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Ambulatory Anesthesiology: Research Reports

Low-Dose 3 mg Levobupivacaine Plus 10 μg Fentanyl Selective Spinal Anesthesia for Gynecological Outpatient Laparoscopy

de Santiago, Jesus DESA, MD*; Santos-Yglesias, Javier MD*; Giron, Jorge MD*; Montes de Oca, Francisco MD; Jimenez, Alejandro PhD; Diaz, Pilar PhD§

Author Information
doi: 10.1213/ANE.0b013e3181ba792e

Abstract

Lidocaine selective spinal anesthesia (SSA) has been confirmed as a satisfactory alternative to general anesthesia (GA) for short-duration outpatient laparoscopy.1–7 SSA has been defined as “the practice of employing minimal doses of intrathecal agents so that only the nerve roots supplying a specific area and only the modalities that require to be anesthetized are affected.”4

However, the possibility of developing transient neurologic symptoms (TNSs) after spinal lidocaine injection at this dosage remains a theoretical limitation of this technique, especially in at-risk patients such as outpatients.8 However, there are no available data on the incidence of TNSs when a very low dose of spinal lidocaine is administered nor have any comparisons been made with long-acting amide local anesthetics, which have the lowest incidence of TNSs.9 Long-acting amide local anesthetics are used at low doses for outpatient spinal anesthesia.10,11 Levobupivacaine, a long-acting amide local anesthetic, may be an alternative to lidocaine for SSA and, moreover, has been suggested to produce less motor block than bupivacaine when administered intrathecally at low doses.12 Intrathecal fentanyl added to low-dose local anesthetics produces a synergistic effect without increasing the sympathetic block or delaying discharge.13

Because lidocaine SSA has proven to be effective for short gynecological outpatient laparoscopy, we chose it as the comparator for this study. The aim of this prospective, randomized, double-blind study was to compare the sensory block resolution time after levobupivacaine-fentanyl versus lidocaine-fentanyl spinal anesthesia during short-duration gynecological laparoscopy, and determine whether levobupivacaine could be used as a substitute for lidocaine. A difference of 25 min on sensory block resolution time can be considered clinically relevant in the short-duration outpatient laparoscopy setting. We hypothesized that the difference of sensory block resolution time between 3 mg levobupivacaine plus 10 μg fentanyl and 10 mg lidocaine plus 10 μg fentanyl spinal anesthesia would not be clinically relevant.

METHODS

After approval from the Hospital Ethics Committee and written patient consent, 52 ASA physical status I–II individuals scheduled for tubal sterilization were enrolled in the study. Patients allergic to any of the study drugs, with morbid obesity (body mass index >40), or having a contraindication to spinal anesthesia were excluded. Patients unable to understand the study protocol because of language problems or other reasons were also excluded. Patients were randomized into 2 groups by means of coded envelopes. Group I received 10 mg lidocaine 2% (0.5 mL, B. Braun Medical SA, Barcelona, Spain), mixed with 10 μg fentanyl (0.2 mL) and made to a total volume of 3 mL with sterile water. This solution had a specific gravity of 1.002 mg/mL3. Group II received 3 mg levobupivacaine 0.5% (0.6 mL, Abbott Laboratories, Madrid, Spain), mixed with 10 μg fentanyl (0.2 mL) and made to a total volume of 3 mL with sterile water. This solution had a specific gravity of 0.998470 mg/mL (density measurement system for liquids and gases, Anton Paar K.G.A-8054, Graz, Austria). The Group II dose was obtained from a pilot dose-finding study performed to reproduce the results obtained by Vaghadia et al.,1–4 but using levobupivacaine at different intrathecal concentrations instead of lidocaine. The objective of this study was to obtain the dosage and concentration of a levobupivacaine spinal solution that produced surgical anesthesia while minimizing loss of lower limb motor and proprioceptive function. In this pilot study, 4 groups of 10 patients each were tested. Each group received 6, 5, 4, or 3 mg of levobupivacaine 0.5%, respectively, plus 10 μg of fentanyl and made to a total volume of 3 mL with sterile water. Modified Bromage scale, unassisted ambulation at the end of surgery, and time to sensory block recovery were assessed. The group receiving 3 mg of levobupivacaine produced results that were most similar to those obtained by Vaghadia et al. with intrathecal low-dose lidocaine; consequently, 3 mg of levobupivacaine was chosen for the study.

