INTRODUCTION:

TIVA has gained preference over inhalational anaesthesia¹due to smoother recovery profiles, improved intra-operative control, and reduced postoperative complications. During 1921 Daniel and Gabriel Bardet published their experiences using somnifaine.²

Fredet and Perlis combined somnifaine with subcutaneous morphine injection to supplement the effects of somnifaine.²Since then the benefit of intravenous anaesthesia has come to light. As no single drug has been found to achieve hypnosis, amnesia, analgesia, and autonomic stability, a combination of drugs has been tried to provide balanced anaesthesia. Addition of a low dose of opioid analgesic can reduce the required dose of a potent anaesthetic agent during the process of induction and maintenance and is believed to make an uneventful recovery from anaesthesia.³^,⁴

Propofol, introduced by Kay and Rolly in 1977⁵, has become the gold standard induction agent in TIVA because of its rapid onset, short elimination half-life, and lower incidence of postoperative nausea. However, as propofol lacks analgesic properties, it can cause patient movement⁶, thus requiring adjunct opioids⁷to attenuate haemodynamic responses, undesirable side effects and unpleasant stimulation of skin incision⁸ during surgical stimulation.

Opioids differ in receptor profile: butorphanol acts as a κ-agonist and µ-antagonist⁹. While fentanyl is a potent µ-agonist. These differences influence onset, duration, analgesic potency, side effects, and haemodynamic effects. Butorphanol causes limited respiratory depression and has a longer sedative effect, was patented in 1971 and got approval for medical use in 1979.¹⁰ Fentanyl, a 4-anilinopiperidine from phenylpiperidine family¹¹, was first synthesized by Paul Janssen in 1959 and in 1968, got approval for medical use in the United States.¹²It acts rapidly and is more potent but can cause nausea and respiratory depression.

This study evaluates the comparative intra-operative efficacy of these opioids when used with propofol for short-duration ENT surgeries under TIVA.

Aim:

To compare intra-operative characteristics of butorphanol and fentanyl as co-induction agents with propofol during short elective ENT procedures under TIVA.

Primary Objective:

· Compare intra-operative analgesia and sedation between butorphanol and fentanyl.

Secondary Objectives:

· Assess haemodynamic stability.

· Record incidence of nausea, vomiting, and restlessness.

MATERIALS AND METHOD:

Sample Size:

Sample size calculation was performed using WWW.OpenEpi.com with the formula of Mean difference. From a previous study done by Dhaval Patel et al.¹³ assuming the duration of anaesthesia in Group 1 (Butorphanol) 61.50±10.47 as primary outcome measure, keeping power at 80% an alpha of 0.05, a sample size of 48 patients would have been required to detect a minimum of 15% difference in the duration of anaesthesia between the two groups. We included 60 patients, 30 in each group to compensate for possible dropouts.

Study Design and Population:

A 6-month prospective randomized double-blind comparative study was conducted on 60 ASA I–II patients aged 18–60 years undergoing short-duration ENT surgeries (<30 minutes)

Inclusion Criteria:

· Age 18–60 years

· Weight 30–70kg

· ASA I–II

· Elective short ENT procedures

· Informed consent provided

Exclusion Criteria:

· ASA III or above

· Cardiac, hepatic, renal disorders; hypertension

· Pregnancy, lactation

· Known drug hypersensitivity

· Patients on beta-blockers

· Need for muscle relaxants

· Emergency surgeries

Randomization:

A sealed-envelope method allocated patients into two groups:

Group B: Propofol 2.5mg/kg + Butorphanol 40µg/kg

Group F: Propofol 2.5mg/kg + Fentanyl 1.5µg/kg

Drug preparation and administration were performed by personnel blinded to group allocation.

Methodology:

Standard preoperative evaluation and fasting protocols were followed. In the operating room, an IV line was established, monitoring initiated (HR, NIBP, SpO₂, ECG), and baseline values recorded.The patients were pre-oxygenated with 100% O2 for 3 min and then pre-medicated with injection midazolam IV (0.01mg/kg) and glycopyrrolate 0.004mg kg-1followed by induction with propofol 2.5mg/kg IV over 60s along the flow of IV fluid which makes the injection of propofol less painful. Once the depth of anaesthesia was assessed by the loss of eyelash reflex, a pharyngeal airway(Guedel) of appropriate size was placed. The patients in Group B were given, IV butorphanol (40µg/kg), and in Group F, IV fentanyl (1.5µg/kg) as co induction agents. The parameters recorded for the study were heart rate, mean arterial pressure, at the base level (T0), on co-induction (T1), at skin incision (T2), then every 5 min for 20 mins (T3,T4,T5,T6) then after 10 min at 30 min (T7) and tabulated. Titrating bolus dose of propofol 10-20mg/ tramadol (rescue analgesia) 1mg/kg IV was given as per clinical response and increase in HR/MAP >25% of baseline, lacrimation, or movement. All patients were on spontaneous breathing, anaesthesia was maintained with oxygen and nitrous oxide (50:50) with a face mask / nasal cannula.

