Laryngoscopy and endotracheal intubation are cornerstone techniques in modern anaesthesia, critical care and trauma management. Established as the standard for tracheal intubation since the early 20th century, direct laryngoscopy is associated with high success rates exceeding 99% in elective and emergency settings.[1,2] Despite its usefulness, laryngoscopy and intubation are potent noxious stimuli that provoke significant haemodynamic responses, including hypertension, tachycardia and arrhythmias.[3] These responses are mediated by vagus (cranial nerve X) and glossopharyngeal (cranial nerve IX) nerve activity, which involves reflex sympathetic activation and leads to catecholamine release.[4] Though such responses are usually tolerable in normotensive individuals, they can pose morbid threats in patients having cardiovascular or cerebrovascular diseases. 

The attenuation of these haemodynamic changes is crucial for safe and uneventful intubation. Various pharmacological strategies, such as the use of opioids, benzodiazepines, beta-blockers and calcium channel blockers, have been implemented, with non-pharmacological techniques like gentle laryngoscopy.[5] Among opioids, fentanyl is known for its rapid onset and effective attenuation of sympathetic responses and has been extensively studied.[6] Pentazocine is a relatively less studied mixed agonist-antagonist opioid also demonstrated efficacy in blunting haemodynamic responses.[7] 

This study evaluates the efficacy of intravenous midazolam-fentanyl and midazolam-pentazocine combinations in mitigating hemodynamic changes—heart rate (HR), blood pressure (BP), rate pressure product (RPP), mean arterial pressure (MAP), and oxygen saturation—during laryngoscopy and intubation under general anaesthesia. It aims to optimize anaesthetic induction protocols for high-risk patients by comparing these combinations.

SUBJECT AND METHODS

This prospective, randomized, controlled study was conducted at a tertiary care hospital with approval from the Institutional Ethics Committee and the Department of Anaesthesia. Sixty patients, aged 18–60 years, of American Society of Anesthesiologists (ASA) physical status grade I or II, undergoing elective surgical procedures under general anaesthesia, were included after obtaining written informed consent. Patients were randomly assigned to one of two groups (30 patients each). Group F received intravenous midazolam 0.03 mg/kg and fentanyl 2 µg/kg, while Group P received intravenous midazolam 0.03 mg/kg and pentazocine 0.6 mg/kg. Patients with ASA grade III or IV, pregnant women, those with difficult airways, and those with hypertension, diabetes mellitus, coronary artery disease or hypersensitivity to local anaesthetics were excluded. After a pre-anaesthetic evaluation, fasting for at least 8 hours was ensured. At the time of surgery, intravenous access and lactated Ringer’s infusion were initiated. Standard monitoring was applied, including non-invasive BP, HR, electrocardiograph (ECG) and pulse oximetry. Premedication included intravenous glycopyrrolate 0.004 mg/kg, followed by the study drugs administered five minutes before induction. Anaesthesia induction was performed with intravenous propofol 2 mg/kg and vecuronium 0.1 mg/kg, with patients ventilated for three minutes before laryngoscopy and intubation using a Macintosh curved blade and a cuffed endotracheal tube. Intubation was completed within 15–20 seconds; those requiring longer were excluded. Anaesthesia maintenance involved 50% nitrous oxide in oxygen with intermittent vecuronium doses. Vital parameters, including HR, systolic and diastolic BP, MAP, RPP and SpO₂, were recorded at baseline, pre-induction and at five intervals up to 10 minutes post-intubation. Side effects, including bradycardia, tachycardia, hypertension or desaturation, were noted. Data were analysed using SPSS v22.0 (©IBM Inc.), with inter-group comparisons conducted using the Chi-square test for categorical variables and t-tests for continuous variables, and intra-group changes were analysed using repeated measures ANOVA, with p<0.05 considered statistically significant.

RESULTS

In this study comparing the haemodynamic effects of midazolam-fentanyl (Group F) and midazolam-pentazocine (Group P) during laryngoscopy and intubation, the mean age of participants was similar between groups (Group F: 38.97 ± 10.99 years; Group P: 36.47 ± 11.68 years; P > 0.05), with an equal gender distribution of 43.3% males and 56.7% females in both groups.

At baseline and T-0, Group P had significantly higher mean heart rates than Group F (P < 0.05), though no differences were observed at T-5, induction, or 7 minutes post-intubation. Both groups showed a significant rise in heart rate during induction and immediately post-intubation compared to baseline (Table 1).

