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*Department of Anesthesiology, Sapporo Medical University School of Medicine; and
Division of Anesthesia, Obihiro Kosei Hospital, Japan
Address correspondence and reprint requests to Masayasu Nakayama, MD, Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuoku, Sapporo 060-8543, Japan. Address e-mail to mnakaya{at}sapmed.ac.jp
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Abstract |
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IMPLICATIONS: An antiemetic dose of IV droperidol causes a decrease in the bispectral index in patients sedated with propofol during spinal anesthesia. We conclude that droperidol may enhance the hypnotic effect of propofol.
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Introduction |
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Methods |
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No premedication was given before surgery. Each patient received a peripheral IV infusion of acetated Ringer’s solution at 10 mL · kg-1 · h-1 throughout the study. Electrocardiography and pulse oximetry were monitored continuously. Arterial blood pressure was measured by an automatic oscillographic method (M1008B; Agilent Technologies, Boeblingen, Germany). BIS (version 3.4) was measured continuously on an electroencephalogram (EEG) monitor (Model A1050; Aspect Medical System, Natick, MA) using BisSensor strips (Aspect Medical System). The strips consisted of three pregelled electrodes: two active and one ground. The impedance of each electrode was maintained at <2 k
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After obtaining baseline values of heart rate (HR), mean arterial blood pressure (MAP), and BIS, spinal anesthesia was performed with a 25-gauge spinal needle at the L3-4 interspace via a median approach with the patient in a lateral horizontal position. An injection of 0.5% tetracaine 2.5–3.0 mL in a 10% dextrose solution was administered, and the patient was immediately turned to the supine position. The upper cutaneous level of analgesia was assessed by pinprick 30 min after the injection.
Thirty minutes after the subarachnoid injection, patients in the conscious group (n = 20) were given 2 mg of droperidol without other sedatives. In the other patients, propofol infusion was started at 2 mg · kg-1 · h-1 and was increased stepwise by 0.5 mg · kg-1 · h-1 to maintain BIS at 60 ± 5. After a steady level of BIS had been achieved, the infusion rate of propofol was kept constant. Then, the patients were given IV saline (placebo group; n = 20), droperidol 1 mg (dro-1 group; n = 20), or droperidol 2 mg (dro-2 group; n = 20) in a randomized order and in a double-blinded fashion. An assistant who was not involved in the study made the testing solution up to 10 mL in saline. Propofol was infused at a constant rate, and no other sedatives were given during the study period.
The changes in HR, MAP, and BIS after droperidol or placebo administration were measured every 2 min for the first 10 min and then every 5 min for 20 min. In the conscious group, the sedation score was assessed using the responsiveness component of the Observer Assessment of Alertness and Sedation rating scale (3). Surgery was started after the protocol ended, and all patients were sedated by propofol infusion to maintain BIS between 40 and 60. The interval between the end of propofol infusion and the response to verbal command was recorded as awakening time. Postoperatively, the patients were asked whether PONV had occurred during the initial 24 h after surgery.
Data are expressed as mean ± SD or median (range). A sample size of 20 patients per group was chosen to have enough power to detect a 10% reduction in BIS because of droperidol. Student’s t-test with Bonferroni correction was used for multiple comparisons among the four groups and for repeated comparisons over time. The 
2 test was used to compare the incidences of PONV among groups. A P value <0.05 was considered statistically significant.
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Results |
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The awakening times in the groups were similar. The frequency of PONV during the initial 24 h after surgery was significantly less in the patients in the conscious and dro-2 groups (to whom 2 mg of droperidol had been given) than in the patients in the placebo and dro-1 groups. No patient exhibited a extrapyramidal reaction to droperidol after surgery.
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Discussion |
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Because there have been no reports on the effect of droperidol on BIS, the reliability of BIS to predict the level of hypnosis induced by droperidol was uncertain. However, the dose of droperidol used in this study was reported to have little effect on the hypnotic state and EEG. It is therefore unlikely to affect the BIS (5), as was demonstrated in the conscious group in the present study. Moreover, because it has been documented that BIS correlates well with the level of propofol-induced hypnosis, we believe that BIS probably reflected the hypnotic level in the present study. A larger dose of droperidol may result in reductions in the sedation score and BIS, but the prolongation of recovery and profound hypotension will limit its use in a clinical setting.
A combination of droperidol and other sedative drugs shows various interactions that affect the degree of sedation and hypnosis (6–8). Barthel et al. (6) reported that droperidol reduced midazolam and meperidine requirements to induce adequate sedation during gastrointestinal endoscopy. Adachi et al. (7) reported that the administration of 20 µg/kg of droperidol reduced the hypnotic dose of propofol during the induction of anesthesia. However, the level of hypnosis was evaluated in these studies by subjective clinical end-points such as a loss of response to stimuli. In this study, we used BIS, which has been used in recent years as a reliable objective predictor of the level hypnosis under anesthesia, and we found that the administration of droperidol caused a significant reduction in BIS in patients sedated with propofol, although it caused no change in BIS in conscious patients. This finding suggests that droperidol might enhance the hypnotic effect of propofol, resulting in a reduction of propofol requirement.
In the propofol-sedated patients, droperidol caused a significant decrease in systemic blood pressure, probably because of its 
-adrenergic blocking effects. However, none of the patients required treatment for severe hypotension. In the case of a minor degree of hypotension, normal cerebral circulatory autoregulation would prevent changes in cerebral blood flow affecting EEG. Thus, the changes in blood pressure might not have affected the BIS measurement in this study.
PONV is a common complication of gynecologic procedures. Prophylactic droperidol at a small dose reduces PONV in various surgical settings (1,2). In this study, we found that 2 mg, but not 1 mg, of droperidol reduced the incidence of postoperative vomiting compared with that in the patients in the placebo group. Because neither dose of droperidol induced any severe adverse effects or prolonged awakening time, 2 mg of droperidol may be an appropriate supplement to propofol for preventing PONV. However, the size of our study was too small to disregard a result of inadequate power.
It is possible that regional anesthesia directly influences the hypnotic level (9,10). Pollock et al. (9) reported that there were significant reductions in BIS and in the sedation scores after spinal anesthesia in volunteers. In contrast, Morley et al. (10) reported that spinal anesthesia caused an increase in BIS in surgical patients. However, in our study, it seems unlikely that spinal anesthesia affected the BIS measurements because there were no significant changes in BIS after spinal anesthesia in the conscious group.
Droperidol has been known to cause prolongation of QT-interval at large doses. However, it was reported that even standard small doses of droperidol can induce the same effects. Therefore, droperidol should not be given in patients at risk for developing QT prolongation, such as electrolyte disturbance, bradycardia, or a family history of sudden death.
In conclusion, the decrease in BIS caused by droperidol suggests that the hypnotic effect of propofol is enhanced by co-administration of an antiemetic dose of droperidol during spinal anesthesia. Therefore, it is possible that the addition of droperidol reduces the propofol dose required for hypnosis.
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This article has been cited by other articles:
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  I. H. Lee and I. O. Lee The Antipruritic and Antiemetic Effects of Epidural Droperidol: A Study of Three Methods of Administration Anesth. Analg., July 1, 2007; 105(1): 251 - 255. [Abstract] [Full Text] [PDF]
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Y. U. Adachi, M. Satomoto, H. Higuchi, and K. Watanabe Subhypnotic Dose of Droperidol May Increase Frequency of PONV After Propofol Anesthesia Anesth. Analg., November 1, 2003; 97(5): 1545 - 1545. [Full Text] [PDF]
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