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EVALUATION OF EFFICACY OF INTRAVENOUS
DEXMEDETOMIDINE IN POST OPERATIVE CARE OF CARDIAC
SURGERY PATIENTS- A PROSPECTIVE STUDY.
BY
MAJ (Dr.) SHISHIR KUMAR
SYNOPSIS FOR REGISTRATION OF SUBJECT FOR DISSERTATION
TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
IN PARTIAL FULFILLMENT OF REGULATIONS FOR THE
AWARD OF
DOCTOR OF MEDICINE
IN
ANAESTHESIOLOGY
DEPARTMENT OF ANAESTHESIOLOGY
COMMAND HOSPITAL (AIR FORCE), BANGALORE – 560 007
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
RAJIV GANDHI UNIVERSITY OF HEALTH
SCIENCES
SYNOPSIS
DISSERTATION TOPIC
EVALUATION OF EFFICACY OF INTRAVENOUS
DEXMEDETOMIDINE IN POST OPERATIVE CARE OF CARDIAC
SURGERY PATIENTS- A PROSPECTIVE STUDY.
By
MAJ (Dr.) SHISHIR KUMAR
PG student (Anaesthesiology)
Command Hospital (Air Force),
Bangalore.
Course
2013-2016
Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka.
Annexure-A
1.Name of candidate :Maj (Dr.) Shishir Kumar
2. Name of Institution :Command Hospital (Air Force), Bangalore
3. Course of study and subject :M.D. (Anaesthesiology)
4. Date of admission :Jul 2013
5. Title Of Topic :Evaluation Of Efficacy Of Intravenous Dexmedetomidine In Post-Operative Care Of Cardiac Surgery Patients- A Prospective Study.
6. Brief resume of intended work Need for the study : APPENDIX ‘A’ Objective of study : APPENDIX ‘B’ Review of literature : APPENDIX ‘C’
7. Material and Methods : APPENDIX 'D' Source of data : APPENDIX ‘D’ Method of collection of data : APPENDIX ‘D’ 8. Does the study require any investigation and interventions to be conducted on patients or other animals? : YES/NO Has ethical clearance been obtained from your institution? : YES/NO
9 . Patient Performa : APPENDIX ‘E’ 10. Statistical Analysis : APPENDIX ’F’11. List Of References : APPENDIX ‘G’12. Patient Consent Form : APPENDIX ‘H’13. Study Information Sheet : APPENDIX ‘I’
14. Signature Of Candidate
15. Remarks of guide An interesting study which will highlight the efficacy of intra-venous Dexmedetomidine in cardiac surgery patients.
16. Name and designations
Guide Gp Capt (Dr.) Sachin ShoucheSenior Advisor & Cardiac AnaesthesiologistDept of Anaesthesiology
& Critical CareCommand Hospital (Air Force)
Bangalore Signature
17. Head of the Department Col (Dr.) K Prabhakaran Senior Advisor & Head of Dept of Anaesthesiology & Critical Care Command Hospital (Air Force) Bangalore
Signature
18. Remarks of the chairman and principal
Signature
Appendix ‘A’ Need for the study
Approximately 7 million invasive cardiovascular procedures are performed
worldwide each year.1 The major complication rates for valve and coronary artery
bypass graft (CABG) procedures are as high as 30.1% in Society of Thoracic
Surgeons (STS) reports.2 Postoperative delirium, infection, acute renal failure, and
major adverse cardio cerebral events (MACEs), which include permanent or
transient stroke, coma, perioperative myocardial infarction (MI), heart block, and
cardiac arrest, represent major postoperative complications.3–5 These complications
translate into increased mortality and prolonged hospital stays with increased
expenditure. The reasons for these adverse events are multifactorial, but a major
contributing factor is the surgical stress response that results in increasing plasma
levels of epinephrine and norepinephrine with consequent myocardial oxygen
supply demand imbalance and myocardial ischemia.6 More than 50% of all
perioperative complications are related to adverse cardiovascular events.7
The α-2 receptor agonists (clonidine, Dexmedetomidine) currently used in clinical
practice have many desirable effects, including analgesia, anxiolysis, inhibition of
central sympathetic outflow, and reduction of systemic norepinephrine release, that
improve hemodynamic stability, positively affect myocardial oxygen supply and
demand, and may provide myocardial protection.8,9. Dexmedetomidine is a highly
selective, shorter-acting intravenous α-2 agonist with an α-2 to alpha-1 selectivity
