In modern day anaesthesia practice rigid laryngoscopy and tracheal intubation still remain the gold standard in airway management. The influence of airway manipulation on heart rate and blood pressure was recognized more than 50 years ago. [1]. It is now well established that laryngoscopy and endotracheal intubation violate patient’s protective airway reflexes and invariably cause hemodynamic changes associated with increased heart rate, increased blood pressure and occasional disturbances in cardiac rhythm.[2,3] These hemodynamic changes arise as a form of sympathoadrenal reflex and due to release of norepinephrine and, to a lesser extent, of epinephrine.[4] In normotensive subjects these hemodynamic changes are short lived [5] and probably of little significance. However, these hemodynamic alterations are hazardous to the patients with hypertension, ischemic heart disease or cerebrovascular disease. [6] In patients with coronary artery disease it may lead to myocardial ischemia because, increase in heart rate and blood pressure associated with laryngoscopy and endotracheal intubation may result in an increase in myocardial oxygen demand and also demand for increased coronary flow. In hypertensive patients these exaggerated responses may lead to left ventricular failure, pulmonary edema and congestive cardiac failure. In patients with intracranial aneurysm or dissecting aneurysm of the aorta, the increase in systemic blood pressure may cause rupture of vessels with life threatening consequences. The magnitude of response is greater with increasing force and duration of laryngoscopy. Elevation of blood pressure and heart rate typically starts within 5 seconds of laryngoscopy, peaks in 1 to 2 minutes and return to baseline level within 5-10 minutes. So, effective attenuation of the sympathoadrenal stress response is an important goal in anaesthesiology. Various pharmacologic and nonpharmacological method have been tried to limit the pressor response following the insertion of endotracheal tube [7]. The success rate is variable with different methods because each method has its own merits and demerits. In several trials drugs like opioids, lidocaine, nitrates, calcium channel blockers, alpha-2 adrenergic agonists, beta blockers and magnesium have been used orally or parenterally to obtund these sympathoadrenal responses. Lignocaine is an aminoethylamide and prototype of amide local anesthetic group. [8] It is the most widely used local anesthetic drug having membrane stabilizing action, so it is commonly used as an anti-arrhythmic drug in patients with ventricular ectopics. In 1961, Bromage showed that its intravenous (IV) use blunted pressure response to intubation. An IV dose of lignocaine 1.5mg/kg [9] has been proved to attenuate stress responses during laryngoscopy and intubation when given prior to induction. Magnesium is the fourth most abundant cation in the body and the second most abundant intracellular cation. It activates many of the enzyme system. Magnesium sulphate inhibits the release of catecholamines from the adrenal medulla and adrenergic nerve endings and is effective in attenuating the blood pressure (BP) response to tracheal intubation[10] Both lignocaine and magnesium sulphate have been used for the attenuation of adrenergic response to laryngoscopy and tracheal intubation. But there are only a few studies comparing lignocaine and magnesium sulphate as an attenuating agent for pressor response. In this randomized, unicentric, prospective, comparative study an attempt has been made to observe, assess and compare the efficacy of 2% lignocaine(1.5 mg/kg body weight) intravenous bolus over 1min, 10 mins prior to induction and 50% magnesium sulphate (30mg/ kg body weight) intravenous bolus over 3 minutes 10 mins prior to induction, in attenuating the haemodynamic response following laryngoscopy and endotracheal intubation in 2 groups of adult patients of either sex undergoing various elective surgeries under general anaesthesia. The study was aimed at comparing the efficacy of lignocaine vs magnesium sulphate in attenuation of hemodynamic stress response to laryngoscopy and intubation in patients posted for elective surgery under general anaesthesia.

MATERIALS AND METHODS

Study design: prospective, randomized study.

Study setting: Ramakrishna Mission Seva Pratishthan, Vivekananda Institute of Medical Sciences.

Period of study: November 2017 to January 2019

Study population: 60 ASA I–II adult patients undergoing elective surgery under general anaesthesia requiring endotracheal intubation, randomly divided into two groups (n=30 each): Group L (2% IV lignocaine) and Group M (50% IV magnesium sulphate).

Sample size: 60

Inclusion criteria:

• ASA I–II patients aged 18–45 years undergoing elective surgery under general anaesthesia requiring endotracheal intubation.
• Patients giving informed written consent.

