Comparison of the efficacy of dexmedetomidine with that of esmolol in attenuating laryngoscopic and intubation response after rapid sequence induction

Abstract

Context:

Laryngoscopy and tracheal intubation produce sympathetic overdrive by catecholamine release resulting in hypertension and tachycardia. Various agents are being tried to combat the intubation response over years.

Aims:

This study is aimed at comparing dexmedetomidine which is a highly selective alpha-2 agonist with an ultra-short acting beta blocker, esmolol to see which among the two is better in attenuating the hemodynamic response to laryngoscopy and tracheal intubation.

Settings and Design:

This was a prospective randomized double-blind control study.

Subjects and Methods:

Sixty patients scheduled for general anesthesia were divided into two groups, D and E with 30 patients in each group. Group-D patients received dexmedetomidine 0.5 mcg/kg and Group-E patients received esmolol 0.5 mg/kg as intravenous premedication over 5 min before a rapid sequence induction and tracheal intubation. Systolic, diastolic and mean arterial pressures along with heart rate were measured using invasive arterial line at various time points. The percentage change of hemodynamic parameters at those time points from the baseline was compared between the groups.

Statistical Analysis Used:

Descriptive and inferential statistical methods were used to analyze the data.

Results:

The percentage change of all hemodynamic parameters from base line were less in the dexmedetomidine group than in esmolol group at all-time points of measurement. However, a statistically significant difference was observed often at the time points within 1 min after tracheal intubation.

Conclusions:

Dexmedetomidine is superior to esmolol in attenuating the hemodynamic response to laryngoscopy and tracheal intubation.

INTRODUCTION

Laryngoscopy and tracheal intubation have become an integral part of anesthetic management and critical care since their description in 1921 by Rowbotham and Magill. Circulatory response to laryngeal and tracheal stimulation was known since 1940 (Reid and Brace).[1] The principle mechanism behind hypertension and tachycardia is an exaggerated sympathetic action due to increased catecholamine release.[2] This rise in heart rate (HR) and blood pressure is usually transient, variable and unpredictable, which may not be of much significance in healthy individuals but can be hazardous in those with hypertension, cardiac dysfunction, coronary artery disease or cerebro-vascular disease. Laryngoscopic response in such individuals can precipitate coronary insufficiency, pulmonary edema, arrhythmias, left ventricular failure and cerebro-vascular hemorrhage.[3] Various pharmacological and nonpharmacological methods are in vogue to counter this hemodynamic response. Alpha-2 agonists have recently gained significance in attenuating the laryngo-sympathetic response.[4] Dexmedetomidine, the pharmacologically active d-isomer of medetomidine (4,[5]-[1-(2,3-dimethylphenyl)-ethyl]) imidazole is a highly specific and selective alpha-2 adrenoreceptor agonist. In recent studies, dexmedetomidine was shown to have clinically significant effects on anesthetic requirement and hemodynamic responses induced by anesthesia and surgery in patients.[5] Since tachycardia appears to be associated more frequently with myocardial ischemia than does hypertension,[6] interesting approach towards attenuating cardiac responses to laryngeal stimulation is the use of β-adrenergic antagonists. Among the β-adrenergic antagonists, esmolol (methyl 3-4-[2-hydroxy-3-(isopropyl amino) propoxy-phenyl] propionate hydrochloride) is an effective option because it is ultra-short acting and can be administered intravenously. Dexmedetomidine is a recently introduced centrally acting alpha-2 agonist. Esmolol is a time tested effective β-blocker. Both of them have a good potential in reducing blood pressure and HR. Thus, we sought to compare the efficacy of both these drugs in countering the increased sympathetic response secondary to laryngoscopy and tracheal intubation. The modality of hemodynamic measurements and the parameters of comparison between the groups are the two essential zones distinguishing our study from several other similar studies done in the past.

