Attenuation of hemodynamic responses to endotracheal intubation: Comparison of clonidine, esmolol, lignocaine and placebo

Abstract               Background: The laryngoscopy and endotracheal intubation produce sympathoadrenal responses that alter in systemic arterial blood pressure, heart rate and cardiac rhythm. It leads to little consequences in healthy individuals, but patients with hypertension, coronary artery diseases, cerebrovascular diseases, intracranial pathology and hyperactive airways produce morbidity and mortality. Aim: To compare the efficacy of intravenous clonidine, esmolol, lignocaine, and placebo in attenuating the hemodynamic stress responses to laryngoscopy and intubation. Methods: 120 patients of ASA I and II belonging to the age group of 15 to 60 years of both genders were divided into groups. Group C (clonidine 2 mcg/kg) – 30 patients were given intravenous clonidine 2 mcg/kg 2 minutes before induction. Group E (esmolol 1mg/kg) --30 patients were given intravenous clonidine 1 mg/kg 2 minutes before induction. Group L (lignocaine 1.5mg/kg) – 30 patients were given intravenous lignocaine 1.5mg/kg 2 minutes before induction. Group P (placebo- normal saline) –30 patients were given normal saline 2 minutes before induction. Results: Patients in group C showed the maximum attenuation of both heart rate and blood pressure following endotracheal intubation. Patients in group L showed no significant difference from group P in attenuating circulatory responses, and both lignocaine and placebo were ineffective. No complications reported. Conclusion: IV clonidine in blunting the hemodynamic responses to laryngoscopy and intubation, followed by esmolol, lignocaine, and placebo were ineffective in blunting the response.

Key Word: clonidine, esmolol, lidocaine, heart rate, intubation, laryngoscopy,

INTRODUCTION

The hemodynamic responses to laryngoscopy and endotracheal intubation have been recognized since 1951.The induction of anesthesia, laryngoscopy, tracheal intubation and surgical stimulation often evoke cardiovascular responses characterized by alteration in systemic arterial blood pressure, heart rate, and cardiac rhythm1.The response following laryngoscopy and intubation peaks at 1. Two minutes and return to baseline within 5 to 10 minutes. Though the sympathoadrenal responses are probably of little consequence in healthy patients, it is hazardous to those patients with hypertension, coronary heart disease, cerebrovascular disease, intracranial pathology and hyperactive airways. In such cases, reflex circulatory responses such as an increase in heart rate, systemic arterial pressure, and disturbances in cardiac rhythm need to be suppressed. Prof. King et al¹.,(1951) documented myocardial ischemic changes due to sympathoadrenal reflex responses immediately following laryngoscopy and intubation with a mean increase in systolic pressure of 40mmHg even in normotensive individuals. Pyrs Roberts et al², (1971) showed the exaggerated form of this response in hypertensive patients. Various systemic, as well as topical agents, have been used to reduce these untoward hemodynamic responses during laryngoscopy. When compared to systemic agents, administration of local anesthetic solutions are likely to be of limited value. The commonest strategies adopted are narcotics, vasodilators, β-blockers, calcium channel blockers, lignocaine, clonidine, and other sympatholytics. In our study, we have compared lignocaine, clonidine, esmolol, and placebo in suppressing stress responses to laryngoscopy and intubation.³   

MATERIALS AND METHODS

It is a prospective randomized controlled study. The study was approved by our institution ethical committee and after obtaining written, informed consent from the patient, this study was conducted. One hundred and twenty patients of ASA physical status 1 or 2 undergoing elective surgical procedure under general anaesthesia with endotracheal intubation were included in this study. Patients belonging to age group 15 to 60 years of both the sexes were included

Inclusion criteria:

1. ASA 1 or 2
2. Patients with airway with modified Mallampati grade class 1 or 2
3. Age group 15 to 60 years of both sexes.

