Anesth Analg 2008; 106:334-338
© 2008 International Anesthesia Research Society
doi: 10.1213/01.ane.0000295786.66822.60
ANALGESIA
Preoperative Gabapentin: The Effect on Ropivacaine Subarachnoid Block and Hemodynamics
Argyro Fassoulaki, MD, PhD, DEAA*,
Vassiliki Chatziara, MD ,
Aikaterini Melemeni, MD, DESA*,
Marianna Zotou, MD, and
Constantine Sarantopoulos, MD, PhD, DEAA
From the *Department of Anesthesiology, Aretaieio Hospital, Medical School, Department of Anesthesiology, St. Savas Hospital, Athens, Greece; and Department of Anesthesiology, Pharmacology and Toxicology, Medical College of Wisconsin, Wisconsin.
Address correspondence and reprint requests to Argyro Fassoulaki, MD, PhD, DEAA, Department of Anesthesiology, Aretaieio Hospital, Medical School, 76 Vassilissis Sofias Ave., 11528 Athens, Greece. Address e-mail to fassoula{at}aretaieio.uoa.gr or afassou1{at}otenet.gr.
Abstract
BACKGROUND: Gabapentin is an adjuvant analgesic and may enhance the spread of subarachnoid block. We investigated the effects of pretreatment with gabapentin on subarachnoid block characteristics and hemodynamics.
METHODS: Seventy patients undergoing transurethral procedures under subarachnoid anesthesia with 2.2 mL of 0.75% ropivacaine were randomly assigned to receive preoperatively 400 mg of gabapentin 6 hourly, up to a total dose of 1200 mg, or placebo. Sensory and motor blocks were assessed every 30 min until regression of sensory block to L4. At the same time intervals, systolic and diastolic arterial blood pressures and heart rate were recorded.
RESULTS: There were no differences between groups in the sensory block levels or degree of motor block. Sensory block 150 min after the subarachnoid injection had regressed to L4 in 26 of 32 patients in the gabapentin group and in 25 of the 33 patients in the control group. Systolic arterial blood pressure was decreased in the gabapentin group (P = 0.002 for the main effect of group, and P = 0.03 at 60 min between the groups). The diastolic arterial blood pressure did not differ between the groups, but overall, the heart rate was more rapid in the gabapentin group (P = 0.002, but only for baseline values between the groups, P = 0.036).
CONCLUSION: Pretreatment with gabapentin had no effect on the spread of sensory block or the regression of motor block but was associated with lower systolic arterial blood pressure values in patients undergoing subarachnoid anesthesia with ropivacaine.
Several drugs may enhance or attenuate the sensory block after subarachnoid anesthesia. These drugs may be administered orally, parenterally, intrathecally, or by inhalation. IV administration of opioids, such as fentanyl and nalbuphine, enhance the spread and/or duration of subarachnoid analgesia in a dose-dependent manner.1,2 Oral clonidine prolongs the duration of sensory and motor block produced by intrathecal administration of tetracaine.3 Inhalation of 50% nitrous oxide for 10 min was found to enhance the level of subarachnoid analgesia produced by lidocaine with no effect on hemodynamics.4
Gabapentin has been used as adjuvant analgesic in the perioperative period for several types of procedures.5 The drug has an analgesic and opioid-sparing effect and can be included in a multimodal analgesic regimen along with other analgesics with a different mode of action.5
The aim of the present study was to explore the effect of pretreatment with oral gabapentin on the spread of sensory block and regression of motor block after subarachnoid injection of ropivacaine as well as on the hemodynamics of these patients.
METHODS
Patients
After obtaining approval from the IRB, the study started on October 25, 2005, and completed on April 5, 2006. Seventy consecutive patients ASA II to III, scheduled for transurethral surgery to remove papillomas of the bladder under subarachnoid anesthesia, gave their written informed consent to participate in the study. Patients with bleeding diathesis, treated with analgesics,  2 agonists, calcium channel blockers, or other antihypertensives, as well as those who refused to receive subarachnoid anesthesia or did not speak the Greek language fluently, were excluded from the study. Although the prevalence of hypertension is expected to be high in the elderly, as are the patients of the present study, patients with papillomas of the bladder visit their doctor frequently for follow-up and are under close medical care, including blood pressure control.
Patient Randomization
Patients were randomly assigned to receive gabapentin or placebo capsules as follows: one capsule of 400 mg gabapentin at 18:00 the evening before surgery, one capsule at midnight and one capsule at 6 o’clock the morning of surgery, for a total dose of 1200 mg. To randomize patients to the gabapentin group or to the control group, we used sealed opaque envelopes containing even or odd numbers from a computer-generated table, even numbers indicating the gabapentin group and odd numbers indicating the control group. The placebo capsules were prepared after emptying the gabapentin capsules and refilling them with thin sugar. All capsules active and placebo were identical so that the anesthesiologists and nurses could not distinguish differences between the active (gabapentin) capsules and those of the inactive placebo. During the preanesthetic visit, the anesthesiologist explained to the patients the procedure of assessing the sensory and motor block.
