PREINDUCTION INTRAVENOUS LABETALOL FOR ATTENUATING INTUBATION STRESS RESPONSE

PREINDUCTION INTRAVENOUS PREINDUCTION INTRAVENOUS LABETALOL FOR LABETALOL FOR

ATTENUATING INTUBATION ATTENUATING INTUBATION STRESS RESPONSESTRESS RESPONSE

DR. A. KARTHIKDR. A. KARTHIK

KILPAUK MEDICAL COLLEGEKILPAUK MEDICAL COLLEGE

GUIDE :GUIDE :

PROF. DR. P.S.SHANMUGAM, MD, DAPROF. DR. P.S.SHANMUGAM, MD, DA

HEAD OF DEPARTMENTHEAD OF DEPARTMENT

DEPARTMENT OF ANAESTHESIOLOGY,DEPARTMENT OF ANAESTHESIOLOGY,

KILPAUK MEDICAL COLLEGE.KILPAUK MEDICAL COLLEGE.

ETHICAL COMMITTEE APPROVAL ETHICAL COMMITTEE APPROVAL OBTAINEDOBTAINED

AIM OF THE STUDYAIM OF THE STUDY

To study and compare the effects of To study and compare the effects of Preinduction intravenous Labetalol at Preinduction intravenous Labetalol at incremental doses of 0.25mg/kg & incremental doses of 0.25mg/kg & 0.5mg/kg in attenuation of intubation 0.5mg/kg in attenuation of intubation stress response in General Anaesthesiastress response in General Anaesthesia

STUDY DESIGNSTUDY DESIGN

• Randomized, Prospective studyRandomized, Prospective study

• Pre study assessment done and consent Pre study assessment done and consent obtained from all the patientsobtained from all the patients

PATIENT SELECTIONPATIENT SELECTION

INCLUSION CRITERIA :INCLUSION CRITERIA :• 45 patients of ASA grade I & II45 patients of ASA grade I & II• Age 18 – 60 yrsAge 18 – 60 yrs• Both sexBoth sex• Elective surgery requiring general Elective surgery requiring general

anaesthesia with endotracheal intubationanaesthesia with endotracheal intubation

EXCLUSION CRITERIAEXCLUSION CRITERIA : :• Patient contraindicated to Patient contraindicated to -blocker; -blocker; eg- eg-

Bronchial Asthma, Peripheral vascular Bronchial Asthma, Peripheral vascular disease, conduction defectsdisease, conduction defects

• Hypertensive patients, patients on Anti-HT Hypertensive patients, patients on Anti-HT drugsdrugs

• Systolic BP < 90mmHg; HR< 50/mtSystolic BP < 90mmHg; HR< 50/mt• Having preoperative airway or intubation Having preoperative airway or intubation

problemsproblems• Awake intubation or intubation taking more Awake intubation or intubation taking more

than 20sec or requiring second attempt are than 20sec or requiring second attempt are excludedexcluded

GROUPSGROUPS GROUP A : 15 patients receiving IV Normal GROUP A : 15 patients receiving IV Normal

saline (Placebo) prior to induction (Control)saline (Placebo) prior to induction (Control)

GROUP B : 15 patients receiving Inj. Labetalol GROUP B : 15 patients receiving Inj. Labetalol 0.25mg/kg prior to induction0.25mg/kg prior to induction

GROUP C : 15 patients receiving Inj. Labetalol GROUP C : 15 patients receiving Inj. Labetalol 0.5 mg/kg prior to induction0.5 mg/kg prior to induction

MONITORINGMONITORING

Pulse oximetryPulse oximetry

NIBPNIBP

ECGECG

METHODOLOGYMETHODOLOGY 45 patients randomized into three groups of 15 45 patients randomized into three groups of 15

eacheach Premedication: Given i.m 45 min prior to surgeryPremedication: Given i.m 45 min prior to surgery

Inj. Glycopyrrolate 10ug/kg Inj. Glycopyrrolate 10ug/kg Inj. Pentazocine 0.5mg /kg Inj. Pentazocine 0.5mg /kg

Preoxygenation : 100% O2 for 5 minPreoxygenation : 100% O2 for 5 min Inj Labetalol/ Normal saline given iv 5 min prior Inj Labetalol/ Normal saline given iv 5 min prior

to inductionto induction Induction : Inj.Propofol 2mg/kg ivInduction : Inj.Propofol 2mg/kg iv

NDMR – Inj Rocuronium 0.9mg/Kg NDMR – Inj Rocuronium 0.9mg/Kg iv iv

Patient ventilated with 100% OPatient ventilated with 100% O22 for for 3 min3 min