Exclusion criteria:

• Age less than 18 years and more than 45 years
• Known allergy to anaesthetic agents
• History of a major psychiatric disorder
• History of substance abuse and current opioid use
• Compromised renal, hepatic, pulmonary, and cardiac status
• Diabetes (treated or untreated), Hypertension
• Anticipated difficult intubation
• Duration of laryngoscopy more than 15 secs
• Compensatory tachycardia
• Baseline pulse less than 60 beats per minute
• Baseline systolic blood pressure (SBP) less than100 mm Hg
• Those on medicines with cardiovascular effects
• Pregnancy

Statistical analysis: For statistical analysis data were entered into a Microsoft Excel spreadsheet and then analyzed by SPSS (version 27.0; SPSS Inc., Chicago, IL, USA) and Graph Pad Prism version 5. Data had been summarized as mean and standard deviation for numerical variables and count and percentages for categorical variables. Z-test (Standard Normal Deviate) was used to test the significant difference of proportions. Once a t value is determined, a p-value can be found using a table of values from Student's t-distribution. If the calculated p-value is below the threshold chosen for statistical significance (usually the 0.10, the 0.05, or 0.01 level), then the null hypothesis is rejected in favor of the alternative hypothesis. P-value ≤ 0.05 was considered for statistically significant.

RESULT

Table 01: Comparison of Heart Rate (HR) between Magnesium Sulphate and Lignocaine Groups at Different Time Intervals

Table 02: Comparison of SBP and DBP between Magnesium Sulphate and Lignocaine at Different Time Points

Table 03: Comparison of MAP and RPP between Magnesium Sulphate and Lignocaine at Different Time Points

Table 04: Comparison of Demographic Variables (Age, Sex, and ASA Status) between Magnesium Sulphate and Lignocaine Groups

Table 05: Distribution of Surgical Procedures between Magnesium Sulphate and Lignocaine Groups

Table 06: Comparison of Adverse Effects between Magnesium Sulphate and Lignocaine Groups

Figure 1: Comparison of Heart Rate (HR) between Magnesium Sulphate and Lignocaine Groups at Different Time Intervals

Figure 2: Sedation score (mean ± SD)

Heart Rate (HR)

Result:

At baseline, the mean heart rate was comparable between the Magnesium Sulphate group (95.97 ± 6.84) and the Lignocaine group (94.97 ± 4.59), with no statistically significant difference (p = 0.509). At 5 minutes after drug administration, the difference remained not significant (p = 0.052). From 10 minutes after drug administration onwards, a significant reduction in HR was observed in the Magnesium Sulphate group compared to the Lignocaine group (101.13 ± 3.54 vs 110.00 ± 3.70; p < 0.001). At induction and intubation, HR was significantly lower in the Magnesium Sulphate group (76.17 ± 2.53 vs 84.07 ± 3.19 at induction; 74.17 ± 2.29 vs 81.83 ± 3.11 at intubation; p < 0.001). Similarly, post-intubation HR (1–10 minutes) remained significantly lower in the Magnesium Sulphate group at all time points (p < 0.001).

Interpretation:

Magnesium Sulphate provides superior attenuation of heart rate response to laryngoscopy and intubation compared to Lignocaine.

Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

SBP

Result:

Baseline SBP was comparable between groups (114.60 ± 6.07 vs 113.87 ± 7.25; p = 0.673). At 5 minutes after drug administration, no significant difference was observed (p = 0.51). However, at 10 minutes, SBP became significantly lower in the Magnesium Sulphate group (119.43 ± 6.34 vs 122.77 ± 6.33; p = 0.046). At induction and intubation, SBP was significantly lower in the Magnesium Sulphate group (112.33 ± 8.10 vs 127.80 ± 5.63; 89.10 ± 5.40 vs 129.80 ± 5.69; p < 0.001). This trend continued throughout all post-intubation time points (1–10 minutes), with highly significant differences (p < 0.001).

DBP

Result:

Baseline DBP showed no significant difference (74.03 ± 3.79 vs 74.83 ± 4.58; p = 0.464). From 5 minutes after drug administration onwards, DBP was significantly lower in the Magnesium Sulphate group (p < 0.001). At induction and intubation, DBP was markedly reduced in the Magnesium Sulphate group (59.07 ± 2.85 vs 79.80 ± 3.83; 51.07 ± 1.96 vs 83.87 ± 3.62; p < 0.001). The difference remained significant throughout the post-intubation period up to 10 minutes.

Interpretation:

Magnesium Sulphate significantly attenuates both systolic and diastolic blood pressure responses to laryngoscopy and intubation compared to Lignocaine.