ratio of 1600:1.10 At our institution, Dexmedetomidine is used for transition of
cardiac surgical patients from the operating room to the intensive care unit (ICU)
and to provide sedation before extubation. Studies evaluating the hemodynamic
stabilizing and sympatholytic effects have shown that α-2 agonists can potentially
reduce postoperative cardiovascular complications. These include studies of
clonidine in cardiac surgery patients and dexmedetomidine in vascular and
noncardiac surgery patients.11-14 Multiple studies have reported that
dexmedetomidine has a protective effect on specific organs, including the heart,
brain, kidney, and lungs.15-19 In addition, dexmedetomidine has been shown to have
anti-inflammatory properties, decreasing mortality and attenuating plasma cytokine
concentrations in laboratory animals exposed to endotoxin in a dose-dependent
fashion.20 Therefore, this study will examine the potential impact of
dexmedetomidine on other major end points such as hemodynamic stability ,
arousability, congestive heart failure, myocardial ischemia, arrhythmia, stroke,
delirium, infection, and acute renal failure during the postoperative period for
patients undergoing cardiac surgery.
Appendix 'B'
Objectives of study
The objectives of the study are
(i) Primary outcome measures
aa) Hemodynamic stability, mortality and postoperative major adverse
cardio cerebral events (stroke, coma, perioperative myocardial infarction,
heart block, or cardiac arrest).
ii) Secondary outcome measures
aa) To concurrently calculate incidence of renal failure, sepsis, delirium,
postoperative ventilation hours, length of hospital stay, and 30-day
readmission.
Appendix ‘C
Review of literature
Cardiac surgery is associated with a high risk of cardiovascular and
other complications that translate into increased mortality and
healthcare costs. The major complication rates for valve and coronary
artery bypass graft (CABG) procedures are as high as 30.1% in
Society of Thoracic Surgeons (STS) reports.2
Dexmedetomidine is a highly selective, shorter-acting intravenous α-2
agonist with an α-2 to alpha-1 selectivity ratio of 1600:1.10 It is
currently used in clinical practice and has many desirable effects,
including analgesia, anxiolysis, inhibition of central sympathetic
outflow, and reduction of systemic norepinephrine release, that
improve hemodynamic stability, positively affect myocardial oxygen
supply and demand, and may provide myocardial protection.9,10.
Multiple studies have reported that dexmedetomidine has a protective
effect on specific organs, including the heart, brain, kidney, and
lungs.15-19
This study is designed to determine whether the post-operative use of
dexmedetomidine could reduce the incidence of complications and
mortality after cardiac surgery.
Appendix ‘D’
Materials and Methods
The project is a prospective study which will run for Two years. All patients undergoing cardiac surgeries will be selected and admitted to ICU will be monitored
a. Inclusion Criteria i) CABG or valve surgery
ii) CABG or valve surgery combined with other procedures.
b. Exclusion criteria:
i) Patients undergoing emergency surgery
ii) Off-pump surgery
iii) Surgery requiring deep hypothermic circulatory arrest
iv) Surgery involving the thoracic aorta
For these surgical patients, after standard monitoring, general anesthesia will be administered with Midazolam as pre medication, induction with Fentanyl (2 µg/kg) along with Thiopentone/Etomidate, skeletal muscle relaxation with Rocuronium and maintained with oxygen and sevoflurane according to the patient’s hemodynamic responses. Ventilation will be controlled to an end-tidal CO2 of 35 to 45 mm Hg by adjustment of tidal volume and respiratory rate. Monitoring in form of invasive intra-arterial BP, Pulmonary arterial occlusive pressure (only in CABG patients), CVP (all valve surgeries), transesophageal echocardiography, cardiac output monitoring by Flowtrac will be used as indicated in valve repair surgeries and patients with poor LV function respectively.