Systolic BP was significantly higher in Group F at induction (P < 0.05), with no other significant inter-group differences observed. Diastolic BP and MAP followed a similar trend, showing significant differences only at induction (P < 0.05), while both groups exhibited significant deviations from baseline at several time points (Table 1).

RPP was significantly higher at T-0 in Group P (P < 0.05), but differences were insignificant at other intervals. SpO₂ remained comparable between groups across all time points, with no significant intra-group variations (Table 1).

List of Tables:

Table 1: Inter and intra-group comparison of heart rate, systolic BP, diastolic BP, Mean Arterial Pressure, Rate Pressure and Spo2 of the patients in Group F and Group P. 

List of Figures

Figure 1(A-F):Graphical representation of inter-group comparison of heart rate, systolic BP, diastolic BP, Mean Arterial Pressure, Rate Pressure and Spo2 of the patients in Group F and Group P.

DISCUSSION

This study compares hemodynamic responses to midazolam-fentanyl (Group F) and midazolam-pentazocine (Group P) during laryngoscopy and intubation, which aligns with and contrasts various prior studies. The comparable age and sex distribution between groups mirrors the demographic balance in studies by Adnet et al. and Heidegger et al., ensuring reliable outcome comparison.[1,2] Group F exhibited more excellent heart rate stability, consistent with Akheela and Chandra's findings on fentanyl’s efficacy in blunting cardiovascular responses.[8] Del Río Vellosillo et al. also noted fentanyl's superiority over other opioids in maintaining hemodynamic stability.[9] Group F’s lower heart rate at T-0 and post-induction aligns with Feng et al. and Gupta and Tank, who highlighted fentanyl's role in mitigating tachycardic responses to intubation.[4,5]

The SBP and DBP trends in Group F, characterized by significant attenuation at induction and post-induction, mirror results from studies by Hassani et al. and Hoda and Khan, which documented fentanyl’s efficacy in hypertensive patients.[3,10] Conversely, pentazocine's comparatively higher SBP and DBP align with Kothari, Sharma, Sadafule, and Karhade, who reported pentazocine's limited ability to attenuate pressor responses.[7,11] The MAP trends observed in this study, where Group F achieved superior control, are consistent with observations by Lee et al. and Swarnamba et al., who emphasized fentanyl’s robust hemodynamic effects.[6,12] The higher RPP in Group P at T-0 resonates with findings by Pang et al. and Ugur et al., indicating that pentazocine's analgesic properties might not sufficiently suppress the sympathetic surge associated with laryngoscopy.[13]

The absence of significant differences in SpO2 between the groups at all time points aligns with findings by Collins and Levitan et al., who reported that fentanyl and pentazocine do not impair oxygenation during intubation.[14] Intra-group analysis revealed fentanyl's ability to maintain hemodynamic stability for longer post-induction, consistent with Janeway, who emphasized its benefits in geriatric and high-risk patients.(15)] Additionally, Miller, Poole-Wilson, and Langer highlighted fentanyl’s role in modulating myocardial oxygen demand, supporting its observed advantages in this study.[16,17]

LIMITATION

Pentazocine’s limited attenuation of hemodynamic responses aligns with findings by Gunalan, Akheela, and Chandra, who noted its inability to entirely suppress stress responses during laryngoscopy, likely due to its partial agonist activity at opioid receptors.[8,18] In contrast, fentanyl consistently demonstrated superior control of SBP, DBP, MAP, and heart rate, as shown in studies by Albertin et al. and del Río Vellosillo et al.. In contrast, pentazocine underperformed, particularly during laryngoscopy and intubation.[9]

CONCLUSION

This study's results reinforce the existing body of evidence suggesting fentanyl’s superiority over pentazocine in achieving hemodynamic stability during laryngoscopy and intubation. These findings are consistent with extensive literature, including studies by Swarnamba et al., Ugur et al., and others, while also highlighting the limitations of pentazocine in this context. Further research could explore combining pentazocine with other agents or optimizing dosing regimens to improve its efficacy in such scenarios.[6,13]