Following the instructions of the corresponding coded envelope, the spinal solution was prepared by a nurse blinded to the study. All spinal anesthetics were administered by one of the authors who was familiar with the technique and was not involved in further patient evaluation.

An IV infusion of Ringer’s lactate solution was established preoperatively at a rate of 10–15 mL · kg−1 · h−1. All patients were premedicated with midazolam 1–2 mg for anxiolysis and dexketoprofen trometamol 50 mg IV. Upon arrival in the operating room, patients were monitored with electrocardiogram, noninvasive arterial blood pressure, and pulse oximetry. Spinal anesthesia was administered in the sitting position with a midline approach at the L3-4 or L4-5 level using a 27-gauge Whitacre spinal needle (Becton Dickinson Medical Systems, Madrid, Spain). After free flow of cerebrospinal fluid was observed, the spinal solution was injected with the needle orifice cephalad at approximately 0.5 mL/s. After sitting for 2 min, patients were placed in a 20°–30° reverse Trendelenburg position for approximately 5–8 min, while they were prepared for surgery and until the level of sensory anesthesia reached T4. The level of sensory anesthesia was determined by loss of pinprick sensation with an 18-gauge needle along the anterior median line at frequent intervals when the patient was placed in reverse Trendelenburg position until the level of sensory anesthesia reached T4. Anesthesia onset time (time to readiness for surgery), defined as the time from local anesthetic injection until the level of sensory anesthesia reached T4 and the maximum level of sensory block, was recorded. Anxiety and shoulder discomfort were prevented in all patients with 1 μg/kg IV fentanyl and 0.05 mg · kg−1 · min−1 propofol IV infusion while T4 sensory level was achieved. Anxiety and abdominal or shoulder tip pain during surgery were treated with increments of propofol 20 mg and fentanyl 25–50 μg if needed. If this treatment proved to be inadequate to complete surgery, then GA was administered. The use of fentanyl/propofol supplementation or GA to complete surgery was recorded. The depth of sedation was assessed at the time when both fallopian tubes were electrocoagulated using the responsiveness component of the Observer’s Assessment of Alertness/Sedation (OAA/S) rating scale14 as follows: responds readily to name spoken in normal tone = 5; lethargic response to name spoken in normal tone = 4; responds only after name is called loudly and/or repeatedly = 3; responds only after mild prodding or shaking = 2; responds only after painful trapezius squeeze = 1; and does not respond to painful trapezius squeeze = 0.

The operating room table was returned to a horizontal position before initiating surgery. Local anesthetic infiltration was not permitted at the site of trocar insertion at the beginning of surgery. Pneumoperitoneum was achieved using a 10-mm Versaport trocar (MGB, Berlin, Germany) inserted through a small infraumbilical incision and was maintained with CO2 adjusted to a pressure of 12 mm Hg. CO2 inflation pressure was not adjusted to a lower pressure value during the procedure. One additional 5-mm trocar was placed under direct laparoscopic vision. Patients were then placed in a steep Trendelenburg position to minimize shoulder tip pain caused by diaphragmatic irritation from the CO2. All surgical procedures were performed using bipolar electrocoagulation by the same surgeon. Surgical time was determined from incision to insertion of the last suture. The surgeon rated the surgical conditions as poor, fair, good, or excellent based on the patient’s verbal response to surgical stimuli and abdominal wall relaxation. In case of an inadequate block (defined as pain when testing the abdomen with toothed forceps), GA was initiated. Upon conclusion of the laparoscopy, all surgical sites for both groups were infiltrated with levobupivacaine 0.25%. If clinically relevant hypotension (>30% reduction in systolic arterial blood pressure from baseline) or bradycardia (heart rate <45 bpm) occurred, it was treated with IV boluses of ephedrine 5 mg or atropine 0.5 mg, respectively. The occurrence of hemodynamic events was recorded.