SUBJECTS AND METHODS

Approval from Institutional Ethics Committee was obtained before starting the study. Written informed consent was obtained from all the patients enrolled in the study. The duration of this prospective randomized double-blind study was 1-year. Patients in the age group of 20-40 years scheduled for general anesthesia from January 2012 to December 2012 were included in the study. Only the patients posted for major surgeries such as neuro-surgery, gastrointestinal surgery, long duration surgeries or surgeries with anticipated major fluid shifts were included in the study. They required invasive arterial line for continuous hemodynamic monitoring. Patients with heart disease, hypertension, diabetes mellitus, thyroid abnormalities and those on treatment with beta blockers were excluded from the study. Patients with an anticipated difficult airway and those in whom tracheal intubation took more than 30 s were also excluded from the study. Patients were randomly segregated into two groups using a computer generated randomization program. Patients in Group-D received dexmedetomidine 0.5 mcg/kg body weight in 20 ml normal saline over 5 min before induction. Patients in Group-E received esmolol 0.5 mg/kg body weight in 20 ml normal saline over 5 min before induction. After shifting the patient into the operating room, noninvasive blood pressure (NIBP) monitor, pulse oxymeter and electro cardiogram were connected, and an intravenous (IV) line was secured with 18-guage canula. Injection midazolam 1 mg was given IV as premedication. Arterial line was secured in the radial artery after giving local anesthesia and base line hemodynamics were recorded. Patient was preoxygenated for 5 min during when the study drug was also administered as IV infusion. The study drug was loaded in 20 ml syringe by an anesthetist who was blinded to the study, coded and handed over to another anesthetist who was blinded to the drug present in the syringe for administration. After 5 min of infusion and pre-oxygenation, anesthesia was induced with pentathol sodium 5 mg/kg body weight and succinylcholine 2 mg/kg body weight in a rapid sequence, followed by tracheal intubation by a reasonably experienced anesthetist. Subsequently fentanyl 2 mcg/kg and vecuronium 0.1 mg/kg body weight were administered IV and the anesthesia was maintained on sevoflurane in oxygen and nitrous oxide gas mixture. Invasive systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and HR were recorded before giving the study drug, before induction of anesthesia, before tracheal intubation, immediately after tracheal intubation, at every 5 s within the 1^st min and at 1 min, 3 min, 5 min, 10 min and 15 min after tracheal intubation. Simultaneously, NIBP was also measured for baseline, before induction, 1 min, 3 min, 5 min, 10 min and 15 min postintubation readings of SBP, DBP and MAP. The data was tabulated and analyzed.

Statistical analysis

Descriptive and inferential statistical methods were used to analyze the data. In descriptive statistics, calculation of means, standard deviation and differences in average blood pressures and HR were done with the help of Microsoft Excel windows 7. In inferential statistics, Student's t-test of difference between two means, Z-test of difference between two proportions was used to analyze the differences.

Difference in the demographic profile was analyzed with the help of t-test of two independent means and Z-test of proportions was used to analyze the difference in proportion of males and females in both the groups. In-silico project support for life sciences online statistical calculator was used for performing t-test and Z-test. Power of the study was calculated using online power calculator for two independent sample studies.

RESULTS

A total of 60 patients were enrolled in the study with 30 in each group. The difference in the percentage change of MAP from the baseline at 10^th s after intubation between the two groups was used to calculate the power of the study. Power of the study with 30 as size in each sample is 91%. So the sample size was adequate. The demographic profile was comparable in two groups [Table 1]. The percentage change of SBP (invasive), from the baseline was observed to be low in the dexmedetomidine group than in esmolol group at all-time points. But the difference was statistically significant only at 7 times points [Table 2]. Similar trend was observed in the percentage change of invasive DBP and MAP. Statistically, significant difference was found between the two groups at 8 times points in DBP [Table 3] and 11 times points in MAP [Table 4]. Difference between the two groups was very rarely significant when the noninvasive SBP, DBP and MAP [Table 5] were analyzed though the percentage change from the baseline appeared to below in the dexmedetomidine group numerically. On the contrary, the percentage change of HR from the baseline was observed to be less in the dexmedetomidine group than in esmolol group, and the difference was statistically significant at almost all the time points of measurement [Table 6].

Table 1.

Demographic profile

Table 2.

Invasive SBP variation

Table 3.

Invasive DBP variation

Table 4.

Invasive mean arterial blood pressure variation

Table 5.

NIBP variation

Table 6.

