Use of Butorphanol, Fentanyl, and Ketamine as Co-Induction Agents with Propofol for Laryngeal Mask Airway Insertion: A Comparative Study.

BACKGROUND: Management of airway is of great importance in the practice of anesthesia. Supraglottic airway devices, such as laryngeal mask airway (LMA), have greatly revolutionized the management of airway both in terms of ease and degree of invasiveness. Propofol, by its inherent property of decreasing airway reflexes, is used to aid in LMA insertion. In this study, we have evaluated the LMA insertion conditions and hemodynamic stability, comparing butorphanol, fentanyl, and ketamine as co-induction agents with propofol.
MATERIALS AND METHODS: A total of 90 female patients planned to undergo minor gynecological procedures were randomly allocated to one of the three study groups. Patients in Group B received butorphanol 20 μg/kg, patients in Group F received fentanyl 1 μg/kg, and patients in Group K received ketamine 0.5 mg/kg intravenously before injection of propofol 2.5 mg/kg. LMA insertion conditions were graded according to the modified scheme of Lund and Stovner, and hemodynamic parameters were recorded. The results were analyzed statistically.
RESULTS: The patients in all the three groups were comparable in their demographic characteristics. The mean total dose of propofol used in Group B was 136.50 mg (standard deviation [SD] 27.70), in Group F was 139.33 mg (SD 28.52), and in Group K was 156.33 mg (SD 38.64). Excellent insertion conditions were observed in 25 (83.3%) patients in Group B, 25 (83.3%) patients in Group F, and 15 (50%) patients in Group K. Group B and Group K showed a more stable hemodynamic profile than Group F.
CONCLUSION: It is concluded that the use of butorphanol as a co-induction agent with propofol provides excellent insertion conditions and stable hemodynamics compared to fentanyl or ketamine.

INTRODUCTION

Management of airway is of paramount importance in the safe practice of anesthesia. Inability to secure airway leads to catastrophic changes costing patient's safety and risking the life of the patient.[1] Supraglottic airway devices, such as laryngeal mask airway (LMA), are important gadgets in the successful management of airway. Initially designed for use in operating room as an alternative to bag and mask ventilation, freeing the hands of the anesthesia provider with the additional benefit of causing less gastric distention,[2] and producing lesser airway trauma,[3] LMA has now largely replaced the endotracheal tube in elective surgeries. LMA has more recently come into use in emergency setting as an important accessory device for the management of the difficult airway.[4] LMA has found an indispensable role in many settings including the operating room, the emergency department, and out-of-hospital settings because it is easy to use and quick to place even in the hands of less experienced personnel. Propofol is conventionally used for LMA insertion because of its ability to suppress pharyngeal reflexes such as coughing, gagging, and laryngospasm.[56] Propofol, as a single induction agent, requires large doses for achieving optimal LMA insertion conditions. The use of drugs such as ketamine, opioids, and benzodiazepines as co-induction agents with propofol will decrease the dose and thereby the side effects of propofol.[7] Planned co-induction of anesthesia is practiced by anesthetists exploiting drug interactions, particularly synergism, principally between midazolam, opioids, and propofol.[8] It can produce an improvement in all phases of anesthesia, including induction, maintenance, and recovery. This study has been conducted to evaluate butorphanol, fentanyl, and ketamine as co-induction agents to propofol for optimal LMA insertion conditions and stable hemodynamics.

Aims and objectives

The aim of this study is to compare equipotent doses of butorphanol, fentanyl, and ketamine as co-induction agents with propofol during LMA insertion and evaluate the hemodynamic stability and ease of LMA insertion during the use of ketamine 0.5 mg/kg, fentanyl 1 μg/kg, or butorphanol 20 μg/kg as co-induction agents with propofol 2.5 mg/kg during LMA insertion.

