1. PREINDUCTION INTRAVENOUS LABETALOL FOR ATTENUATING INTUBATION STRESS RESPONSE DR. A. KARTHIK KILPAUK MEDICAL COLLEGE KILPAUK MEDICAL COLLEGE

2. GUIDE : GUIDE : PROF. DR. P.S.SHANMUGAM, MD, DA PROF. DR. P.S.SHANMUGAM, MD, DA HEAD OF DEPARTMENT HEAD OF DEPARTMENT DEPARTMENT OF ANAESTHESIOLOGY, DEPARTMENT OF ANAESTHESIOLOGY, KILPAUK MEDICAL COLLEGE. KILPAUK MEDICAL COLLEGE. ETHICAL COMMITTEE APPROVAL OBTAINED

3. AIM OF THE STUDY To study and compare the effects of Preinduction intravenous Labetalol at incremental doses of 0.25mg/kg & 0.5mg/kg in attenuation of intubation stress response in General Anaesthesia To study and compare the effects of Preinduction intravenous Labetalol at incremental doses of 0.25mg/kg & 0.5mg/kg in attenuation of intubation stress response in General Anaesthesia

4. STUDY DESIGN Randomized, Prospective study Randomized, Prospective study Pre study assessment done and consent obtained from all the patients Pre study assessment done and consent obtained from all the patients

5. PATIENT SELECTION INCLUSION CRITERIA : INCLUSION CRITERIA : 45 patients of ASA grade I & II 45 patients of ASA grade I & II Age 18 – 60 yrs Age 18 – 60 yrs Both sex Both sex Elective surgery requiring general anaesthesia with endotracheal intubation Elective surgery requiring general anaesthesia with endotracheal intubation

6. EXCLUSION CRITERIA : EXCLUSION CRITERIA : Patient contraindicated to  -blocker; eg- Bronchial Asthma, Peripheral vascular disease, conduction defects Patient contraindicated to  -blocker; eg- Bronchial Asthma, Peripheral vascular disease, conduction defects Hypertensive patients, patients on Anti-HT drugs Hypertensive patients, patients on Anti-HT drugs Systolic BP < 90mmHg; HR< 50/mt Systolic BP < 90mmHg; HR< 50/mt Having preoperative airway or intubation problems Having preoperative airway or intubation problems Awake intubation or intubation taking more than 20sec or requiring second attempt are excluded Awake intubation or intubation taking more than 20sec or requiring second attempt are excluded

7. GROUPS GROUP A : 15 patients receiving IV Normal saline (Placebo) prior to induction (Control) GROUP A : 15 patients receiving IV Normal saline (Placebo) prior to induction (Control) GROUP B : 15 patients receiving Inj. Labetalol 0.25mg/kg prior to induction GROUP B : 15 patients receiving Inj. Labetalol 0.25mg/kg prior to induction GROUP C : 15 patients receiving Inj. Labetalol 0.5 mg/kg prior to induction GROUP C : 15 patients receiving Inj. Labetalol 0.5 mg/kg prior to induction

8. MONITORING Pulse oximetry Pulse oximetry NIBP NIBP ECG ECG

9. METHODOLOGY 45 patients randomized into three groups of 15 each 45 patients randomized into three groups of 15 each Premedication: Given i.m 45 min prior to surgery Premedication: Given i.m 45 min prior to surgery  Inj. Glycopyrrolate 10ug/kg  Inj. Pentazocine 0.5mg /kg Preoxygenation : 100% O2 for 5 min Preoxygenation : 100% O2 for 5 min Inj Labetalol/ Normal saline given iv 5 min prior to induction Inj Labetalol/ Normal saline given iv 5 min prior to induction Induction : Inj.Propofol 2mg/kg iv Induction : Inj.Propofol 2mg/kg iv

10. NDMR – Inj Rocuronium 0.9mg/Kg iv NDMR – Inj Rocuronium 0.9mg/Kg iv Patient ventilated with 100% O 2 for 3 min Patient ventilated with 100% O 2 for 3 min Intubated with appropriate size ET tube Intubated with appropriate size ET tube Maintained with O2 : N2O – 1:2 Maintained with O2 : N2O – 1:2 Volatile inhalational agents used only 10min after intubation Volatile inhalational agents used only 10min after intubation

