Investigación Científica y Tecnológica

Gazi Parvez^*, Mohamad Ommid^*, Arun Kumar Gupta^**, Humariya Heena*^**, A.H. Hashia****

* MD Senior Resident, Dept. of Anaesthesiology and Critical Care. SKIMS, Soura, Jammu & Kashmir, India.

** MD Assistant Professor, Dept. of Anaesthesiology and Critical Care. Rural Medical College, Loni, Maharashtra, India. guptaarun71@gmail.com

*** Post Graduate, Dept. Of Community Medicine, SKIMS, Soura, J&K, India.

**** MD Professor and Head, Dept. of Anaesthesiology and Critical Care. Govt. Medical College, Srinagar, J&K, India.

Recibido: julio 21 de 2010. Enviado para modificaciones: agosto 4 de 2010. Aceptado: agosto 24 de 2010

Age may be an important factor influencing cardiovascular response to tracheal intubation. Various drugs and techniques have been used for blunting the hemodynamic response to laryngoscopy and intubation with variable degrees of success. In hypertensive patients cardiovascular response to laryngoscopy and intubation is exaggerated (1). Arterial lumen narrowing, blunted baro reflex response and increased sympathetic activity have been proposed to be factors responsible for exaggerated hemodynamic changes (2). Beta adrenoreceptor blockade minimizes increase in heart rate and myocardial contractility by attenuating the positive chronotropic and ionotropic effects of increased adrenergic activity (1,3,4). Calcium channel blockers are also preferred because myocardial depression produced is minimized by reduction in afterload so that cardiac output remains unchanged, but they have no effect on observed tachycardia (5,6). This study was done in Indian Kashmiri population as most of the studies have been done in general Indian population but not in Kashmiri population specifically as kashmiri population used to take a high salt diet and oily food leads to more incidence of hypertension and this study intended to find a better alternative by comparision amongst diltiazem and esmolol to attenuate the pressor response to laryngoscopy and intubation: the response being more so in hypertensive patients.

It is a prospective parallel randomized placebo controlled double blind study done on one hundred fifty hypertensive patients of both sexes (American Society of Anesthesiologists Physical Status Classification System - ASA II), controlled on antihypertensive drugs, between age range of 40-60 years scheduled for routine surgical procedures under general anesthesia (Open and Laparoscopic Cholecystectomy, Hydated Cystectomy, Common Bile Duct Exploration, Abdomino Perineal Resection, Thyroidectomy, Mastectomy, Exploratory Laparotomy for Carcinomas of Gut and Pancreas, interval Appendicectomy, Hernioplasty), after proper approval from Institutional Ethics Committee. An informed consent to participate in the study was taken from all the patients. It is a Hospital based, operation theatre setting study.

Patients on treatment with β-blockers or calcium channel blocker, history of bronchial asthma; history of cardiac disease; uncontrolled hypertension; History of allergy to any of the study drugs; and patients with predicted difficult intubation were not included.

After taking informed consent from the patients, the patients were prepared by overnight fasting and sedation with Tablet Alprazolam 0.5 mg given orally at bedtime on the night before surgery. Antihypertensive therapy was continued till the morning of surgery. In the morning every patient was given Tab Alprazolam 0.5 mg with a sip of water two hours before the expected time of surgery. The patients were randomly divided by simple randomization by computer allocated numbers into three groups of 50 patients each (Figure 1).

Group A: Comprised of 50 patients who received 10 ml of 5 % dextrose following intravenous induction. This served as a control group for the present study.

Group B: Comprised of 50 patients who received Inj Diltiazem 0.2 mg/kg diluted in 10 ml of 5 % dextrose following intravenous induction.

Group C: Comprised of 50 patients who received Inj Esmolol 1.5 mg/kg diluted in 10 ml of 5% dextrose following intravenous induction.

Baseline parameters, i.e. heart rate, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and rate pressure product were noted just before administration of any drugs. Rate pressure product was calculated by multiplying systolic blood pressure and heart rate.

