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Can Calcium and Sodium Channel Blockers Attenuate Hemodynamic Responses to Endotracheal Intubation?

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CAN CALCIUM AND SODIUM CHANNEL BLOCKERS ATTENUATE HEMODYNAMIC RESPONSES TO ENDOTRACHEAL INTUBATION? Manjunath Honnavara Govindaiah1, Venkatesh Gubbi Suryanarayana1, Prima Vas2, Jennifer Leigh Vlk2, Sathees Beladakere Channaiah Chandra2* Rajiv Gandhi University, Mysore Medical College, 1Krishna Rajendra Hospital and Cheluvamba Hospital, India, Roosevelt University, 2Department of Biological, Physical Sciences, Chicago, USA Aim: Direct laryngoscopy and endotracheal intubation following induction of anesthesia almost always triggers powerful cardiovascular responses. The purpose of this study was to investigate the efficacy of diltiazem (calcium channel blocker), lidocaine (sodium channel blocker) and a combination of these two drugs in the attenuation of circular responses to endotracheal intubation in normotensive patients. Methods: 120 Patients were randomly assigned to one of the following four groups. Group I received a single 0.2 mg/kg IV bolus of diltiazem 1 minute prior to laryngoscopy and intubation (n=30), Group II received a single 1.5 mg/kg IV bolus of lidocaine (n=30) 3 minutes prior and Group III received combination of these two drugs 1 minute prior to laryngoscopy and intubation (n=30). Group IV served as the control and received a single 5 mL IV bolus of normal saline. Changes in heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured and then compared within and between groups. Rate pressure product (RPP) was calculated and evaluated as well. Results:Either diltiazem or lidocaine alone blunts unwanted hemodynamic responses to intubation. However, significantly less circulatory responses were experienced by patients receiving both than those receiving either lidocaine or diltiazem alone. Conclusion: Given the difference in the pharmacological mechanisms of these two drugs, the prophylactic therapy with combination of diltiazem+lidocaine is significantly more effective than any one alone for attenuating hemodynamic changes to laryngoscopy and tracheal intubation, without producing increased risk of hypertension. Key words: Calcium channel, sodium channel, circulatory response, endotracheal intubation, hemodynamic change Eur J Gen Med 2008;5(4):198-207 INTRODUCTION hemodynamic changes due to sympatho- Cardiovascular complications are adrenal stimulation (7,8). This increased one of the most common causes of sympatho-adrenal activity normally causes anesthesia-related morbidity (1). The hypertension, tachycardia or myocardial hemodynamic consequences of drugs ischemia in patients with coronary artery and the techniques used for induction of disease, intracranial tumors and previous anesthesia have been well documented myocardial infarction (9). This increase in (2-6). Laryngoscopy and endotracheal blood pressure and heart rate are usually intubation are often mandatory for transitory, variable and unpredictable. patients undergoing a variety of surgical Transitory hypertension and tachycardia procedures. It is well known that are generally of no consequence laryngoscopy and endotracheal intubation in healthy individuals, but either or following induction of anesthesia both may be hazardous to those with is almost always associated with hypertension, myocardial insufficiency or Correspondence:Sathees B.C. Chandra, Ph.D Associate Professor of Biology/Genetics, Department of Biological, Chemical and Physical Sciences, Roosevelt University, 430 S Michigan Avenue, Chicago, IL 60605 USA Phone: 8476197968, Fax: 8476198555 Email: [email protected] 199 Govindaiah et al. Table1. Study participant’s demographic data (values represent means ± SD) Control Group 1 Group 2 Group 3 (Saline) (Diltiazem ) (Lidocaine) (Diltiazem+ Lidocaine) n 30 30 30 30 Sex (M/F) Ratio 15/15 13/17 16/14 18/12 Age (yr) 38 ± 10.2 43.5 ± 9.6 40 ±10.6 42 ± 11.3 Weight (kg) 56.4 ± 5.33 68.7 ± 10.17 65.9 ± 10.25 69.4 ± 11.3 cerebrovascular diseases (10). than receiving either lidocaine or diltiazem Many pharmacological methods have alone. been devised to reduce the extent of MATERIAL AND METHODS hemodynamic events including high This study was undertaken at dose of opioids such as fentanyl, K.R.Hospital attached to Government remifentanil, alfentanil (11-13), alpha- and Medical College, Mysore, coming under beta-adrenergic blockers (14,15), and Rajiv Gandhi University of Health vasodilatation drugs like nitroglycerine sciences, Bangalore, Karnataka state, (16). Each of these drugs has a unique India. Following institutional approval by advantage and disadvantage in blunting the ethical committee at Mysore Medical the pressor response to intubation. College, informed consent was obtained During the last decade, calcium and from 120 