11. Pulse rate & NIBP were recorded: Pulse rate & NIBP were recorded: Preoperatively Preoperatively 45 min after premedication 45 min after premedication In the operating table before IV Labetalol/Normal saline In the operating table before IV Labetalol/Normal saline For every min after IV Labetalol/Normal saline for 5 min For every min after IV Labetalol/Normal saline for 5 min After Induction After Induction After giving NDMR After giving NDMR At laryngoscopy At laryngoscopy For every 1 min after Endotracheal intubation for 10min For every 1 min after Endotracheal intubation for 10min

12. Labetalol — Mechanism Competitive, selective  1 and non-selective  -blocker Competitive, selective  1 and non-selective  -blocker  >  blocking potency oral is 3:1, iv is 7:1  >  blocking potency oral is 3:1, iv is 7:1 It has intrinisic partial B2 agonistic activity hence causes vasodilation It has intrinisic partial B2 agonistic activity hence causes vasodilation Onset: 5-10 min Onset: 5-10 min Duration of action: 3-6hrs Duration of action: 3-6hrs T1/2 – 5-8hrs T1/2 – 5-8hrs Competitive, selective  1 and non-selective  -blocker Competitive, selective  1 and non-selective  -blocker  >  blocking potency oral is 3:1, iv is 7:1  >  blocking potency oral is 3:1, iv is 7:1 It has intrinisic partial B2 agonistic activity hence causes vasodilation It has intrinisic partial B2 agonistic activity hence causes vasodilation Onset: 5-10 min Onset: 5-10 min Duration of action: 3-6hrs Duration of action: 3-6hrs T1/2 – 5-8hrs T1/2 – 5-8hrs

13. CVS Effects Decrease SVR leading to decrease in BP is by alpha -1 blockade Decrease SVR leading to decrease in BP is by alpha -1 blockade Vasodilation also produced by partial B2 agonist activity Vasodilation also produced by partial B2 agonist activity Reflex tachycardia due to peripheral vasodilation is attenuated by B blockade Reflex tachycardia due to peripheral vasodilation is attenuated by B blockade Cardiac output remains unchanged Cardiac output remains unchanged Presynaptic alpha-2 receptors are spared- hence release of Norepinephrine is intact, which inhibits further release of catecholamine (Neg feedback mech) Presynaptic alpha-2 receptors are spared- hence release of Norepinephrine is intact, which inhibits further release of catecholamine (Neg feedback mech)

14. Adverse effects Orthostatic hypotension Orthostatic hypotension Bronchospasm Bronchospasm Others- CCF, bradycardia, Heart block Others- CCF, bradycardia, Heart block Increased plasma aminotransferase Increased plasma aminotransferase Paresthesia – scalp tingling Paresthesia – scalp tingling Urinary retention Urinary retention

15. STATISTICAL ANALYSIS

16. STATISTICAL TEST USED ANOVA test ANOVA test F test F test If significance is there, then subjected to Post Hoc Test If significance is there, then subjected to Post Hoc Test

17. ANALYSIS OF AGE AMONG THE GROUPS P value = 0.834, which is not significant P value = 0.834, which is not significant AGE 95% Confidence Interval for Mean Group NMean Std. Deviation Std. Error Lower Bound Upper Bound A 15 38.47 11.5562.98432.0744.87 B15 36.00 11.0912.86429.8642.14 C15 37.87 12.2933.17431.0644.67

18. COMPARISON OF PREOP HEART RATE AMONG THE GROUPS PRE OP HR 95% Confidence Interval for Mean NMean Std. Deviation Std. ErrorLower BoundUpper Bound A15 85.87 12.6773.27378.8592.89 B 15 86.87 8.8232.27881.9891.75 C15 85.13 11.2502.90578.9091.36 P=0.911, NOT SIGNIFICANT

19. COMPARISON OF PREOP SYSTOLIC BP AMONG THE GROUPS PRE OP SBP 95% Confidence Interval for Mean NMean Std. Deviation Std. Error Lower Bound Upper Bound A15 120.47 8.4422.180115.79125.14 B15 124.40 12.9333.339117.24131.56 C15 124.67 13.9113.592116.96132.37 P=0.567, NOT SIGNIFICANT

20. COMPARISON OF PREOP DIASTOLIC BP AMONG THE GROUPS PRE OP DBP 95% Confidence Interval for Mean NMean Std. Deviation Std. Error Lower Bound Upper Bound A15 79.33 6.2871.62375.8582.81 B15 80.13 8.6842.24275.3284.94 C15 82.87 7.7171.99378.5987.14 P=0.420, NOT SIGNIFICANT