Intubated with appropriate size ET Intubated with appropriate size ET tubetube

Maintained with O2 : N2O – 1:2Maintained with O2 : N2O – 1:2 Volatile inhalational agents used Volatile inhalational agents used

only 10min after intubationonly 10min after intubation

Pulse rate & NIBP were recorded:Pulse rate & NIBP were recorded: PreoperativelyPreoperatively 45 min after premedication 45 min after premedication In the operating table before IV In the operating table before IV

Labetalol/Normal salineLabetalol/Normal saline For every min after IV Labetalol/Normal For every min after IV Labetalol/Normal

saline for 5 minsaline for 5 min After InductionAfter Induction After giving NDMRAfter giving NDMR At laryngoscopyAt laryngoscopy For every 1 min after Endotracheal For every 1 min after Endotracheal

intubation for 10minintubation for 10min

Labetalol — Labetalol — MechanismMechanismLabetalol — Labetalol — MechanismMechanism

Competitive, selective Competitive, selective 11 and non-selective and non-selective -blocker-blocker > > blocking potency oral is blocking potency oral is

3:1, iv is 7:1 3:1, iv is 7:1 It has intrinisic partial B2 It has intrinisic partial B2

agonistic activity hence causes agonistic activity hence causes vasodilationvasodilation

Onset: 5-10 minOnset: 5-10 min Duration of action: 3-6hrsDuration of action: 3-6hrs T1/2 – 5-8hrsT1/2 – 5-8hrs

Competitive, selective Competitive, selective 11 and non-selective and non-selective -blocker-blocker > > blocking potency oral is blocking potency oral is

3:1, iv is 7:1 3:1, iv is 7:1 It has intrinisic partial B2 It has intrinisic partial B2

agonistic activity hence causes agonistic activity hence causes vasodilationvasodilation

Onset: 5-10 minOnset: 5-10 min Duration of action: 3-6hrsDuration of action: 3-6hrs T1/2 – 5-8hrsT1/2 – 5-8hrs

CVS Effects CVS Effects Decrease SVR leading to decrease in BP is by Decrease SVR leading to decrease in BP is by

alpha -1 blockade alpha -1 blockade Vasodilation also produced by partial B2 Vasodilation also produced by partial B2

agonist activityagonist activity Reflex tachycardia due to peripheral Reflex tachycardia due to peripheral

vasodilation is attenuated by B blockadevasodilation is attenuated by B blockade Cardiac output remains unchangedCardiac output remains unchanged Presynaptic alpha-2 receptors are spared- Presynaptic alpha-2 receptors are spared-

hence release of Norepinephrine is intact, hence release of Norepinephrine is intact, which inhibits further release of catecholamine which inhibits further release of catecholamine (Neg feedback mech) (Neg feedback mech)

Adverse effectsAdverse effects

Orthostatic hypotensionOrthostatic hypotension BronchospasmBronchospasm Others- CCF, bradycardia, Heart Others- CCF, bradycardia, Heart

blockblock Increased plasma aminotransferaseIncreased plasma aminotransferase Paresthesia – scalp tinglingParesthesia – scalp tingling Urinary retentionUrinary retention

STATISTICAL ANALYSISSTATISTICAL ANALYSIS

STATISTICAL TEST STATISTICAL TEST USEDUSED

ANOVA testANOVA test F testF test If significance is there, then If significance is there, then

subjected to Post Hoc Testsubjected to Post Hoc Test

ANALYSIS OF AGE ANALYSIS OF AGE AMONG THE GROUPSAMONG THE GROUPS

P value = 0.834, which is not significantP value = 0.834, which is not significant

AGE

95% Confidence Interval for Mean

Group N Mean Std. Deviation

Std. Error

Lower Bound

Upper Bound

A 15 38.47 11.556 2.984 32.07 44.87

B 15 36.00 11.091 2.864 29.86 42.14

C 15 37.87 12.293 3.174 31.06 44.67

COMPARISON OF PREOP COMPARISON OF PREOP HEART RATE AMONG THE HEART RATE AMONG THE

GROUPSGROUPS

PRE OP HR

95% Confidence Interval for

Mean

N Mean Std. Deviation Std. Error Lower Bound Upper Bound

A 15 85.87 12.677 3.273 78.85 92.89

B 15 86.87 8.823 2.278 81.98 91.75

C 15 85.13 11.250 2.905 78.90 91.36

P=0.911 , NOT SIGNIFICANT

COMPARISON OF PREOP COMPARISON OF PREOP SYSTOLIC BP AMONG THE SYSTOLIC BP AMONG THE

GROUPSGROUPS

PRE OP SBP


N Mean Std. Deviation

Std. Error

Lower Bound

Upper Bound

A 15 120.47 8.442 2.180 115.79 125.14

B 15 124.40 12.933 3.339 117.24 131.56

C 15 124.67 13.911 3.592 116.96 132.37


COMPARISON OF PREOP COMPARISON OF PREOP DIASTOLIC BP AMONG THE DIASTOLIC BP AMONG THE

GROUPSGROUPS

PRE OP DBP



Std. Error

Lower Bound

Upper Bound

A 15 79.33 6.287 1.623 75.85 82.81

B 15 80.13 8.684 2.242 75.32 84.94

C 15 82.87 7.717 1.993 78.59 87.14


COMPARISON OF HR AFTER COMPARISON OF HR AFTER 5MIN OF LABETALOL IV5MIN OF LABETALOL IV

5 MINUTES STUDY HR

95% Confidence

Interval for Mean

N MeanStd.

