A COMPARATIVE STUDY OF ORAL DEXMEDETOMIDINE VERSUS ORAL MIDAZOLAM IN PAEDIATRIC ELECTIVE
SURGERIES
Dissertation Submitted to
THE TAMILNADU Dr.M.G.R. MEDICAL UNIVERSITY CHENNAI - 600 032
With partial fulfillment of the regulations for the award of the degree of M.D. ANAESTHESIOLOGY
BRANCH-X
COIMBATORE MEDICAL COLLEGE COIMBATORE
MAY 2020
REGISTRATION NO : 201720652
CERTIFICATE I
Certified that this is the bonafide dissertation done by Dr.N.Chandrakalaand submitted in partial fulfillment of the requirements for the Degree of M.D.,Anaesthesiology, Branch X of The TamilnaduDr.M.G.R.
Medical University, Chennai.
Date: Dr.K.KALYANASUNDARAM., Associate Professor
Department of Anaesthesiology
Date: Dr.K. SANTHA ARULMOZHI M.D.,D.A., Professor & Head of Department
Department of Anaesthesiology
Date: Dr.B.ASOKAN MS,M.Ch
Dean
Coimbatore Medical College, Coimbatore
CERTIFICATE – II
This is to certify that this dissertation work titled “A COMPARATIVE STUDY OF ORAL DEXMEDETOMIDINE VERSUS ORAL MIDAZOLAM IN PAEDIATRIC ELECTIVE SURGERIES ”of the candidate Dr.N.CHANDRAKALA with registration Number- 201720652 for the award of M.D 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 4 % ( four percentage) of plagiarism in the dissertation.
Guide & Supervisor sign with Seal.
DECLARATION
I Solemnly declare that the dissertation titled “ A COMPARATIVE STUDY OF ORAL DEXMEDETOMIDINE VERSUS ORAL MIDAZOLAM IN PAEDIATRIC ELECTIVE SURGERIES ” was done by me from MAY 2018 to MAY 2019 under the guidance and supervision Of Prof.Dr.K.KALYANASUNDARAM.M.D.,
This dissertation is submitted to The TamilnaduDr.M.G.R. Medical University towards the partial fulfilment of the requirement for the award of MD degree in Anaesthesiology (Branch X)
Place: Coimbatore Dr.N.CHANDRAKALA
Date:
ACKNOWLEDGEMENT
I wish to express my sincere thanks to our respected Dean Prof.Dr.B.ASOKAN M.S.,MCh,(Plastic Surgery) for having allowed me to conduct this study in our hospital.
I express my heartfelt thanks and deep gratitude to the Head of the Department of Anaesthesiology Prof.Dr.K.SANTHA ARULMOZHI M.D.,D.A., for her generous help and guidance in the course of the study.
I sincerely thank my Associate Professor and Guide Prof.Dr.K.KALYANASUNDARAM ,M.D., for his constant support, invaluable guidance and encouragement throughout my study and post graduate programme.
I am extremely grateful to Prof.Dr.RAJAMANI M.S.MCH, HOD, Department of Paediatric Surgery for his valuable help and cooperation and allowing me to use institutional facilities.
I am extremely grateful to, Prof.Dr.SANTHI M.D., HOD, Department of Pharmacology, for her valuable help and cooperation and allowing me to use institutional facilities.
I sincerely thank my co-guide Dr.S.MADHANAGOPALAN M.D., andfor their guidance and help.
I also thankful to all my assistant professors for their guidance and help.
I thank all my PATIENTS, who formed the backbone of this study without whom this study would not have been possible.
Lastly, I am ever grateful to the ALMIGHTY GOD for always showering His blessings on me and my family.
Dr.N.CHANDRAKALA
ETHICAL COMMITTEE APPROVAL CERTIFICATE
TABLE OF CONTENTS
SL.NO TITLES PAGE.NO
1 INTRODUCTION 1
2 AIM AND OBJECTIVES OF STUDY 2-3
3 MIDAZOLAM - PHARMACOLOGY 8-17
4 DEXMEDETOMIDINE -
PHARMACOLOGY
18-24
5 REVIEW OF LITERATURE 25-35
6 MATERIALS AND METHODS 40-47
7 STATISTICAL ANALYSIS 42-72
8 DISCUSSION 73-77
9 SUMMARY 78
10 CONCLUSION 80
11 BIBLIOGRAPHY 81
12 ANNEXURES
A1.PROFORMA
A2.CONSENT FORM
A3.MASTER CHART
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Untreated anxiety
may lead to difficult induction, increased postoperative pain, greater rescue analgesic needs, emergence delirium (ED), and postoperative psychological effects and
behavioral issues [4–6].
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AS PREMEDICATION IN PAEDIATRIC ELECTIVE SURGERIES INTRODUCTION Almost 50% of children shows sign of significant preoperative anxiety and fear and may be uncooperative to surgeries and anaesthesia.
Untreated anxiety
may lead to difficult induction , increased postoperative pain, rescue analgesic
needs , emergence delirium and postoperative psychological effects and
behavioural issues.
Distress and psychological trauma for both children and parents are major
challenges in paediatric anesthesia.
The anticipation of pain , separation from family and fear of surgery are few factors that trigger preoperative anxiety.
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pCOMPARATIVE STUDY OF ORAL DEXMEDETOMIDINE VERSUS ORAL MIDAZOLAM AS PREMEDICATION IN PAEDIATRIC
ELECTIVE SURGERIES INTRODUCTION
Most of the children posted for surgery shows sign of significant preoperative anxiety with fear and may be uncooperative to surgeries and anaesthesia. Untreated anxiety may lead to difficulty in induction , increased postoperative pain and stress, need of rescue analgesics, emergence delirium and postoperative psychological effects and behavioural issues.