Standardized anaesthesia technique was used in all the patients. All patients were pre-oxygenated for three minutes, followed by Sodium Thiopentone (5 mg/kg of 2.5 % solution) intravenously until loss of eyelash reflex. This was followed by administration of study drug. Endotracheal intubation was facilitated with intravenous Succinylcholine 1.5mg/kg. Intubation was performed 90 seconds after administration of Succinylcholine. Total duration of laryngoscopy was noted and in cases where duration exceeded 30 seconds and patients in whom more than one attempt of laryngoscopy was required was excluded from study.

After confirming the position of endotracheal tube, anaesthesia was maintained using nitrous oxide and oxygen with volatile anaesthetic agent (Isoflurane 0.2 %) delivered through closed circuit. Muscle relaxation was achieved with bolus dose of Injection Atracurium besylate 0.5 mg / kg intravenous initially followed by top up doses to maintain muscle relaxation.

At the end of surgery, the residual effect of muscle relaxant was reversed with Neostigmine (2,5 mg) and glycopyrrolate (0,5 mg) Extubation of trachea was done after full clinical recovery was achieved and after thorough Oropharyngeal suctioning. Thereafter patients were shifted to recovery room. The study period extended from the induction of anaesthesia to five minutes after intubation. During study period surgical stimuli was not allowed.

Following parameters were noted at baseline level, after giving study drug, immediately after laryngoscopy and intubation, at 1 minute, 3 minutes and 5 minutes after the tracheal intubation Heart rate, Systolic blood pressure, Diastolic blood pressure, Mean blood pressure and Rate pressure product (systolic blood pressure x heart rate).

At the end of the study all parameters were statistically evaluated by using student’s t-test and chi-square test. Power of study and sample size was estimated assuming any p-value less than 0.05 i.e. (p < 0.05) was going to be statistically significant.

There was no statistically significant difference between the groups with respect to age and sex (table 1).

Baseline heart rates in the three groups and changes in their levels soon after laryngoscopy and intubation was observed and tabulated in (table 2) in all the three groups.In groups A,B and C respectively showing a highly statistical difference on comparison. The rise was significantly attenuated in the Esmolol group. Thereafter when Group B and A were compared, the heart rate in both the groups showed increase after intubation, that was statistically significant (p < 0.05) and it persisted upto 5 five minute after intubation. However the rise in heart rate was statistically more significant in Group A when compared with Group B. When heart rate in Group C and Group B were compared, the rise in heart rate was attenuated in Group C while in Group B there was significant (p < 0.05) rise in the heart rate.

In Group A, the systolic blood pressure at baseline was 126.50 + 6.95. A statistically significant rise in systolic blood pressure soon after laryngoscopy and intubation 161.64 + 16.64 and the increase in systolic blood pressure remained statistically significant till 5 minutes after intubation In Group B and C the systolic blood pressure (table 3) at baseline were 132.04 + 10.80 and 128.77 + 9.59. The drug B and C successfully attenuated any rise in systolic blood pressure soon after laryngoscopy and intubation 128.84 + 14.19 and 124.76 + 10.24 and continued to do so upto 5 min after the intubation 130.98 + 10.63 and 124.94 + 8.36 respectively.

Diastolic blood pressure (table 4) in Group A showed statistically significant rise from baseline 77.78 + 5.03 to 105.60 + 18.08 soon after laryngoscopy and intubation and remained statistically significantly high upto five minutes after intubation 88.52 + 8.26. The diastolic blood pressure in Group B showed a fall from baseline 80.55 + 8.27 to 71.00 + 7.82 at 3 minutes after intubation. The diastolic blood pressure in Group B soon after laryngoscopy and intubation was 76.67 + 9.82. Diastolic blood pressure in Group C insignificantly changed from baseline 81.28 + 7.61. The diastolic blood pressure was 80.44 + 9.79 soon after laryngoscopy and intubation and 80.75 +8.27 at 5 minute after intubation.

Rate pressure product (Figure 2) in Group A rose from baseline, peaking at laryngoscopy and intubation 18966.66 + 3032.22 and at 5 minutes after laryngoscopy and intubation 13202.04 + 2043.80. When rate pressure product in Group B was compared at different intervals with baseline 12235.22 + 2258.24, there was insignificant (p > 0.05) difference at laryngoscopy and intuba tion 12508.28 + 2982.23 and at 5 minutes after intubation 12318.86 + 1678.84. Rate pressure product in Group C when compared at different interval with baseline 12027.06 + 2271.43, there was insignificant (P>0.05) difference at different intervals at laryngoscopy and intubation 12521.35 + 2003.04 and at 5 minutes after laryngoscopy and intubation 11824.51 + 1786.00.

