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FFECTIVENESS OF DEXMEDITOMIDINE LOADING AND MAINTENANCE DOSE IN ATTENUATION OF HAEMODYNAMIC STRESS RESPONSE
DURING LAPAROSCOPIC SURGERIES”
Dissertation submitted to the
THE TAMIL NADU DR.M.G.R. MEDICAL UNIVERSITY In partial fulfilment of the regulations for the award of the degree of
DOCTOR OF MEDICINE In
M.D.ANAESTHESIOLOGY- BRANCH X
DEPARTMENT OF ANAESTHESIOLOGY
GOVERNMENT VELLORE MEDICAL COLLEGE AND HOSPITAL
THE TAMILNADU DR.M.G.R MEDICAL UNIVERSITY CHENNAI
APRIL 2020
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ENDORSEMENT BY THE DEAN/
THE HEAD OF THE INSTITUTION
This is to certify that the dissertation titled “EFFECTIVENESS OF DEXMEDITOMIDINE LOADING AND MAINTENANCE DOSE IN ATTENUATION OF HAEMODYNAMIC STRESS RESPONSE DURING LAPAROSCOPIC SURGERIES” is a genuine work done by
DR.DINESH.M.K., Reg.No. 201720802 Post Graduate student (2017 – 2020) in the Department of Anaesthesiology, Government Vellore Medical College, Vellore under the guidance of Prof. Dr. M.GOMATHI MD., Professor and Head of the Department of Anaesthesiology, Government Vellore Medical college , Vellore in partial fulfilment of the regulations of Tamil Nadu Dr.M.G.R Medical University, Chennai. I forward this to the Tamil Nadu Dr.M.G.R Medical University, Chennai Tamil Nadu, India.
Prof. Dr. R. SELVI, M.D., The Dean,
Government Vellore Medical College, Vellore - 632011.
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CERTIFICATE BY THE HEAD OF DEPARTMENT
This is to certify that dissertation entitled “EFFECTIVENESS OF
DEXMEDITOMIDINE LOADING AND MAINTENANCE DOSE IN ATTENUATION OF HAEMODYNAMIC STRESS RESPONSE DURING LAPAROSCOPIC SURGERIES” is a bonafide research work done by
DR.DINESH.M.K., in the Department of Anaesthesiology, Government Vellore Medical College, Vellore under partial fulfilment of the regulations of The Tamil Nadu Dr.M.G.R Medical University for the degree of M.D. in Anaesthesiology.
Prof. Dr. GOMATHI, M.D., Professor& HOD,
Department of Anaesthesiology, Govt. Vellore Medical College, Vellore.
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BONAFIDE CERTIFICATE
This is to certify that the dissertation named entitled “EFFECTIVENESS OF DEXMEDITOMIDINE LOADING AND MAINTENANCE DOSE IN ATTENUATION OF HAEMODYNAMIC STRESS RESPONSE DURING
LAPAROSCOPIC SURGERIES” is a bonafide work performed by Dr.DINESH.M.K.
postgraduate student, Department of Anaesthesiology, Govt. Vellore Medical college with registration number 201720802 under my guidance and supervision in partial
fulfilment of regulations of The Tamil Nadu Dr. M.G.R Medical University for the award of M.D. Degree during the academic year 2017 -2020.
GUIDE: CO-GUIDE:
Dr.GOMATHI ,MD., Dr.G.DEEPA,,MD.,
Professor of Anaesthesiology, Assistant Professor of Anaesthesiology, Govt. Vellore Medical College, Govt. Vellore Medical College,
Vellore. Vellore.
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CERTIFICATE – II
This is to certify that this dissertation work titled“EFFECTIVENESS OF DEXMEDITOMIDINE LOADING AND MAINTENANCE DOSE IN ATTENUATION OF HAEMODYNAMIC STRESS RESPONSE DURING LAPAROSCOPIC SURGERIES” of the candidate DR.DINESH.M.K. with registration Number: 201720802 for the award of M.D. DEGREE in the branch of
ANAESTHESIOLOGY. I personally verified the urkund.com website for the purpose of plagiarism Check. I found that the uploaded thesis file contains from introduction to conclusion pages and result shows 7% percentage of plagiarism in the dissertation.
Guide & Supervisor sign with Seal
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DECLARATION
I, DR.DINESH.M.K., Reg. No: 201720802 solemnly declare that this dissertation titled
“EFFECTIVENESS OF DEXMEDITOMIDINE LOADING AND
MAINTENANCE DOSE IN ATTENUATION OF HAEMODYNAMIC STRESS RESPONSE DURING LAPAROSCOPIC SURGERIES” is a bonafide work done by me in the Department of Anaesthesiology, Government Vellore Medical College and Hospital, Vellore under the guidance and supervision of Prof.Dr.M.GOMATHI ,M.D.
This dissertation is submitted to the Tamil Nadu Dr. M.G.R. Medical University, Chennai in partial fulfilment of the university regulation for the award of M.D., Degree in Anaesthesiology (Branch – X).
Place : Vellore DR. DINESH.M.K
Date: MD Postgraduate Student,
Department of Anaesthesiology, Govt. Vellore Medical College, Vellore.
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TABLE OF CONTENTS
S.NO. TITLE PAGE NO.
1. INTRODUCTION 10
2. AIM AND OBJECTIVES OF THE STUDY 12 3. LAPROSOPIC SURGERY-PHYSIOLOGY
AND SPECIAL CONSIDERATIONS
13 4. STRESS RESPONSE AND SURGERIES 19 5. VIRTUES OF A LAPAROSCOPIC
SURGERIES
23 6. ROLE OF ALPHA-2 ADRENO
RECEPTORS
25 7. DEXMEDETOMIDINE-PHARMACOLOGY 28 8. REVIEW OF LITERATURE 35 9. METHODOLOGY AND METHODS 41 10. OBSERVATION AND RESULT 46
11. DISCUSSION 71
12. SUMMARY 73
13. CONCLUSION 74
14. REFERENCES 75
15. CONSENT FORM 88
16. PLIAGARISM CERTIFICATE 90
17. MASTER CHART 95
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ABBREVATIONS
• PNS -PERIPHERAL NEREVOUS SYSTEM
• CNS-CENTRAL NERVOUS SYSTEM
• ICT-INTRACRANIAL TENSION
• CCF-CONGESTIVE HEART FAILURE
• S.C – SUBCUTANOEOUS
• TEE-TRANS ESOPHAGEAL ECHO
• CVP -CENTRAL VENOUS PRESSURE
• PAP -PULMONARY ARTERY
• ETT-ENDO TRACHEAL TUBE
• PCA- PATIENT CONTROLLED ANALGESIA
• COX-2-CYCLOOXYGENASE-2
• PG -PROSTAGLANDINS
• NSAIDS-NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
• CAMP -CYCLIC ADENOSINE MONOPHOSPHATE
• PACU-POST ANAESTHESIA CARE UNIT
• ACTH-ADRENO CORTICOTROPHIC HORMONE
• SBP-SYSTOLIC BLOOD PRESSURE
• DBP-DIASOTOLIC BLOOD PRESSURE
• MAP-MEAN ARTERIAL BLOOD PRESSURE
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INTRODUCTION
In this new era of growing trends toward minimally invasive and minimal scar surgeries.
abdominal procedures e.g.: hernia, cholecystectomy etc. are most commonly done through laparoscopy even in small centers.faster recovery, avoidance of big surgical incision, less tissue trauma, hospital stay time reduction with consequent reduction in economic burden has made Laparoscopic surgeries popular(1) although in normal patients it has high safety margin.it is safer not in a patient with cardiac or respiratory comorbidity.it comes at a cost of risking or affecting normal homeostatic systems through a variety of effects induced by use of pneumoperitoneum, leading to alterations in
cardiovascular, lung physiology and stress response. a series of endocrinal,
immunological, and hematological effects occurs due to a result of stress response(2).