Distress and psychological trauma for both children and parents are major challenges in paediatric anesthesia 2. The anticipation of pain , separation from family and fear of surgery are few factors that trigger preoperative anxiety. Parental separation in stressful situation of surgery makes children more violent and restless. Unaccustomed place and situation under the strangers care during surgery is the cause for all the haemodynamic responses and psychological behavioural disorder.
Premedication not only causes amnesia but allays fear and anxiety from their minds. Makes the child detached from the surroundings in the state of deep sleep.
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Hence premedication is required for reducing anxiety in children struggling against mask acceptance during induction of anaesthesia and proper premedication provide calm and cooperative child for smooth induction.
AIM
Comparison of oral dexmedetomidine versus oral midazolam as premedication in Paediatric elective surgeries in terms of Acceptance of premedication, Anxiolysis, Sedation , Parental separation Anxiety, Mask acceptance behavior ,and Hemodynamic responses.
OBJECTIVES
In children issues of premedication are made more difficult as intravenous access is frequently absent and child may view the placement of IV cannula or administration of medication by intramuscular route are much invasive than by procedure itself 4 . Hence this study is conducted with oral preparation of premedication drugs to which children will be more compliant.
PRIMARY OBJECTIVE
Comparison of oral dexmedetomidine versus oral midazolam as premedication in paediatric elective surgeries in terms of Acceptance of premedication, Anxiolysis, Sedation, Parental separation, Mask acceptance behavior.
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SECONDARY OBJECTIVE
To compare haemodynamic responses between oral dexmedetomidine and oral midazolam pre operative , intra operative and postoperative periods for two hours.
Sedation can be defined as a state of drowsiness or sleep from which a subject can be aroused whereas anaesthesia is an un arousable state in which vital respiratory reflexes may be lost. So only conscious sedation is recommended as premedication. Using sub anaesthetic dose of anaesthetic drugs to cause sedation is not adviceable. So non anaesthetic sedative drugs are preferred.
When selecting a premedication few important factors which should be remembered are 21.
A child’s major fear about hospitalization is because of pain from needles and injections. For them hospitalization is synonymous with needles. Children tends to remember the premedication injection more than the operative procedure pain .Thus any form other than intramuscular is preferred for
premedication.
Children with frequent hospitalization need more preoperative medication than do the children coming for the first surgery. Experiences in the previous hospitalization forms the basis for their fears , so questions about
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the past experience are invaluable. The previous anaesthetic record if available should be reviewed with careful attention to the premedication agent.
Premedication effects in children vary producing different effects with some children sedated but some excited and restless. Few children may require about twice the recommended dose to produce desired level of sedation.
COMMON SEDATIVE DRUGS OPIOIDS
Not preferred in infants younger than 6months.Premedication with opioid may cause unpleasant dysphoria, preoperative and postoperative vomiting. Various routes of administration by which opioids can be given are oral, rectal, intravenous, intramuscular ,intranasal and oral transmucosal forms of administration has been focused with interest in recent years.
Fentanyl 0.5ug/kg intravenously Morphine 0.1-0.2mg/kg intramuscular Meperidine 1-2mg/k
Sufentanil 1-3ug/kg BENZODIAZEPINES
Midazolam is water soluble and has rapid onset and shorter duration of action.
Peak plasma concentration of midazolam occurs 45 minutes after Oral
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administration. Duration of action is 2hours. Oral dose is 0.25-0.75mg/kg.
Intravenous preparation can be given orally along with fruit juices, flavoured syrup and has been proved effective in many studies 32
Nasal midazolam is highly effective in reducing anxiety in 10-12 minutes but with disadvantage of nasal irritation.
Sublingually 0.2-0.3mg/kg . Rectally 0.5-1mg/kg.
Flunitrazepam can be given as rectal premedication 0.04mg/kg
Triazolam 0.02mg/kg orally effective, reaches peak serum concentrations in 1- 2hours
Diazepam has greater fat solubility and CNS effects. Oral dose 0.3mg/kg to 0.5mg/kg. It is not preferred choice in children because of the immature liver function.
PHENCYCLIDINE DERIVATIVES Ketamine ;
Blocks the NMDA receptor. Mechanism of action is by central dissociation of cortex from limbic system, providing analgesia and sedation . Preserves the upper airway muscle tone and respiratory drive. It is a bronchial
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smooth muscle relaxant and used in case of bronchospasm. Since it increases secretions antisialogogue has to be administered. Hallucination may occur at the time of recovery which can be avoided by benzodiazepines. It can be administered in a dose of oral 2-3mg/kg, nasal 3mg/kg ,intramuscular 2- 10mg/kg .
CHLORAL HYDRATE AND TRICLOFOS
When given orally both induce sedation effectively. They are metabolized to trichlorethanol which cause residual effect and prolonged sedation. Former tastes unpleasant while later is palatable, less potent and slower to act.
Chloral hydrate contraindicated in liver disease as it may lead to metabolic acidosis, renal failure and hypotonia.
MELATONIN
Induces natural sleep successfully when given in dose of 2-10mg orally ALPHA AGONIST
CLONIDINE
Centrally acting alpha2 agonist reliably produce preoperative sedation and anxiolysis in children. Excellent bioavailability after oral administration
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although onset of action is slow. Can be given orally , rectally with a dose of 1- 10 mcg/kg .Peak plasma concentration of clonidine occurs 60- 90 minutes for oral formulation and 50 minutes for rectal preparation 5 .