Variation in HR

DISCUSSION

Many factors influence the cardiovascular changes associated with laryngoscopy and intubation. Age, drugs, type and duration of procedures, depth of anesthesia, hypoxia, hypercarbia etc., influence the pressor response. HR changes decrease with increasing age. Young patients show more extreme changes. Marked fluctuations in hemodynamic responses are often seen in geriatric patients.[7,8] In our study, we selected the optimal age range of 20-40 years. Patients on antihypertensive drugs may exhibit a decrease in the pressor response. We excluded the patients on antihypertensive medications from our study.

A variable combination of drugs used for premedication, induction, relaxation and maintenance of anesthesia can influence the sympathetic response to laryngoscopy and intubation. Midazolam decreases the blood pressure and increases the HR.[9] Glycopyrrolate premedication can moderately increase the HR.[10] Fentanyl is also a known modifier of laryngoscopic response. So we avoided these drugs before induction and intubation to see the exact effect of study drugs on larynogoscopic and intubation response. Thiopentone was selected for induction since it still continues to be the most popular agent for induction. In normovolemic patients, thiopentone 5 mg/kg can transiently decrease 10-20 mm Hg of blood pressure and increase the HR by 15-20 beats/min.[11] There is an increase in catecholamine levels, both noradernaline and adrenaline.[11] Succinylcholine has negative inotropic and chronotropic effect. It acts on the muscarinic receptors of sinoatrial node. A marked nor-adrenergic response was noted when intubation was performed under succinylcholine.[12]

The most significant factor during laryngoscopy influencing cardiovascular responses was found to be the duration of laryngoscopy.[13] A linear increase in HR and MAP during the first 45 s was observed. Further prolongation had little effect. As the duration of laryngoscopy is normally <30 s, the results of studies in which it takes longer than this have less clinical relevance. The force applied during laryngoscopy has only minor effect.[13] In our study, the duration of laryngoscopy and intubation was limited to 20 s.

A substantial amount of clinical research was done so far evaluating the efficacy of dexmedetomidine[14,15,16] in attenuating pressor response to laryngoscopy. In those studies NIBP monitoring was used to measure the hemodynamic parameters at different time points. Studies were also there employing invasive monitoring for hemodynamic measurements in evaluating the role of dexmedetomidine in countering the pressor response.[17,18] Esmolol was also evaluated alone[19] as well as in comparison with other pharmacological agents[20,21] regarding its role in attenuating laryngoscopic and intubation response. In most of the above previous clinical trials, the parameters of comparison were blood pressure and HR at different points of time before and after laryngoscopy and tracheal intubation. The mean SBP, DBP, MAP and HR were compared at similar points of time between the groups. But technically the most appropriate factor of clinical relevance in a laryngoscopic response is the fluctuation of hemodynamic parameters from the baseline than the absolute value. Thus in our study we principally compared the percentage change in all the four hemodynamic parameters from the baseline at similar points of time before and after laryngoscopy and tracheal intubation. Another difference in the methodology of our study is employing invasive arterial blood pressure monitoring along with conventional NIBP monitoring. It usually takes an average of 40 s to measure blood pressure in oscillometry through NIBP monitoring. However, hemodynamic fluctuations occur continuously during and after laryngoscopy and tracheal intubation. Thus with NIBP, recording the hemodynamic variations before 40 s is not possible. The differences in the results were very evident in our study.

When compared between dexmedetomidine and esmolol, statistically significant difference was observed in percentage change of invasive SBP at 7 times points in <1 min, but no statistically significant difference was found in percentage change in noninvasive SBP which was measured at 1, 3, 5, 10, 15 min after intubation. Similar trend is also observed in DBP where a statistically significant difference was observed at 8 times points when measured invasively, but the difference was only at 1 time point, that is, at 3^rd min when measured noninvasively. MAP also has the same trend showing a difference at 11 times points when measured invasively and at only 1 time point when measured noninvasively. The common point observed here is that the fluctuations in blood pressure are more within 1 min after intubation that could be traced only with the help of invasive arterial pressure monitoring. Statistically significant difference was observed in percentage change in HR at 11 times points in <1 min and at 1, 3, 5 and 10^th min after tracheal intubation emphasizing the superiority of dexmedetomidine over esmolol in blunting the laryngo-tracheal response.

CONCLUSION

We conclude that the dexmedetomidine is superior to esmolol in attenuating the hemodynamic response to laryngoscopy and tracheal intubation.