REFERENCES

1. Adnet F, Racine SX, Borron SW, Clemessy JL, Fournier JL, Lapostolle F, et al. A survey of tracheal intubation difficulty in the operating room: a prospective observational study. Acta Anaesthesiol Scand. 2001 Mar;45(3):327–32.
2. Heidegger T, Gerig HJ, Ulrich B, Kreienbühl G. Validation of a simple algorithm for tracheal intubation: daily practice is the key to success in emergencies--an analysis of 13,248 intubations. Anesth Analg. 2001 Feb;92(2):517–22.
3. Hoda A, Khan FA. Effect of one minimum alveolar concentration sevoflurane with and without fentanyl on hemodynamic response to laryngoscopy and tracheal intubation. J Anaesthesiol Clin Pharmacol. 2011 Oct;27(4):522–6.
4. Feng CK, Chan KH, Liu KN, Or CH, Lee TY. A comparison of lidocaine, fentanyl, and esmolol for attenuation of cardiovascular response to laryngoscopy and tracheal intubation. Acta Anaesthesiol Sin. 1996 Jun;34(2):61–7.
5. Gupta S, Tank P. A comparative study of efficacy of esmolol and fentanyl for pressure attenuation during laryngoscopy and endotracheal intubation. Saudi J Anaesth. 2011 Jan;5(1):2–8.
6. Swarnamba UN, Veena K, Shaikh SI. Comparison of the efficacy of lornoxicam and fentanyl in attenuating the hemodynamic response to laryngoscopy and intubation. Anesth Essays Res. 2016;10(3):478–82.
7. Kothari D, Sharma CK. Effect of nalbuphine and pentazocine on attenuation of hemodynamic changes during laryngoscopy and endotracheal intubation: A clinical study. Anesth Essays Res. 2013;7(3):326–30.
8. Akheela MK, Chandra A. Comparative Evaluation of Nalbuphine and Fentanyl for Attenuation of Pressor Response to Laryngoscopy and Tracheal Intubation in Laparoscopic Cholecystectomy. Cureus. 2021 May 20;13(5):e15142.
9. del Río Vellosillo M, Gallego García J, Soliveres Ripoll J, Abengochea Cotaina A, Barberá Alacreu M. [Bolus administration of fentanyl vs continuous perfusion of remifentanil for control of hemodynamic response to laryngoscopy and orotracheal intubation: a randomized double-blind trial]. Rev Esp Anestesiol Reanim. 2009 May;56(5):287–91.
10. Hassani V, Movassaghi G, Goodarzi V, Safari S. Comparison of fentanyl and fentanyl plus lidocaine on attenuation of hemodynamic responses to tracheal intubation in controlled hypertensive patients undergoing general anesthesia. Anesthesiol Pain Med. 2013;2(3):115–8.
11. Sadafule NN, Karhade SS. Comparative Study of Efficacy of Preoperative Nalbuphine Hydrochloride and Pentazocine Lactate on Hemodynamic Response to Tracheal Intubation and Postoperative Analgesia. Anesth Essays Res. 2018;12(1):218–22.
12. Lee YS, Baek CW, Kim DR, Kang H, Choi GJ, Park YH, et al. Comparison of hemodynamic response to tracheal intubation and postoperative pain in patients undergoing closed reduction of nasal bone fracture under general anesthesia: a randomized controlled trial comparing fentanyl and oxycodone. BMC Anesthesiol. 2016 Nov 17;16(1):115.
13. Ugur B, Ogurlu M, Gezer E, Nuri Aydin O, Gürsoy F. Effects of esmolol, lidocaine and fentanyl on haemodynamic responses to endotracheal intubation: a comparative study. Clin Drug Investig. 2007;27(4):269–77.
14. Collins SR. Direct and indirect laryngoscopy: equipment and techniques. Respir Care. 2014 Jun;59(6):850–62; discussion 862-864.
15. Janeway HH. Intra‐tracheal anesthesia from the standpoint of the nose, throat and oral surgeon with a description of a new instrument for catheterizing the trachea. The Laryngoscope [Internet]. 1913 Nov [cited 2025 Jan 16];23(11):1082–90. Available from: https://onlinelibrary.wiley.com/doi/10.1288/00005537-191311000-00009
16. Miller RA. A new laryngoscope for intubation of infants. Anesthesiology. 1946 Mar;7:205.
17. Poole-Wilson PA, Langer GA. Effect of pH on ionic exchange and function in rat and rabbit myocardium. Am J Physiol. 1975 Sep;229(3):570–81.
18. Gunalan S. Comparative Evaluation of Bolus Administration of Dexmedetomidine and Fentanyl for Stress Attenuation During Laryngoscopy and Endotracheal Intubation. J Clin Diagn Res [Internet]. 2015 [cited 2025 Jan 16]; Available from: http://jcdr.net/article_fulltext.asp?issn=0973- 709x&year=2015&volume=9&issue=9&page=UC06&issn=0973-709x&id=6431