Indian Journal of Anaesthesia

: 2009  |  Volume : 53  |  Issue : 6  |  Page : 662--666

Comparison of Midazolam and Propofol for BIS-Guided Sedation During Regional Anaesthesia

Priyanka Khurana1, Ankit Agarwal2, RK Verma3, PK Gupta4,  
1 Ex.P.G.Student, Deptt. Of Anaesthesiology, BHU, Varanasi, India
2 Sr.Resident, Deptt. Of Anaesthesiology, BHU, Varanasi, India
3 Reader, Deptt. Of Anaesthesiology, BHU, Varanasi, India
4 Professor, Deptt. Of Anaesthesiology, BHU, Varanasi, India

Correspondence Address:
Ankit Agarwal
Sr.Resident, Deptt. Of Anaesthesiology, BHU, Varanasi


Regional anaesthesia has become an important anaesthetic technique. Effective sedation is an essential for regional techniques too. This study compares midazolam and propofol in terms of onset& recovery from sedation, dosage and side effects of both the drugs using Bispectral Index monitoring. Ninety eight patients were randomly divided into two groups,one group recieved midazolam infusion while the other recieved propofol infusion until BIS reached 75. We observed Time to reach desired sedation, HR, MABP, time for recovery, dose to reach sedation and for maintenance of sedation and side effects if any. The time to reach required sedation was 11 min in Midazolam group(Group I) while it was 6 min in Propofol group(Group II) (p=0.0). Fall in MABP was greater with propofol. Recovery in with midazolam was slower than with propofol (18.6 ± 6.5 vs 10.10±3.65 min) (p=0.00). We concluded that both midazolam and propofol are effective sedatives, but onset and offset was quicker with propofol, while midazolam was more cardiostable.

How to cite this article:
Khurana P, Agarwal A, Verma R K, Gupta P K. Comparison of Midazolam and Propofol for BIS-Guided Sedation During Regional Anaesthesia.Indian J Anaesth 2009;53:662-666

How to cite this URL:
Khurana P, Agarwal A, Verma R K, Gupta P K. Comparison of Midazolam and Propofol for BIS-Guided Sedation During Regional Anaesthesia. Indian J Anaesth [serial online] 2009 [cited 2021 Jul 26 ];53:662-666
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In the recent days regional techniques have come to take an upper hand in anaesthesia over general ana­esthesia owing to its certain, often underestimated ad­vantages such as lesser chances of airway compromise and aspiration, facilitation of postoperative analgesia, inherent benefit in some preexisting medical conditions and avoidance of operation theatre pollution. The con­cept of Monitored Anaesthesia Care has come to high­light the fact that a vigil on patient's vitals and monitor­ing of various aspects of regional anaesthesia are as important as in general anaesthesia [1] .

Amongst the armamenterium of monitoring equip­ment available to the modern anaesthetist, BIS is per­haps the latest and the best suited tool. [2] Besides pro­viding an idea about the hypnotic state of the patient, it also enables titration of anaesthetic agents so as to avoid adverse effects as awareness due to inappropriate dos­age as well as unwanted effects of overdosage.

We performed a study comparing sedative effects of propofol and midazolam using BIS in regional ana­esthesia. Although literature is flooded with reports on use of BIS during general anaesthesia, it was still defi­cient in studies involving regional anaesthesia. We there­fore evaluated BIS while under sedation. Propofol and midazolam both are established sedative agents both intraoperatively and in an ICU [3],[4]

The aim of our study was to find out the time for onset and recovery from sedation with both drugs, us­ing BIS as a standard measure of depth of sedation and to evaluate and compare the properties of propofol and midazolam in terms of haemodynamics, side ef­fects and dosage requirement as adjuncts to spinal ana­esthesia.


The study was conducted in 98 ASA grade I and II patients between age 20-50 years undergoing lower abdominal, perineal and lower limb surgeries under combined spinal epidural block upto T 10 level.

Patients were randomly allocated to one of the following two groups:

Group I- (n=50) Midazolam 0.1% infusion start­ing with 0.5 -1 .h -1 till BIS level reached 75 and then dose reduced and titrated to maintain a BIS of 65-85.

Group II- (n=48) Propofol 1% infusion starting with -1 .h -1 till BIS level reached 75 and then dose was reduced and titrated to maintain a BIS of 65-85.

A written informed consent was taken from all patients. They were fasted for a minimum of 6 hours before surgery. No preoperative opioids or prophy­lactic antiemetics were given. No other preoperative medication was allowed. Patients suffering from heart disease, hypertension, diabetes, spinal deformity, neu­rological problem or any bleeding disorder were ex­cluded from the study. All patients were monitored with an electrocardiograph, noninvasive blood pressure, pulse oximeter and BIS monitor. Baseline readings were recorded. Preloading was done with -1 of Ringer lactate prior to block. Combined spinal and epidural block was given. Epidural catheter was put at L3-4 or L2-3 level, 3 ml of 0.5% bupivacaine was given into the subarachnoid space and the epidural cath­eter was maintained for providing postoperative anal­gesia. 1 % propofol or 0.1% midazolam infusion was started with the help of a manually controlled variable rate infusion pump.

Propofol infusion was given at a rate of­-1 .hr -1 and midazolam at 0.5 -1 .hr -1 and after reach­ing a BIS value of 75, the rate of infusion was reduced to half and then with subsequent observations, the anaesthetics were titrated to keep a BIS level between 65 and 85.