DEXMEDETOMIDINE
Newer , centrally acting alpha 2 agonist with more selective action on Alpha 2 adrenoceptor and a shorter half life. It has been shown to produce effective sedation, anxiolysis and analgesia in children without respiratory depression. It has limited effects on cardiorespiratory function .
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PHARMACOLOGY MIDAZOLAM
CHEMICAL STRUCTURE OF MIDAZOLAM
CHEMICAL STRUCTURE
8 –Chloro – 6 – ( 2-flurophenyl )-1 –methyl -4H –imidazo (1,5- a )(1,4)benzodiazepine hydrochloride.
INTRODUCTION
Midazolam was developed by Hoffman -la-roche in 1970’s 32.
Midazolam is a water soluble benzodiazepine with a imidazole ring 31 which contributes to the basicity and rapid metabolism and stability in aqueous solution .
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In physiological PH 90 % is un protonated and lipid soluble. Midazolam is a good amnestic and twice as potent as diazepam. It is available as a closed and open structure which is PH dependent .
PHYSICAL PROPERTIES 30
The pk of midazolam is 6.5 , which permits preparation of salts that are water soluble. Due to N2 ring which is pronated , injectable solution buffered to acidic PH of 3.5. This is significant because the structure of midazolam whether open ring or closed ring is dependent on the PH with the ring remaining open at PH < 4, maintaining water solubility.
The ring will close at PH >4 . Basicity of the drug allows it to be mixed with salts like lactic acid, hydrochloric acid which is responsible for the water solubility. The hydrochloride solution is better tolerated when given intravenously or intramuscular.
Water solubility obviates the need for a solubilising preparation such as propylene glycol which may interfere with absorption after intramuscular injection or may cause veno irritation when given intravenously. Midazolam is compatible with lactated ringer solution and mixed with acidic salts of other drugs including opioids and anticholinergics.
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MECHANISM OF ACTION
Midazolam acts by facilitating the effects of gamma-aminobutyric acid which is the inhibitory neuro transmitter of the central nervous system.
Midbrain and Ascending reticular formation is responsible for wakefulness , Limbic system for thought and mental function .Primary medullary site for muscle relaxation. Cerebellum for ataxia. It increases the affinity of the receptors for GABA by binding allosterically to specific site instead of stimulating them directly, resulting in enhanced chloride conductance and produce hyperpolarisation of the post synaptic cell membrane. Postsynaptic neurons are rendered more resistant to excitation which is responsible for anxiolysis , sedation , anterograde amnesia , anticonvulsant and skeletal muscle relaxant. Benzodiazepine interacts with alpha and gamma subunits of GABA a receptor.
a1-5 for sedation, a2-5 for anxiolysis , a1 brain ,
a2 hippocampus and amygdala , a5 extra synaptic,
GABA a receptor is large macromolecule contains physically separate
11
binding sites for GABA ,Benzodiazepine , Barbiturates , Etomidate, Propofol , Neurosteroid and alcohol producing synergistic effect 31.
Decreases Adenosine degradation by inhibiting nucleoside transporter.
Adenosine decreases cardiac oxygen demand by decreasing heart rate , vasodilatation.
PHARMACOKINETICS 29
Midazolam undergoes rapid absorption from the gastroinstestinal tract and promptly passes across blood brain barrier but has slow effect site equilibration time. So the intravenous dose should be sufficiently spaced. Only about 50% of orally given drug is available in systemic circulation because of substantial first pass metabolic effect.
Midazolam is extensively plasma protein bound. The lipid solubility of midazolam leads to rapid redistribution from brain to other inactive adipose peripheral tissues because of which it is short acting. Half life is 1-4 hours doubled in case of geriatric patients which reflects age related decrease in hepatic blood flow. Prolonged after cardio pulmonary bypass.
Onset of action -10 -20 minutes Duration of sedation 20 -180 minutes Volume of distribution 1.1 L /kg Clearance 1.6 ml/kg/mt
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METABOLISM
Midazolam is rapidly metabolized by cytochrome P 450 enzymes of liver and small instestine to both active and inactive metabolites. Principal metabolite is 1 hydroxy midazolam having half the activity of the parent compound. This metabolite is conjugated to
1- hydroxymidazolam glucuronide 31 and subsequently cleared by kidneys. The glucuronide metabolite has substantial pharmacologic activity when present in high concentrations which may occur in critically ill patients with renal insufficiency receiving continuous intravenous infusion.
EFFECTS ON VARIOUS SYSTEMS CENTRAL NERVOUS SYSTEM
Midazolam causes a reduced cerebral metabolic oxygen requirements and decreases cerebral blood flow. Vasomotor tone to carbon dioxide is preserved. Midazolam is potent anticonvulsant effective in treatment of status epilepticus. Withdrawal encephalopathy occurs in prolonged paediatric use.
EEG alpha wave decreases ,beta wave increases [midazolam unable to produce isoelectric EEG]
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RESPIRATORY SYSTEM
Midazolam produces dose dependent decrease in ventilation, depresses reflex of swallowing and decrease upper airway activity. When administered rapidly that too with opioid , transient apnea may occur.
CARDIOVASULAR SYSTEM
Midazolam produces a decrease in systemic blood pressure by decreasing systemic vascular resistance and increase in heart rate. Cardiac output is not altered by midazolam.
CLINICAL USES 30
Midazolam is the most widely used benzodiazepine for premedication in paediatric patients , intravenous sedation and induction of anaesthesia .
PREMEDICATION
Midazolam is the most often used oral premedication for children. Oral midazolam syrup when at the dose of 0.5mg/kg is effective for producing sedation and anxiolysis with minimal effects on ventilation. Maximum upto 20mg or 1mg/kg can be used. There is no delayed awakening with 0.5 mg /kg .
