Weaning off from general anesthesia often provokes hemodynamic changes and airway reflexes. The goals of smooth extubation are to maintain stable hemodynamics, reduce airway irritation, keep consistent oxygen delivery to the lungs, and prevent complications like straining, coughing, breath-holding, and laryngospasm. Patients with cardiovascular, and neurological conditions, smokers, and individuals with chronic airway diseases are at higher risk for complications related to extubation [1-4]. Sympathetic stimulation during tracheal extubation can lead to myocardial infarction, myocardial ischemia, cerebral hemorrhage, and pulmonary edema. These reactions are often associated with transient but tachycardia, and hypertension which can be a major concern for anaesthesiologists. Theories explaining these responses include surges in catecholamines, airway irritation, postoperative pain, and emergence phenomena. While extensive research has focused on managing hemodynamic responses to intubation, similar attention is less commonly given to extubation. Various drugs have been employed to mitigate extubation responses, such as intravenous lignocaine, verapamil, clonidine, short-acting opioids like fentanyl and remifentanil, esmolol, labetalol, and dexmedetomidine, MgSO4 [5-7]. These adverse responses are especially pronounced in patients with hypertension, coronary artery disease, and cerebrovascular disease. However there is still a lack of a dependable method for smooth extubation.

Lignocaine is a local anesthetic and antiarrhythmic drug, it acts as” NMDA receptor antagonism, sodium channel antagonism and suppression of atrioventricular nodal activity” [4].  Lignocaine before extubation is more effective in preventing coughing or hemodynamic responses during emergence than an intravenous injection given 3 minutes before extubation, leading to smooth extubation in neurosurgery [5]. Lignocaine blunts hemodynamic fluctuations to tracheal extubation by its direct action as a myocardial depressant and peripheral vasodilation. Lignocaine suppresses the cough reflex as it acts on neurotransmission.

Dexmedetomidine influences hemodynamics through both peripheral and central routes. It causes vasoconstriction by acting on alpha2beta-receptors located on vascular smooth muscles. Consequently, a rapid infusion of dexmedetomidine might initially cause transient hypertension. Additionally, dexmedetomidine may function as a peripheral ganglionic blocker, which can further enhance its sympatholytic effects. Administering dexmedetomidine at the end of a procedure can help prevent excessive hemodynamic responses during extubation, facilitating a smoother and more comfortable recovery.

Like other α2 adrenoceptor agonists, dexmedetomidine has minimal effects on ventilation, so there is no significant change in respiratory function in patients receiving it. Administering dexmedetomidine at a dose of 0.5 mcg/kg, 5 minutes before the end of surgery, has been demonstrated to stabilize hemodynamics, ease extubation, improve recovery comfort, and enable early neurological assessments, particularly after intracranial surgeries [2].

Magnesium sulfate is a “non-competitive inhibitor of inositol triphosphate (IP3)-gated calcium channel”. It acts “as an endogenous calcium antagonist by modulating calcium uptake and distribution”. Magnesium (Mg) suppresses the "calcium-mediated release of acetylcholine from presynaptic nerve terminals" at the neuromuscular junction. A depressive effect is produced in the central nervous system by inhibiting "N-methyl-D-aspartate (NMDA) glutamate receptors" and lowering catecholamine release. Furthermore, via modulating potassium and sodium currents, Mg alters membrane potential.

 The stress extubation is due to “catecholamine release”. Mg increases contractility and causes coronary vasodilatation by blocking the release of catecholamines from the adrenal medulla and adrenergic nerve terminals. It lowers the frequency of arrhythmias as well [3]. In terms of hemodynamic stability, Mg is helpful because it blocks catecholamine receptors directly and inhibits the release of catecholamines from the adrenal medulla and peripheral adrenergic nerve ends.