MATERIALS AND METHODS

This was a prospective randomized double-blinded study conducted in a tertiary health institution between January 2013 and June 2014. After obtaining institutional ethical committee approval, 90 female patients in the age group of 20–50 years belonging to the American Society of Anesthesiologists (ASA) physical status Classes I and II undergoing short gynecological procedures such as transabdominal tubectomy, medical termination of pregnancy, and fractional curettage were chosen for the study. After obtaining informed consent from the participants, they were randomly allocated to one of the three study groups, i.e. Group B (butorphanol–propofol group), Group F (fentanyl–propofol group), and Group K (ketamine–propofol group). Patients with full stomach, patients with risk of aspiration or history of gastroesophageal reflux disease and hiatus hernia, patients with anticipated difficult intubation, morbidly obese patients, hypertensive patients, and patients with a history of allergy to the study drugs were excluded from the study.

All patients were kept on 6 h starvation. Patients were premedicated with injection glycopyrrolate 0.2 mg intramuscularly half an hour before surgery. After preoxygenation with 100% oxygen for 3 min, injection midazolam 0.04 mg/kg was given intravenously. Then, the patients were given the assigned drugs over 10 s intravenously.

Group K – Ketamine 0.5 mg/kg

Group F – Fentanyl 1 μg/kg

Group B – Butorphanol 20 μg/kg.

Then, intravenous (IV) propofol 2.5 mg/kg over 15 s was given intravenously. The trapezius squeeze test was performed to assess the depth of anesthesia.[9] Negative test is defined as when the response to squeezing trapezius muscle produced no body or toe movement. If necessary, an additional dose of propofol 0.5 mg/kg IV was given till the trapezius squeeze test became negative. The LMA was then inserted 60 s after the test became negative. If the first attempt was unsuccessful, an additional dose of propofol 0.5 mg/kg was given. Insertion was attempted for a maximum of three times. Insertion conditions during the first attempt were graded as excellent, good, poor and unacceptable according to the modified scheme of Lund and Stovner.[10] Patients were maintained on spontaneous respiration. Anesthesia was maintained with N2O:O2 in the ratio of 60:40 with halothane 1%. At the end of surgery, N2O and halothane were stopped and LMA was removed. Hemodynamic parameters, namely, heart rate (HR), systolic and diastolic blood pressure (BP), and SPO2 were recorded before induction, immediately following induction, and then at 1-, 3-, 5-, and 15-min post-LMA insertion. Electrocardiography was continuously monitored during the study period. The following parameters were also noted during insertion of the LMA. Top-up dose of propofol required, total dose of propofol used, number of attempts for LMA insertion, presence of apnea >30 s, coughing and gagging, patient movements and laryngospasm (noted on a three-point scale – nil, mild, and severe), and jaw relaxation according to Young's criteria[11] (Grade I – absolutely relaxed with no muscle tone, Grade II – moderately relaxed with some muscle tone, and Grade III – poorly relaxed with full muscle tone).

The overall conditions were graded according to the modified scheme of Lund and Stovner.[10]

Excellent – No gagging or coughing, no patient movement, or no 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

Unacceptable – Laryngospasm with or without severe gagging, coughing, or patient movement.

The data from our study were collected, compiled, and statistically analyzed using SPSS statistics software version 20 (IBM, New York, USA). Statistical tests used for analysis were ANOVA test, and intergroup comparison was done using Chi-square test. P < 0.05 was taken as statistically significant.

During the postoperative period, the patients' hemodynamics was monitored.

RESULTS

The demographic data, such as age and weight, were comparable in all the three groups. The mean age in butorphanol group was 26.50 (standard deviation [SD] 3.85) years, in fentanyl group was 26.27 (SD 3.76) years, and in ketamine group was 27.90 (SD 3.58) years. The mean weight in butorphanol group was 53.20 (SD 10.12) kg, in fentanyl group was 54.13 (SD 11.41) kg, and in ketamine group was 53.90 (SD 9.18) kg. The patients belonged to either ASA physical Status 1 or 2 and were comparable in all three groups.

Insertion conditions

The incidence of apnea was higher in fentanyl group compared to butorphanol or ketamine group with no statistical significance between butorphanol and ketamine groups [Figure 1].