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Various routes of administration and doses of midazolam are Intravenous 0.05 - 0.1mg/kg , intramuscular 0.07-0.1 mg/kg , intrarectal 0.35-0.45mg/kg, intranasal 0.2mg/kg were used.
INTRAVENOUS SEDATION
Midazolam when given intravenously for sedation is effective during regional anaesthesia as well as for brief therapeutic procedures. Reduced hypoxic drive can lead to depressed ventilation and it is the most significant side effect of midazolam which is exaggerated when used along with opioids and CNS depressant drugs , COPD and elderly. 1-2.5 mg /intravenously [ onset 30- 60 sec, peak effect occurs within 5-6 minutes and of duration 15-80 minutes ]
INDUCTION OF ANAESTHESIA
Anaesthesia can be induced by the dose of 0.1-0.2 mg/kg /intravenously over 30-60 seconds which is facilitated by small dose of opioid. With use of synergistic drugs dose required can be reduced .
MAINTENANCE OF ANAESTHESIA
Midazolam may be administered to supplement opioid ,propofol , and inhaled anaesthetics during maintenance. Contact sensitivity half life increases
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modestly with increased duration of continuous infusion. Graudual awakening occurs .
POSTOPERATIVE SEDATION
Long term intravenous midazolam used for sedation in intubated patients usually results in relative saturation of peripheral tissues with midazolam and clearance from the systemic circulation become less dependent on redistribution into peripheral tissues and more dependent on hepatic metabolism . Pharmacologically active metabolites may accumulate with prolonged intravenous administration.
CONTRAINDICATIONS
Hyper sensitivity , acute narrow angle glaucoma ,shock , hypotension or head injury . Kidney or liver disease may slow down the elimination leading to prolonged duration of action and exaggerated effects.
SIDE EFFECTS
Long term use is associated with deficits in memory.
Depression may be worsened.
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With intravenous injections , paradoxical excitement can occur causing anxiety , involuntary movements ,aggressive or violent behaviour , uncontrollable crying or verbalization.
Sleepiness and impaired psychomotor and cognitive functions may persist next day as hangover effects.
Respiratory depression, hypotension and increased heart rate.
TOLERANCE AND WITHDRAWL
Use for more than 4 weeks may result in dependence , tolerance and withdrawal if stopped abruptly . Withdrawal symptoms can range from insomnia and anxiety to seizure and psychosis . Tolerance and resultant withdrawal syndrome are due to the receptor down regulation and GABA-A receptor expression alteration . These effects can be minimized by gradual reduction of dose of midazolam.
OVERDOSE
Symptoms of midazolam overdose include ataxia, dysarthria, nystagmus, slurred speech, somnolence, mental confusion, hypotension, respiratory arrest, vasomotor collapse, impaired motor functions, impaired coordination, impaired balance, dizziness, coma and death .
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TREATMENT OF OVERDOSE
Flumazenil is a specific benzodiazepine antagonist which is given in the dose of -0.02mg/kg . Repeat dose is given every 1 minute . The onset of action occurs in 1- 2 minutes and its effects last for 30- 60 minutes .
Opioids and other sedatives are not antagonized . Prolonged observation is necessary as resedation can occur in one hour . Flumazenil should not be used for routine dose reversal . Children may have exacerbations with flumazenil .
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DEXMEDETOMIDINE
Dexmedetomidine is a medetomidine stereoisomer with 4-[ (1S) -1-(2,3 – dimethylphenyl )ethyl ]- 1H- imidazole as a chemical formula.
C13H16 N2 HCL
It has high selectivity for alpha2 adrenergic receptor as agonist with a relatively high alpha 2 / alpha 1 activity ratio (1620 / 1 )
CHEMICAL FORMULA
MECHANISM OF ACTION
The alpha2 adrenoceptors by virtue of their sedative, analgesic, sympatholytic, anaesthetic sparing and haemodynamic stabilizing properties, have been used as an adjunct . Action on locus ceruleus, pons nucleus- mediates vigilance, memory, analgesia, arousal effects Centrally dexmedetomidine cause analgesia, sedation by inhibition of substance P in the
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nociceptive pathway at the dorsal root neuron and by activation of alpha2 receptor in locus ceruleus. Suppressing activity in descending noradrenergic pathway modulating nociceptive neuro transmission terminates propagation of pain signals producing analgesia .
There is decrease in proinflammatory products from immune cells to the injury site and increasing anti-inflammatory cytokines. This reinforce neuroprotective role of dexmedetomidine by decreasing perineural inflammation .
Its sedative and anxiolytic properties are exerted through alpha 2 adrenoreceptor in locus cereleus of pons . Binding at these G protein receptors causes inhibition of adenyl cyclase, which in turn, decreases CAMP production ,alters ion channel conductance and prevents norepinephrine release. The analgesic effects of dexmedetomidine are exerted through stimulation of alpha2 adrenoceptor in dorsal horn of spinal cord , which inhibits substance p release .
PHARMACOKINETICS 5
Dexmedetomidine exhibits linear pharmacokinetics. Bioavailability of oral route is 16 % , intranasal route is 65 %, buccal route is 82% Intramuscular route is 99 %,intravenous route is 93% . 94% protein bound ,half life 2-3 hours, volume of distribution in adults 1.31 L/kg and in children 1.5 -2.2L /kg .
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Undergoes complete hydroxylation through direct glucuronidation and cytochrome p450 metabolism in liver . Metabolites excreted in urine 95% , feces 4%. . Clearance adults 39 l/hour , children 0.56 – 1l /kg / hour .