Outcome Measures:

· Duration of analgesia: Time from opioid administration to first need of rescue analgesia

· Duration of sedation: Time from induction to spontaneous eye opening/response

· Adverse effects: Nausea, vomiting, restlessness, laryngospasm, respiratory depression

Statistical Analysis:

Student’s unpaired t-test and chi-square test were applied. p < 0.05 was considered statistically significant.

OBSERVATION AND RESULT:

Table 1: Demographic Parameters

Variable	Group B (Mean ± SD)	Group F (Mean ± SD)	p value
Age (years).	38.73±13.38	40.10±12.26	0.68 (NS)
Weight (kg)	52.06±12.00	48.63±11.65	0.26 (NS)
Gender (M: F)	14:16	11:19	0.60 (NS)

Table 2: Comparison of events during the surgical procedure

Variables	Group	Mean	± SD	p value
Duration of analgesia (min)	Butorphanol	6.53	0.74	0.0001 (S)
Duration of analgesia (min)	Fentanyl	15.61	2.06
Duration of sedation (min)	Butorphanol	18.21	3.86	0.0001 (S)
Duration of sedation (min)	Fentanyl	5.75	0.90
Duration of procedure (min)	Butorphanol	25	8.0	0.63 (NS)
Duration of procedure (min)	fentanyl	24	8.2
Incidence of nausea (number / % of patients)	butorphanol	4 (13.33%)		0.03 (S)
	fentanyl	12 (40%)

Graph 1: Comparison of Heart rate (HR) among the study participants at different time intervals

Graph 2: Comparison of Mean arterial pressure among the study participants at different time interval

Table 3: Showing comparison of type of surgeries in both the groups.

Type of Surgery	Group B		Group F
	No.	%	No.	%
Exicision aural polyp	4	13.3	3	10
Removal foreign body from the external auditory meatus	6	20	4	13.3
Tracheostomy tube replacement	5	16.7	5	16.7
Sub mucous diathermy (SMD)	4	13.3	6	20
Diagnostic nasal endoscopy (DNE)	2	6.7	3	10
Removal of wax	3	10	4	13.3
Syringing for debris	4	13.3	2	6.7
Treatment of furunculosis	2	6.7	3	10
Total	30	100	30	100

DISCUSSION:

TIVA offers a smoother recovery profile, and capability to intra-operative wake-up while preserving amnesia.¹⁴

Choice of drug: Because the drug butorphanol is a potent analgesic, minimally potential for substance abuse and less toxic^15,16and Fentanyl, a μ(mu) receptor synthetic opioid about 100 times more potent than the natural opioid morphine.¹⁷

Selection of dose: Trivedi et al had published in 2019 that for butorphanol, the recommended dose can be 40μ g/kg.¹⁸

Similarly, a study published by Rao et al¹⁹ in 2013 with Fentanyl, using 2μg/kg and Butorphanol 40μg/kg with an induction dose of thiopentone 5mg/kg. Regmi et al ^[²⁰^]published in 2014 a comparative study using Butorphanol 20μg/kg while induction was done by Propofol 1.5mg/kg.

Thus the previous studies guided us to select the safe doses of the drugs [butorphanol 40μg/kg and fentanyl 1.5μg/kg]. In our study, along with the co-inductiuon dose of the study drugs, the induction dose was 2.5mg/kg of propofol which was adequate for loss of eye less reflex unlike Gupta et al (2011)²¹who had used propofol 0.5mg/kg increment if required till the loss of consciousness and eye lash reflex after administering 2.5mg/kg for induction .

As per demographic data in our study, both the groups were comparable [Table 1] with respect to age [38.73±13.38 in group B vs 40.10±12.26 in group F, p >0.05] , weight [52.06±12.00 in group B vs 48.63±11.65 p>0.05 ] and Gender (M: F)14:16 in group B vs 11:19 in group F which was statistically non significant (p>0.05).