Tachycardia and hypertension are well documented sequels of laryngoscopy and endotracheal intubation (1,7). In hypertensive patients cardiovascular response to laryngoscopy and intubation is exaggerated (1). Arterial luminal narrowing, blunted baroreflex response and increased sympathetic activity have been proposed to be factors responsible for exaggerated hemodynamic changes (2). Heart rate is major determinant of myocardial oxygen consumption and there is an increasing evidence that tachycardia is poorly tolerated in patients with coronary artery disease. Several recent studies have shown that there is an inincidence of myocardial ischemia when intra operative heart rates exceed 110/min (8,9).

After intubation in Group C (Esmolol) there was significant attenuation in rise of heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and rate pressure product as compared to base line values. These findings are consistent with the result of Miller et al (10). Esmolol is a cardio selective beta blocker with ultra short duration of action and has been indicated for the treatment of tachycardia and hypertension during tracheal intubation (11). In the Esmolol group we observed that the increase in heart rate after laryngoscopy and intubation were significantly attenuated and remained throughout the study period.

Multiple studies have shown similar results (8,12,13). After laryngoscopy and intubation there was a significant rise in heart rate in Group B (Diltiazem group) and remained so throughout study period when compared with the control group (14,15). Comparison of Esmolol and Diltiazem showed a significant attenuation by group C and a similar study by Kumar Santosh et al also concluded with the same results (13).

Systolic blood pressure rose significantly in the control group following laryngoscopy and intubation and remained high thereafter for five minutes following intubation. Diltiazem and Esmolol successfully attenuated the rise in SBP and on comparison showed a statistically significant difference with the control group. These findings were similar to those of the Mikawa et al and Fuji et al (15,16).

Similarly when Diastolic blood pressure and Mean arterial pressures were observed during the study period we found that diastolic blood pressure showed a significant rise during laryngoscopy and intubation in group A and persisted upto 5 min. as compared to group B and C. On comparing Groups B and C the rise in diastolic blood pressure was attenuated in Group C while in Group B the diastolic blood pressure showed falling pattern from administration of drug till 3 minutes and then again, at 5 minutes the diastolic blood pressure showed a rise. Mean arterial pressure rose in the control group and persisted for 5 min but both Group B and C attenuated the rise in MAP, more efficiently by Esmolol Group.

Rate pressure product is calculated by multiplying systolic blood pressure with heart rate and is good estimate of myocardial oxygen requirement (17). Group A showed significant (p < 0.05) rise from baseline, peaking at laryngoscopy and intubation 18966.66 (+ 3032.22) and at 5 minutes after laryngoscopy and intubation 13202.04 (+ 2043.80). When rate pressure product was compared between Group B and Group C, there seemed to have significant differences at respective time intervals, but in both groups the rise in rate pressure product is insignificant Menkhaus et al and Miller et al also concluded that esmolol is effective in controlling systolic, diastolic and mean arterial pressure following laryngoscopy and intubation (10,18). Findings in Group B (Diltiazem group) showed significant attenuation in rise in systolic, diastolic and mean arterial pressure when compared with base line. These are consistent with the findings of the Mikawa et al and Fuji et al (15,16). When the changes in heart rate, systolic blood pressure, mean arterial pressure and rate pressure product after intubation were compared between Group C (Esmolol) and Group B (Diltiazem) it was found that esmolol attenuated the rise in above mentioned parameters better. These findings are consistent with the findings of Kumar Santosh et al (13).

The attenuating effect of pressor response of Esmolol when compared with Diltiazem was found to be significantly more when alterations in heart rate, systolic blood pressure and rate pressure product were compared between the two study groups. Diltiazem does not prevent rise in the heart rate observed during laryngoscopy and intubation. Esmolol is concluded to be very effective agent in attenuating the pressor response of laryngoscopy and intubation in controlled hypertensive patients in Kashmiri population.

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