PROPERTIES
Dexmedetomidine is clear , colorless , isotonic ,Preservative free ,with no additives chemical stabilizer free . Molecular weight of about 236. Its pka is 7.1 , partition coefficient is 2.89. Compatible with 0.9 normal saline in water , 5% dextrose in water , 20% mannitol magnesium sulphate solution , 0.3%
potassium chloride solution. When given orally onset of action is by 30- 45 minutes , whereas intranasally within 25 minutes .
PHYSIOLOGICAL EFFECTS 34 CARDIOVASCULAR SYSTEM
Decreased heart rate [ direct effect on sinus and AV node]
Biphasic blood pressure response . Hypertension is followed by dose dependent hypotension . Reduced plasma catecholamines. Transient increase in pulmonary vascular resistance .
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RESPIRATORY SYSTEM
Dexmedetomidine has ability to maintain respiratory drive and preserve airway patency in presence of increasing sedation .
CENTRAL NERVOUS SYSTEM
Preserves both somatosensory and motor evoked potentials. Arousable sedation – patients appear asleep but are arousable to verbal commands . No effects on intracranial or cerebral perfusion pressures.
GIT
Dose dependent reduction in transit time
THERMAL REGULATION
Decreases shivering , vasoconstriction and non shivering thermogenesis . It is used successfully to terminate postoperative shivering in children . Dexmedetomidine reduces centrally mediated metabolic heat production and inhibits lipolysis , interfering with non shivering thermogenesis .
OVERDOSE
Dexmedetomidine overdose associated with transient hypertension and prolonged sedation , with an absence of respiratory depression .
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Effects of dexmedetomidine are antagonized easily by administering alpha 2 adrenoreceptor antagonist Atipamezole .
CLINICAL APPLICATIONS 33 PREMEDICATION
Dexmedetomidine is novel premedication agent producing anxiolysis, sedation, analgesia and haemodynamic stability . May offer additional benefits of antisialogogue and reduced gastric secretions .
SEDATION FOR NON INVASIVE PROCEDURES
Dexmedetomidine provide effective sedation for non invasive procedures such as CT , MRI , and EEG recording . Used as sole agent or in combination of other agent. Loading dose of 1mcg / kg over 10 minutes followed by an infusion 0.5 mcg /kg /hour .During dexmedetomidine sedation the EEG resembles of non rapid eye movement sleep and it does not interfere with ability to detect EEG activity .
SEDATION FOR INVASIVE PROCEDURE
Dexmedetomidine has been used as sedation for central line placement , chest tube insertion , bronchoscopy , lithotripsy and cardiac catheterization . In
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adult combination with propofol or fentanyl for upper and lower gastroinstestinal endoscopic procedures .
PREVENTION AND TREATMENT OF EMERGENCE DELIRIUM Prophylactic dexmedetomidine at dose of 1mcg /kg IV at the end of surgery has shown to reduce the incidence of emergence delirium in children following anaesthesia with sevoflurane .
ANALGESIA
Dexmedetomidine has proven opioid sparing effect in adult . In children 1mcg/kg of it produces comparable analgesia to morphine 100mcg/kg
INTENSIVE CARE UNIT
In adult and paediatric intensive care unit dexmedetomidine has a role as a primary sedative , as second line following benzodiazepines or opioid sedation ,as bridge for extubation ,for substance withdrawl and to decrease ICU delirium .
SCOLIOSIS SURGERY
Dexmedetomidine preserves both somatosensory and motor evoked potentials it may be of particular benefit as adjunct for total IV anaesthesia .
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CARDIAC SURGERY
In both adult and children IV dexmedetomidine attenuates the haemodynamic and neuroendocrine responses at the time of incision , sternotomy, and after bypass
IN CHALLENGING PATIENTS
Used in patients with obstructive sleep apnea, difficult airway, or mediastinal masses for sedation without significant respiratory depression . Use to treat cyclical vomiting in children, tachy arrythmias and shivering .
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REVIEW OF LITERATURE
1. JANNU V , MANE R et al 1 . in Saudi journal of anaesthesia . 2016;10(4);
390 -394 , had published “ comparison of oral midazolam and oral dexmedetomidine as a premedication in paediatric anaesthesia ” assessing preoperative sedation ,anxiolysis ,response to parental separation ,mask acceptance quality and postoperative agitation . Sixty children,ASA I @ II ,aged 1-7 years posted for elective surgeries were allocated into two groups receiving oral midazolam 0.75 mg/kg and dexmedetomidine 4 ug/kg respectively 40 minutes prior to induction of anaesthesia . All the children of the both groups produced desired sedation level before induction .(P > 0.05 ) . Peak sedative effect for midazolam at 23.4 ± 4.92 minutes and 40.3 ± 3.93 minutes (P <0.05). There is no significant difference in parental separation and mask acceptance quality . In PACU group D had low agitation score compared to group M .
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2. FARITUS S Z et al 2 ,in anaesthesiology of pain medicine .2015;5 (3).
Oral dexmedetomidine versus oral midazolam as anaesthetic premedication in children undergoing congenital heart surgery. Sixty children aged 2- 12 years, scheduled for on pump congenital heart surgery was randomly allocated into two groups receiving oral midazolam 0.5 mg/kg and dexmedetomidine 2 ug/kg 45 minutes prior to anesthesia .children’s anxiety, mask acceptance behavior ,haemodynamic measures, and cardiopulmonary outcomes was recorded and compared. Both the drugs has same effects on cardiopulmonary outcomes and haemodynamic measures (P> 0.05). No significant statistical difference in sedation score P(> 0.05) between the groups. Dexmedetomidine has better mask acceptance behavior than midazolam P (<0.05).
