Previous studies1–6 have reported that epidural anesthesia with various local anesthetics may reduce the requirements for general anesthesia or decrease the plasma concentration of cortisol, one of the hypothalamic-pituitary-adrenal stress hormones. However, the effects of low concentrations of ropivacaine administered epidurally on general anesthesia have not been previously evaluated. In this prospective, randomized, placebo-controlled study, we investigated combined epidural anesthesia with ropivacaine 0.375% on the stress hormone responses and anesthetic requirements in patients undergoing nephrectomy.
Forty consecutive patients, ASA I or II, undergoing nephrectomy for renal carcinoma with a surgical duration of about 2 h, were enrolled in this study. Each patient was randomly assigned to one of two groups, group R, combined general and epidural anesthesia during surgery; group C, standard general anesthesia for surgery. Informed written consent was obtained from all patients. The study was approved by the institutional ethics committee. Patients taking regular medication or who had a history of diabetes, hypertension, neuromuscular disease or bleeding diathesis, hypersensitivity to amide local anesthetics, or previous lumber surgery were excluded. No patients had any sign of autonomic dysfunction or cardiovascular disease, as detected by routine clinical laboratory tests.
All patients were premedicated with diazepam 0.1 mg/kg orally 30 min before the induction of anesthesia. In the operating room, after placement of the epidural catheter at T9–10, a test dose of 10 mL of 1% lidocaine (group R), or 10 mL of 0.9% normal saline (group C) was administered to exclude intrathecal catheter placement. Ten minutes later, group C received 0.9% normal saline and group R received 0.375% ropivacaine epidurally at 5 mL/h. The upper and lower levels of loss of pinprick sensations were determined using a short beveled 25-gauge needle in the midclavicular line bilaterally 15 min after the test dose. Motor block was assessed in both legs using the modified Bromage scale.
General anesthesia was initiated with combined target-controlled infusion of propofol-sufentanil. The propofol infusion was set to produce a blood concentration of 4 μg/mL and the sufentanil infusion was set to 1.5 ng/mL. The bispectral index score (BIS) was monitored using a BIS sensor (Aspect, Medical System, Natick, MA). Once the BIS value reached 40–50, the trachea was intubated. Ventilation was controlled with a tidal volume of 10 mL/kg and respiratory rate adjusted to maintain end-tidal carbon dioxide between 30 and 35 mm Hg. After endotracheal intubation, the target concentration of propofol was titrated to maintain BIS between 40 and 50. The doses of propofol and sufentanil for induction of anesthesia were noted.
Inadequate analgesia was defined as an increase of systolic arterial blood pressure (SBP) and/or heart rate (HR) by >20% baseline for >5 min in response to a surgical stimulus. In cases of inadequate analgesia, the target concentration of sufentanil was titrated upwards. Bradycardia, HR <55 bpm, was treated with 0.5 mg of atropine IV, and hypotension, decrease of SBP by more than 30% or SBP less than 90 mm Hg, was treated by infusion of lactated Ringer's solution and, if necessary, with ephedrine 5 mg IV.
Plasma samples were taken immediately before (T1), 2 min after tracheal intubation (T2), immediately after incision (T3), immediately after the initiation of celiac exploration (T4), 1 h after operation (T5), and immediately after extubation (T6) for measurements of epinephrine, glucose, and cortisol in each of the two groups. Concentrations of cortisol and epinephrine were determined by radioimmunoassay and glucose was determined by glucose analyzer (Lifescan company, America).
Sample size, based on the study by Shono et al.,7 was determined on the basis of the effect on one of the variables, cortisol concentration. Changes in the plasma concentrations of epinephrine, cortisol, glucoses, mean arterial blood pressure, and HR were calculated from relative changes from the baseline. Mean and changes in the plasma concentrations of epinephrine, cortisol, and glucoses were analyzed using repeated-measures analysis of variance and Dunnett's test or Student's t-test for post hoc testing. P < 0.05 was considered statistically significant.
Of the 40 patients enrolled in the study, two patients in each group had more than 400 mL blood loss intraoperatively and were excluded from the study. In addition, two patients in group R had no sensory block, whereas two patients in group C had detectable sensory levels. Thus, 32 patients (16 in each group) completed the study (Table 1). No patient had awareness, hypersensitivity reaction to ropivacaine, backache, or accidental dural tap.
Plasma concentrations of glucoses and cortisol were found to be higher at time T5 and T6 in group C when compared with group R (Fig. 1a and b, P < 0.05). The concentration of glucose remained constant until T5 and T6 when it increased significantly compared with baseline in each group (Fig. 1a, P < 0.01). The concentration of cortisol decreased significantly at T5 (P < 0.05) at time T3, T4, in group R compared with baseline values, whereas in group C at T5 and T6, significant increases (P < 0.05) were observed (Fig. 1b). At T5 and T6, cortisol levels were higher in group C compared with group R (P < 0.05).
The plasma concentration of epinephrine decreased immediately after start of incision (T3) compared with baseline in each group (P < 0.05), but there were no statistical differences between groups. However, at T4 and T6, the concentration increased significantly compared with the baseline values in group C (Fig. 1c, P > 0.05).
There was no statistical difference in the induction and maintenance doses of propofol in group R (Table 2). A significant reduction in the sufentanil requirement during maintenance of anesthesia was observed in group R compared with group C (P = 0.02) whereas the sufentanil induction was comparable in both groups. Six patients in group R and four in group C had hypotension, which was treated by additional lactated Ringer's solution infusion and IV ephedrine. Four patients in group R and two in group C had bradycardia, which was treated by atropine (Table 2).
Previous studies4–6 have suggested that epidural anesthesia may reduce the requirements for general anesthesia with different epidural anesthetics. Agarwal et al.4 administered 10 mL of 0.1% bupivacaine 20 min before induction of anesthesia and then a maintenance infusion at 6 mL/h. They reported a significant reduction in the dose requirement of propofol for induction and maintenance of anesthesia in patients who received epidural bupivacaine before anesthesia. Lu et al.8 administered 15 mL of 2% lidocaine epidurally with a maintenance infusion rate of 6 mL/h and reported that epidural lidocaine reduced the end-tidal concentration of desflurane required to maintain an adequate clinical effect by 42% compared with general anesthesia alone. Our study demonstrated that epidural 0.375% ropivacaine infused at 5 mL/h reduced the demand for sufentanil during maintenance of anesthesia perioperatively.
The most interesting finding of our study is that epidural 0.375% ropivacaine attenuates the plasma concentration of cortisol during nephrectomy. The effects of combined epidural/general anesthesia on the plasma concentrations of cortisol have been investigated in several studies. Aono et al.3 demonstrated that catecholamines did not increase significantly in patients receiving general anesthesia combined with epidural anesthesia, whereas cortisol levels increased in the two anesthesia techniques. They considered that thoracic epidural anesthesia depressed the sympathetic response presumably by blocking afferent sympathetic pathways, and concluded2,3,7 that epidural anesthesia suppressed the increase of hormonal response during lower abdominal surgery while incompletely inhibited the stress response during upper abdominal or thoracic surgery. Our finding that combined epidural/general anesthesia with 0.375% ropivacaine during upper abdominal surgery (nephrectomy) suppressed the increase of cortisol responses was surprising. However, the underlying mechanism needs further research.
In conclusion, epidural ropivacaine 0.375%, compared with general anesthesia alone, reduced the demand for sufentanil during maintenance of anesthesia and suppressed stress hormone responses intraoperatively and in the early postoperative period for patients undergoing nephrectomy.
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