Mean Arterial Pressure (MAP) and Rate Pressure Product (RPP)

MAP

Result:

Baseline MAP was comparable (87.56 ± 2.85 vs 87.84 ± 3.97; p = 0.747). However, from 5 minutes onwards, MAP was significantly lower in the Magnesium Sulphate group (p < 0.001). At intubation, MAP was markedly reduced in the Magnesium Sulphate group (63.74 ± 2.49 vs 99.18 ± 3.00; p < 0.001). Similar significant reductions persisted during the post-intubation period (1–10 minutes).

RPP

Result:

Baseline RPP was comparable (11000.63 ± 1024.60 vs 10820.33 ± 947.71; p = 0.482). At 5 minutes, the difference remained not significant (p = 0.096). From 10 minutes onwards, RPP was significantly lower in the Magnesium Sulphate group (p < 0.001). At induction and intubation, RPP showed a marked reduction in the Magnesium Sulphate group (8554.43 ± 664.88 vs 10741.80 ± 591.28; 6612.17 ± 505.62 vs 10620.90 ± 596.96; p < 0.001). This significant difference persisted throughout all post-intubation time points.

Interpretation:

Magnesium Sulphate provides superior myocardial stress attenuation compared to Lignocaine as evidenced by lower MAP and RPP.

Demographic Variables (Age, Sex, ASA Status)

Result:

Age distribution was comparable between groups with no significant difference (p = 0.854). Most patients were in the 30–39 years age group. Sex distribution was also comparable (p = 0.796), with near equal male and female representation. All patients belonged to ASA Grade I in both groups.

Interpretation:

Both study groups were demographically comparable, ensuring baseline homogeneity.

Surgical Distribution

Result:

The distribution of surgical procedures was comparable between groups with no statistically significant difference (p = 0.989). Both groups included a similar mix of laparoscopic, ENT, general, and gynecological surgeries.

Interpretation:

Both groups were well matched in terms of surgical characteristics.

Adverse Effects

Result:

There was no statistically significant difference in adverse effects between the groups (p = 0.865). Hypoxemia occurred equally in both groups (6.67%). PONV was slightly higher in the Lignocaine group. Shivering was also slightly more frequent in the Lignocaine group. Most patients had no adverse effects (76.67% in Magnesium Sulphate vs 66.67% in Lignocaine).

Interpretation:

Both drugs had comparable safety profiles with no significant difference in adverse events.

DISCUSSION

Endotracheal intubation is a well-established noxious stimulus that provokes a marked sympathetic response, resulting in tachycardia, hypertension, and increased myocardial oxygen consumption. This hemodynamic stress response is mediated by catecholamine release due to laryngoscopy and tracheal stimulation and may be particularly hazardous in patients with limited cardiovascular reserve. The present study compared the efficacy of intravenous Magnesium Sulphate and Lignocaine in attenuating this response during induction and intubation. Both groups in the present study were comparable with respect to demographic variables and surgical characteristics, ensuring adequate baseline homogeneity. Such comparability is essential to eliminate confounding factors while assessing pharmacological modulation of stress response, as highlighted in previous perioperative studies [11,12]. In the present study, Magnesium Sulphate demonstrated superior attenuation of heart rate response compared to Lignocaine. From induction onwards, heart rate was significantly lower in the Magnesium group. This effect can be attributed to its physiological properties, including inhibition of catecholamine release, calcium channel antagonism, and suppression of sympathetic nervous system activity [13,14]. Lignocaine, while effective in blunting airway reflexes, provides a comparatively transient effect on sympathetic stimulation due to its limited duration of action and primarily local anesthetic mechanism [15]. Similar findings have been reported in earlier studies where Magnesium Sulphate was associated with better control of hemodynamic responses during intubation [16,17]. With respect to systolic and diastolic blood pressure, Magnesium Sulphate consistently showed significantly lower values at induction, intubation, and post-intubation periods compared to Lignocaine. The vasodilatory effect of magnesium is mediated through calcium influx inhibition in vascular smooth muscle, resulting in reduced systemic vascular resistance and improved hemodynamic stability [18,19]. In contrast, Lignocaine primarily suppresses airway reflexes without exerting sustained peripheral vascular effects, which explains its comparatively lesser efficacy in blood pressure control [20]. Overall, the findings of this study suggest that Magnesium Sulphate provides more effective attenuation of the sympathetic hemodynamic response to laryngoscopy and intubation compared to Lignocaine. This makes it a potentially superior agent for use in situations where cardiovascular stability is critical, particularly in patients with underlying cardiac risk factors.