Deviation

Std. Error

Lower Bound

Upper Bound

A 15 87.47 13.799 3.563 79.83 95.11

B 15 81.67 12.793 3.303 74.58 88.75

C 15 81.20 13.497 3.485 73.73 88.67


COMPARISON OF SYSTOLIC COMPARISON OF SYSTOLIC BP AFTER 5MIN OF BP AFTER 5MIN OF

LABETALOL IVLABETALOL IV

5 MINUTES STUDY SBP

95% Confidence

Interval for Mean


Std. Error

Lower Bound

Upper Bound

A 15 121.47 8.782 2.268 116.60 126.33

B 15 122.00 12.012 3.101 115.35 128.65

C 15 122.13 12.432 3.210 115.25 129.02


COMPARISON OF DIASTOLIC COMPARISON OF DIASTOLIC BP AFTER 5MIN OF BP AFTER 5MIN OF

LABETALOL IVLABETALOL IV 5 MINUTE STUDY DBP

95% Confidence

Interval for Mean

N MeanStd.

Deviation

Std. Error

Lower Bound

Upper Bound

A 15 79.27 6.076 1.569 75.90 82.63

B 15 73.40 9.635 2.488 68.06 78.74

C 15 71.80 9.445 2.180 66.12 76.48

P=0.105, NOT SIGNIFICANT

COMPARISON OF HEART COMPARISON OF HEART RATE AT LARYNGOSCOPYRATE AT LARYNGOSCOPY

HR AT SCOPY



A 15 109.00 13.810 3.566 101.35 116.65

B 15 89.33 13.839 3.573 81.67 97.00

C 15 88.13 14.272 3.685 80.23 96.04

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)