3. AKIN A,BAYRAM et al 6 “ dexmedetomidine vs midazolam for premedication of paediatric patients undergoing anaesthesia” paediatr anaesth 2012;22;871-6. Good mask acceptance was achieved in group M 82.2% And 60% in group D. No significant difference in sedation and anxiolysis. Number of patients who required postoperative analgesia was higher for midazolam group.
4. KAMAL K ,SOLIMAN et 17 al in ain shams j anaesthesiology .2008 ;1;1 18 . Oral dexmedetomidine versus oral midazolam as premedication in children. Prospective randomized study in 90 children of 4-12 years for ophthalmic surgery. Study concluded that oral midazolam is superior to oral
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dexmedetomidine and oral clonidine with faster onset of sedation, higher sedation score, lower anxiety score ,easy parent separation and excellent mask accepatance.
5 .PRABHU M.MEHANDALE 4 in Indian journal of anaesthesia 2017 ;61 (2);p “comparison of oral dexmedetomidine versus oral midazolam as premedication to prevent emergence agitation after sevoflurane anaesthesaia in paediatric patients”. This study is prospective double blinded study involved 90patients of age 1-10 years,undergoing <2hours of elective surgeries under sevoflurane genral anaesthesia randomized in two groups midazolam( group A) and dexmedetomidine (group B) as oral premedication and sedation level before induction ,haemodynamic parameters,and recovery time ,incidence and severity of EA, postoperative pain and requirement of rescue analgesic were assessed. Premedication of oral dexmedetomidine provides smooth induction with good recovery, reduced EA and also provided better analgesia.
6 . KUMARI S, et al 5 in anaestnesia “comparison of oral clonidie, oal dexmedetomidine and midazolam for premedication in paediatric patients undergoing elective surgery” . anaesthesia essays and researchers. 2017;11 (1) In this prospective ,double –blind ,randomized controlled study showed that oral clonidine 4ug/kg ,dexmedetomidine 4ug/kg and midazolam 0.5mg/kg provided effective sedation, anxiolysis, acceptable separation from parents, and
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satisfactory mask acceptance in children of age 4- 12 years undergoing ophthalmic surgery under genral anaesthesia. Found oral midazolam was better than other drugs showing easy separation and excellent mask acceptance behavior. Onset of sedation was delayed in clonidine and dexmedetomidine( 30 minutes) when compared to midazolam group( 15 minutes).
7, Sultan keles, Ozlem kocaturk .et al. In Europe PMC , in “ the study the effect of oral dexmedetomidine premedication on preoperative cooperation and emergence delirium in children undergoing dental procedures”, 50 children of age 2- 6 years received 1ug/kg of oral dexmedetomidine in apple juice 45 minutes before induction whereas group c received plain apple juice. Ramsay sedation score and mask acceptance behavior was significantly higher in DEX group.
8. Sun y,lu y,Huang Y, Jiang H 16 . Is dexmedetomidine superior to midazolam as premedication in children ? A meta analysis of randomized controlled trials. Paediatr Anaesthesia.2014 : 24 ;863-74.[pubmed]. Showed that dexmedetomidine premedication is superior to midazolam in producing satisfactory sedation on parent separation and mask acceptance. Also suggested that their conclusions shall be viewed in light of heterogeneity by differences in various studies as regards to childrens age ,doses and routes of administration.
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9. Yuen VM, Hui TW, Irwin MG, Yuen MK 9 . “A comparison of intranasal dexmedetomidine and oral midazolam for premedication in paediatric anaesthesia”; A double blinded randomized controlled trial. anaesth analg.2008;106;1715-21.[pubmed]. In their study showed nasal dexmedetomidine 1ug/kg produced same effect as oral midazolam 0.5mg/kg in providing satisfactory parent separation and mask acceptance at induction.
Children of dexmedetomidine group was more sedated which showed intranasal route had reached peak effect faster and has higher bioavailability as compared to oral dexmedetomidine.
10. Mohamed A Daabiss and Mohamed Hashish,9 23 published a study in the british journal of medical practitioners December 2011,study in the British journal of medical practitioners December 2011,volume 4 ,n0;4,named
“dexmedetomidine versus ketamine combined with midazolam; a comparison of anxiolytic and sedative premedication”. The aim of the study is to evaluate the efficacy of oral dexmedetomidine as hypnotic and anxiolytic when compared with oral ketamine and midazolam for paediatric premedication. 66 children were randomized into two groups receiving dexmedetomidine 3mcg/kg and other given with 0.25mg/kg of oral midazolam with 2.5mg/kg of ketamine. Haemodynamic variables, sedation and anxiolytic score recorded before and every 5min of post drug administration for 30minutes. Parent separation and mask acceptance score recorded at 30 minutes. The study
30
concluded that premedication with midazolam/ketamine was superior to dexmedetomidine providing haemodynamic stability and good parental separation although later was accepted by the children. No significant side effects in both the medications and emergence from anaesthesia.
11. SINGH N ,et al 11 , in a study in the journal of clinical paediatric dentistry 2002 winter ;26 (2),161 -164, “ A comparative evaluation of oral midazolam withother sedatives as premedication in paediatric dentistry “ evaluated the efficacy and safety of oral midazolam as a sedative compared with other older agents like trichlofos and promethazine in paediatric dentistry . The study was conducted on ninety children in age grou of 3 – 9 years of ASA requiring some short dental procedure.on the basis of drug administered randomly divided into three groups . the effects were evaluated in terms of onset of action , sedative effect, ease of treatment completion ,recovery time and postoperative amnesia.