patients. The study population sodium channel blockers has been consisted of randomly selected ASA utilized to mitigate the hemodynamic physical status I or II male and female responses to intubation. Diltiazem is adults, between the ages of 18-60 yr, one of the calcium channel blockers which were scheduled for various elective being used as antianginal, antiarrythmic surgical procedures. Patients having pre- and antihypertensive agent. Lidocaine existing systemic disorders, ischemic (lignocaine) is a common local anesthetic heart disease, hypertensive heart disease, and a sodium channel blocker known to diabetes mellitus, bronchial asthma, reduce pressor response to intubation. previous myocardial infarction, renal Although these two drugs have been used disease, cerebrovascular insufficiency or in various studies alone or combined with association with any co-morbid disease other opioids, only two reports have so far were excluded from the study. examined the benefits of combining both calcium and sodium channel blockers. Study design The first study looked at the combination Each patient was randomly assigned to of these two drugs only in hypertensive one of four study groups. Group I received patients (10). Based on an English- a single 0.2 mg/kg IV bolus of diltiazem translated abstract, a second study by diluted to 5 mL with normal saline 1 minute Lee et al. (17) also appeared to look prior to laryngoscopy and intubation (n: at the combination of these two drugs. 30). Group II received a single 1.5 mg/kg However in their work, the researchers IV bolus of lidocaine (lignocaine) diluted only measured the heart rate and mean to 5mL with normal saline 3 minutes prior arterial pressure which sharply contrasted to laryngoscopy and intubation (n:30). with what we found in our study. The Group III received a combined single present work was undertaken to compare IV bolus containing both 0.2 mg/kg of the effect of diltiazem, lidocaine and diltiazem and 1.5 mg/kg lidocaine diluted combination of these two drugs on to 5mL with normal saline 1 minute prior blunting the hemodynamic responses to to laryngoscopy and intubation (n:30). endotracheal intubation in normotenseive Group IV served as control and received patients. Because the mechanism a single 5ml IV bolus dose of normal for control of hemodynamic changes saline given 1 minute before laryngoscopy is different between these two drugs and intubation (n=30). Heart rate (HR), (18,19), we hypothesized that significantly systolic blood pressure (SBP), diastolic less circulatory responses would be blood pressure (DBP) and mean arterial experienced by patients receiving both pressure (MAP) were recorded via a Hemodynamic responses to intubation 200 Figure 1. Changes in Heart Rate with standard deviations in each group. All values are expressed as mean ±SD. Group I: diltiazem; Group II:lidocaine and Group III: diltiazem+lidocaine. p<0.05 vs. control and p<0.001 between Group III vs Group I/ Group II after intubation Siemens SC-7000 multi-channel monitor and 0.5 mg alprozolam the night before for each patient prior to administration surgery. of the study drug, at pre-induction and after intubation at the time increments of Surgical Protocol 1, 3 and a maximum of 5 minutes as after 1 mg Midazolam and 15mg Pentazocine surgery has commenced, multiple factors was given to all the patients before like various surgical stimuli may also play induction as Pre-medication. The patients role in hemodynamic response. Rate were preoxygenated for three minutes using Pressure Product (RPP) was calculated 100% oxygen by facemask with Mapleson and evaluated as well. The rate pressure A circuit. In the operating room, an 18- product was calculated by multiplying gauge intravenous cannula was inserted heart rate with systolic blood pressure. and an infusion of dextrose with normal saline was started. The patients were Pre-surgical Protocol connected to the Siemens multi-channel The day prior to surgery all patients monitor and HR, SBP, DBP, and MAP was underwent a pre-anesthetic evaluation recorded. After recoding the baseline with special consideration to elicit a reading (basal), the study drug (0.2 mg/kg history of hypertension, diabetes mellitus, IV bolus of diltiazem, 1.5 mg/kg IV bolus chest pain, dyspnoea, convulsions, and of lidocaine or combination of both) or wheezing, myocardial infarction, as well the control placebo (5 mL normal saline) as previous anesthetic history and drug was administered as follows. Anesthesia sensitivity. Patient information collected was induced with Thiopentone 5 mg/kg as during the pre-anesthetic evaluation also 2.5% solution and endotracheal intubation included nutritional status, weight, airway was facilitated with succinylcholine assessment by the Mallampatti scoring 1.5 mg/kg administered
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