Journal of Medical Society

: 2014  |  Volume : 28  |  Issue : 3  |  Page : 185--189

Comparative evaluation of fentanyl and midazolam with propofol induction on laryngeal mask airway insertion conditions: A study

Sivaramakrishnan Dhamotharan, Nongthombam Ratan Singh, Sanasam Sarat Singh, Maisnam Brajagopal Singh 
 Department of Anesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India

Correspondence Address:
Nongthombam Ratan Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal - 795 004, Manipur


Background: Propofol alone for laryngeal mask airway (LMA) insertion is unsatisfactory. To overcome the problems associated with it, a number of co-induction drugs have been introduced. The present study was conducted to compare the insertion conditions using midazolam and fentanyl co administered with propofol during intravenous induction of anesthesia. Materials and Methods: This prospective, double-blinded, randomized study was conducted at a tertiary healthcare teaching hospital at Imphal. Ninety American Society of Anesthesiologists (ASA) I and II patients aged 18-60 years were randomly divided into three equal groups and received intravenous (IV) fentanyl 2 μg/kg (Group I), IV midazolam 0.05 mg/kg (Group II), and control (saline) group (Group III) followed by induction with propofol 2.5 mg/kg. LMA was inserted after 90 s. The insertion conditions and hemodynamic changes were noted. Data were collected and analyzed with Statistical Package for Social Sciences (SPSS) v.20. Results: There were no statistical differences in the demographic profile (P > 0.05). Adequate jaw relaxation was present in 21 (70%) patients in Group II and 14 (46.6%) patients in Group I (P > 0.05). Excellent insertion conditions were present in 80% of the patients in both fentanyl and midazolam groups, respectively. Conclusion: Midazolam and fentanyl provides adequate conditions for LMA insertion, although midazolam provides better jaw relaxation.

How to cite this article:
Dhamotharan S, Singh NR, Singh SS, Singh MB. Comparative evaluation of fentanyl and midazolam with propofol induction on laryngeal mask airway insertion conditions: A study.J Med Soc 2014;28:185-189

How to cite this URL:
Dhamotharan S, Singh NR, Singh SS, Singh MB. Comparative evaluation of fentanyl and midazolam with propofol induction on laryngeal mask airway insertion conditions: A study. J Med Soc [serial online] 2014 [cited 2022 Jun 25 ];28:185-189
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Laryngeal mask airway (LMA) is a noninvasive supraglottic airway device which has the advantage of being less stimulating than the tracheal intubation as visualization of cords and entry into larynx is not required. [1] With LMA, there is an ease of insertion without a laryngoscope or muscle relaxant. The cardiovascular response to insertion of LMA is much lower than that of endotracheal intubation, [2] and the incidence of postoperative sore throat is lower after LMA use as compared to endotracheal intubation. [3]

Successful insertion of LMA requires adequate mouth opening and suppression of upper airway reflexes to prevent coughing, gagging, and laryngeal spasm.

Propofol 2.5-3 mg/kg is the induction agent of choice for LMA insertion and many studies have shown propofol to be superior to thiopentone in this respect. [4],[5] However, it frequently causes cardiopulmonary suppression such as apnea, hypotension, and bradycardia. [6] These undesired effects can be mitigated by the use of "co-induction" technique where a small dose of sedative or other anesthetic agent is administered to reduce the total dose of the induction agent.

The addition of adjuvants, such as midazolam, [7] ketamine, [8] low-dose muscle relaxants, [7] opioids, [9] and sevoflurane have been advocated to further improve the LMA insertion conditions. Of these, opiates are the most commonly used and among them fentanyl is frequently used with intravenous anesthetics during induction of anesthesia.

Midazolam when used in sub anesthetic doses reduces the dose of propofol required for induction with a synergistic action, [10] which improves conditions for LMA insertion than when using propofol alone. It also provides hemodynamic stability without prolonging recovery and is useful as a short-acting co-induction agent with propofol in day-care anesthesia for ambulatory surgery. [10]

Hence, the present study was undertaken to compare and evaluate the effectiveness of midazolam and fentanyl as co-induction agents with propofol for LMA insertion, and also to compare the hemodynamic changes during LMA insertion and immediately afterwards among these groups.