Drugs common in use are of opioids, alpha 2 agonist, beta blockers etc. for reducing stress response induced by pneumoperitoneum. Fentanyl, a narcotic drug which acts on
‘mu’ opioid receptor Responsible for analgesia and sedation) and its principal site of action is CNS.
It is most often used in the operating room and sometimes in the ICU for anaesthetics and analgesics implications. (3)
the alpha‑2 agonists modulate sympathetic nervous system by reducing the sympatho- adrenal and cardiovascular response produced by surgical stimuli thereby inhibiting stress response.
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clonidine is α2 agonist and has the property of sympatholytic, dexmedetomidine is more specific for α2 receptors when compared to it(4) and its Alpha 2 sensitivity is 8 times that of alpha 1. Research on stress response during laparoscopic procedures has been minimal.
In experienced hands, laparoscopic procedures could last for maximum of 4 hours.
Evidence has been found to associate prolonged laparoscopic procedures with increased stress responses. Dexmedetomidine limits the release of renin and thus provides
hemodynamic stability(5–7). Dexmedetomidine has been shown to decrease the levels of cortisol This study was designed in a prospective, randomized, double-blinded fashion with the primary aim of assessing the stress response by measuring cortisol levels and secondary aims of assessing hemodynamic response and analgesia requirement in first 24 h of postoperative recovery in routine intravenous fentanyl use vs addition of
intravenous dexmedetomidine loading and maintenance dose in patients undergoing laparoscopic surgery which is laparoscopic cholecystectomy under general anaesthesia.
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AIM AND OBJECTIVES OF THE STUDY
The aim of this study was to compare routine intravenous fentanyl vs addition of intravenous dexmedetomidine loading and maintenance dose to routine use and to study the effectiveness of dexmedetomidine in attenuating the stress response and arterial pressure Increase in patients posted for elective laparoscopic cholecystectomy surgeries.
PRIMARY OBJECTIVE
To compare the effectiveness of dexmedetomidine and routine fentanyl use by determining
1. Serum cortisol levels
2. Hemodynamic stress response like (HR, SBP, DBP, MAP) to maneuvers like a) LARYNGOSCOPY & ENDOTRACHEAL INTUBATION b) CREATION & RELEASE OF PNEUMOPERITONEUM c) EXTUBATION
SECONDARY OBJECTIVE
To determine
1. Post operative pain and sedation using a) Ramsay sedation score b) Visual analogue scale
2. Post op analgesia requirement[cumulative analgesia in 24 hours (in mg) and time for first rescue analgesics requirement (in mins)]
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LAPROSOPIC SURGERY-PHYSIOLOGY AND SPECIAL CONSIDERATIONS The effects unique to laparoscopic surgeries is due to creation of pneumoperitoneum which is done by co2 insufflation to separate organs from abdominal wall. most common employed parameters for insufflation are initial rate of 2-4L/min followed by a constant rate of 200-400ml/min.intrabdominal pressure kept at 12-15mmhg.
In laparoscopic surgeries, intraoperative problems due to creation of pneumoperitoneum can be related to changes in cardiovascular, respiratory, renal, gastrointestinal, metabolic Encountered problems may be due to diminished venous return, reflex tachycardia and arrhythmias. Problems in respiratory system are due to cephalad displaced diaphragm leading to function residual capacity and decrease in lung compliance.
ETCO2 monitoring is mandatory mainly due to hypercarbia that may result from co2 absorption from pneumoperitoneum and this may affect cardiovascular system via direct and indirect effects. Changes include changes in cardiac contractility, tachycardia and reduction in diastolic filling leading to decreased myocardial oxygen supply to demand ratio and may increase the probability of myocardial ischemia. co2 has a rapid pulmonary excretion rate and it is transparent, noninflammable, and well dissolvable in blood so co2 is used in insufflation during laparoscopy.
there is an increase in airway resistance in cardiopulmonary disease patients and in obese patients. Hypoxemia may also occur due to intrapulmonary shunting and atelectasis development.
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Changes due to increased intraabdominal pressure are decrease in renal blood flow and glomerular filtration rate and are due to increase in renal vascular resistance. These changes are more prone to occur when intraabdominal pressure is more than 20mmhg.
SPECIAL CONSIDERATIONS IN LAPAROSCOPIC SURGERIES(8):
other problems which can be encountered can be of significant consideration to both anesthetist and surgeon are changes in respiratory and cardio vascular systems include
I. SUBCUTANEOUS EMPHYSEMA
CLINICAL PRESENTATION: Sudden & swift increase in PETCO 2 and a very pronounced increase in PaCO2(100 mmHg) coincident with SCE in the upper body (face, neck and thorax)(9,10)
MECHANISM:
Direct subdiaphragmatic injury or through infradiaphragamatic as C02 can pass through the diaphragmatic foramina into the mediastinum and from there to the S.C tissue planes of the head and neck (9,11)or along a low resistance conduit from trocar into S.C tissue planes driven by insufflating
pressure. can cause upper airway obstruction by compression(12) MANAGEMENT: I Ruling out the presence of pneumothorax.
2 Increased ventilation to maintain an acceptable PETCO2 and/or PaCO2.
3 Evaluation of the upper airway at procedures end
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4 Reassurance of the patient II. PNEUMOTHORAX
CLINICAL PRESENTATION:
abrupt and marked increase in PETCO2, airway pressure (Paw) and a decrease in dynamic compliance & decreased arterial desaturation (reduced SpO2).(13,14) MECHANISM:
insufflated gas can reach the pleural space through the vena caval orifice in the diaphragm(15–17).
OTHERS INLCUDE pleuro-peritoneal communication in patients with ascites(18), “bare area" formed between two layers of the falciform ligament, if ligament perforated, gas can enter the
Mediastinum(16,19).
MANAGEMENT:
1. The discontinuation of insufflation and release of the pneumoperitoneum.
2. Thoracentesis
3. Hyperventilation to limit the increase in PCO 2
4. use of 5 cm H20 positive end-expiratory pressure (PEEP).
III. CARBON DIOXIDE EMBOLISM:
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CLINICAL PRESENTATION: precipitous reduction in PETCO2, auscultation of a
"mill-wheel" murmur hypotension & desaturation
MECHANISM: due to the high solubility of CO 2 in blood compared with that in air CENTRAL VENOUS PRESSURE AND PULMONARY ARTERY PRESSURE pulmonary artery pressures are markedly increased during laparoscopic surgery in the reverse Trendelenburg position
The "driving" pressure for embolization is the difference between intraabdominal
pressure and intracardiac pressure. That pressure difference will determine the volume of gas introduced into the circulation
MANAGEMENT: TEE is considered the “gold standard" for the detection of emboli patient placed immediately in the left lateral position. This will relieve the mechanical obstruction of the gas "lock" to blood flow through the right ventricular outflow tract.