21. COMPARISON OF HR AFTER 5MIN OF LABETALOL IV 5 MINUTES STUDY HR 95% Confidence Interval for Mean NMean Std. Deviation Std. Error Lower Bound Upper Bound A15 87.47 13.7993.56379.8395.11 B15 81.67 12.7933.30374.5888.75 C15 81.20 13.4973.48573.7388.67 P=0.368, NOT SIGNIFICANT

22. COMPARISON OF SYSTOLIC BP AFTER 5MIN OF LABETALOL IV 5 MINUTES STUDY SBP 95% Confidence Interval for Mean NMean Std. Deviation Std. Error Lower Bound Upper Bound A15 121.47 8.7822.268116.60126.33 B15 122.00 12.0123.101115.35128.65 C15 122.13 12.4323.210115.25129.02 P=0.985, NOT SIGNIFICANT

23. COMPARISON OF DIASTOLIC BP AFTER 5MIN OF LABETALOL IV 5 MINUTE STUDY DBP 95% Confidence Interval for Mean NMean Std. Deviation Std. Error Lower Bound Upper Bound A15 79.27 6.0761.56975.9082.63 B15 73.40 9.6352.48868.0678.74 C15 71.80 9.4452.18066.1276.48 P=0.105, NOT SIGNIFICANT

24. COMPARISON OF HEART RATE AT LARYNGOSCOPY HR AT SCOPY 95% Confidence Interval for Mean NMean Std. Deviation Std. ErrorLower BoundUpper Bound A15 109.00 13.8103.566101.35116.65 B15 89.33 13.8393.57381.6797.00 C15 88.13 14.2723.68580.2396.04 P=0.000, SIGNIFICANT By Post Hoc Test: There was a difference between the control & Labetalol groups, but there was no significant difference between the two Labetalol groups (P=0.815)

25. COMPARISON OF HEART RATE AT 1 MIN AFTER INTUBATION SCOPY OF 1 MINUTE HR 95% Confidence Interval for Mean NMean Std. Deviation Std. ErrorLower BoundUpper Bound A15 104.00 11.9463.08597.38110.62 B15 87.20 13.2623.42479.8694.54 C15 86.27 15.2853.94777.8094.73 P=0.001, SIGNIFICANT By Post Hoc Test: There was a difference between the control & Labetalol groups, but there was no significant difference between the two Labetalol groups (P=0.851)

26. COMPARISON OF HEART RATE AT 3 MIN AFTER INTUBATION SCOPY OF 3 MINUTES HR 95% Confidence Interval for Mean NMean Std. Deviation Std. ErrorLower BoundUpper Bound A15 96.67 11.5922.99390.25103.09 B15 83.13 13.0813.37875.8990.38 C15 83.07 13.4883.48375.6090.54 P=0.007, SIGNIFICANT By Post Hoc Test: There was a difference between the control & Labetalol groups, but there was no significant difference between the two Labetalol groups (P=0.989)

27. COMPARISON OF HEART RATE AT 5 MIN AFTER INTUBATION SCOPY OF 5 MINUTES HR 95% Confidence Interval for Mean NMean Std. Deviation Std. ErrorLower BoundUpper Bound A15 92.93 11.9853.09486.3099.57 B15 81.93 12.9813.35274.7489.12 C15 80.93 12.3553.19074.0987.78 P=0.02, SIGNIFICANT By Post Hoc Test: There was a difference between the control & Labetalol groups, but there was no significant difference between the two Labetalol groups (P=0.827)

28. COMPARISON OF HEART RATE AT 10 MIN AFTER INTUBATION P=0.022, SIGNIFICANT By Post Hoc Test: There was a difference between the control & Labetalol groups, but there was no significant difference between the two Labetalol groups (P=0.805) SCOPY OF 10 MINUTES HR 95% Confidence Interval for Mean NMeanStd. DeviationStd. ErrorLower BoundUpper Bound A15 90.40 12.3853.19883.5497.26 B15 80.27 11.1392.87674.1086.43 C15 79.20 11.6393.00572.7585.65