Blood pressure, heart rate, oxygen saturation, and BIS level were assessed every 2 min till maintenance dose was reached ie a BIS level of 65-85 and then every 10 min till 105 min or till the end of surgery which­ever was earlier and every 15 min (if duration of sur­gery extended beyond that).

O 2 inhalation by ventimask was given when SpO 2 came down below 90% and vasopressor was given if MAP decreased beyond 20% of baseline.

Following observations were made:

1. Time to reach required level of sedation.

2. Duration of surgery

3. Duration of infusion

4. HR, Mean Arterial pressure, arterial saturation of oxygen were recorded every 2 minutes till required sedation level was reached and then every 10 min till 105 min or end of the surgery whichever was earlier and then every 15 minutes.

5. Time taken for recovery (for comparison, BIS>90 was taken as a recovery parameter )

6. Side effects

a. Awareness

b. Nausea& Vomiting c. Pain in arm

7. Dose to reach required level of sedation.

8. Dose to maintain required level of sedation

Statistical analysis was done with independent t test for age, weight, duration of surgery and end infu­sion, time for recovery, heart rate, mean arterial pres­sure, and SpO 2 at various intervals. Chi square test was applied for sex distribution and for adverse effects as respiratory obstruction, apnea, laryngospasm, nau­sea& vomiting, awareness, hypotension, and oxygen supplementation. Paired t test was applied for intra­group variation in heart rate and mean arterial pres­sure. Fischer's exact test was used for incidence of complications.


The mean age, sex and body weight in the two groups were statistically similar. The mean of various time intervals in the two groups is as shown in [Table 1]. The mean time to reach the required level of sedation in group I was 11.0 ± 0.5 minutes which was about 5 minutes later than in group II (6.2 ± 0.2min) (p=0.00), thus the difference in mean time to reach required se­dation level was statistically highly significant. The dif­ference in mean duration of infusion in the two groups was statistically insignificant (73.2 ± 23.9 vs 71.1 ± 18.0) (p=0.50). The time for recovery in group I (midazolam group) was more than in group II (propofol group) (18.6 ± 6.5 vs 10.10 ± 3.65 min) (p=0.00) and it was highly significant.

The mean ± SD of heart rates at various time in­tervals is shown in [Table 2]. In Group I, the initial mean heart rate was 86.0 ± 11.9 which gradually decreased to 78.0 ± 10.6 at 25 min while in Group II initial mean heart rate of 85.37 ± 11.97 per min which gradually decreased to 75.6 ± 12.3 at 25 min. In between group comparison of mean heart rate at various time intervals using independent t test in the two groups revealed the difference was not significant at almost all time inter­vals. However, the comparison of heart rate at various time interval with the baseline within the same group using t test showed significant difference at various time intervals

Mean arterial pressures: The mean ± SD of MAP values are shown in [Table 3]. The mean arterial pressure in Group I initially was 81.7 ± 6.8 mmHg which gradually decreased to 76.8 ± 6.9 mm Hg while, in Group II mean MAP at baseline was 83.1 ± 8.5 mm Hg which gradually decreased to 68.25 ± 2.98 mm Hg.

Between-group comparison showed that the dif­ference was not significant up to 35 min, but it become significant at 45,55,75,85& 95 min to become non­significant again at105 and 120 min.

The incidence of complications is as shown in [Table 4].

Hypotension defined a decrease of MAP > 20% from baseline was seen in 8 (16%) cases in Group I while in group II, it was seen in 13 cases (27.1%); the difference was not significant.

To maintain the desired sedation ie BIS 65-75, maintenance dose of 2.2 ±0.5 mg/kg/h propofol and 0.12±0.38 mg/kg/h for midazolam had to be given in the two groups respectively.

Oxygen supplementation: It was provided when SpO2 level was below 90. The incidence of oxygen supplementation was 14 (28%) in group I as compared to 10 (20.8%) in group II (pet al [5] in a compari­son of the effects of propofol and midazolam on the cardiovascular autonomic nervous system during com­bined spinal epidural anaesthesia.

Arterial oxygen saturation in both the groups de­creased significantly after the start of sedation. The num­ber of patients requiring supplemental oxygen was also similar in both the groups. Almost similar results were found in Win's study [6].

The mean recovery time (as defined by BIS >90) was significantly lower in the propofol group than the midazolam group (10.1±3.6 vs 18.6±6.5 min) (p=0.00). Similarly recovery times were observed by Wilson et al [7] (9.2±1.5 vs 2.1±0.3 min).

As the desired sedation level was reached, the dose of anaesthetic agents was reduced and a mainte­nance dose of 2.2 ±0.5 mg/kg/h propofol and 0.12±0.38 mg/kg/h for midazolam had to be given. The dose for midazolam was found to be similar to Nishiyama et al 8 who found that during combined spi­nal epidural block, midazolam 0.6 mg/kg/h was given until closing of eyes followed by midazolam 0.15 mg/ kg/h with a Ramsay sedation score of 4 along with stable haemodynamics and respiration. The incidence of side effects related to airway maintenance were similar in both the groups. However, the incidence of restless­ness and pain in arm was more in propofol group but the difference was insignificant.

This study showed that though both midazolam and propofol are effective sedative agents, the time to reach effective sedation was less with propofol than midazolam and similarly the time to recovery time from sedation was lesser with propofol. Though complica­tions were insignificant with both the drugs, propofol caused a greater fall in MABP, thus providing lesser haemodynamic stability than midazolam.[8]


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