The change in the position places the outflow tract below the right atrium. insufflation discontinued and pneumoperitoneum must be released. Complete cardiopulmonary by- pass may be required to evacuate the gas "lock".
IV. ENDO- BRONCHIAL INTUBATION CLINICAL PRESENTATION
increase in Paw and a decrease in SpO2 MECHANISM
Cephalad Displacement of Diaphragm by Position and Pneumoperitoneum
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MANAGEMENT:
REPOSITIONING OF THE ETT
PNEMOTHORAX MUST BE RULED OUT by considering:
(a) TIMING: earlier in the procedure in the case of bronchial intubation
(b) PETCO2: no initial increase with bronchial intubation (c) repositioning the endotracheal tube will rapidly
improve SpO2 and Paw with bronchial intubation
V. THROMBOEMBOLIC COMPLICATIONS
CLINICAL PRESENTATION:
lower limb pain mostly in postop
MECHANISM: increased intraabdominal pressure and head –up position results in venous stasis in lower limbs, predisposing to the development(20)
MANAGEMENT: preoperative stockings
shortened procedure duration post op early mobilization VI. ARRHYTHMIAS
CLINICAL PRESENTATION:
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ECG CHANGES MECHANISM:
reflex increase in vagal tone by co2 insufflation.(21) MANAGEMENT:
stop insufflations &medicate accordingly
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STRESS RESPONSE AND SURGERIES
The hormonal and metabolic changes which follow injury or trauma is known as stress response, it is a part of a systemic reaction to injury which includes a wide range of endocrinological, immunological and hematological effects. The characteristics of a stress response to surgery is increased secretion of pituitary hormones and sympathetic nervous system activation. The overall endocrine response to surgery is increased catabolism to provide energy sources and mechanisms to retain salt and water and maintain fluid and volume and cardiovascular homeostasis.
ACTIVATION OF STRESS RESPONSE:
from the site of injury afferent neuronal impulses travel along sensory nerve roots
through dorsal root of spinal cord to medulla to activate hypothalamus thus activating the endocrine stress response. Cytokines which include interleukins (mainly IL-1 & 6, TNF- α) and interferons are produced from activated leucocytes, fibroblasts and endothelial cells as an early response to tissue injury. The cortisol levels increase during surgery by cytokines particularly IL-1 & IL-6.THE INCREASED cortisol suppresses IL-6 levels thus affecting immune system.the anatomy of stress is depicted in figure1(22)
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ROLE OF CORTISOL IN STRESS
Cortisol is a catabolic glucocorticosteroid hormone synthesized from cholesterol in the adrenal cortex in zona fasciculata. Its scientific name is 11-beta,17-alpha,21-trihydroxypregn-4-ene-3,20-
Figure 1:anatomy of stress response and HPA axis
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dione. metabolized by 11-beta-hydroxysteroid dehydrogenase. Regulation of its secretion is depicted in figure1.in periods of stress it leads to hyperglycemia, and other gluconeogenic substrates from increased protein breakdown and triglyceride breakdown into fatty acids and glycerol which can affect the quality of postop conditions
The cortisol levels increase during surgery. The increased concentrations of circulating cortisol inhibit further secretion of ACTH thus inhibiting further secretion of itself by a feedback mechanism. this control mechanism is futile after surgery ultimately resulting in increased concentration of both hormones (ACTH & cortisol).
Even though laparoscopic surgery causes less tissue injury than conventional procedures the classical stress responses like catecholamines, cortisol and glucose are not reduced
ANAESTHESIA AND ANALGESIA TO REDUCE THE STRESS RESPONSE AND PAIN:
In almost 90% of the patients the intensity of the pain experienced is postoperative pain moderate-to severe after major surgery(23). Neuropathic and nociceptive pain leads to Exaggeration of the stress response and this exaggerated response occurs by Increased inflammation, coagulation disorders, organ hypoperfusion, decreased wound healing, and possibly cognitive dysfunction (24,25).
Combining general anaesthesia with infusion agents, epidural and/or intravenous (IV
) (e.g. opioids, local anaesthetics). Ultimately, this strategy also reduces the need for steroids, often associated with increased infections (27,28), and opioid use, which reduces post-operative complications of GI. This strategy also ultimately reduces the steroids
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requirement, which often have been associated with increased infections (26,27), and opioid use, which reduces GI post-operative complications .
EFFECT OF ANAESTHESIA ON STRESS TRESPONSE TO SURGERY:
GENERAL ANAESTHESIA:
1. OPOIDS: both hypothalamic and pituitary secretion is suppressed by therapeutic doses of morphine.
2. ETOMIDATE: it causes reversible inhibition of the enzyme 11 β-OHlase and leads to suppression of both cortisol and aldosterone production for 6-12 hours
3. BENZODIAZEPINE: midazolam and benzodiazepines both inhibit cortisol production.
4. CLONIDINE: it reduces stress responses and can reduces postop-analgesia requirement
REGIONAL ANAESTHESIA:
In Pelvic and Lower Limb Surgeries stress response attenuation can be done by both extensive epidural and local anaesthetic agents and it affects both afferent and efferent pathways in HPA axis. In upper abdominal surgery it is not possible even with extensive epidural blockade due to inadequate or incomplete afferent somatic and sympathetic blockade.
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VIRTUES OF A LAPAROSCOPIC SURGERIES I. STRESS REPONSE: compared to conventional open technique laparoscopic
approach results in reduced levels of c – reactive protein(crp) and interleukin -6 (il-6) which are markers of acute phase reaction(28).
also, an improvement in immune function and nitrogen balance by cutbacks in metabolic responses like hyperglycemia.etc(29).
II. POST OPERATIVE PAIN: surgical incisions, stretching of nerve endings and irritation of the diaphragm by residual CO2 pneumoperitoneum are the main pathophysiological mechanisms contributing to postoperative pain(30). These factors cause peripheral nerve endings and peritoneal irritation, and then cause abdominal or shoulder pain. to reduce the pain after laparoscopic procedures.
Intravenous narcotic analgesics (opioids) delivered by patient controlled analgesia (PCA) or Controlled release of local anaesthetics, including ropivacaine ,
bupivacaine , lidocaine and levobupivacaine , are infiltrated subcutaneously or instilled intraperitoneally ., surgical trauma induces the expression of COX- 2,leading to the PG which sensitized the peripheral sensory sensors and produce local hyperalgesia (peripheral sensitization and tissue damage causes the
expression of COX-2 in spinal cord neurons, which leads to increased neuronal excitability and the incurring of secondary hyperalgesia (central sensitization)for this NSAIDs are commonly used for post-operative pain control(31–34).
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POST OPERATIVE PULMONARY DYSFUNCTION(35–40): main causes of morbidity after abdominal surgery are Pulmonary complications like hypoxemia,
atelectasis and pneumonia. Diaphragmatic dysfunction leading to pulmonary impairment are more consistent following open Upper abdominal surgeries. laparoscopic surgeries offer advantages like reduced intraoperative bleeding, less post-operative pain, less injury to the abdominal wall muscles and may have better outcome and significant reduction in the probability of adverse events, reduced postoperative morbidity and pain, rapid
recovery, shorter hospital stays and faster discharge.
COMPLEXITIES OF LAPAROSCOPIC SURGERIES:
minimal complications such as peritoneal injury and pneumoderm will not cause grave consequences. However, some serious complications including the hemorrhage of major abdominal vessels and organ injury, if treated improperly, ensures mortality(41). Hence anesthetist must be aware of complications and timely management is vital.