Exclusion criteria:

1. Patients with full stomach
2. Patients posted for emergency surgery
3. Patients with difficult airway
4. Hypertension, diabetes, ischemic heart disease and pregnancy
5. Patients with contraindications to study drugs.
6. Patient refusal

One hundred and twenty patients of both the sexes of ASA 1 or 2 undergoing surgical procedure were randomly allocated into four groups. Group C (clonidine 2 mcg/kg)–30 patients were given intravenous clonidine 2 mcg/kg 2 minutes before induction. Group E (esmolol 1mg/kg) -- 30 patients were given intravenous clonidine 1 mg/kg 2 minutes before induction. Group L (lignocaine 1.5mg/kg)–30 patients were given intravenous lignocaine 1.5mg/kg 2 minutes before induction Group P (placebo- normal saline)–30 patients were given normal saline 2 minutes before induction. The data was analyzed using Microsoft Excel, and SPSS 10.0 for windows. Hemodynamics variables were represented by mean ± SD. Statistical significance in mean difference was assessed by the use of One-way analysis of variance. Tukey's HSD was applied to evaluate intergroup comparisons. A p value of < .05 was considered statistically significant.

RESULTS

One hundred and twenty patients under this study were categorized into four groups. 30 in each group.They compromised both sexes in the age group of 15 to 60 years. In the group C, the mean age was 26.03±7.10 years, ranging from 16 to 41. In the group E, the mean age was 26.67±7.87 years, and the range is 16 to 45. In the group L, the mean age was 24.97 ±7.90, the range is 16 to 48, and in the group P, it was 27.90±6.30, the range is 18 to 46. Thus, there is no significant difference between the four groups as their p=0.4739. In the group C, the mean weight was 49.40±7.16 ranging from 35 to 65 kg. In the group E, the mean weight was 52.37±8.05 ranging from 42 to73 kg. In the group L, the mean weight was 50.07±6.79 ranging from 40 to 70 kg. In the group P, the mean weight was 52.77±6.10 ranging from 44 to 70 kg. There was no statistically significant difference in the baseline hemodynamic parameters between the four groups. Patients in group C showed the maximum attenuation of both heart rate and blood pressure following endotracheal intubation. Patients in group E showed a significant attenuation of heart rate as effective as group C, but attenuation of blood pressure ( though effective than groups L and P) was not as effective as group C. Patients in group L showed no significant difference from group P in attenuating circulatory responses and both lignocaine and placebo were ineffective. All the patients were recovered well from anaesthesia, and none of them developed complications like severe bradycardia (HR< 50/min) or profound hypotension (SBP < 80 mmHg).

Table 1 : Heart Rate Changes (Beats / Min)

Table 2: Mean Arterial Pressure Changes (mmhg)

DISCUSSION

Laryngoscopy and endotracheal intubation produce hemodynamic stress responses characterized by hypertension and tachycardia. These neuroendocrine responses can cause a variety of complications in patients with cardiac disease due to the imbalance of myocardial oxygen supply and demand like ischemic changes, ventricular arrhythmias, and cardiac failure. Batra YK et al.⁴, in 1988 studied the attenuation of circulatory responses to laryngoscopy and intubation by oral clonidine (5 mcg/kg) and concluded that oral clonidine does circumvent the response. This study result added more supports to earlier studies conducted by Orko R, et al⁵ in 1987. Carabine et al. compared different doses of intravenous clonidine in attenuating intubating responses in 1991.⁶ Zalunardo et al. compared intravenous clonidine with intravenous esmolol in attenuating intubation responses and found out that intravenous clonidine (3 mcg/kg i.v) was statistically significant ( p-value < 0.05) in attenuating intubation responses when compared to intravenous esmolol (2mg/kg i.v).⁷ Various studies have reported that lignocaine is effective in blunting these responses. Recent studies, however, have questioned lignocaine's efficacy. In Singh et al.⁸, van den Berg et al⁹ and Kindler et al¹⁰ study IV Lignocaine 1.5 mg/kg was ineffective in controlling the acute hemodynamic response following laryngoscopy and intubation. In two different studies, it was shown that lignocaine 1.5 and 2 mg/kg is ineffective in blunting the responses during rapid sequence induction. Bachofen studied blood pressure responses to endotracheal intubation with 1.5 mg/kg lignocaine in patients with intracranial vessel malformations or brain tumors. In both groups, no significant effect of lignocaine on the pressure response could be observed¹¹ In our study, comparison of intravenous clonidine (2mcg/kg), lidocaine (1.5mg/kg), esmolol (1mg/kg) and placebo was done in attenuating circulatory responses to endotracheal intubation. Our study results with regard to heart rate match with Vucevic et al. which proved the efficacy of esmolol and Carabine et al. which proved the efficacy of clonidine^6,12 The inefficiency of lidocaine in attenuating rise in heart rate in our study can be explained by comparing it with Singh et al., Van der begh et al. and Kindlers et al. all of whom questioned lidocaine efficacy.^8-10 The heart rate in group C stayed significantly lower than all other groups even at 5 minutes after intubation ( p-value = 0.001), but in group E it stayed significantly lower than group L and group P till 3 minutes after intubation. After this, there was no significant difference among group E,L, and P which can be explained by the short duration of action of esmolol. Thus it is inferred that though clonidine and esmolol are equally effective in blunting the rise in heart rate immediately following intubation. Clonidine provides better hemodynamic stability than esmolol for a longer duration following intubation. Attenuation of pressor responses by group E in our study matches with studies conducted by Helfman et al.¹³ The difference between group C and group E matches with study conducted by Zulandaro MP et al in 2001which proved clonidine was more effective than esmolol in attenuating pressor response to endotracheal intubation⁷