29. COMPARISON OF SYSTOLIC BP AT LARYNGOSCOPY SBP AT LARYNGOSCOPY 95% Confidence Interval for Mean NMean Std. Deviation Std. ErrorLower BoundUpper Bound A15 143.47 10.1482.620137.85149.09 B15 139.07 14.7093.798130.92 147.21 C15 134.00 16.2484.195125.00143.00 P=0.189, NOT SIGNIFICANT

30. COMPARISON OF SYSTOLIC BP AT 1 MIN AFTER INTUBATION SCOPY 1 MINUTES SBP 95% Confidence Interval for Mean NMean Std. Deviation Std. ErrorLower BoundUpper Bound A15 137.07 6.0061.551133.74140.39 B15 134.07 14.7823.817125.88142.25 C15 128.60 16.1374.167119.66137.54 P=0.212, NOT SIGNIFICANT

31. COMPARISON OF SYSTOLIC BP AT 3 MIN AFTER INTUBATION SCOPY 3 MINUTES SBP 95% Confidence Interval for Mean NMean Std. Deviation Std. ErrorLower BoundUpper Bound A15 130.07 4.4481.148127.60132.53 B15 125.20 15.2323.933116.76133.64 C15 122.07 13.6143.515114.53129.61 P=0.200, NOT SIGNIFICANT

32. COMPARISON OF SYSTOLIC BP AT 5 MIN AFTER INTUBATION SCOPY 5 MINUTES SBP 95% Confidence Interval for Mean NMeanStd. DeviationStd. ErrorLower BoundUpper Bound A15 128.47 4.4701.154125.99130.94 B15 122.07 12.8813.326114.93129.20 C15 117.53 11.6673.012111.07123.99 P=0.021, SIGNIFICANT

33. COMPARISON OF SYSTOLIC BP AT 10 MIN AFTER INTUBATION SCOPY 10 MINUTES SBP 95% Confidence Interval for Mean NMean Std. Deviation Std. ErrorLower BoundUpper Bound A15 126.60 5.3561.383123.63129.57 B15 121.07 13.1233.388113.80128.33 C15 117.20 11.1622.882111.02123.38 P=0.051, NOT SIGNIFICANT

34. COMPARISON OF DIASTOLIC BP AT LARYNGOSCOPY DBP AT LARYNGOSCOPY 95% Confidence Interval for Mean NMeanStd. DeviationStd. ErrorLower BoundUpper Bound A15 92.40 7.9082.04288.0296.78 B15 85.27 12.9593.34678.0988.44 C15 83.87 9.9702.57476.3587.39 P=0.039, SIGNIFICANT

35. COMPARISON OF DIASTOLIC BP AT 1 MIN AFTER INTUBATION SCOPY 1 MINUTES DBP 95% Confidence Interval for Mean NMean Std. Deviation Std. ErrorLower BoundUpper Bound A15 88.67 6.3771.64785.1492.20 B15 80.33 11.4372.95374.0086.67 C15 80.65 9.4532.44176.7085.17 P=0.023, SIGNIFICANT

36. COMPARISON OF DIASTOLIC BP AT 3 MIN AFTER INTUBATION SCOPY 3 MINUTES DBP 95% Confidence Interval for Mean NMean Std. Deviation Std. ErrorLower BoundUpper Bound A15 84.80 6.4721.67181.2288.38 B15 77.27 11.4552.95870.9283.61 C15 78.93 9.8692.03273.5883.29 P=0.063, NOT SIGNIFICANT

37. COMPARISON OF DIASTOLIC BP AT 5 MIN AFTER INTUBATION SCOPY 5 MINUTES DBP 95% Confidence Interval for Mean NMean Std. Deviation Std. ErrorLower BoundUpper Bound A15 82.40 5.8161.50279.1885.62 B15 74.40 10.7822.78468.4380.37 C15 71.87 8.6241.96867.6476.09 P=0.028, SIGNIFICANT

38. COMPARISON OF DIASTOLIC BP AT 10 MIN AFTER INTUBATION SCOPY 10 MINUTES DBP 95% Confidence Interval for Mean NMean Std. Deviation Std. ErrorLower BoundUpper Bound A15 80.87 6.7391.74077.1384.60 B15 72.47 10.5012.71166.6578.28 C15 71.60 9.1522.10565.2976.31 P=0.021, SIGNIFICANT