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ROLE OF ALPHA-2 ADRENO RECEPTORS INTRODUCTION AND PHYSIOLOGICAL RESPONSES
Two evident classes of adrenoreceptors are classified by Ahlquist in 1948,alpha(α) and beta (β(42,43)).these receptors are bound to membrane(44) and catecholamines,
adrenaline and noradrenaline mediate their action through them. Alpha receptors are further divided into alpha1 post synaptic in location and mediating
responses in effector organs and alpha 2 presynaptic in location and is role is regulation of noradrenaline release. Sympathetic nervous system modulation is mainly done by alpha 2 adrenoreceptors distributed widely throughout CNS and peripheral tissues.
Furthermore α2 receptors are further divided into 3 subtypes(α2a,α2b,α2c)and
neurotransmitter release from sympathetic nerves in heart and from central noradrenergic
FIGURE 2 ADRENO-RECEPTOR CLASSIFICATION(45)
neurons are normally regulated by alpha 2 receptors(46). These receptors belong to a group of receptors called G-protein-coupled receptors and by means of a second
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messenger signaling or modulation of ion channels they modulate their acticity.
Activation of α2 receptors results in the inhibition of adenylyl cyclase and decrease in 3’
5’ –cAMP formation. This reduces protein kinase activity leading to decreased
phosphorylation of regulatory proteins. Other second messenger systems associated are PhospholipaseA2activity enhancement, metabolism of arachidonic acid etc. increased adenylyl cyclase activity and increased intracellular Ca2+ occurs at high concentrations of alpha 2 agonist , Which might be the reason for smooth muscle contraction
(47).inhibition of neurotransmitter release is by reduction in firing rate of excitable cells produced by cell membrane hyperpolarization through activation of g protein gated k+ channels.
Decreased neurotransmitter release from the nerve terminal is by G Protein coupled α2 adrenoceptor activation leading to a decrease in
Ca2+ conductance through direct regulation of voltage gated Ca2+ ion
Channels(48).majority of alpha receptors subtypes α2a & α2c are found in CNS whereas α2a & α2b are found in periphery.vigilance,attention&stress response are regulated by locus ceruleus of brain stem which has high density of α2 receptors.which on activation contribute to hypnotic and sedative effects.
Parts of the ventrolateral medulla and raphe in areas such as the nucleus tractus solitarius. may pallidus can contribute to cardiovascular changes
since they have high densities of alpha2 adrenoreceptors. Analgesic action Is mediated through α2receptors located in substantia gelatinosa and intermediolateral cell column of
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spinal cord
FIGURE 2 Location and physiological responses mediated through α2 adrenergic receptors (49)
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DEXMEDETOMIDINE-PHARMACOLOGY
Dexmedetomidine is the dextro isomer and pharmacologically active component of medetomidine.it is a potent α2 adrenergic agonist much more selective for α2vs α1
receptors (1620:1).
MECHANISM OF ACTION(50):
Main site of an α2 receptor is presynaptic. The responses mediated by α2 receptors differ with position and can be found in PNS AND CNS, platelets, and a number of organs including the liver, pancreas, kidney, and eye. Neuronal hyperpolarization is an important mechanism of action of α2-adrenoceptor agonists from an anesthesiologic point of view DEXMEDITOMIDINE actions are
• Terminating the propagation of pain signals thereby analgesic action- by presynaptic activation of the α2 adrenoceptor inhibiting the release of norepinephrine
• Inhibition of sympathetic activity thus can decrease blood pressure and heart rate - by Postsynaptic activation of α2 adrenoceptors in the CNS
• Hypnotic and sedative effects- by activation of α2recpetors in a
• Regional analgesia is by action in substantia geltinosa of dorsal horn of spinal cord
PHARMACODYNAMICS AND PHARMACOKINETICS:
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Dexmedetomidine has a rapid onset but a short duration of clinical effect because it conforms to a 2-compartment model of distribution and elimination with an elimination half life (T1/2b) of 2 hours, but it is a highly lipophilic drug that is rapidly distributed and redistributed, with a distribution half-life (T1/2a) of only 6 minutes. These properties makes it an agent for infusion techniques.
Metabolism by glucuronidation and CYP2A6-mediated metabolism with up to 90%
excretion in urine and up to 13% in faeces. hence in renal impairment patients it should be cautiously used.
The context-sensitive half-time of dexmedetomidine ranges
from 4 minutes after a 10-minute infusion to 250 minutes after an 8-hour infusion.
dexmedetomidine protein binding capacity of about 94 percent, with marginal protein binding displacement by morphine, ketorolac, theophylline, digoxin and lidocaine, all medications widely used during anaesthesia and in ICU.
CLINICAL APPLICATION:
Main applications include
• IN CRITICAL CARE SETTING: for critically ill patients requiring prolonged sedation and mechanical ventilatory support, it possesses all the characteristics of an ideal sedative for intensive care like It lacks respiratory depression, is analgesic and anxiolytic, has a rapid onset, is titratable, and produces sedation with hemodynamic stability.
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• SEDATIVE AGENT FOR PROCEDURAL SEDATION: it can used with agents such as opoids,benzodiazepines and Propofol to enhance sedation and maintain hemodynamic stability or used alone by a continuous infusion by loading dose followed by a maintenance infusion.it may be useful in patients with difficult airway or in obese patients because it does not produce respiratory depression(51).it is used for awake fiberoptic intubation(52), and in awake carotid endarterectomies with stable hemodynamics(53).
• OBTUNDING THE EMERGENCE DELIRIUM(54,55) : Pediatric patients, patients with special needs and elderly are particularly prone to emergence delirium following anaesthesia, especially when benzodiazepines and potent inhalational agents are used and in mechanically ventilated patients
dexmedetomidine reduce the occurrence of emergence delirium.
• PREMEDICATION: Dexmedetomidine is used in premedication because of its sedative, anxiolytic, analgesic, sympatholytic and stable hemodynamics. It reduces intraoperative (up to 8%) and postoperative oxygen consumption (up to 17%)(56)
• AS AN ADJUVANT IN LOCAL & REGIONAL TECHNIQUES:
regardless of route of administration (epidural, caudal or spinal it Extends the duration of sensory and motor blockage caused by local anaesthetics).
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• INTRAARTICULAR USE(57,58): In patients undergoing knee surgery by arthroscopy, both quality and duration of postoperative analgesia is improved
• MONITORED ANAESTHESIA CARE: Dexmedetomidine has been used for sedation for monitored anaesthesia care in gynecological, urological, burns patients and trauma patients.
• IN MRI AND CT SCAN(59): for sedation of children undergoing MRI High dose dexmedetomidine has been used successfully.
• PAIN AND PALLIATIVE CARE(60,61): in intractable neuropathic pain and in cancer patients with intractable pain, agitation or delirium.
• NEUROSURGERY: it avoids abrupt ICT changes during intubation,
extubation and pin placement, decreases neurocognitive dysfunction (delirium and agitation) and allows for immediate postoperative neurological assessment.
Useful during cerebral ischemia as it has neuroprotective effects.
DOSE:
• Usually administered in intravenous route at a loading dose of 1 microgram/ kg IV to run over a period of 10 minutes and followed by infusion at a rate of 0.2-0.8 micrograms/kg/hour IV.