Anesthetic Technique
No premedication was given except for the drugs predetermined by the study protocol. In the operating room, a venous catheter was inserted in a peripheral vein and a lactated Ringer’s solution was started. Spo2, electrocardiogram, heart rate, and noninvasive arterial blood pressure were monitored (S/5TM Anesthesia Monitor, Datex Ohmeda Division, P.P. Box 900, FIN-00031, Finland). All patients received intra- and postoperatively 35% oxygen via a Venti-mask.
With the patient in the sitting position, the skin was locally infiltrated with 2% lidocaine and 2.2 mL of 0.75% ropivacaine was injected in the subarachnoid space at the L3-4 interspace using a 25-gauge Whitacre needle with the bevel having a cephalad orientation. After the subarachnoid injection, the patients were placed in the lithotomy position.
Measurements
All measurements were recorded with the patient in the supine position. To statistically analyze the height of sensory subarachnoid block, we designated the dermatomes with numbers; L1 corresponded to 13, L2 to 14, L3 to 15, and so forth.
Sensory block was assessed using a pressure palpator (Pressure FEELER 650 g Sedatelec Chemin des Muriers, F-69540 Irigny, France). The palpator was moved along the left posterior, middle and anterior axillary lines as well as along the line 4–5 cm medial to the left anterior axillary line4,6,7 in a cephalad to caudad direction. During each measurement, we recorded the dermatome on which the patient did not respond at all to the pressure palpator. This has been validated7,8 and used in previous studies.4,6,9 These four values were averaged to a mean number corresponding to the dermatome of each sensory level. Sensory block was assessed 30 min after subarachnoid injection and every 30 min thereafter until regression to L4.
Motor block was also assessed every 30 min using the modified Bromage scale as follows: 0 = no block, able to flex hips, knees, ankles, 1 = able to move knees, unable to raise extended legs, 2 = able to flex ankles, unable to flex knees, 3 = complete motor block, unable to move any part of the lower extremities.
At these same time intervals, we recorded systolic and diastolic arterial blood pressure, and heart rate.
Statistics
Data entry/analyses were performed by an anesthesiologist who was unaware of group allocation (CS). The spread of sensory block was the primary outcome of the study. Initial sample size estimation showed that, to ensure power of 0.80, approximately 35 patients were needed in each group to detect a difference of approximately 0.75 dermatome between the gabapentin and control group at each time point. This difference was based on the increase in dermatomal levels produced by other analgesics/anesthetics.1,2,4 Standard deviations estimated from an initial pilot observations sample were approximately one for each group. An error was assumed at 0.05. Sample size estimation was calculated online using the Java applets for power and sample size software.10
We used the SPSS 11.0 (Version 11.0.4 for Mac OS X, Chicago, IL) for statistical analysis. The normality of distribution of variables was assessed using the Kolmogorov-Smirnov test. We compared the demographics and the time for regression of motor block between the two groups with unpaired independent samples Student’s t-test. Sensory block and hemodynamic changes were compared with SPSS General Linear Model Analysis of Variance function, testing the main effects of time and group. Intergroup post hoc comparisons at each time point for a statistically significant group effect were performed using unpaired Student’s t-test wherever appropriate. Motor changes (expressed in Bromage scale values) did not follow normal distribution and were analyzed (regarding the overall model effect) with Friedman’s test. Regarding the group main effect significance, intergroup comparisons between the gabapentin and control groups, at each time point, were performed by individual Mann–Whitney U-test.
RESULTS
Of the 70 patients assessed for eligibility, 34 were assigned to receive gabapentin and 36 to receive placebo. In two patients in the gabapentin group and three in the control group, the subarachnoid block failed as patients experienced pain during the procedure and general anesthesia was administered. Their data were not included in the analysis. Therefore 32 patients in the gabapentin group and 33 patients in the control group were included in the analysis for sensory and motor block as well as the effect of gabapentin on the hemodynamics under subarachnoid anesthesia. According to the study protocol, once regression of the sensory block to L4 was obtained, no more measurements were made. For this reason, no sensory block data are reported after 180 min after subarachnoid block in the gabapentin group.
All surgical procedures were completed within the first 30 min after subarachnoid injection.
There were no significant differences in demographics between groups (Table 1). Regression of the sensory block over time (assessed by dermatome on which the patient did not respond at all to the pressure palpatory) did not differ between the gabapentin and control group (Fig. 1). Sensory block had regressed to L4 (median value) 150 min after the subarachnoid injection in 26 of the 32 patients in the gabapentin group and 25 of the 33 patients in the control group (Fig. 1).