COMPARISON OF HEART COMPARISON OF HEART RATE AT 1 MIN AFTER RATE AT 1 MIN AFTER

INTUBATIONINTUBATION SCOPY OF 1 MINUTE HR



A 15 104.00 11.946 3.085 97.38 110.62

B 15 87.20 13.262 3.424 79.86 94.54

C 15 86.27 15.285 3.947 77.80 94.73

P=0.001, SIGNIFICANT



INTUBATIONINTUBATION

SCOPY OF 3 MINUTES HR



A 15 96.67 11.592 2.993 90.25 103.09

B 15 83.13 13.081 3.378 75.89 90.38

C 15 83.07 13.488 3.483 75.60 90.54




INTUBATIONINTUBATION SCOPY OF 5 MINUTES HR



A 15 92.93 11.985 3.094 86.30 99.57

B 15 81.93 12.981 3.352 74.74 89.12

C 15 80.93 12.355 3.190 74.09 87.78

P=0.02, SIGNIFICANT






SCOPY OF 10 MINUTES HR



A 15 90.40 12.385 3.198 83.54 97.26

B 15 80.27 11.139 2.876 74.10 86.43

C 15 79.20 11.639 3.005 72.75 85.65

COMPARISON OF COMPARISON OF SYSTOLIC BP AT SYSTOLIC BP AT LARYNGOSCOPYLARYNGOSCOPY

SBP AT LARYNGOSCOPY



A 15 143.47 10.148 2.620 137.85 149.09

B 15 139.07 14.709 3.798 130.92 147.21

C 15 134.00 16.248 4.195 125.00 143.00


COMPARISON OF SYSTOLIC COMPARISON OF SYSTOLIC BP AT 1 MIN AFTER BP AT 1 MIN AFTER


SCOPY 1 MINUTES SBP



A 15 137.07 6.006 1.551 133.74 140.39

B 15 134.07 14.782 3.817 125.88 142.25

C 15 128.60 16.137 4.167 119.66 137.54




SCOPY 3 MINUTES SBP



A 15 130.07 4.448 1.148 127.60 132.53

B 15 125.20 15.232 3.933 116.76 133.64

C 15 122.07 13.614 3.515 114.53 129.61




SCOPY 5 MINUTES SBP



A 15 128.47 4.470 1.154 125.99 130.94

B 15 122.07 12.881 3.326 114.93 129.20

C 15 117.53 11.667 3.012 111.07 123.99




SCOPY 10 MINUTES SBP



A 15 126.60 5.356 1.383 123.63 129.57

B 15 121.07 13.123 3.388 113.80 128.33

C 15 117.20 11.162 2.882 111.02 123.38


COMPARISON OF COMPARISON OF DIASTOLIC BP AT DIASTOLIC BP AT LARYNGOSCOPYLARYNGOSCOPY

DBP AT LARYNGOSCOPY



A 15 92.40 7.908 2.042 88.02 96.78

B 15 85.27 12.959 3.346 78.09 88.44

C 15 83.87 9.970 2.574 76.35 87.39

P=0.039 , SIGNIFICANT

COMPARISON OF DIASTOLIC COMPARISON OF DIASTOLIC BP AT 1 MIN AFTER BP AT 1 MIN AFTER


SCOPY 1 MINUTES DBP



A 15 88.67 6.377 1.647 85.14 92.20

B 15 80.33 11.437 2.953 74.00 86.67

C 15 80.65 9.453 2.441 76.70 85.17




SCOPY 3 MINUTES DBP



A 15 84.80 6.472 1.671 81.22 88.38

B 15 77.27 11.455 2.958 70.92 83.61

C 15 78.93 9.869 2.032 73.58 83.29




SCOPY 5 MINUTES DBP



A 15 82.40 5.816 1.502 79.18 85.62

B 15 74.40 10.782 2.784 68.43 80.37

C 15 71.87 8.624 1.968 67.64 76.09




SCOPY 10 MINUTES DBP



A 15 80.87 6.739 1.740 77.13 84.60

B 15 72.47 10.501 2.711 66.65 78.28

C 15 71.60 9.152 2.105 65.29 76.31


CONCLUSIONCONCLUSION

Heart Rate: Heart Rate: Preinduction iv labetalol decreased the heart Preinduction iv labetalol decreased the heart

rate prior to induction in the Labetalol groups rate prior to induction in the Labetalol groups (decrease in Group C>Group B>Group A) at 5 (decrease in Group C>Group B>Group A) at 5 min after labetalol injection. But it is not min after labetalol injection. But it is not statistically significantstatistically significant

Attenuation of heart rate at Laryngoscopy, at Attenuation of heart rate at Laryngoscopy, at 1min, 3min, 5min, 7min & 10min after 1min, 3min, 5min, 7min & 10min after intubation (decrease in Group C>Group intubation (decrease in Group C>Group B>Group A) is statistically significant.B>Group A) is statistically significant.

Preop HR was achieved at 1 min after intubationPreop HR was achieved at 1 min after intubation

HEART RATEHEART RATEANOVA

F Sig.

SCOPY (0 MINUTE) HR Between Groups 10.543 .000

SCOPY OF 1 MINUTE HR Between Groups 8.116 .001

SCOPY OF 3 MINUTES HR Between Groups 5.664 .007





Systolic BP: Systolic BP: Preinduction iv labetalol had no change in Preinduction iv labetalol had no change in

the systolic BP prior to induction in the the systolic BP prior to induction in the Labetalol groups at 5 min after labetalol Labetalol groups at 5 min after labetalol injection. injection.

Attenuation of Systolic BP at Laryngoscopy, Attenuation of Systolic BP at Laryngoscopy, at 1min, 3min, 7min & 10min after at 1min, 3min, 7min & 10min after intubation is not statistically significant intubation is not statistically significant (decrease in Group C>Group B>Group A)(decrease in Group C>Group B>Group A)

Preop systolic BP value was reached 3-5min Preop systolic BP value was reached 3-5min after intubationafter intubation

SYSTOLIC BPSYSTOLIC BPANOVA

F Sig.

SCOPY 0 MINUTES SBP Between Groups 1.731 .189







Diastolic BP: Diastolic BP: Preinduction iv labetalol decreased the diastolic Preinduction iv labetalol decreased the diastolic

BP prior to induction in the Labetalol groups BP prior to induction in the Labetalol groups (decrease in Group C>Group B>Group A) at 5 (decrease in Group C>Group B>Group A) at 5 min after labetalol injection. But it is not min after labetalol injection. But it is not statistically significantstatistically significant

Attenuation of Diastolic BP at Laryngoscopy, at Attenuation of Diastolic BP at Laryngoscopy, at 1min, 5min, 7min & 10min after intubation is 1min, 5min, 7min & 10min after intubation is statistically significant (decrease in Group statistically significant (decrease in Group C>Group B>Group A)C>Group B>Group A)

Preop diastolic BP was reached 2-3min after Preop diastolic BP was reached 2-3min after intubationintubation

DIASTOLIC BPDIASTOLIC BPANOVA

F Sig.

SCOPY 0 MINUTE DBP Between Groups 2.154 .039

SCOPY 1 MINUTES DBP Between Groups 4.126 .023





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

PREINDUCTION INTRAVENOUS LABETALOL FOR ATTENUATING INTUBATION STRESS RESPONSE

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