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• Dose for premedication is 0.33- 0.67mg/kg I.V. or 2.5 microgram/kg i.m.
injection given 15 min before surgery.
• Dose for spinal anaesthesia is 0.1-0.2 mcg/kg.
• Dose for epidural is 1-2 mcg/kg.
• In intravenous regional anaesthesia at a dose of 0.5 microgram/kg(62).
• In elderly patient’s dose reduction must be done as its use resulted in hypotension and bradycardia.
ADVERSE EFFECTS(61–63):
✓ Hypotension or hypertension
✓ Bradycardia
✓ Dryness of mouth
✓ Nausea
✓ Atrial fibrillation REVERSAL AGENTS:
clinical effects of α-2 agonist drugs can be reversed using
ATIPAMEZOLE(64).it reverses both sedative and sympatholytic effects of dexmedetomidine.it has an half-life of 1.5 to 2hours(65)
DRUG INTERACTIONS:
agents such as hypnotics, sedatives and opioids doses should be decreased when administered, as dexmedetomidine enhances the effects of these agents.
Vasodilators and negative inotropic agents should be cautiously used as it can worsen bradycardia and hypotension associated with dexmedetomidine.
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PRECAUTIONS:
There may be transient hypertension that can associated with rapid administration of loading dose of dexmedetomidine and it is due to action on α1 receptors on blood vessels at higher plasma concentration usually attained during a loading dose of dexmedetomidine. Adequate hydration prior to administration must be ensured to prevent hypotension. If hypotension occurs treated by stoppage of infusion, elevation of foot end of the patient and vasopressor administration. in certain clinical
situtations,like in hypovolemic patients or patients with fixed stroke volume,in pre existing heart block and CCF the actions of α2-adrenoceptor agonists may be deleterious because of its sympatholytic or bradycardic actions
PRE-OPERATIVE EFFECTS:
especially for patients susceptible to preoperative and intraopererative stress it can be a useful adjunct for premedication. Because dexmedetomidine possesses anxiolytic, sedative, analgesic, and sympatholytic properties (66,67). Dexmedetomidine intraoperatively (up to 8 percent) and postoperatively (up to 17 percent) were able to reduce oxygen consumption. Regardless of the form of administration (intravenous, variable or even local block)(57) Dexmedetomidine potentiates any intraoperative anaesthetic effect(66).
INTRAOPERATIVE EFFECTS:
Goals Of Anaesthesia are to reduce stress-induced sympathoadrenal responses and to protect the patient from hemodynamic changes and noxious sympathetic stimuli
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throughout surgery. With its anaesthetic
sparing efficacy, dexmedetomidine improves hemodynamic stability and decreases reacti ons to endotracheal intubation thereby helps to achieve this goals. Regarding an aesthetic agents use dexmedetomidine decreases cardiac output thus altering the pharmacokinetics of intravenous anaesthetic agents(67).in one study by khan et al isoflurane requirement reductions up to 35-50 % in patients either treated with high or low doses of
dexmedetomidine(68).in another study sevoflurane maintenance requirement was down to 17% after administration of dexmedetomidine(69).it also provides an analgesic effect thus reducing opioid requirement in both intraoperative and postoperative period(70).
Ultimately, the use of dexmedetomidine in patients makes it possible to use lower doses of anaesthetic agents, resulting in faster recovery from anaesthesia and a decreased need for pain medication in the PACU, thereby decreasing the length of stay.dexmeditomdine also inhibits thermoregulatory responses like shivering(71).
POST OPERATIVE EFFECTS: pain and elevated catecholamine concentration results after Recovering from anaesthesia
And anaesthetic residuals compromise breathing.Because of their sympatholytic and analgesic effects without respiratory
Depression dexmedetomidine may prove beneficial. A study by Hall and colleagues showed that When stimulated, patients can return to their basic level of
consciousness(72).
35
REVIEW OF LITERATURE
Clinical studies in the past that were used to assess the efficacy of dexmedetomidine in laparoscopic surgeries
1. Lovina Neil et al analysed “Effect of Dexmedetomidine Versus Fentanyl on Haemodynamic Response to Patients Undergoing Elective Laparoscopic Surgery” studied between two groups Group F, fentanyl 0.5 microgram/kg as loading dose over 10 minutes prior to induction followed by 0.2-0.7
microgram/kg/hr. as maintenance dose and in Group D, Dexmedetomidine 0.5 microgram/kg as loading dose over 10 minutes prior to induction followed by 0.2 microgram/kg/hr-0.7 microgram/kg/hr. as maintenance dose till surgery was over. And Concluded that dexmedetomidine is better than fentanyl in order to maintain the hemodynamic response during the intubation and intraoperative period (73).
2. Jayshree P Vaswani et al analyzed “Comparative Study of the Effect of Dexmedetomidine Vs. Fentanyl on Hemodynamic Response in Patients Undergoing Elective Laparoscopic Surgery” Group D received
dexmedetomidine and Group F received fentanyl. Patients received intravenous 0.5microgram/kg of the study drug as loading dose over 10
minutes prior to intubation followed by 0.2-0.7microgram/kg/hr. as infusion till surgery was over. Concluded that Dexmedetomidine causes greater attenuation of stress response to tracheal intubation compared to fentanyl after
36
pneumoperitoneum and intraoperatively resulting in greater reduction of HR, SBP, DBP, MAP compared to fentanyl, resulting in improved hemodynamic stability in patients undergoing elective laparoscopic surgery(74).
3. Vinayak Panchgar et al studied “The Effectiveness of Intravenous
Dexmedetomidine on Pererative Hemodynamics, Analgesic Requirement, and Side Effects Profile in Patients Undergoing Laparoscopic Surgery Under General Anaesthesia” Patient received either NS or dexmedetomidine in group NS and group dexmedetomidine, respectively, depending upon the allocation.