39. CONCLUSION Heart Rate: Heart Rate: Preinduction iv labetalol decreased the heart rate prior to induction in the Labetalol groups (decrease in Group C>Group B>Group A) at 5 min after labetalol injection. But it is not statistically significant Preinduction iv labetalol decreased the heart rate prior to induction in the Labetalol groups (decrease in Group C>Group B>Group A) at 5 min after labetalol injection. But it is not statistically significant Attenuation of heart rate at Laryngoscopy, at 1min, 3min, 5min, 7min & 10min after intubation (decrease in Group C>Group B>Group A) is statistically significant. Attenuation of heart rate at Laryngoscopy, at 1min, 3min, 5min, 7min & 10min after intubation (decrease in Group C>Group B>Group A) is statistically significant. Preop HR was achieved at 1 min after intubation Preop HR was achieved at 1 min after intubation

40. HEART RATE ANOVA FSig. SCOPY (0 MINUTE) HRBetween Groups10.543.000 SCOPY OF 1 MINUTE HRBetween Groups8.116.001 SCOPY OF 3 MINUTES HRBetween Groups5.664.007 SCOPY OF 5 MINUTES HRBetween Groups4.292.020 SCOPY OF 7 MINUTES HRBetween Groups4.195.022 SCOPY OF 10 MINUTES HRBetween Groups4.164.022

41. CONCLUSION Systolic BP: Systolic BP: Preinduction iv labetalol had no change in the systolic BP prior to induction in the Labetalol groups at 5 min after labetalol injection. Preinduction iv labetalol had no change in the systolic BP prior to induction in the Labetalol groups at 5 min after labetalol injection. Attenuation of Systolic BP at Laryngoscopy, at 1min, 3min, 7min & 10min after intubation is not statistically significant (decrease in Group C>Group B>Group A) Attenuation of Systolic BP at Laryngoscopy, at 1min, 3min, 7min & 10min after intubation is not statistically significant (decrease in Group C>Group B>Group A) Preop systolic BP value was reached 3-5min after intubation Preop systolic BP value was reached 3-5min after intubation

42. SYSTOLIC BP ANOVA FSig. SCOPY 0 MINUTES SBPBetween Groups1.731.189 SCOPY 1 MINUTES SBPBetween Groups1.610.212 SCOPY 3 MINUTES SBPBetween Groups1.673.200 SCOPY 5 MINUTES SBPBetween Groups4.217.021 SCOPY 7 MINUTES SBPBetween Groups3.086.056 SCOPY 10 MINUTES SBPBetween Groups3.226.051

43. CONCLUSION Diastolic BP: Diastolic BP: Preinduction iv labetalol decreased the diastolic BP prior to induction in the Labetalol groups (decrease in Group C>Group B>Group A) at 5 min after labetalol injection. But it is not statistically significant Preinduction iv labetalol decreased the diastolic BP prior to induction in the Labetalol groups (decrease in Group C>Group B>Group A) at 5 min after labetalol injection. But it is not statistically significant Attenuation of Diastolic BP at Laryngoscopy, at 1min, 5min, 7min & 10min after intubation is statistically significant (decrease in Group C>Group B>Group A) Attenuation of Diastolic BP at Laryngoscopy, at 1min, 5min, 7min & 10min after intubation is statistically significant (decrease in Group C>Group B>Group A) Preop diastolic BP was reached 2-3min after intubation Preop diastolic BP was reached 2-3min after intubation

44. DIASTOLIC BP ANOVA FSig. SCOPY 0 MINUTE DBPBetween Groups2.154.039 SCOPY 1 MINUTES DBPBetween Groups4.126.023 SCOPY 5 MINUTES DBPBetween Groups3.896.028 SCOPY 7 MINUTES DBPBetween Groups3.252.049 SCOPY 10 MINUTES DBPBetween Groups4.236.021

45. CONCLUSION Both Group B & C showed attenuation of intubation stress response(HR, Diastolic BP & to a certain extent Systolic BP) compared to control group (Group A), but the difference between the two Labetalol groups is very less & not statistically significant. Hence Labetalol 0.25mg/kg is quiet effective & economical in attenuating stress response. Both Group B & C showed attenuation of intubation stress response(HR, Diastolic BP & to a certain extent Systolic BP) compared to control group (Group A), but the difference between the two Labetalol groups is very less & not statistically significant. Hence Labetalol 0.25mg/kg is quiet effective & economical in attenuating stress response.