CONCLUSION

It is concluded that the hemodynamic changes associated with endotracheal intubation can be safely and effectively obtunded by using intravenous clonidine before induction of anesthesia. Clonidine is found to be effective in blunting hemodynamic responses to laryngoscopy and intubation, followed by esmolol. Lignocaine and placebo were ineffective in attenuating these responses to laryngoscopy and endotracheal intubation.

REFERENCES

1. King, B.D. Harris.L.C. jr. Creifenskin. F.E Elder. J.D and Dripps R.D (1951 Circulatory responses to direct laryngoscopy and tracheal intubation – BJA 65: 216-219.
2. Prys – Roberts, C.Green, L.T. Melochel and Foe.P. (1971) – Hemodynamic responses to laryngoscopy and intubation. BJA – 43: 531
3. Stephans J.E. and Lewis Gaskin (1963) – A study of intravenous lignocaine as a suppressant of cough reflex. Anaesthesia : 24: 28
4. Batra YK, Indu B.Puri G.D (1988)– Attenuation of pulse rate and Blood pressure response to larygoscopy and intubation by clonidine. Clin pharmacology. Toxicol.1988; july; 26(7): 360-63.
5. Orko R, Pouttu J, Ghignone M, Rosenberg PH. Effect of clonidine on haemodynamic responses to endotracheal intubation and on gastric acidity. Acta Anaesthesiol Stand 1987;31: 325-9
6. Carabine U.A., Wright P.M.C and Moore J. Preanaesthetic medication with clonidine: A dose response study. British Journal of
   Anaesthesia 1991;67;79-83
7. Zalunardo M P, Zollinger A ; Comparison of intravenous clonidine and esmolol for cardiovascular stress protection during induction of anaesthesia. Der Anaesthesist 50(1):21-5, 2001 Jan
8. Singh H, Vichitvejpaisal P, Gaines GY, White PF. Comparative effects of lidocaine, esmolol, and nitroglycerin in modifying the
   hemodynamic response to laryngoscopy and intubation. Clin Anesth.1995; 7(1):5-8.
9. Van den Berg AA, Savva D, Honjol NM. Attenuation of the haemodynamic responses to noxious stimuli in patients undergoing
   cataract surgery. A comparison of magnesium sulphate, esmolol, lignocaine, nitroglycerine and placebo given IV with induction of
   anaesthesia. Eur J Anaesthesiol. 1997; 14(2):134-47.
10. Kindler CH, Schumacher PG, Schneider MC, Urwyler A. Effects of intravenous lidocaine and/or esmolol on hemodynamic responses to laryngoscopy and intubation: a double-blind, controlled clinical trial. Clin Anesth. 1996;8(6):491-6.
11. Bachofen M. Suppression of blood pressure increases during intubation: lidocaine or fentanyl. Anaesthesist. 1988 Mar;37(3):156-61.
12. Vacevic M, Pordy G.M.Ellid. F.R. (1992) – Esmolol hydrochloride for management of cardiovascular responses to laryngoscopy and tracheal intubation Br.J.Anaesth.1992 May 68(5) 529 – 30.
13. Helfmann SM, Gold MI, Delisser EA. Which drug prevents tachycardia and hypertension associated with tracheal intubation
    lignocaine, fentanyl or esmolol. Anaesth Analg 1991; 72: 482-86.