Post-operative Dexmedetomidine use is defined as an intravenous infusion (0.24 to 0.5 μg·kg−1·h−1) initiated without loading dose after cardio- pulmonary bypass before sternal closure titrated to conscious sedation and continued for <24 hours postoperatively till 15 minutes post-extubation in the ICU. The infusion rate of Dexmedetomidine will be adjusted according to the manufacturer’s package insert and in response to the patients’ hemodynamic changes in response to stimulation.
Appendix ‘E’
Patient Proforma
Pt Name:…………………………..Age/Sex……………….Wt……….....................Sr. No……
Diagnosis……………………………………………………………………………………………
ASA …………………………………………………………………………………………….…
MONITORS:
TIME
(hhmm)
TEMP
(0F)
PULSE
(/min)
RR
(/min)
IBP
(mm
Hg)
PAOP
(mm
Hg)
SPO2
(%)
CVP
(cm H2O)
DEXEMEDOTI
MIDINE
DOSE (mcg/kg/h)
VENTIATOR SETTINGS:
TIME
(HHMM)
MODE FiO2 (%) RATE
(/min)
P SUPPORT/CPAP
(cm of H2O)
VTE (ml)
EXTUBATED AT _______________________________
DEXEMEDOTIMIDINE STOPPED AT ________________________________
EFFECT ON POST-OP COMPLICATIONS AND MORTALITY:
COMPLICATIONS YES NO
PERI-OP MI
CARDIAC ARREST REQUIRING
PHARMACOLOGICAL INTERVENTION
HEART BLOCK
SIGNIFICANT HYPOTENSION REQUIRING
PHARMACOLOGICAL INTERVENTION
SIGNIFICANT BRADYCARDIA REQUIRING
PHARMACOLOGICAL INTERVENTION
RESPIRATORY DEPRESSION REQUIRING
VENTILATORY SUPPORT (INVASIVE/ NON
INVASIVE)
STROKE
COMA
DELIRIUM
SEPSIS
POST-OP RF
POST-OP DIALYSIS
30 DAY RE-ADM
IN HOSP MORTALITY
MORTALITY WITHIN 30 DAYS
Appendix ‘F’
Statistical analysis
Statistical analysis will be done using student–t test, Chi-square test.
Statistical significance is assumed for P<0.05.
Appendix ‘G’
References
1. Patel MR, Jneid H, Derdeyn CP, Klein LW, Levine GN, Lookstein RA,
White CJ, Yeghiazarians Y, Rosenfield K; American Heart Association
Diagnostic and Interventional Cardiac Catheterization Committee of the
Council on Clinical Cardiology, Council on Cardiovascular Radiology and
Intervention, Council on Peripheral Vascular Disease, Council on
Cardiovascular Surgery and Anesthesia, and Stroke Council. Arteriotomy
closure devices for cardiovascular procedures: a scientific statement from
the American Heart Association. Circulation. 2010;122:1882–1893.
2. Shahian DM, O’Brien SM, Filardo G, Ferraris VA, Haan CK, Rich JB,
Normand SL, DeLong ER, Shewan CM, Dokholyan RS, Peterson ED,
Edwards FH, Anderson RP; Society of Thoracic Surgeons Quality
Measurement Task Force. The Society of Thoracic Surgeons 2008 cardiac
surgery risk models, part 3: valve plus coronary artery bypass grafting
surgery. Ann Thorac Surg. 2009;88(suppl):S43–S62.
3. Mangano DT, Browner WS, Hollenberg M, London MJ, Tubau JF, Tateo
IM. Association of perioperative myocardial ischemia with cardiac
morbidity and mortality in men undergoing noncardiac surgery: the Study of
Perioperative Ischemia Research Group. N Engl J Med. 1990;323:1781–
1788.
4. Mangano DT. Perioperative cardiac morbidity. Anesthesiology.
1990;72:153–184.
5. Cao L, Young N, Liu H, Silvestry S, Sun W, Zhao N, Diehl J, Sun J.
Preoperative aspirin use and outcomes in cardiac surgery patients. Ann Surg.
2012;255:399–404.
6. Halter JB, Pflug AE, Porte D Jr. Mechanism of plasma catecholamine
increases during surgical stress in man. J Clin Endocrinol Metab. 1977;45:936–
944.