Beyond 10 min of post co-induction of study drugs, in 12 patients (40%) of group F there was eye opening but no movement against the surgical procedure. So repeat dose of propofol 10 mg at intervals till the end of surgery was needed. As per our observation [Table 2], the duration of analgesia (min) was 6.53 ±0.74 in Group B vs 15.61±2.06 in Group F, the difference is statistically significant (p= 0.0001). Conversely, in the butorphanol group 25 patients (83.33%) needed rescue analgesic as there was movement against the procedures among all these patients but no eye opening. The duration of sedation (min) was 18.21 ± 3.86 in Group B vs 5.75±0.90 in Group F, the difference is statistically significant (p= 0.0001). Butorphanol is therefore associated with more sedation than fentanyl which is consistent with Mi WD et al.²²This had made the patients in Group B to delayed recovery considering the return of protective airway reflexes like coughing and gagging and response to verbal commands.

The duration of the procedures in minutes [25±8 in group B vs 24±8.2 in group F, p>0.05] was statistically non significant between our study groups [Table 2]. Regmi et al ²⁰ also published a study in 2014 of elective short surgical procedures done under TIVA within less than 60 minutes.

The number of patients having incidence of nausea/retching [Table 2] in group F was12 (40%) vs 4 in group B (13.33%), the comparison is significant (p<0.05) . Central emetic effects of fentanyl may be the reason of this higher incidence ²³but antiemetic effect of propofol contributed to the reason of no episode of vomiting in any of the groups.²⁴

We found that the comparison of pulse rate(HR) and mean arterial pressure (MAP) status [Graph 1,2 ] till the 5th min post co-induction (T3) reading starting from baseline (T0) ,induction (T1), incision (T2) were non significant in both our study groups. But both HR and MAP started rising beyond the 5th min reading in the butorphanol group signifying less duration of analgesia. And the statistical comparison in HR [102.37 ± 5.35 in Group B vs 98.10± 7.85 in Group F, p<0.05] and MAP [120.37 ± 7.26 in Group B vs 111.13 ± 7.04 in Group F, p<0.05] became significant at 10th min. Consequently, IV top up doses of tramadol needed to be injected in Group B. In the fentanyl group only sedation was needed from 10th min onward because of opening of eyes in the midst of procedure. This is due to less duration of sedation in Group F. So in the following reading at 15th min [HR 80.27 ±5.30 in Group B vs 79.93± 5.36 in Group F, p>0.05 ; MAP 101.33 ± 8.07 in Group B vs 100.40 ± 5.96 in Group F, p>0.05] the statistical comparison became non significant. This finding of ours is consistent with Beverly K. et al (1991) ²⁵who found more sedation in Butorphanol group as compared to Fentanyl group. At 20th min again HR [97.53 ± 5.44 in Group B vs 87.57± 7.73 in Group F, p<0.05] and MAP [123.63 ± 4.55 in Group B vs 111.70 ± 7.49 in Group F, p<0.05] started rising in the butorphanol group, the statistical comparison became statistically significant between the study groups. Group B patients became conscious with eyes opened, had movement of limbs. So IV top up doses of propofol and rescue analgesia tramadol were administered. In Group F only IV top up doses of propofol needed to be given because the patients became conscious with eyes opened but had limb movement in 5 patients needing rescue analgesia of tramadol. Thus control of haemodynamic status was done and at 30th min the reading in both the groups became non significant statistically [HR 106.63 ± 7.70 in Group B vs 106.30± 6.94 in Group F, p>0.05; MAP 123.30 ± 6.06 in Group B vs 124.07 ± 4.95 in Group F, p>0.05 ].

The number and the percentage of the procedures done were equal in both the groups [Table 3]

There was no intra-operative adverse effect as respiratory depression or restlessness similar to the study ^[^26] performed under TIVA but with different set of drugs. In our study, the antiemetic effect of propofol contributed to the reason of no episode of vomiting in any of the groups.

CONCLUSION:

Both drug combinations are effective and safe for TIVA in short ENT surgeries. However:

Fentanyl + Propofol:

· Superior haemodynamic control

· Longer analgesia

· Shorter sedation (faster recovery)

· Higher incidence of nausea/retching

Butorphanol + Propofol

· Longer and deeper sedation (less desirable for quick-turnover cases or elderly)

· Shorter analgesia requiring supplementation

· Fewer emetic episodes

Clinical Implication:

Fentanyl is preferable for cases prioritizing haemodynamic stability and rapid recovery, whereas butorphanol may be used when deeper sedation is advantageous.

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Received on 27.08.2025 Revised on 13.12.2025

Accepted on 17.02.2026 Published on 01.07.2026

Available online from July 04, 2026

Research J. Pharmacy and Technology. 2026;19(7):2968-2972.

DOI: 10.52711/0974-360X.2026.00423

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