Figure 1

Incidence of Apnea χ2 = 11.97 (df = 2), P = 0.003 < 0.05 (significant)

LMA could be inserted in the first attempt in greater proportion (93%) in butorphanol group followed by fentanyl group (80%) and ketamine group (70%). However, there is no statistically significant difference between the three groups [Figure 2].

Figure 2

Number of Attempts χ2 = 5.367 (df 2), P (0.068) >0.05 (not significant)

Jaw relaxation was comparatively better in butorphanol group with no statistically significant difference between the fentanyl and the ketamine groups [Figure 3].

Figure 3

χ2 = 9.73(df 4), P (0.045) <0.05 (significant)

Additional doses of propofol have been used in patients where optimal conditions of insertions were not met. Significantly higher number of cases in ketamine group (56.7%) required additional doses of propofol compared to fentanyl or butorphanol group [Figure 4].

Figure 4

Number of patients requiring additional dose of propofol χ2 = 11.700 (df 2), P (0.003) <0.05 (significant)

The total dose of propofol required for LMA insertion was significantly higher in ketamine group compared to the other two groups [Figure 5].

Figure 5

Total dose of propofol required ANOVA, F = 3.369 (df 2, 87), P (0.039) <0.05 (significant)

The overall condition of LMA insertion was better in butorphanol and fentanyl groups compared to ketamine group. However, there was no significant difference between the butorphanol and fentanyl groups [Figure 6].

Figure 6

Overall conditions for laryngeal mask airway insertion χ2 = 13.101(df 4), P (0.011) <0.05 (significant)

Hemodynamic profile

The patients in the butorphanol and fentanyl groups experienced a mild fall in HR postinduction, but patients in ketamine group had a mild rise in HR, but the difference was not statistically significant.

The comparison of mean change in HR between the three groups showed statistically significant difference only at 3 min and 15 min [Figure 7].

Figure 7

Variation in heart rate

Statistically significant fall in postinduction systolic BP from the baseline BP is noted in fentanyl group as compared to butorphanol and ketamine groups. However, the variation (fall) in systolic BP at 1-, 3-, 5-, and 15-min post-LMA insertion is not statistically significant between the three groups. The postinduction fall in BP between butorphanol and ketamine groups is not statistically significant [Figure 8].

Figure 8

Variation in systolic blood pressure

The variation (fall) in diastolic BP from the preinduction BP, postinduction, and postinsertion was noted and was not statistically significant between the three groups. However, the postinduction fall in diastolic BP was highest in fentanyl group compared to butorphanol and ketamine groups [Figure 9].

Figure 9

Variation in diastolic blood pressure

DISCUSSION

Supraglottic airway devices have become standard equipment in the airway management, filling a niche between the face mask and the endotracheal tube, both in terms of anatomical position and degree of invasiveness. From the time of introduction of Laryngeal Mask Airway by Dr. Archie Brain in1983 and commencement of its clinical use since 1988, these devices have achieved a great success in the practice of anaesthesiology.[12] LMA insertion is facilitated by IV induction agents or inhalational induction agents conventionally. This study was conducted to find a better co-induction agent with propofol among butorphanol, ketamine, and fentanyl for LMA insertion.

The demographic characteristics such as age, weight, and ASA status of the study population were similar in all the three groups, with no statistically significant difference.

After induction with the study drug and propofol, the incidence of apnea was higher in fentanyl group when compared to butorphanol or ketamine group. Among ketamine and butorphanol groups, there was no statistically significant difference in the incidence of apnea. These results are consistent with the study conducted by Gupta et al.[13] Chari and Ghai[14] and Goh et al.[15] also recorded increased incidence of apnea in patients receiving fentanyl. The increased incidence of apnea in fentanyl group can be explained by its inherent property of producing respiratory depression.[16] The lower incidence of apnea in butorphanol group is probably due to its κ-receptor agonism and μ-receptor antagonism.[13]