7. Dawood MM, Gutpa DK, Southern J, Walia A, Atkinson JB, Eagle KA.
Pathology of fatal perioperative myocardial infarction: implications regarding
pathophysiology and prevention. Int J Cardiol. 1996;57:37–44.
8. Muzi M, Goff DR, Kampine JP, Roerig DL, Ebert TJ. Clonidine reduces
sympathetic activity but maintains baroreflex responses in normotensive humans.
Anesthesiology. 1992;77:864–871.
9. Ellis JE, Drijvers G, Pedlow S, Laff SP, Sorrentino MJ, Foss JF, Shah M,
Busse JR, Mantha S, McKinsey JF. Premedication with oral and transder- mal
clonidine provides safe and efficacious postoperative sympatholysis. Anesth
Analg. 1994;79:1133–1140.
10. Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor
agonists: their pharmacology and therapeutic role. Anaesthesia. 1999;54:146–165.
11. Nishina K, Mikawa K, Uesugi T, Obara H, Maekawa M, Kamae I, Nishi N.
Efficacy of clonidine for prevention of perioperative myocardial ischemia: a
critical appraisal and meta-analysis of the literature. Anesthesiology. 2002;96:323–
329.
12. Wijeysundera DN, Naik JS, Beattie WS. Alpha-2 adrenergic agonists to
prevent perioperative cardiovascular complications: a meta-analysis. Am J Med.
2003;114:742–752.
13. Biccard BM, Goga S, de Beurs J. Dexmedetomidine and cardiac protec-
tion for non-cardiac surgery: a meta-analysis of randomised controlled tri- als.
Anaesthesia. 2008;63:4–14.
14. Yeh YC, Sun WZ, Ko WJ, Chan WS, Fan SZ, Tsai JC, Lin TY.
Dexmedetomidine prevents alterations of intestinal microcirculation that are
induced by surgical stress and pain in a novel rat model. Anesth Analg.
2012;115:46–53.
15. Wijeysundera DN, Bender JS, Beattie WS. Alpha-2 adrenergic agonists for
the prevention of cardiac complications among patients undergoing surgery
[review]. Cochrane Database Syst Rev. 2009; 7:CD004126.
16. Yang CL, Chen CH, Tsai PS, Wang TY, Huang CJ. Protective effects of
dexmedetomidine-ketamine combination against ventilator-induced lung injury in
endotoxemia rats. J Surg Res. 2011;167:e273–e281.
17. Gu J, Sun P, Zhao H, Watts HR, Sanders RD, Terrando N, Xia P, Maze M,
Ma D. Dexmedetomidine provides renoprotection against ischemia-reper- fusion
injury in mice. Crit Care. 2011;15:R153.
18. Sanders RD, Xu J, Shu Y, Januszewski A, Halder S, Fidalgo A, Sun P,
Hossain M, Ma D, Maze M. Dexmedetomidine attenuates isoflurane- induced
neurocognitive impairment in neonatal rats. Anesthesiology. 2009;110:1077–1085.
19. Okada H, Kurita T, Mochizuki T, Morita K, Sato S. The cardioprotec- tive
effect of dexmedetomidine on global ischaemia in isolated rat hearts.
Resuscitation. 2007;74:538–545.
20. Taniguchi T, Kurita A, Kobayashi K, Yamamoto K, Inaba H. Dose- and
time-related effects of dexmedetomidine on mortality and in- flammatory
responses to endotoxin-induced shock in rats. J Anesth. 2008;22:221–228.
Appendix ‘H’
COMMAND HOSPITAL AIR FORCE, BANGALORE 560007CONSENT FORM
Patient’s name……………………Age…….Rank………………….. Unit………………………………Ward………………………………
I hereby authorize the performance of the following procedures upon myself/my relative (name of the patient ………………………………)- Administration of intravenous Dexmedotimidine in cardiac surgery.
The kind of procedure to be performed has been fully explained to me and all my questions and doubts about the procedure have been cleared to my satisfaction. All the risks involved have been explained to me and I understand those risks and I accept them.
I understand that the procedure and the medication have their own advantages and disadvantages and each is associated with its own share of risks. I understand that all due care will be taken during the above said procedure.