At the end of surgery, patients were assessed for motor block, proprioception, vibration sense, light touch, and Romberg’s test. Motor block was evaluated with a modified Bromage scale2: 1 = complete motor block; 2 = able to move feet only; 3 = able to move feet and to bend knees; 4 = able to perform a straight leg raise <30°; and 5 = able to perform a straight leg raise >30°. Proprioception was tested at both big toes: 0 = failure to identify movement; 1 = correct identification of movement. Vibration sense was tested at both medial malleoli with a tuning fork: 0 = does not feel vibration; 1 = feel vibration. Light touch was tested at both legs with gauze: 0 = absent; 1 = present. To perform the Romberg’s test, the patients were asked to stand erect with feet together and eyes closed. This test was performed in those patients who had complete motor recovery (Bromage of 5 in both legs), were hemodynamically stable, and were conscious (OAA/S of 5) with no sensation of dizziness. If test results were satisfactory, patients were allowed to walk out unassisted from the operating room to their respective beds. If the patient was unable to walk, further assessments were done either in the postanesthesia care unit (PACU) or in the day surgery unit (DSU) every 15 min after arrival. Sensory block level was assessed at the following times: 5, 10, and 15 min after the injection of the spinal solution and then every 15 min until complete resolution of spinal block. The 5-min assessment was done before the initiation of surgery, and at the 10- and 15-min assessment, the sensory block was high enough to be tested without interfering with surgery. Sensory block resolution time was defined as recovery of sensory block at the S3 level.

When patients arrived in the PACU (Phase 1), nurses (who were blinded to the anesthetic solution) evaluated whether they should go directly to the DSU (Phase 2) and bypass the PACU. Patients could bypass the PACU only with the following criteria15: PACU bypass score of 10, no need to treat pain (visual analog scale [VAS] score <3), no postoperative nausea and vomiting (PONV), no need to treat pruritus, no shivering, no hypotension, and no orthostatic symptoms. In those cases when a patient was admitted to the PACU, the presence of symptoms and the need for treatment were recorded. Patients complaining of pain in the PACU were administered fentanyl (in 25-μg increments at 10-min intervals) until pain relief was satisfactory (VAS score <3). PONV was assessed with a VAS for nausea (0 = no nausea and 10 = severe nausea) and treated with metoclopramide 10 mg IV. Pruritus was assessed with a VAS for pruritus (0 = no pruritus and 10 = maximum pruritus). Patients with VAS ≥6 for pruritus received naloxone 100 μg IV.

In the DSU, patients were assessed every 15 min for unassisted ambulation, time to first voiding, and home-readiness. Times for recovery of unassisted ambulation, first voiding, and home-readiness were recorded. The decision to discharge home was made by the DSU nurses after a score of ≥9 on the postanesthesia discharge scoring system.16 Voiding was required for hospital discharge. There was no minimum time required for patients to remain in the DSU. Adverse events in the DSU were recorded. Postoperative analgesia in the DSU and at home consisted of 25 mg oral dexketoprofen trometamol every 8 h and rescue analgesia with 1 g oral paracetamol. Need for rescue analgesia was recorded. One week after surgery, a postoperative follow-up via telephone was done by a research assistant, blinded to the anesthetic solution used, who collected data about the occurrence of pain, TNSs, overall satisfaction with anesthesia (satisfaction score 1–10), and willingness to have the same anesthesia if needed. TNSs were defined as pain or abnormal sensations including hypoesthesias or dysesthesias in the gluteal region and radiating to the lower extremities.9

Study End Points

The primary end point was sensory block resolution time. A difference of 25 min for sensory block resolution was considered clinically relevant.

Secondary end points were intraoperative effectiveness, other anesthetic recovery times (ambulation time and discharge time), and postoperative patient satisfaction. Intraoperative efficacy included anesthesia onset time, surgical conditions, and conversion to GA.

Statistical Analysis

Sensory block resolution time was used to determine the power analysis. Because estimated surgery time in these patients is approximately 6–10 min, a difference of 25 min in sensory recovery block was considered clinically relevant compared with a lidocaine control group with mean ± sd of 70 ± 30 min.1–3,6,7,17 A sample size of 24 patients per group would provide 80% power to detect a difference of 25 min assuming a type I error of 5%. The final sample size was increased to 26 patients per group in case of dropouts.

Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS 15.0, Chicago, IL) and StatXact version 5.0.3 (Cytel Co., Cambridge, MA), and sample size was performed using Sample Power version 2 (SPSS). Assumption of normality was assessed using the Kolmogorov-Smirnov test. Differences in demographic, surgical, anesthetic, and postoperative variables were tested by independent Student’s t-test (continuous data) or by χ2 test, Fisher’s exact test, or Kruskal-Wallis test for singly ordered rxc tables (categorical data), as appropriate. Maximum sensory block height was compared using the Mann-Whitney U-test. To compare the level of sensory block, the dermatomes S2–T1 were coded from lowest to highest as 1–19. Continuous data that were normally distributed were expressed as means ± sd. If assumption of normality for continuous variables was not assumed, medians (ranges) were given. Discrete categorical variables are presented as frequency (%). Given that the frequency distribution of sensory block differed from the normal distribution across some of the levels of variable time, we used the Kruskal-Wallis test for singly ordered rows by columns tables, with the exact value of P, to compare groups across time. In this analysis, the multiple comparisons effect was corrected by applying the Bonferroni correction,18 and only P values <0.0045 (0.05/11) were considered statistically significant.

RESULTS

The 52 patients assessed for eligibility were randomized and all completed the study. There were no significant differences between groups with respect to sex, age, height, weight, and ASA physical status (Table 1).

Table 1
Table 1:
Demographic Data and ASA Physical Status

Intraoperative Effectiveness

Intraoperative outcomes are summarized in Table 2. Anesthesia onset time was similar in both groups. Nine patients (6 in Group I [23%] and 3 in Group II [11%] [P = 0.28]) required propofol supplementation during surgery; however, in all cases, surgical conditions were good or excellent, and no case required GA to complete surgery. Most patients were lightly sedated or completely awake. The median (range) maximum sensory level block was significantly higher in Group II (T3 [T2-4]) than in Group I (T4 [T4-6] (P < 0.001). After adjusting for multiple comparisons, we found an interaction effect between time and group. Sensory block level was higher in the lidocaine group at 5 min (P = 0.0035), but from 10 to 90 min, sensory level was higher in the levobupivacaine group. Figure 1 shows the evolution of sensory block in both groups.

Table 2
Table 2:
Intraoperative Outcomes
Figure 1
Figure 1:
Figure 1.

Anesthesia Recovery and Patient Satisfaction

Anesthesia recovery and patient satisfaction outcomes are summarized in Table 3. Sensory block resolution time was shorter in Group I (93 [65–120] min) than in Group II (105 [78–150] min) (P = 0.019) but with an average difference of only 12 min (Fig. 1). Both groups were comparable with respect to recovery of motor block, vibration, proprioception, and light touch. The Romberg test was not performed because of a Bromage scale score lower than 5 in 2 patients in Group I and 5 patients in Group II (P = 0.23), and because of an OAA/S score <5 or dizziness sensation in 7 patients in Group I and 5 patients in Group II (P = 0.51). Seventeen patients (65%) in Group I and 16 (61%) in Group II (P = 0.78) walked from the operating room unassisted at the end of surgery.

Table 3
Table 3:
Postoperative Recovery of Spinal Cord Function, Postoperative Outcomes, Recovery Times, and Patient Satisfaction Score

All patients from both groups bypassed the PACU. Pruritus was mild (VAS <6) in all patients (66% from 52 patients) and none required treatment. No adverse events were reported in the DSU. Times to ambulation, to first void, and to discharge home were comparable between groups. Three patients in Group I and 2 patients in Group II needed rescue analgesia at home (P = 0.64). No patient reported TNSs at 1-wk follow-up. Global patient satisfaction and patient willingness to have the same anesthesia were comparable between groups.

DISCUSSION

In this study, we have demonstrated that 3 mg levobupivacaine-fentanyl SSA produced a longer sensory block, although not clinically relevant, compared with 10 mg lidocaine-fentanyl SSA. No differences were found in intraoperative effectiveness, ambulation time, discharge time, and patient satisfaction between groups. These findings suggest that levobupivacaine might be a suitable alternative to lidocaine for short-duration outpatient laparoscopic surgery.