The infusion rate was adjusted according to; loading dose (1microgram/kg) over 10 min and maintenance dose (0.5microgram/kg/h) and intraopererative hemodynamics was recorded and Concluded that Dexmedetomidine
intraoperatively regulated the hemodynamic stress response in patients undergoing laparoscopic surgery in the dosage of 1 microgram / kg body weight as a bolus over 10 min and 0.5 microgram / kg / h as a maintenance dose.(75)
4. Rafat Shamim et al studied “Effect of Two Different Doses of
Dexmedetomidine on Stress Response in Laparoscopic Pyeloplasty: A Randomized Prospective Controlled Study” Ninety patients were assigned to one of the three groups: Group A, Group B, and GROUP C. Group B received dexmedetomidine 1 mcg/kg as loading dose, followed by 0.7 mcg/kg/h for maintenance; GROUP C received dexmedetomidine 0.7 mcg/kg as a loading
37
dose, followed by 0.5 mcg/kg/h for maintenance. Group A received normal saline. Stress responses were assessed by the variations in hemodynamic parameters, blood glucose levels, and serum cortisol levels and concluded that Dexmedetomidine improves stress response and is ideal for anaesthesia
maintenance (76)
5. Nandlal Bhaga et al studied “Dexmedetomidine in Attenuation of
Hemodynamic Response and Dose Sparing Effect on Opioid and Anaesthetic Agents in Patients undergoing Laparoscopic Cholecystectomy- A Randomized Study” and concluded that Patients were randomly divided into 2 groups group D and group N. Prior to induction, group D received 1 microgram/kg of
Dexmedetomidine and group N received Normal saline infusion over 20 minutes. Group D also received maintenance Dexmedetomidine
intraoperatively. Bispectral index and minimum alveolar concentration
monitoring was done in both the groups. Hemodynamic parameters were noted till 100 minutes post laryngoscopy. Opioid and anaesthetic agent consumptions were also noted, and cost analysis was done. And concluded that
Dexmedetomidine is effective in attenuating hemodynamic responses in laparoscopic surgery and having dose sparing effect on Fentanyl, Propofol and Isoflurane(77)
6. Gourishankar reddy manne et al studied “Effects of low dose dexmedetomidine infusion on hemodynamic stress response, sedation and post-operative
38
analgesia requirement in patients undergoing laparoscopic cholecystectomy”
three groups of 20 patients each. Group NS patients received normal saline, Group Dex 0.2 and Group Dex 0.4 patients received dexmedetomidine infusion at 0.2 mcg/kg/h and 0.4 mcg/kg/h respectively, starting 15 min before
induction and continued till end of surgery. Parameters noted were pulse rate, mean arterial pressure, oxygen saturation, post-operative sedation and
analgesia requirements and concluded that Low dose dexmedetomidine in the 0.4 mcg / kg / h range effectively attenuates the reaction of hemodynamic pressure during laparoscopic surgery with reduced post-operative analgesic requirements (78)
7. Kumkum gupta et al studied “Blood glucose estimation as an indirect assessment of modulation of neuroendocrine stress response by
dexmedetomidine versus fentanyl premedication during laparoscopic cholecystectomy” divided into two groups. Group D patients were given intravenous dexmedetomidine 1microgram/kg and Group F patients received fentanyl 2 microgram/kg, given over a 10-min period, before induction of anaesthesia. Perioperative blood glucose levels were analyzed preoperatively, at 30 min after beginning of surgery, and 2.5 h after surgery. Anaesthetic and surgical techniques were standardized. All patients were also assessed for intraoperative hemodynamic changes of heart rate and mean arterial pressure at specific timings and concluded that dexmedetomidine was better(79)
39
8. Meyong picho bhutia et al studied “Attenuation of Hemodynamic Parameters in Response to Pneumoperitoneum during Laparoscopic Cholecystectomy: A Randomized Controlled Trial Comparing Infusions of Propofol and
Dexmedetomidine” two groups of 30 patients each: Group D to receive dexmedetomidine in dose of 0.2-0.7microgram/kg/hr. titrated as per clinical response and GROUP P to receive propofol in dose of 25-
75microgram/kg/min (1.5-4.5 milligram/kg/hr.) titrated as per clinical response after standard anaesthetic induction. Data recording was done for changes in hemodynamic parameters, time to extubation and post extubation sedation score and concluded that Dexmedetomidine in a dose of 0.2-0.7 microgram / kg / hr. provides stable haemodynamics in patients undergoing laparoscopic cholecystectomy without any side effects(80)
9. Sarbari Swaika et al “A comparative study of the efficacy of intravenous Paracetamol and Dexmedetomidine on peri-operative hemodynamics and post- operative analgesia for patients undergoing laparoscopic cholecystectomy” two groups, GROUP P that had 40 patients received IV 1 g Paracetamol infusion over 10 min pre-operatively and 6 hourly thereafter and Group With 40
patients received IV Dexmedetomidine 1 microgram/kg bolus over 10 min pre- operatively and 0.2-0.4 microgram/kg/h thereafter for 24 h. Peri-operative hemodynamic variables, post-operative pain scores, and the need for rescue analgesics were recorded and compared and concluded that intra-operative
40
hemodynamic changes were similar in both groups in respect to heart rate (HR), diastolic blood pressure, mean arterial pressure except in the systolic blood pressure where Dexmedetomidine significantly reduced it in compare to Paracetamol(81)
10. Naz anjum et al “Effects of dexmedetomidine and clonidine as propofol adjuvants on intra-operative hemodynamics and recovery profiles in patients undergoing laparoscopic cholecystectomy: A prospective randomized
comparative study” studied three groups. GROUP C patients received bolus of clonidine 3 microgram/kg followed by a continuous infusion; Group D patients received dexmedetomidine 1 microgram/kg and a continuous infusion; and GROUP P patients received a bolus of normal saline followed by an infusion.
Intra-operative mean arterial pressure and pulse rate were measured throughout the surgery and concluded Both clonidine and dexmedetomidine attenuate sympathetic reaction to laryngoscopy and extubation when co-administered with propofol which cause delay in anaesthesia recovery. Dexmedetomidine impairs cognitive functions after surgery(82)
41
METHODOLOGY AND METHODS
STUDY DESIGN: It is single blinded randomized study done at government Vellore medical college and hospital, Vellore.
SOURCES OF DATA
Data was collected from 100 ASA I and II patients scheduled for
laparoscopic cholecystectomy surgeries aged between 18 – 60 years at government Vellore medical college and hospital, Vellore. Both study groups and control were selected from these patients. The study was conducted over a period of ten
months.
INFORMED CONSENT:
Written and informed consent was obtained from each patient in the prescribed format prior to performance of any study related procedures, before physical examination, laboratory screening or any other investigational procedure and before administration of any study related medication. The patients and patients relatives were explained in detail about the nature, procedure and
importance of the study. Result values were recorded using a proforma sheet for all cases.
INCLUSION CRITERIA:
• ASA I and II patients
• Both gender
42
• Age 18 -60yrs
• elective surgery EXCLUSION CRITERIA:
• Patient on any drug treatment which may interfere with dexmedetomidine
• Hypertension
• Diabetes mellitus
• Cardiovascular & kidney disease
• Acute cholecystectomy
• Endocrine or metabolic diseases
• Autonomic neuropathy
• Patients on chronic β blocker therapy MONITORING:
• Pulse oximetry
• NIBP
• ECG
• Et CO2
• Urine output monitoring
• Temperature monitoring
43
CONDUCT OF ANAESTHESIA:
After ascertaining the inclusion criteria preoperative investigations were recorded which included complete hemogram, blood sugar, urea, creatinine, serum electrolytes, blood grouping, blood coagulation tests, urine routine, chest X-ray and ECG.
• After shifting the patients to operation theatre patients are connected to
• ECG, pulse oximetry, and NIBP monitors.
• All patients are started with ringer lactate at 75 ml/hr.
• pre oxygenated with 100% oxygen for 3 – 5 minutes.
• study group (GROUP P) received I.V dexmedetomidine 1microgram/kg bolus dose over 10 minutes followed by 0.5μ/kg/min infusion and control group (GROUP C) received normal saline at same infusion rate. In both the groups infusion was continued till pneumoperitoneum was released.
• All patient was given fentanyl 2 microgram/kg IV
• In all the patients, trachea was intubated after induction of anaesthesia with I.V propofol 2 mg/kg and I.V atracurium 0.5
• Anaesthesia maintained with 1.5-2% sevoflurane and 1:1 N2O/O2 at 3 liters/ minute and muscle relaxation with i.v.atracurium
• noninvasive blood pressure and heart rate are measured at base line, after loading dose of drug, after starting of dug infusion,1 minute after induction and intubation,1minute after pneumoperitoneum and
44
15min,30min,45min,60min,90min,120min and after release of pneumoperitoneum, and after drug stoppage and 1 min after extubation
• Serum cortisol samples are taken at early in the morning between 6-7am, 1min after intubation,30minute after pneumoperitoneum and 10 minutes after extubation
• After completion of surgery, pneumoperitoneum deflated slowly and after the patient had adequate respiratory attempts patient reversed with glycopyrrolate and neostigmine IV.