The study concluded that oral midazolam is the best drug out of all three .
12. ARATHI PAPINENI ,et al , 25 , in international journal of paediatric dentistry 2014 ,24 ,2-14 ,published a study on “ safety of oral midazolam sedation use in paediatric dentistry ;a review “ .the study aimed at evaluating the side effects and other adverse outcomes when oral midazolam was used for behavior management in paediatric dentistry . The review of published literature relating to the safety and side effects of oral midazolam used in
31
paediatric dentistry was done. Both randomized controlled trials and non randomized trial were assessed. The side effects reported was recorded and classified as significant or not. The percentage prevalence of significant or minor side effects per episode of treatment was calculated .sixteen papers in randomized controlled trials met the inclusion criteria. Minor side effects reported (14%) ,with nausea and vomiting being the most frequent . 11 papers of non randomized studies were also recorded. With paradoxical reaction being most common at 3.8%. The author concluded that significant and major side effects were rare and minor events may occur , but precise figure of it could not achieved due to poor report of such events;
13, K.E.WILSON et al , 27 in British dental journal ,April 2002 ,volume 192 ,n0 8 ,457 -462 ,published “ A study of effectiveness of oral midazolam sedation for orthodontic extraction of permanent teeth in children ;A prospective , randomized ,controlled ,crossover trial ” . The aim of the study was to assess the effectiveness ,safety and acceptability of oral midazolam as a sedative when used for orthodontic extraction of permanent teeth in children . 26 children of age 10-16 years ( ASA1) , reffered for orthodontic extraction of premolar or canine teeth under sedation , were included in the study. Each child had two treatment sessions for the extraction of the equivalent teeth on opposite sides of the mouth . Each subject was sedated with oral midazolam
32
( 0.5mg/kg ) or nitrous oxide and oxygen (70 / 30%) at first visit and the alternate form at second visit. At each visit two teeth extracted. Heart rate, oxygen satuaration, respiration rate, sedation and behavioural scores were recorded every five minutes. The mean heart rate and respiratory rate in both group is similar. The lowest mean oxygen saturation for nitrous oxide and midazolam sedation were 97.7 and 95.0% respectively. Though desaturation was within safe limits. The mean sedation level was greater in midazolam group. The study concluded oral midazolam appeared to be safe and effective form of sedation in children coming for dental procedures.
14. Saad A Sheta , et al ,2 in the international journal of paediatrics 2009, compared different doses of oral midazolam for premedication in paediatric age group. The doses of oral midazolam in 0.5mg/kg, 0.75mg/kg and 1mg/kg were for effectiveness in anxiolysis during parental separation and vene puncture.
Found that 0.75 mg/kg oral midazolam as effective and acceptable dose as premedication and does not alter recovery time after general anaesthesia.
15. THOMAS R VETTER 27 , in the journal of clinical anesthesiology ,January – February 1993, volume 5,issue 1,58-61,by a study “ A comparison of midazolam, diazepam and placebo as oral premedicants in younger children
“ concluded that neither midazolam nor diazepam is necessary in children < 6 years and the routine use of premedication is not necessary in this age group.
33
Premedication should be given based on the selective children at risk and with psychological imbalances.
16. Iuz Maria Gomez B et al 23 , in Colombian journal of anaesthesiology 2013 41(1) 4-9 have published a study on “ efficacy of anaesthetic premedication in paediatric patients using oral midazolam and acetoaminophen. Observation study”. A prospective descriptive observational study was conducted to analyse the efficacy of the premedication with a mix of midazolam and acetaminophen ,sedation –anxiety scores were given and the parent separation score and mask acceptance score were analysed .216 children ASA PS1 or 11, scheduled for procedure that required general anaesthesia.
Anxiety –sedation scales, and tolerance to parent separation were assessed.
This study concluded that midazolam and acetoaminophen proved effective as premedication in children and reduced the anxiety in children at the time of parent separation and also acceptance of the inhalation anaesthetic induction in a better way,thus improving the whole experience both for children and parents.
17. Chandni Sinha, et al 20 , in journal of anesthesiology clinical pharmacology had published a study on “ comparative evaluation of midazolam and butarphanol as oral premedication in paediatric patients”. The aim of study was to compare the efficacy of oral midazolam of 0.05mg/kg with
34
oral butarphanol in the dose of 0.2mg/kg with regards to sedation ,anxiolysis, rescue analgesic requirement and recovery profile. In this double blinded study ,60 paediatric patients of ASA1 and 11 of age group 2-12 years posted for elective surgery were randomized to Receive either oral midazolam or oral butarphanol 30 min before induction of Anaesthesia. The children evaluated for levels of sedation and anxiety at the time `of parent separation ,venepuncture and at facemask application for induction. The author had concluded that Butarphanol had better sedation levels than oral midazolam but had comparable anxiolysis at separation of children from parent and also proved that midazolam as a better anxiolytic on venepuncture and facemask application. Butarphanol demonstrated additional analgesics property and reduced need for supplemental analgesics .
18. Feld LH, Negus JB, White PF 8 . Oral midazolam preanaesthetic medication in paediatric outpatients. Anesthesiology .1990;73;831-4 [pubmed].
As early as 1990 In this study showed oral midazolam 0.5 -0.75mg/kg was safe and effective premedication in paediatric surgical patients. Bioavailability of oral midazolam varies 15- 27% in children.