LMA was inserted in the first attempt in 28 out of 30 patients (93.3%) in butorphanol group, 24 out of 30 patients (80%) in fentanyl group, and 21 out of 30 patients (70%) in ketamine group [Figure 2]. Similar observation had been made by Gupta et al. too where patients receiving butorphanol showed significantly lower number of attempts compared to patients receiving fentanyl or ketamine.[13] Significantly higher number of patients in the ketamine group required additional doses of propofol for successful LMA insertion when compared to the patients in fentanyl or butorphanol group [Figure 4] resulting in the usage of higher dose of propofol in ketamine group [Figure 5]. The difference between fentanyl and butorphanol groups is not statistically significant. Similar results were observed by Gupta et al.[13] and Chari and Ghai.[14]

The incidence of coughing and gagging was significantly higher in ketamine group than in butorphanol or fentanyl group. This is probably due to the better preservation of pharyngeal and laryngeal reflexes by ketamine.[17] The antitussive action of butorphanol and its limited skeletal muscle action explain the lower incidence of coughing and gagging in the butorphanol group.[18]

Laryngospasm can occur during LMA insertion due to inadequate depth of anesthesia.[19] Five patients among the total 90 patients in the study population showed laryngospasm, out of which four patients in ketamine group and one patient in fentanyl group had laryngospasm. Patients who had laryngospasm were treated with 100% oxygen and additional doses of propofol to which they responded well.[20] Gupta et al. recorded severe laryngospasm in one patient of ketamine group.[13]

Jaw relaxation was graded on an ordinal scale according to Young's criteria.[11] Jaw relaxation was significantly better in butorphanol group than fentanyl and ketamine groups [Figure 3].

The overall insertion conditions of LMA were graded using modified score of Lund and Stovner.[10] The insertion conditions were graded as excellent in 25 out of 30 patients (83.3%) in butorphanol group, 23 out of 30 patients (76.7%) in fentanyl group, and 15 out of 30 patients (50%) in ketamine group. Statistically, the insertion conditions were better in butorphanol and fentanyl groups than ketamine group.

The variation in HR from baseline, at postinduction, and at 1-, 3-, 5-, and 15-min post-LMA insertion was compared among the three groups. Mild fall in HR from the baseline was noted after induction in fentanyl and butorphanol groups. In the ketamine group, the HR steadily increased from the baseline. However, the variation in HR is not statistically significant.

In all the three groups, both the systolic and the diastolic BP were observed to fall from the baseline in the postinduction period and the postinsertion period till 3 min, and thereafter, it started to rise gradually reaching almost the baseline. There was a significant fall in systolic BP during the postinduction period in the fentanyl group when compared to ketamine and butorphanol groups. The significant fall in fentanyl group could be explained by the additive effect of cardiovascular depressant properties of fentanyl and propofol.[2122] Both ketamine and butorphanol showed a relatively stable hemodynamic profile when used in conjunction with propofol. The cardiovascular stimulant effect of ketamine on systemic and pulmonary circulations is probably blunted by the prior administration of benzodiazepines or the concomitant administration of inhaled anesthetics.[23] This could possibly explain the initial mild fall in BP in the ketamine group.

None of the patients showed bradycardia <60/min or a fall in BP >20% of the baseline. In the postoperative period, there was no incidence of vomiting in any of the patients. No patient was excessively sedated or irritable during the postoperative period.

There are certain limitations in this study. Only female patients undergoing short gynecological procedures were included in the study. First, advantage of using butorphanol as a co-induction agent needs to be studied in both genders and pediatric population. Second, monitoring the depth of anesthesia using bispectral index could have been done for more accurate assessment of insertion conditions and hemodynamic profile.

CONCLUSION

The use of butorphanol, fentanyl, and ketamine as co-induction agents with propofol in LMA insertion helps in reducing the total dose of propofol required and improving the insertion conditions. Among the three study drugs, butorphanol–propofol provided good jaw relaxation, excellent insertion conditions, and better hemodynamic stability than ketamine–propofol or fentanyl–propofol. Hence, we recommend the use of butorphanol 20 μg/kg as a co-induction agent along with propofol for LMA insertion.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.