• Adequate oral suctioning done, and the patients are extubated SERUM CORTISOL ASSAY
serum samples are taken in plain tube and then allowed to coagulate and centrifuged to separate serum and stored under 8 degree Celsius in a refrigerator
and Assay done with CORTISOL ELISA 96 TEST DIAMETRA 3822 KIT.
VISUAL ANALOGUE SCALE :
Assessed At 1,15,30,45,120 Minutes Postoperatively.
45
RAMSAY SEDATION SCORE Assessed At 1,15,30,45,120 Minutes
46
OBSERVATION AND RESULTS A total of 100 patients were divided and studied
• GROUP P- 50 PATIENTS RECIEVING DEXMEDITOMIDINE
• GROUP C -50 PATIENTS RECEIVING NORMAL SALINE
The demographic parameters like age distribution, weight of the patient(kg), height of the patient(cm), and other parameters like duration of anaesthesia, duration of surgery, pulse rate, systolic, diastolic and mean arterial pressure, SERUM CORTISOL, ramsay sedation score and visual analogue scale were compared between the two groups
(GROUP P & GROUP C).
DEMOGRAPHIC CHARACTERISTICS OF STUDY POPULATION
AGE DISTRUBUTION BETWEEN GROUPS
GROUP Total
P C
AGE GROUP
UP TO 30 YEARS
Count 13 15 28
% within
GROUP 26.0% 30.0% 28.0%
31-40 YEARS
Count 18 16 34
% within
GROUP 36.0% 32.0% 34.0%
41-50 YEARS
Count 6 11 17
% within
GROUP 12.0% 22.0% 17.0%
51-60 YEARS
Count 9 6 15
% within
GROUP 18.0% 12.0% 15.0%
47
ABOVE 60 YEARS
Count 4 2 6
% within
GROUP 8.0% 4.0% 6.0%
Total
Count 50 50 100
% within GROUP
100.0
%
100.0
%
100.0
% Pearson Chi-Square=2.998 P=0.558
Chart-1 Age distribution between two groups Group Statistics GROUP N Mean Std.
Deviation
Std. Error Mean AGE P 50 40.2400 13.97163 1.97589
C 50 39.1200 12.60651 1.78283
0%
5%
10%
15%
20%
25%
30%
35%
40%
UP TO 30 YEARS 31-40 YEARS 41-50 YEARS 51-60 YEARS ABOVE 60 YEARS 26%
36%
12%
18%
8%
30% 32%
22%
12%
4%
P C
48
The age, gender, weight, distribution was comparable in GROUP P and GROUP C. The P Value for mean age, gender, weight and BMI was not statistically significant Since the p value is greater than 0.05.
RELATIONSHIP BETWEEN THE GENDER DISTRIBUTION.
Pearson Chi- Square=0.00 P=1.00
0 5 10 15 20 25 30 35 40 45
P
C 40.24
39.12
AGE GROUP
Crosstab
GROUP Total
P C
SEX
MALE
Count 26 26 52
% within
GROUP 52.0% 52.0% 52.0%
FEMALE
Count 24 24 48
% within
GROUP 48.0% 48.0% 48.0%
Total
Count 50 50 100
% within
GROUP 100.0% 100.0% 100.0%
49
CHART: SEX DISTRUBUTION BETWEEN TWO GROUPS
WEIGHT (IN KG) BETWEEN BOTH GROUPS Crosstab
GROUP Total
P C
BMI CLASS
UNDERWEIGH T
Count 18 18 36
% within
GROUP 36.0% 36.0% 36.0%
NORMAL
Count 29 31 60
% within
GROUP 58.0% 62.0% 60.0%
OVERWEIGHT
Count 3 1 4
% within
GROUP 6.0% 2.0% 4.0%
Total
Count 50 50 100
% within
GROUP 100.0% 100.0% 100.0%
Pearson Chi-Square=1.067 P=0.587
52% 52%
48% 48%
46%
47%
48%
49%
50%
51%
52%
53%
P C
MALE FEMALE
50
CHART: WEIGHT (IN KG) BETWEEN BOTH GROUPS
BMI COMPARISON BETWEEN TWO GROUPS Group Statistics
GROUP N Mean Std.
Deviation
Std. Error Mean
BMI P 50 19.8108 4.00680 .56665
C 50 19.8433 3.38051 .47808
0%
10%
20%
30%
40%
50%
60%
70%
P C
36% 36%
58% 62%
6% 2%
UNDERWEIGHT NORMAL OVERWEIGHT
51
DURATION OF SURGERY
Group Statistics
GROUP N Mean Std.
Deviation
Std.
Error Mean
t value p value
DURATION OF
SURGERY IN MINUTES
P 50 73.9400 19.90530 2.81503 0.412 0.965 C 50 72.3400 18.92370 2.67622
73.94 72.34
0 10 20 30 40 50 60 70 80
P C
DURATION OF SURGERY
52
COMPARISON OF PULSE RATE
Mean
Standard Error of
Mean Count
Standard
Deviation Lower Upper
GROUP P PULSE RATE base line 79.48 2.22 50 15.69
75.13 83.83
PR after loading dose 67.90 2.21 50 15.64 63.56 72.24
PR starting of infusion 67.76 1.96 50 13.87 63.92 71.60
PR 1 min after induction and intubation
71.94 1.85 50 13.07
68.32 75.56
PR 1 min after
pneumoperitoneum 70.88 1.69 50 11.94
67.57 74.19
PR 15min 69.38 1.48 50 10.49 66.47 72.29
PR 30min 68.74 1.24 50 8.76 66.31 71.17
PR 45min 67.74 1.09 50 7.72 65.60 69.88
PR 60min 66.97 1.07 50 6.52 65.17 68.78
PR 90min 67.40 1.21 50 4.67 66.10 68.70
PR 120 min 68 1 50 1 67.61 68.39
1min after release
pneumoperitoneum 68.30 1.04 50 7.32
66.27 70.33
after drug stoppage 67.34 .96 50 6.82 65.45 69.23
1 min after extubation 68.66 .80 50 5.63
67.10 70.22
C PULSE RATE base line 79.70 1.42 50 10.07 76.91 82.49
PR after loading dose 80.24 1.44 50 10.16 77.42 83.06
PR starting of infusion 83.76 1.45 50 10.16 80.94 86.57
PR 1 min after induction and intubation
90.56 1.58 50 11.16
87.47 93.65
PR 1 min after
pneumoperitoneum 95.18 1.63 50 11.54
91.98 98.38
PR 15min 92.90 1.45 50 10.25 90.06 95.74
PR 30min 88.18 1.33 50 9.37 85.58 90.78
PR 45min 84.53 1.24 50 8.70 82.12 86.94
PR 60min 81.39 1.64 50 9.82 78.67 84.11
PR 90min 79.00 2.44 50 9.15 76.46 81.54
PR 120 min 75 50
1min after release
pneumoperitoneum 85.62 1.61 50 11.40
82.46 88.78
after drug stoppage 87.64 1.99 50 14.10 83.73 91.55
1 min after extubation 96.54 1.92 50 13.60 92.77 100.31
53
Tests of Within-Subjects Effects
Source Type III Sum of
Squares
df Mean Square F Sig.