 Materials and Methods

A prospective, randomized, controlled, double-blinded study was conducted in a tertiary care teaching hospital at Imphal, Manipur during the period from October 2011 to September 2013. After getting the ethical committee clearance from the institute and written informed consent of the patients, 90 patients aged between >18 and <60 years (American Society of Anesthesiologists (ASA) I and II) undergoing short elective surgical procedures were included in the study.

Based on the previous study by Gupta et al., [11] the sample size of the study was calculated. Using formula for binomial distribution about proportion of categorical data having α value as 0.05 and power value as 0.8 we got sample size as 30 per group.

The study population was randomly divided based on a computer generated randomization chart into three groups with 30 patients in each group. The study drug was diluted with normal saline to make a total volume of 5 ml.

Group I (n = 30): Received fentanyl 2 μg/kg and propofol 2.5 mg/kg

Group II (n = 30): Received midazolam 0.05 mg/kg and propofol 2.5 mg/kg

Group III (n = 30): Received normal saline 5 ml and propofol 2.5 mg/kg

All the patients were premedicated with glycopyrolate 0.2 mg intramuscularly (im) along with inj. ondansetron 4mg and inj. ranitidine 50 mg IV 30 min before the surgery. After preoxygenation with 100% oxygen for 3 min, the patients were given their assigned drugs over 10 s, that is, Group I received inj. fentanyl IV, Group II received inj. midazolam IV, and Group III received inj. normal saline IV. The study drug was prepared by the anesthesiologist who was not involved in this study and dispensed in an unlabelled syringe. The observer was another anesthesiologist who was not involved in the study.

Two minutes after giving test drug, general anesthesia was induced with propofol 2.5 mg/kg IV over 15 s. If required, further increments of propofol 0.5 mg/kg was administered every 30s until loss of consciousness and loss of eye lash reflex. Insertion of LMA was performed 90 s after injection of propofol by a blinded investigator.

LMA insertion conditions were assessed using six variables on a 3-point scale as follows: [12]

Jaw opening: Full-3; Partial-2; Nil-1Ease of LMA insertion: Easy-3; Difficult-2; Impossible-1Gagging: Nil-3; Slight-2; Gross-1Coughing: Nil-3; Slight-2; Gross-1Limb/head movements: Nil-3; Slight-2; Gross-1

Overall insertion conditions were assessed according to the modified Scheme of Lund and Stovener: [11]

Excellent: No gagging or coughing, no patient movement or laryngospasm.Good: Mild to moderate gagging, coughing, or patient movement with no laryngospasm.Poor: Moderate to severe gagging, coughing or patient movement with no laryngospasm.

If failed on first attempt, an additional bolus dose of propofol 0.5 mg/kg was given. Insertion of LMA was attempted to a maximum of three attempts. In between the attempts, the patient's lungs were ventilated using a face mask. If LMA insertion was unsuccessful after three attempts, patient's trachea was intubated. After securing the LMA in position, patient was left on spontaneous respiration and anesthesia was maintained with up to 1.5% isoflurane and 66% N 2 O with oxygen. No further data was collected. Only the patients in which LMA insertion was done in the first attempt was taken for comparing the hemodynamic changes and LMA insertion conditions. The following parameters were observed heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MAP), and SpO 2 (peripheral oxygen saturation) were monitored continuously. These parameters were recorded at the following time intervals: Baseline value, immediately before insertion, and every minute till the end of 5 min after LMA insertion. Beyond that no more recordings were made and the study ended with 5 min. Incision was not made till the end of 5 min. The patient was maintained with 0.8-1% isoflurane and 66% N 2 O with oxygen and inj. atracurium 0.5 mg/kg was given and intermittent positive pressure ventilation (IPPV) was maintained till the end of operative procedure.