Esmolol is a “short-acting, cardio-selective beta-blocker and class II antiarrhythmic agent”, it acts as a “competitive antagonist of beta-1-adrenergic receptors in myocytes”.esmolol reduces myocardial contractility, slows heart rate, and decreases conduction through the atrioventricular node is due to inhibition of epinephrine and norepinephrine, Additionally, it decreases the myocardium's oxygen demand and lengthens the atrioventricular refractory period. Although primarily selective for β-1 receptors, esmolol can exhibit minor β-2-adrenergic blockade at high IV infusion doses. Notably, esmolol does not possess “membrane-stabilizing activity” or “α-adrenergic blocking” properties [6]. The stress response to extubation was seen with esmolol before extubation and it attenuates the increase in heart rate response to extubation more effectively than the increase in blood pressure response [3].

Labetalol is an antihypertensive adrenergic antagonist it acts by selectively blocking alpha-1 receptors and “non-selectively blocks beta-1 and beta-2 receptors”. It acts quickly, reaching peak effectiveness within 5 to 15 minutes following intravenous administration. By blocking α1 receptors, labetalol reduces blood pressure through decreased systemic vascular resistance without affecting cardiac output, while its β-blockade prevents reflex tachycardia [7]. Labetalol at a dose of 0.2mg/kg helps reduce hemodynamic response to extubation. It was found that the extubation time and the emergence from anesthesia were shorter, and the patients becoming fully awake was more rapid in the labetalol group [8,9].

Fentanyl

Fentanyl is a synthetic opioid widely used for managing moderate to severe pain, particularly in acute settings. It has a rapid onset and provides analgesia for 30 to 60 minutes following a single intravenous injection, making it ideal for perioperative pain management. Beyond its pain-relieving properties, fentanyl is also valued for maintaining hemodynamic stability and offering a favorable recovery profile during and after extubation. In patients having ENT operations, administering fentanyl before the completion of the procedure may successfully minimize the hemodynamic response to tracheal extubation [8].

Remifentanil is an opioid known for its immediate onset and rapid elimination, unaffected by age or liver and kidney function. Considering that it does not result in respiratory depression or delayed recovery following continuous infusion, which makes it a promising drug for reducing hemodynamic and respiratory problems during anesthesia. Administration of remifentanil before extubation can attenuate hemodynamic response during extubation, it also prevents post-op cough in post-op thyroidectomy cases [10].

Verapamil is a “novel antiarrhythmic, antianginal agent weak local anesthetic”, it selectively depresses nodal tissues, likely through its unique action on the “calcium-mediated slow response”, distinguishing it from other antiarrhythmic agents [11,12]. Administering verapamil before extubation is an effective prophylactic approach for reducing cardiovascular responses to extubation response in patients with ASA physical status I.

Clonidine is a centrally acting antihypertensive agent that is effective in treating mild, moderate, and severe hypertension, either on its own or in combination with other medications. Clonidine is α-2 adrenergic receptor agonists, which help mitigate airway responses and prevent bronchoconstriction through its analgesic and sedative effects [13,14]. Administering clonidine before extubation effectively reduces hemodynamic and airway reflexes during anesthesia emergence.

Anesthesiologists are particularly concerned about complications related to extubation, recovery, and emergence, as these issues tend to occur more frequently than those associated with intubation. Additionally, there is often uncertainty due to the lack of clear guidelines or protocols. Tracheal extubation can lead to significant hemodynamic changes typically a 10–30% increase that may persist for 5–15 minutes. Complications related to the respiratory system following tracheal extubation are approximately three times more common than those during tracheal intubation, with rates of 12.6% compared to 4.6% [15,16].

 The immediate post-extubation period is a critical time, as anaesthesiologists are aware that patients are particularly vulnerable during this phase. Complications such as laryngospasm, aspiration, compromised airway patency, or inadequate ventilation can arise, often leading to hypoxemia. While hypoxemia is usually resolved within minutes, it has the potential to escalate quickly, causing significant morbidity [17-19]. Hence to avoid such complications certain drugs can be given before extubation like, clonidine, dexmedetomidine, fentanyl, remifentanil, esmolol, labetalol, verapamil, lignocaine, magnesium sulfate can be considered.

