Comparison of dexmedetomidine, fentanyl, and lidocaine in attenuation of hemodynamic responses during intubation in patients undergoing laparoscopic cholecystectomy

Background & objective:

"The anesthesiologists have been trying various strategies to lessen the adverse effects of endotracheal intubation on hemodynamic parameters. The aim of this study was to explore a better and safer drug to attenuate the pressor response to laryngoscopy and intubation by comparing dexmedetomidine (Precedex; Brookes Pharma), fentanyl (Fentra; Brookes Pharma), and lidocaine (Xylocaine; Barret Hodgson)."

Methodology:

"In this double-blind, randomized controlled trial, a total of 90 patients of ASA physical status I and II, undergoing laparoscopic cholecystectomy under general anesthesia were included. Sample size was calculated using OPEN EPI sample size calculator. Patients were randomized into three groups by sealed envelope method. Patients in Group D received intravenous dexmedetomidine 0.6 µg/kg, Group F received intravenous fentanyl 2 µg/kg and Group L received intravenous lidocaine 1.5 mg/kg over 10 min before induction. Hemodynamic variables were recorded at baseline, at laryngoscopy, 1, 3, 5 and 10 min after intubation. Perioperative complications and postoperative sedation and recovery were also noted at 0 and 10 min in Post Anesthesia Care Unit (PACU)."

Results:

"As compared to dexmedetomidine, there was no significant impact of lidocaine (P = 0.774) and fentanyl (P = 0.992) in managing the heart rate (HR) of patients, while time had a significant impact on the HR. There was no substantial effect of fentanyl (P = 0.123) or lidocaine (P = 0.616) in managing SBP and no effect of fentanyl (P = 0.580) or lidocaine (P = 0.752) in managing DBP, in contrast to dexmedetomidine. Although statistically significant reduction in HR, SBP and DBP was observed in Group D, soon after study drug infusion, but overall long-term stability was noticed. Ramsey sedation scores were significantly higher in the Group D at arrival in PACU, but after 10 min all three study groups showed almost similar results. Aldrete score was statistically significant in the fentanyl group compared to Group D and L in PACU, both at arrival and after 10 min (P = 0.001 and 0.010 respectively)."

Conclusion:

"We conclude that intravenous dexmedetomidine demonstrated better attenuation of hemodynamic response to laryngoscopy and intubation in patients undergoing laparoscopic cholecystectomy by controlling rise in heart rate and by providing long-term stability in systolic and diastolic blood pressure. Fentanyl and lidocaine showed inconsistencies in heart rate, systolic and diastolic blood pressure over time. Fentanyl showed better hemodynamic profile compared to lidocaine. Patients included in fentanyl group exhibited early recovery than dexmedetomidine and lidocaine."

Precedex is a highly selective alpha-2 adrenergic receptor agonist that works primarily through the following mechanisms:

Physiology Refresh

Primary Mechanism: Alpha-2 Adrenergic Receptor Activation

Dexmedetomidine binds with high selectivity to alpha-2 receptors (particularly the alpha-2A subtype) with an alpha-2 selectivity ratio of approximately 1600:1. This is significantly higher than clonidine, another alpha-2 agonist.

Central Nervous System Effects

1. Locus Coeruleus: The primary site of action is the locus coeruleus in the brainstem, where dexmedetomidine inhibits norepinephrine release by presynaptic activation of alpha-2 receptors.
2. Sedation: Unlike traditional sedatives (benzodiazepines, propofol), dexmedetomidine produces a unique "arousable sedation" resembling natural sleep. Patients can be easily awakened and remain cooperative even during sedation.
3. Anxiolysis: Reduces anxiety without significant respiratory depression.

Analgesic Effects

Dexmedetomidine produces analgesia through:

• Inhibition of substance P release in the dorsal horn of the spinal cord
• Activation of alpha-2 receptors in the spinal cord
• Modulation of descending noradrenergic pathways

The analgesic effect is moderate but can significantly reduce opioid requirements.

Sympatholytic Effects

1. Hemodynamic effects: Produces a biphasic cardiovascular response:
   • Initial transient hypertension (due to peripheral alpha-2B receptor activation)
   • Followed by hypotension and bradycardia (due to central sympatholytic effects)
2. Reduces plasma catecholamine levels by up to 90%

Other Physiological Effects

1. Minimal respiratory depression: Unlike opioids and other sedatives, dexmedetomidine preserves respiratory drive even at higher doses.
2. Anti-shivering properties: Useful for hypothermia management and post-anesthetic shivering.
3. Neuroprotective potential: May reduce ischemic injury through several mechanisms including modulation of apoptosis.
4. Organ-protective effects: Some evidence suggests protective effects on heart, kidney, and brain tissue, likely through anti-inflammatory and anti-oxidant properties.

Excerpts

Group D (n = 30) received dexmedetomidine 0.6 μg/kg in 100 mL of 0.9% normal saline over 10 min before laryngoscopy.

Group F (n = 30) received fentanyl 2 μg/kg in 100 mL of 0.9% normal saline over 10 min before laryngoscopy.

Group L (n = 30) received lidocaine 1.5 mg/kg in100 mL of 0.9% normal saline over 10 min before laryngoscopy.

Dexmedetomidine gives better control of hemodynamic parameters during laryngoscopy and intubation than both fentanyl and lidocaine. Patients received dexmedetomidine exhibited higher sedation scores at arrival in PACU but it became equivalent in all three groups at 10 min. Patients in the fentanyl group showed early attainment of Aldrete sedation score, hence, meeting discharge criteria more quickly than the dexmedetomidine and lidocaine groups.

Citation

Urooj S, Javaid H, Andleeb S, Mughal A, Naz A, Shah SJ, Jabeen R, Siddiqui SZ. Comparison of dexmedetomidine, fentanyl, and lidocaine in attenuation of hemodynamic responses during intubation in patients undergoing laparoscopic cholecystectomy. Anaesth. pain intensive care 2024;28(3):524−533; DOI: 10.35975/apic.v28i3.1737

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