TIME 8601.252 10 860.125 20.244 p<0.001
TIME * GROUP 12474.068 10 1247.407 29.358 p<0.001
Error(TIME) 40789.294 960 42.489
The mean values of baseline pulse rate in the both groups (GROUP-P & C)
were 79.48and 79.70 respectively and p value statistically non-significant showing both were comparable in respect to baseline heart rate. Whereas the mean values of pulse rate after loading dose, starting of infusion, 1 min after induction and intubation,1 min after pnemoperitoneum,15min,30min, 45min, 60min, 90min, 120 min, 1min after release pnemoperitoneum,after drug stoppage, 1 min after extubation had wide varaitions in both groups with the GROUP P having significantly lower values when compared to GROUP C.THE P VALUE OF GROUP P IS STATISTICALLY SIGNIFICANT. The chart below depicts the same.
54
COMPARISON OF SBP
Mean
Standard Error of
Mean Count
Standard
Deviation Lower Upper
GROUP P SBP BASELINE 122.74 1.35 50 9.57 120.09 125.39
AFTER LOADING DOSE 114.18 1.60 50 11.28 111.05 117.31
STARTING OF
INFUSION 110.36 1.69 50 11.93
107.05 113.67
1 MIN AFTER INDUCTION AND INTUBATION
108.00 1.66 50 11.72
104.75 111.25
1 MIN AFTER
PNEMOPERITONEUM 106.48 1.68 50 11.89
103.18 109.78
15MIN 103.82 2.60 50 18.37 98.73 108.91
30MIN 105.26 1.44 50 10.18 102.44 108.08
45MIN 104.26 1.31 50 9.28 101.69 106.83
60MIN 103.70 1.53 50 9.31 101.12 106.28
90MIN 107.43 2.65 50 9.93 104.68 110.18
120MIN 114 4 50 5 112.13 114.87
1 MIN AFTER RELEASE OF
PNEMOPERITONEUM
105.50 1.37 50 9.69
102.81 108.19
AFTER STOPPAGE OF
DRUG 105.34 1.24 50 8.76
102.91 107.77
0 20 40 60 80 100 120
Base line After loading dose Starting of infusion 1 min after induction and intubation 1 min after pnemoperitoneum 15min 30min 45min 60min 90min 120 min 1min after release pnemoperitoneum After drug stoppage 1 min after extubation
COMPARISON OF PULSE RATE
P C
55 1MIN AFTER
EXTUBUATION 105.88 1.44 50 10.19
103.06 108.70 C SBP BASELINE 121.18 1.15 50 8.13 118.93 123.43
AFTER LOADING DOSE 119.94 1.06 50 7.53 117.85 122.03
STARTING OF
INFUSION 121.74 1.04 50 7.39
119.69 123.79
1 MIN AFTER INDUCTION AND INTUBATION
126.66 .95 50 6.69
124.81 128.51
1 MIN AFTER
PNEMOPERITONEUM 129.48 1.28 50 9.08
126.96 132.00
15MIN 125.74 1.11 50 7.82 123.57 127.91
30MIN 122.36 1.29 50 9.13 119.83 124.89
45MIN 118.38 1.37 50 9.67 115.70 121.06
60MIN 115.03 1.66 50 9.79 112.31 117.74
90MIN 113.93 2.30 50 8.92 111.46 116.41
120MIN 106 50
1 MIN AFTER RELEASE OF
PNEMOPERITONEUM
118.96 1.46 50 10.31
116.10 121.82
AFTER STOPPAGE OF
DRUG 120.04 1.57 50 11.10
116.96 123.12
1MIN AFTER
EXTUBUATION 125.72 1.12 50 7.89
123.53 127.91
Source Type III Sum of
Squares
df Mean Square F Sig.
TIME 9346.925 10 934.693 20.211 p<0.001
TIME * GROUP 13127.129 10 1312.713 28.385 p<0.001
Error(TIME) 45322.491 980 46.247
56
The mean values of baseline SBP in the both groups (GROUP-P & C) were 122.74 and 121.18 respectively and p value statistically non-significant showing both were
comparable in respect to baseline SBP. Where as the mean values of SBP after loading dose, starting of infusion, 1 min after induction and intubation,1 min after
pnemoperitoneum,15min,30min, 45min, 60min, 90min, 120 min, 1min after release pnemoperitoneum,after drug stoppage, 1 min after extubation had wide varaitions in both group with GROUP P SHOWING statistically significant results.
57
COMPARISON OF DBP
Mean
Standard Error of
Mean Count Deviation Standard
Upper value
Lower value
GROUP P DBP BASELINE 80.58 1.21 50 8.56 78.21 82.95 AFTER
LOADING DOSE
75.82 1.54 50 10.88
72.80 78.84 STARTING OF
INFUSION
71.86 1.60 50 11.33
68.72 75.00 1MIN AFTER
INDUCTION AND
INTUBATION
70.90 1.31 50 9.26
68.33 73.47 1 MIN AFTER
PNEMOPERITO NEUM
68.44 1.64 50 11.59
65.23 71.65 15MIN 68.54 1.87 50 13.24 64.87 72.21 30MIN 68.38 1.51 50 10.69 65.42 71.34 45MIN 66.72 1.47 50 10.39 63.84 69.60 60MIN 65.59 2.01 50 12.20 62.21 68.98
0 20 40 60 80 100 120 140
Base line After loading dose Starting of infusion 1 min after induction and intubation 1 min after pnemoperitoneum 15min 30min 45min 60min 90min 120 min 1min after release pnemoperitoneum After drug stoppage 1 min after extubation
COMPARISON OF SBP
P C
58
90MIN 70.93 4.78 50 17.90 65.97 75.89 PR 120 MIN 68 1 50 1 67.61 68.39 1 MIN AFTER
RELEASE OF PNEMOPERITO NEUM
68.36 1.70 50 12.04
65.02 71.70 AFTER
STOPPAGE OF DRUG
67.06 1.12 50 7.92
64.87 69.25 1 MIN AFTER
EXTUBATION
67.66 1.83 50 12.91
64.08 71.24 C DBP BASELINE 75.04 1.32 50 9.31 72.46 77.62
AFTER
LOADING DOSE
88.56 14.10 50 99.69
60.93 116.19 STARTING OF
INFUSION
74.82 .96 50 6.82
72.93 76.71 1MIN AFTER
INDUCTION AND
INTUBATION
80.04 1.22 50 8.62
77.65 82.43 1 MIN AFTER
PNEMOPERITO NEUM
82.76 1.03 50 7.30
80.74 84.78 15MIN 80.82 1.07 50 7.58 78.72 82.92 30MIN 77.44 1.10 50 7.76 75.29 79.59 45MIN 75.82 1.26 50 8.90 73.35 78.29 60MIN 71.88 1.39 50 8.10 69.64 74.13 90MIN 72.67 2.16 50 8.36 70.35 74.98
PR 120 MIN 75 50
1 MIN AFTER RELEASE OF PNEMOPERITO NEUM
75.04 1.31 50 9.24
72.48 77.60 AFTER
STOPPAGE OF DRUG
76.24 1.29 50 9.13
73.71 78.77 1 MIN AFTER
EXTUBATION
81.28 .93 50 6.60
79.45 83.11