1. Rani P, Hemanth Kumar VR, Ravishankar M, Sivashanmugam T, Sripriya RM. Trilogasundary Rapid and reliable smooth extubation Comparison of fentanyl with dexmedetomidine: A randomized, double?blind clinical trial. 2016; 597-601.
2. Sharma VB, Prabhakar H, Rath GP, Bithal PK. Comparison of dexmedetomidine and lignocaine on attenuation of airway and pressor responses during tracheal extubation. 2014; 01: 050-055
3. Agrawal CG, Khadke SJ. Comparison of IV magnesium sulphate and IV esmolol in attenuating hemodynamic extubation response after general anesthesia.
4. Horalali S, Mahadeva MKR, Mulla R,Dr. Nataraj MS, Prasad CGS. Comparison of magnesium sulfate with lignocaine for blunting response to laryngoscopy and intubation.
5. George, Elizabeth S, Singh, Georgene, Mathew, Susan B, et al. Comparison of the effect of lignocaine instilled through the endotracheal tube and intravenous lignocaine on the extubation response in patients undergoing craniotomy with skull pins A randomized double blind clinical trial. J Anaes Cli Pharm. 2013; 29:168-172.
6. Pevtsov A, Kerndt CC, Ahmed I, Patel P, Katherine L. Fredlund. Esmolol
7. Shetabi H. Conceptualization, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Resources Comparative study of the effect of two different doses of intravenous labetalol on the cardiovascular response to endotracheal extubation.
8. Lemma DT, Alemnew EF, Gemeda LA, Goshu EM. Effects of lidocaine versus fentanyl on attenuation of hemodynamic responses to extubation after ear, nose and throat surgery in a resource limited setting: A prospective observational study. Int J Surg Op. 2020; e 24:129-135
9. Younes MM, Mahareak AA, Salem EA, Nooreldin T. Attenuation of cardiovascular responses to tracheal extubation with labetalol. Al-Azhar Assiut Med J. 2017; 15: 216-222.
10. Mahoori A, Noroozinia H, Hasani E, Karami N, Pashaei N, Hatami S. The effect of low-dose remifentanil on the hemodynamic responses of endotracheal extubation. Acta Medica Iranica. 2014; 844-847.
11. Singh BN, Ellrodt G, Peter CT. Verapamil: a review of its pharmacological properties and therapeutic use. Drugs. 1978; 15: 169-197.
12. Mikawa K, Nishina K, Maekawa N, Obara H. Attenuation of cardiovascular responses to tracheal extubation: verapamil versus diltiazem. Anesthesia & Analgesia. 1996; 82:1205-1210.
13. Lowenthal DT, Matzek KM, MacGregor TR. Clinical pharmacokinetics of clonidine. Clinical Pharmacokinetics. 1988; 14: 287-310
14. Vankayalapati SD, Ramsali MV, Kulkarni DK, Pasupuleti S. Effect of Clonidine and Dexmedetomidine on Haemodynamic and Recovery Responses During Tracheal Extubation: A Randomised Double-Blind Comparative Study. Anesth Analg. 2019; 6: 91-7.
15. Salim B, Rashid S, Ali MA, Raza A, Khan FA. Effect of pharmacological agents administered for attenuating the extubation response on the quality of extubation: a systematic review. Cureus. 2019; 11.
16. Sharma VB, Prabhakar H, Rath GP, Bithal PK. Comparison of dexmedetomidine and lignocaine on attenuation of airway and pressor responses during tracheal extubation. J Neuroanaesthesiology and Critical Care. 2014; 1: 50-55.
17. Nagrale MH, Indurkar PS, Pardhi CS. Comparative study on haemodynamic response to extubation: Attenuation with lignocaine, esmolol, propofol. Int J Res Med Sci. 2016; 4:144-151.
18. Savitha KS, D'Souza JS, Kothari AN. Attenuation of hemodynamic response to extubation with iv lignocaine: a randomized clinical trial. Journal of Evolution of Medical and Dental Sciences. 2014; 3: 838-847.
19. Benowitz NL, Meister W. Clinical pharmacokinetics of lignocaine. Clinical pharmacokinetics. 1978; 3: 177-201.