CONCLUSION

In this study, both Magnesium Sulphate and Lignocaine were effective in attenuating the hemodynamic stress response to laryngoscopy and endotracheal intubation; however, Magnesium Sulphate demonstrated superior efficacy in controlling heart rate, systolic and diastolic blood pressure, mean arterial pressure, and rate pressure product at most peri-intubation time points. Although baseline parameters and adverse effects were comparable between the groups, Magnesium Sulphate provided more consistent and sustained cardiovascular stability during induction, intubation, and the post-intubation period. Thus, Magnesium Sulphate can be considered a more effective agent than Lignocaine for attenuation of the sympathoadrenal response to laryngoscopy and intubation, with a comparable safety profile.

REFERENCES

1. King BD, Harris LC, Greifenstein FE, Elder JD, Dripps RD. Reflex circulatory responses to direct laryngoscopy and tracheal intubation performed during general anesthesia. Anesthesiology 1951; 12: 556-66.
2. Randell T. Hemodynamic responses to intubation: what more do we have to know? Acta Anaesthesiol Scand 2004; 48: 393-95.
3. Boralessa H, Senior DF, Whitman JC. Cardiovascular response to intubation. Anesthesia 1983; 38: 623-27.
4. Pernerstorfer T, Krafft P, Fitzgerald RD, Krenn CG, Chiari A, Wagner O, Weinstabl C. Stress response to tracheal intubation: direct laryngoscopy compared with blind oral intubation. Anesthesia 1995; 50: 17-22.
5. Forbes AM, Dally FG. Acute hypertension during induction of anesthesia and endotracheal intubation in normotensive man. Br J Anaesth 1970; 42: 618-24.88
6. Fox EJ, Sklar GS, Hill CH, Villanueva R, King BD. Complications related to the pressor response to endotracheal intubation. Anesthesiology 1977; 47: 524-25.
7. Bukhar SA, Naqash I, Zargar J, et al. Pressor responses and intraocular pressure changes following insertion of laryngeal mask airway: comparison with tracheal tube insertion. Indian J Anaesth 2003; 47(6): 473-75.
8. Sachin Padmawar , Manish Patil. A Comparative Study of 2% Lignocaine vs 50% Magnesium Sulphate for Attenuation of Stress Responses to Laryngoscopy and Endotracheal Intubation. International Journal of Contemporary Medical Research 2016 August 8: : 2317-2321
9. Bromage PR, Robson JG. Concentrations of lignocaine in the blood after intravenous, intramuscular epidural and endotracheal administration. Anaesthesia. 1961;16:461– 478
10. James MF, Beer RE, Esser JD. Intravenous magnesium sulfate inhibits catecholamine release associated with tracheal intubation. Anesth Analg. 1989;68:772-776.
11. Kovac AL. Controlling the hemodynamic response to laryngoscopy and endotracheal intubation. J Clin Anesth. 2015;27(7):513–524.
12. Srivastava S, Gupta D. Perioperative Management of Intracranial Aneurysm. Perioperative Critical Care. 2020 Nov 30;30:197.
13. McCann ME, Lee JK, Inder T. Beyond anesthesia toxicity: anesthetic considerations to lessen the risk of neonatal neurological injury. Anesthesia & Analgesia. 2019 Nov 1;129(5):1354-64.
14. Dahake JS, Verma N, Bawiskar D. Magnesium sulfate and its versatility in anesthesia: A comprehensive review. Cureus. 2024 Mar 17;16(3).
15. Miller RD, Cohen NH, Eriksson LI. Miller’s Anesthesia. 8th ed. Philadelphia: Elsevier; 2015.
16. Sohn HM, Kim BY, Bae YK, Seo WS, Jeon YT. Magnesium sulfate enables patient immobilization during moderate block and ameliorates the pain and analgesic requirements in spine surgery, which can not be achieved with opioid-only protocol: A randomized double-blind placebo-controlled study. Journal of Clinical Medicine. 2021 Sep 22;10(19):4289.
17. Jee D, Park SY, et al. Effects of magnesium sulfate on intubation response. Korean J Anesthesiol. 2018;71(3):191–197.
18. Altura BM, Altura BT. Magnesium and vascular smooth muscle regulation. Magnes Res. 2016;29(1):3–8.
19. de Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in human physiology. Physiol Rev. 2015;95(1):1–46.
20. Herroeder S, Schönherr ME, De Hert SG, Hollmann MW. Magnesium--essentials for anesthesiologists. Anesthesiology. 2011 Apr 1;114(4):971-93.