The data were collected and statistically analyzed using chi-square (χ2 ) test, analysis of variance (ANOVA) with Bonferroni's t-test for statistical analysis, frequencies and crosstabs, Student's t-test, and P- value (P < 0.05) was taken as significant. Statistical Package for Social Sciences (SPSS) version 20 software windows was utilized for analysis.


As shown in [Table 1], the mean ages expressed in year ΁ standard deviation (SD) were comparable in the three groups (P = 0.0602). There were more of female patients in all the three groups; 26, 23 and 24 female patients as compared to 4, 7, and 6 male patients in Groups I, II, and III, respectively. This might have been because of the prevalence of cholelithiasis in females than males as the study was done mostly in patients undergoing cholecystectomy. The minimum weights in kilograms were 35 in fentanyl group, 35 in midazolam group, and 34 in control group. The mean weights of the cases were comparable in all the groups (P > 0.05).{Table 1}

The baseline mean of MAP of all three groups are comparable and is statistically not significant. After induction with propofol, the decrease in MAP is higher in Group I and it is statistically significant when compared to Groups II and III (P = 0.000) as shown in [Figure 1]. The HR decreased after induction and remained constant throughout in fentanyl group. There was not much change in HR in midazolam group. Compared to control group, decrease in HR in fentanyl group was highly significant (P = 0.000) from 1 st min onwards. In the midazolam group, the changes in HR, compared to control value, are significant only in the 2 nd , 4 th and 5 th min [Figure 1].{Figure 1}

[Figure 2] shows that there were no statistical differences in the baseline mean SBP among the three groups. After induction with propofol and before LMA insertion, the SBP decreased in all the three groups, more pronounced in Group I. Compared to the control group, the decrease in SBP in the fentanyl group is significant from pre-insertion level (after induction with propofol) onwards; whereas in the midazolam group, the changes are significant only in the 2 nd , 3 rd],[ and 4 th min (P = 0.000). After induction with propofol and prior to LMA insertion, the DBP decreased in all the three groups. There was no statistical difference between Groups II and III after induction with propofol. After LMA insertion, the DBP began to rise in Groups II and III; whereas, there were no much changes in Group I and it was statistically highly significant (P < 0.005) when compared to other two groups.{Figure 2}

LMA insertion was easy in 24 patients (80%) in Group I, 24 patients (80%) in Group II, and only in 10 patients (33.33%) in Group III. Statistically significant variations were found between Groups I and III (P < 0.05) and between Groups II and III (P < 0.05). There were no statistical variations between Groups I and II (P > 0.1) [Figure 3].{Figure 3}

As it is evident from [Figure 4], 14 patients (46.67%) of Group I, 21 patients (70%) in Group II, and 12 patients (40%) of Group III had full jaw opening. There was statistically significant difference only between Groups II and III (P < 0.05).{Figure 4}

In the three groups, slight movements were observed in three, four, and eight patients in Groups I, II, and III, respectively; whereas, the incidence of gross movements were zero, one, and four patients, respectively, in the three groups [Table 2].{Table 2}

[Table 3] shows that 25 patients (83.33%) in Group I, 24 patients (80%) in Group II, and 10 patients (33.33%) in Group III did not have coughing and gagging reflexes during LMA insertion, while severe gagging reflex was present in four patients (13.34%) in Group III, which was statistically significant (P < 0.05).{Table 3}


The present study was made blind regarding the age, weight, and ASA status as shown by the statistical insignificance of the study sample. Four different doses of fentanyl (0.5, 1.0, 1.5 and 2.0 μg/kg) co administered with propofol 2.5 mg/kg were compared by Wong et al., [13] and they observed that a standard dose of that 1.0 μg/kg fentanyl provided optimal conditions in 65% of the cases. Hence, we chose 2 μg/kg as the dose of fentanyl in our study.

