising that the sensory block and hemodynamic data did not increase with increasing age in the first 30 min. This is a further advantage of this study design. Previous studies have shown a higher level of sensory block in elderly patients after bupivacaine and ropivacaine administration compared with younger patients (1–3).

This study was designed to compare two distinct populations of different ages. Patients enrolled were divided preoperatively into two groups, and during the study design we selected the threshold of 70 years as the limit between these two age groups to ensure that the elderly patients would be physiologically old patients. It should be noted that in this study almost half of the young group comprised patients aged more than 50 years. Therefore, the age difference between the two groups was not large. Age is generally thought to influence motor and sensory analgesia (1–3). It is evident that ropivacaine has the property of separation between motor and sensory analgesia in small doses. In our study, in the two age groups, the degree of motor blockade was more intense, but sensory analgesia remained the same in the elderly group.

In conclusion, we present the motor block EC₅₀ (MMLAC) for ropivacaine after epidural ropivacaine administration in elderly patients undergoing transurethral urological or minor lower limb surgery. Although we cannot completely exclude a theoretically minor influence of ASA physical status and MAP on the EC₅₀ of local anesthesia, this study demonstrates for the first time that with advancing age, the motor block EC₅₀ of ropivacaine decreases significantly. In clinical practice we can titrate the dose of ropivacaine according to the EC₅₀ for elderly patients undergoing transurethral urological or minor lower limb surgery where muscle relaxation is not necessary. However, further studies are required to determine the optimum dose for epidural anesthesia in the elderly patient for other operations requiring complete muscle relaxation.

	Footnotes

 
Accepted for publication January 24, 2006.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Li, Y. Articles by Jin, X. Search for Related Content PubMed PubMed Citation Articles by Li, Y. Articles by Jin, X. Related Collections Regional Anesthesia Pharmacology