I understand that though best efforts will be put into the present condition no guarantee of the outcome can be given.
I agree to cooperate fully with my doctor and to follow the instructions to best of my ability.
This consent to be of my own free act of will
Signature of Witness Signature of patient/NOK
Appendix ‘I’
Study Information Sheet for Patients/NOK
Title: Evaluation Of Efficacy Of Intravenous Dexmedetomidine In Post-
Operative Care Of Cardiac Surgery Patients- A Prospective Study.
Investigator: Maj Shishir Kumar
Dear Sir/Madam
You/your relation are suffering from an illness which requires invasive
surgery and further medical management for cardiac hemodynamic stability.
The method proposed in this study is administration of intravenous
dexmedetomidine for conscious sedation and management until extubation.
Multiple studies have reported that dexmedetomidine has a protective effect
on specific organs, including the heart, brain, kidney, and lungs.
We seek your consent to participate in this study.
Alternative to participation:
The patient is free not to participate in the study. If the patient chooses not to
participate in the study he will not be administered dexmedetomidine.
Confidentiality
All information that will be provided during the study will be kept
confidential.
Contacts
If you have any further questions, any time during the course of the study
you can contact the following
Maj Shishir Kumar
Resident
Dept. of Anaesthesiology and Critical Care
Command Hospital Air force
Bangalore 560007
Gp Capt Sachin Shouche
Senior Advisor & Cardiac Anaesthetist
Dept. of Anaesthesiology and Critical Care
Command Hospital Air force
Bangalore 560007
CERTIFICATE FROM THE HEAD OF THE INSTITUTION
Permission is hereby accorded to the student Maj (Dr.) Shishir Kumar, to
undergo MD (Anaesthesiology) course being conducted at Command Hospital (Air
Force) Bangalore affiliated to the Rajiv Gandhi University of Health Sciences
commencing from Jul 2013 under the guidance of Gp Capt (Dr.) Sachin Shouche
(Senior Advisor & Cardiac Anaesthesiologist), Dept of Anaesthesiology,
Command Hospital (Air Force) Bangalore.
Date: (R Bhalwar)
Air Vice Marshal
Commandant and Principal
Command Hospital, Air Force
Bangalore – 560007
CERTIFICATE FROM ETHICAL COMMITTEE
1. The committee has examined the scope including the need, objectives, methods
and human /animal interventions and the follow-up study to be carried out by Maj
(Dr.) Shishir Kumar, MD student (Anesthesiology) under guidance of Gp Capt
Sachin Shouche, the title of which is Evaluation Of Efficacy Of Intravenous
Dexmedetomidine In Post-Operative Care Of Cardiac Surgery Patients- A
Prospective Study.
2. The committee has no objections for undertaking this study at Command
Hospital (Air Force) Bangalore.
(MS Prakash) (SC Dash) (SK Jha) (H Sahni)Brig Col Col Gp Capt Prof and HOD Prof and HOD OIC OICDept of medicine Dept of Surgery PG Cell AFMRCMember Member Member Member Secretary
(S Kaistha) (Shalini chaudhary) (Dr.V.Sinha) (Mrs.Vasanta kishore) Wg Cdr Sqn Ldr Scientist Counsellor Rep of AFWWA OIC, Legal Cell Physiologist E-Support Member Member Member Member
(MK Bedi) Air Cmde AOC, MTC Chairman Ethical Committee Command Hospital (Air Force) Bangalore- 560007
CERTIFICATE OF ACCEPTANCE BY THE GUIDE
1. I, Gp Capt Sachin Shouche, hereby accept Maj Shishir Kumar as a
candidate of MD (Anesthesiology) course. The title of his dissertation is as
follows:-
“ Evaluation Of Efficacy Of Intravenous Dexmedetomidine In Post-
Operative Care Of Cardiac Surgery Patients- A Prospective Study.”
2. He will be under my guidance during the period of his study and thesis
work.
Date: Gp Capt (Dr.) Sachin Shouche
Senior Advisor & Cardiac Anesthesiologist
Dept of Anesthesiology &
Critical Care
Command Hospital Air Force
Bangalore 560007