Low-dose SSA is a viable technique for short-duration outpatient laparoscopic surgery. It possesses the ideal characteristics required for the ambulatory setting: rapid recovery, adequate postoperative analgesia, low incidence of PONV, and brief discharge-home time.3–7,16,19 However, this technique was developed using low doses of lidocaine. The possibility to develop TNSs after spinal lidocaine injection at this dosage remains a theoretical limitation of this technique, especially in groups of patients at risk such as outpatients.8 Ben-David et al.20 reported TNSs with the lowest dose of spinal lidocaine, where they found an incidence of 3.6% after 20 mg; however, there are no reports of TNSs in the literature with 10 mg (0.33%) lidocaine. Nevertheless, a recent publication demonstrated that lidocaine induces apoptosis in neuronal cells beginning at concentrations of approximately 0.08% in cerebral spinal fluid.21 Furthermore, the relative risk for developing TNSs after spinal anesthesia with lidocaine compared with other amide local anesthetics at a conventional dosage is 7.31 (95% confidence interval 4.16–12.86).9 It may be inferred that this risk is reduced when low doses are used. The major reason to use lidocaine for SSA is that there is no ideal alternative. Safer amide local anesthetics have longer recovery of sensory block thus making them poorer candidates for short-duration laparoscopy in the outpatient setting. The main finding of this study is that we propose a safer long-acting amide local anesthetic, such as levobupivacaine, with the same selective differential neuraxial block as lidocaine SSA and with resolution of sensory block, although statistically longer, is clinically equivalent.

Both local anesthetics yielded similar intraoperative results, suggesting that this low dose of levobupivacaine, 3 mg, is similar to lidocaine 10 mg in providing acceptable surgical anesthesia for outpatient gynecological laparoscopy. Nevertheless, some differences were found. First, levobupivacaine is a long-acting amide local anesthetic, and as a result, to achieve the same intraoperative effectiveness goals as lidocaine, it produced a longer sensory block. Second, the peak of maximum sensory block in the levobupivacaine group was higher than that attained in the lidocaine group, probably because of the different specific gravities of the solutions studied, but this characteristic did not produce more hemodynamic events in the levobupivacaine group.

Ultra-low dense spinal solutions have been reported in the literature to produce selective spinal block, but none used levobupivacaine. Intrathecal levobupivacaine has the advantage to produce differential neuraxial block, preserving motor function, when used at low concentrations.12 In our study, we used 3 mg of levobupivacaine at 0.1% concentration achieving reliable surgical anesthesia with vibration, light touch, proprioception, and motor function preservation comparable with the lidocaine-fentanyl group. This rapid recovery of spinal cord function allowed all patients to bypass the PACU.

Ambulation times were comparable between groups and to previous studies.1–4,6,7 Sensory block resolution time was significantly shorter in Group I than in Group II (93 [65–120] min vs 105 [78–150] min, respectively; P = 0.019). Our results showed a slight increase in sensory block resolution time (defined as level of sensory block <S3) in the lidocaine group with respect to the predicted mean (93 ± 14 vs 70 ± 30 min, respectively) and in the levobupivacaine group with respect to the predicted mean (105 ± 20 vs 95 ± 30 min, respectively). In previous reports, patients were discharged home without voiding1–4,6,7 because patients with short-acting blocks can be discharged home without an increase in the incidence of urinary retention.22 Based on these data, Group I would have been discharged home earlier than Group II. However, voiding before home discharge is a normal practice in our hospital and was also a requirement of the study protocol for home-readiness. Because all of our patients’ bladders were catheterized at the beginning of surgery, first voiding and thus, home-readiness time were prolonged to 3–4 h. Therefore, discharge home times were not comparable to those reported in the literature in which voiding was not a requirement for home-readiness.

Another limitation of our study was that we enrolled only women. It remains to be seen if our results are applicable to men in the context of outpatient laparoscopy.

In conclusion, 3 mg levobupivacaine-fentanyl SSA may be used as a suitable option to 10 mg lidocaine-fentanyl SSA for short-duration outpatient gynecological laparoscopy. It provided a clinically equivalent time for resolution of a sensory block, similar intraoperative effectiveness, and comparable patient satisfaction.

ACKNOWLEDGMENTS

The authors thank all anesthesiologists and PACU nursing staff at USP La Colina Hospital, the Department of Physics and Chemistry from the University of La Laguna (Tenerife), and Dr. Carlos L. Errando (Servicio de Anestesiología, Reanimación y Tratamiento del Dolor, Consorcio Hospital General Universitario de Valencia, Valencia, Spain).

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