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Figure 1. Sensory block (dermatomes) in the gabapentin (gray columns) and the control (white columns) groups. Values shown are as follows: median (line), upper and lower quartiles (top and bottom of each box), interquartile distance (distance between upper and lower quartile), minimum and maximum within the data set that are within ± 1.5 interquartile distance from the upper or lower quartile respectively (lines extending from the top and bottom of each box), and outliers (open circles representing values either more than upper quartile + 1.5 interquartile distance or less than lower quartile – 1.5 interquartile distance).
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Regression of motor block did not differ between the groups (Fig. 2). The time to resolution of the motor block was 132 ± 51 min in the gabapentin group and 128 ± 41 min in the control group and did not differ between the groups.
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Figure 2. Motor block in the gabapentin (gray columns) and the control (white columns) groups. Values shown are as follows: median (line), upper and lower quartiles (top and bottom of each box), interquartile distance (distance between upper and lower quartile), minimum and maximum within the data set that are within ± 1.5 interquartile distance from the upper or lower quartile respectively (lines extending from the top and bottom of each box), and outliers (open circles representing values either more than upper quartile + 1.5 interquartile distance or less than lower quartile – 1.5 interquartile distance.
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Systolic arterial blood pressure values between the groups did not differ at baseline, but overall were lower in the gabapentin group after subarachnoid anesthesia (P = 0.002) (Table 2). Diastolic arterial blood pressure did not differ significantly between groups.
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Table 2. Systolic Arterial Blood Pressure in the Gabapentin and the Control Groups 30, 60, 90, 120, 150, 180, 210, and 240 min After the Subarachnoid Injection of Ropivacaine
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Heart rate values were overall higher in the gabapentin group (main effect P = 0.002) at baseline only (post hoc comparison P = 0.036) (Table 3).
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Table 3. Heart Rate in the Gabapentin and the Control Groups 30, 60, 90, 120, 150, 180, 210, and 240 min After the Subarachnoid Injection of Ropivacaine
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DISCUSSION
Our results showed that pretreatment with gabapentin had no effect on the sensory or motor block produced by subarachnoid ropivacaine but was associated with decreased systolic arterial blood pressures versus placebo. As with previous investigators, we observed a large variability in the level of subarachnoid block after a single dose of local anesthetic.11
Several drugs may enhance or attenuate the sensory block produced by subarachnoid anesthesia.12 Gabapentin does not enhance the sensory block after subarachnoid anesthesia, which is the primary outcome of the study. This may have been due to the large variability in the level of subarachnoid block obtained in both the gabapentin and the control groups. This variability has been reported by other investigators as well.11
We did not investigate postoperative pain in these patients, which may be considered a limitation of our study. Likewise, although, due to limitations of our study, we failed to demonstrate an enhancement of the subarachnoid block by gabapentin, a possible interaction cannot be excluded. Higher doses of gabapentin and perhaps more frequent assessments of the block might reveal an effect on the spread of subarachnoid anesthesia.
Information on the effect of gabapentin on the cardiovascular system is very limited. Considering that this drug may be used perioperatively since it produces postoperative analgesia,5 its effects along with general and/or neuraxial anesthesia may be important in clinical cardiovascular practice. Turan et al. reported that 1200 mg of gabapentin given the morning of surgery and the first and second postoperative days had no effect on the mean blood pressure and heart rate, though they did not report any data.13 Gabapentin 400 mg given the day before surgery (noon) 6 hourly in a total dose of 1600 mg attenuated the pressor response to direct laryngoscopy and intubation of the trachea, but the heart rate did not differ between the gabapentin and the control group.14
In the present study, we found a statistically significant but clinically small decrease in systolic arterial blood pressure intraoperatively in the gabapentin group. These changes may be more prominent in patients hemodynamically unstable or under hypotensive treatment. The diastolic arterial blood pressure did not differ between the groups though, in a previous study, gabapentin attenuated the diastolic arterial blood pressure increases due to laryngoscopy and tracheal intubation.14 This difference may be attributed either to the lower dose of gabapentin administered in the present study (1200 mg versus 1600 mg in the previous study), or to the decreased peripheral resistance produced by the subarachnoid block, overriding a possible gabapentin effect.
We observed more rapid heart rates in the gabapentin group, which were not clinically significant, and may have been due to baroreceptor reflex alterations in response to the tendency of gabapentin to decrease systolic arterial blood pressure. Gabapentin that has been shown to block voltage-gated calcium currents15 may act in a fashion similar to nifedipine.16
In conclusion, gabapentin under the present study design had no effect on sensory or motor block but was associated with lower values of systolic arterial blood pressure.
Footnotes
Accepted for publication September 21, 2007.
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