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Anesth Analg 2003;96:765-768 © 2003 International Anesthesia Research Society
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Abstract |
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We investigated the effect of IV droperidol on the bispectral index (BIS) in conscious and propofol-sedated patients during spinal anesthesia. Thirty minutes after the induction of spinal anesthesia, 20 patients were given 2 mg of droperidol IV without administration of other sedatives (conscious group). Another group of patients were sedated with a propofol infusion to maintain BIS at 60 ± 5 and were administered 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. Although BIS remained the same in the conscious and placebo groups, it significantly decreased after administration of droperidol in the dro-1 and dro-2 groups. The decrease in BIS was significantly larger in the dro-2 group than in the dro-1 group. These results suggest that an antiemetic dose of droperidol enhances the hypnotic effect of propofol in a dose-dependent manner during spinal anesthesia.
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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Droperidol, a short-acting butyrophenone, is used as a neuroleptic drug in neuroleptanesthesia. Moreover, droperidol effectively reduces the incidence of postoperative nausea and vomiting (PONV) (1,2). Although small doses (10–20 µg/kg) of droperidol are prophylactically administered before or during anesthesia to prevent PONV, its effect on the hypnosis induced by other anesthetics is not known. The bispectral index (BIS) was reported to provide a reliable measurement of the hypnotic effect on propofol (3,4). In this study, by measuring BIS, we tested the hypothesis that an antiemetic dose of IV droperidol deepens the level of sedation induced by propofol in patients under spinal anesthesia.
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Methods |
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Eighty ASA physical status I or II patients, 40–60 yr old, scheduled for gynecological surgery (hysterectomy or salpingo-ovariectomy) under spinal anesthesia were enrolled in this study. Our local ethics committee approved the study, and informed consent for participation in the study was obtained from each patient. None of the patients had cardiopulmonary or neurological disorders.
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 four groups were comparable with regard to demographic data and duration of surgery (Table 1). There were no intergroup differences in baseline HR, MAP, and BIS. Median analgesic height of spinal anesthesia was the same in the groups (Table 2). Spinal anesthesia significantly decreased MAP but did not change BIS in all four groups.
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The changes in BIS after the administration of droperidol are shown in Figure 1. In the conscious group, droperidol did not cause any change in BIS or the sedation score. Propofol infusion caused decreases in BIS to around 60 in the 3 propofol-sedated groups (time 0 in Fig. 1). In the placebo group, droperidol caused no significant change in BIS during the study period. In contrast, BIS had significantly decreased at 2 min after the injection of droperidol in both the dro-1 and dro-2 groups. The decreases in BIS reached plateaus at 4 and 8 min after the droperidol injection in the dro-1 and dro-2 groups, respectively, and remained almost constant during the remainder of the study period. The maximum decrease in BIS in the dro-2 group was significantly larger than that in the dro-1 group (Table 2).
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After administration of droperidol, MAP did not change in the conscious group but decreased significantly in the dro-1 and dro-2 groups. The maximum decreases in MAP after the administration of droperidol in the dro-1 and dro-2 groups were not different (Table 2). None of the patients required a vasopressor because of hypotension (systolic blood pressure <70% of baseline value) after the administration of droperidol. Droperidol did not cause a change in HR in any of the groups.
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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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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This study was undertaken to determine whether an antiemetic dose of IV droperidol would affect the level of sedation, as assessed by BIS, in patients under spinal anesthesia. The results demonstrated that droperidol caused a decrease in BIS in a dose-dependent manner during the propofol-sedated state despite the fact that the same dose of droperidol did not cause any change in BIS of the conscious patients.
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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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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- Sniadach MS, Alberts MS. A comparison of the prophylactic antiemetic effect of ondansetron and droperidol on patients undergoing gynecologic laparoscopy. Anesth Analg 1997; 85; 797–800.[Abstract]
- Janknegt R, Pinckaers JWM, Rohof MHC, et al. Double-blind comparative study of droperidol, granisetron and granisetron plus dexamethasone as prophylactic anti-emetic therapy in patients undergoing abdominal gynaecological, breast or otolaryngological surgery. Anaesthesia 1999; 54: 1059–68.[Web of Science][Medline]
- Glass PS, Bloom M, Kearse L, et al. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997; 86: 836–47.[Web of Science][Medline]
- Johansen JW, Sebel PS. Development and clinical application of electroencephalographic bispectrum monitoring. Anesthesiology 2000; 93: 1336–44.[Web of Science][Medline]
- Bissonnette B, Swan H, Ravussin P, Un V. Neuroleptanesthesia: current status. Can J Anaesth 1999; 46: 154–68.[Web of Science][Medline]
- Barthel JS, Marshall JB, King PD, et al. The effect of droperidol on objective markers of patient cooperation and vital signs during esophagogastroduodenoscopy: a randomized, double-blind, placebo-controlled, prospective investigation. Gastrointest Endosc 1995; 42: 45–50.[Web of Science][Medline]
- Adachi YU, Uchihashi Y, Watanabe K, Satoh T. Small dose midazolam or droperidol reduces the hypnotic dose of propofol at the induction of anaesthesia. Eur J Anaesthesiol 2000; 17: 126–31.[Web of Science][Medline]
- Klein DS. Nalbuphine and droperidol combination for local standby sedation. Anesthesiology 1983; 58: 397.[Web of Science][Medline]
- Pollock JE, Neal JM, Liu SS, et al. Sedation during spinal anesthesia. Anesthesiology 2000; 93: 728–34.[Web of Science][Medline]
- Morley AP, Chung DC, Wong ASY, Short TG. The sedative and electroencephalographic effects of regional anaesthesia. Anaesthesia 2000; 55: 864–9.[Web of Science][Medline]
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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