In our study, the decrease in MAP was more in fentanyl group when compared to midazolam and saline group in our study, and it was statistically significant (P < 0.05). Similar decrease in MAP following induction was observed by Sizlan et al., [14] when they administered fentanyl 1 μg/kg along with propofol 2.5 mg/kg for LMA insertion. They found significantly lower MAP following LMA insertion than with propofol alone group.

Dutt et al., [15] observed a significant decrease in SBP (a fall of 20% from baseline value) at 1, 2, 3, 4, and 5 min and mean arterial pressure at 2 and 3 min after LMA insertion. Similarly, a decrease of 18% in SBP and mean arterial pressure was observed in our study.

A fixed induction dose of 2.5 mg/kg propofol was used in our study for all patients. Salem [7] used 0.04 mg/kg midazolam with propofol for LMA insertion. They observed only 4% decrease in mean arterial pressure from the baseline, whereas in our study the decrease in mean arterial pressure was 8% when compared to the baseline. This variation in decrease in MAP may be attributed to the fixed induction dose of propofol used in our study. Nakazawa et al., [16] compared fentanyl and midazolam for LMA insertion with propofol; they mentioned that blood pressure in fentanyl group after LMA insertion was lower than midazolam group. This result is comparable to our findings.

In the present study, there were not much significant changes in HR in the midazolam group and similar results were observed by Salem. [7] However, there was decrease in HR in the fentanyl group in this study when compared to the baseline, and it was statistically significant when compared with midazolam. Three patients had bradycardia in fentanyl group. The bradycardia observed was within clinical limits, but three patients required inj. atropine 0.6 mg IV to reverse the bradycardia. Similar results were observed by Dutt et al., [15] where they used fentanyl 2 μg/kg with 2.5 mg/kg propofol.

Excellent insertion conditions were present in 80% of the patients in both fentanyl and midazolam groups, respectively in our study. Gagging was very high in the patients who received propofol alone. Driver [17] showed that fentanyl 1 μg/kg with propofol 2.5 mg/kg given 90 s prior to LMA insertion provided excellent insertion conditions in 77% of the patients which is similar to our study.

Hui et al., [18] compared alfentanil and fentanyl for LMA insertion with propofol. Thirty percent of their patients had head or limb movements, which was comparatively higher than the findings of our study where 10% had slight limb or head movements.

Dutt et al., [15] observed that with 2 μg/kg fentanyl, mouth opening was full in 80% of patients; whereas in our study, full mouth opening was observed only in 52.22% of the patients. Insertions were easier in 90% of patients in their study compared to 64.44% in our study. This variation in mouth opening and ease of insertions might have been due to the difference in assessment of depth of anesthesia in both the studies. They used jaw thrust as an indicator of adequate depth of anesthesia, while we used loss of eyelash reflex as the adequate depth.

Gupta et al., [11] showed that with fentanyl 1 μg/kg absolute jaw relaxation was present in 53.33% patients. This may be favorably compared to the findings of the study which showed that 52.22% of the cases had full jaw relaxation. We felt that increasing the dose of fentanyl did not cause any improvement in jaw relaxation. Moreover, fentanyl has been shown to cause muscle rigidity at increased doses.

In a study by Gill et al., [19] a combination of fentanyl, midazolam, and lidocaine were co administered with propofol for LMA insertion. They concluded that patients who received both fentanyl and midazolam required lesser amount of propofol and also had better insertion conditions.


From this study, we conclude that addition of either fentanyl 2 μg/kg or midazolam 0.05 mg/kg is an ideal adjuvant for LMA insertion with propofol 2.5 mg/kg and provided similar insertion conditions though the incidence of jaw relaxation was higher in midazolam group.

Future directions

The main drawback of midazolam is that, it lacks analgesic property. With fentanyl, there were incidences of bradycardia and also hypotension which required lowering of volatile anesthetics for some time in our study. Therefore, we suggest that a combination of fentanyl 1 μg/kg and midazolam 0.05 mg/kg premedication would be an ideal combination with propofol for LMA insertion with stable hemodynamics.


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