19. Mc Millan CO ,Sphahr- Schopfer IA, Sikich N 7 , Premedication of children with oral midazolam.Can J Anaesth. 1992;39;545- 50.[pubmed] in
35
their study found that oral midazolam in dose of 0.5mg/kg was safe and effective for premedication ,but a dose of 0.75 mg/kg were caused more side effects like loss of balance ,blurred vision ,and dysphoric reactions with no additional benefits.
20. Suman Arora et al 34 , prospective ,randomized, double blinded clinical trial conducted with 80 children of age 1-4 years. Children divided into three groups group M received 0.5mg /kg, of oral midazolam, group C received 4 ug/kg of oral clonidine , group D received 4 ug/kg of dexmedetomidine 90 minutes before surgery mixed in honey. Sedation score, mask acceptance score, parental separation score were measured on four point scale. Study showed comparable sedation with all three drugs, parental separation was easy in group M and satisfactory mask acceptance in group M.
36
MATERIALS AND METHODOLOGY STUDY DESIGN
This is a prospective double blinded randomized controlled clinical trial.
Since it is time bound study all cases who met inclusion criteria during the study period had included. Randomization was done by draw of lots method.
Midazolam and Dexmedetomidine written on equal number of lots ,50 each.
When the patients meets criteria for study, the patient was asked to pick up a lot and drug in the lot was given by the assistant professor posted in the theatre who was not included in the study. The assistant professor maintained a list of the names of the patient, and the group to which they belong.
STUDY PLACE
Coimbatore medical college hospital ; paediatric surgery operation theatre.
STUDY PERIOD
Period of one year may 2018 –may 2019
STUDY POPULATION
After clearance from institutional ethical committee and after obtaining informed written consent from parents this study was conducted with sample size of 100 children of both sexes of age 2-12 years scheduled for paediatric elective surgeries of American society of anaesthesiology of physical status I
37
and II Sample size was calculated with G*power 3.13 version with reference to parent Study.
SELECTION CRITERIA INCLUSION CRITERIA
ASA I and II physical status
2-12 years weighing less than 20 kg
Elective paediatric surgeries
EXCLUSION CRITERIA
ASA physical status III and 1V
Hepatic and renal complication
Emergency operation
Mental disability
History of allergy to midazolam and dexmedetomidine
Abnormal airway
Active respiratory tract infection
Raised intracranial pressure
Depressed conscious level
38
GROUPS
GROUP M ; 50 children receiving oral midazolam 0.5 mg/kg GROUP D ; 50 children receiving oral dexmedetomidine 2ug/kg
MATERIALS
Prepared oral midazolam formulation prepared by mixing 0.5mg/kg of midazolam taken from a preservative free midazolam ampoule 5mg/ml to which 5% dextrose was added .
Prepared oral dexmedetomidine formulation prepared by mixing 2ug/kg of dexmedetomidine taken from a preservative free dexmedetomidine ampoule 100ug/ml to which 5% dextrose was added.
Drug filler
22G intravenous cannula and IV fluids
With all emergency and general anaesthetic drugs cart
2ml and 5ml syringes
METHODOLOGY
100 children with average age of 2-12 years undergoing elective paediatric surgeries under general anaesthesia were randomized into two groups of 50 each by draw of lots method. A complete pre anaesthetic evaluation was done and the parents were explained about the effects ,possible risks and complication of the premedicants in detail and informed written
39
consent was obtained.The child was shifted to premedication room along with their parents. Baseline Haemodynamic parameters such as heart rate ,respiratory rate, blood pressure, oxygen saturation are recorded as baseline.
Oral midazolam 0.5mg/kg (IV drug containing 5mg/ml made into total volume of 0.2ml/kg mixed with 5% dextrose). Oral dexmedetomidine 2ug/kg (IV containing 100ug/ml mixed with 5% dextrose into total volume of 0.2ml/kg).
Amount of drug adjusted to 5ml for all. The drug was administered using drug filler according to stipulated group the child belongs to ,by the assistant professor who was not involved in the study 45 minutes prior to induction of anaesthesia. Haemodynamic paramaters were monitored every 15 minutes after Premedication, intra operatively and for postoperative periods of 2hours.
The following paramaters were assessed and recorded 6 .
ACCEPTANCE OF PREMEDICATION ON THREE POINT SCALE
1 = Accepts it / likes the taste
2 = Accepts it / but dislikes the taste
3 = Spits / vomits the premedication
Score 1 or 2 was considered as satisfactory acceptance of oral Premedication.
40
On arrival in operation theatre ,the children ‘s baseline heart rate, blood pressure, respiratory rate ,oxygen saturation was recorded.
Following parameters was assessed and recorded using appropriate scales respectively
DEGREE OF SEDATION ON THREE POINT SCALE
1 = Awake
2 = Drowsy
3 = Asleep
Score of 2 or 3 was considered as acceptable sedation.
41
ANXIETY SCALE ASSESSED ON A FIVE POINT SCALE
1 = Quiet and comfortable
2 = Uneasy
3 = Worried or anxious
4 = Very worried or very upset
5 = Frightened or terrified
Score of 1 or 2 was considered as acceptable anxiolysis.
Behavior of child on separation from parents was assessed and recorded on four point scale.
PARENT SEPARATION ANXIETY SCALE
1 = Easy separation
2 = Whimpers but is easily reassured
3 =Cries and cannot be easily reassured ,but not clinging to parents
4 = Cries and clinging to parents
Score of 1 and 2 was considered as acceptable.
42
MASK ACCEPTANCE BEHAVIOUR ASSESSED ON FOUR POINT SCALE
1 = Calm and cooperating
2 = Anxious but without resistance
3 = Anxious with slight resistance
4 = Crying and /or struggling against mask Score of 1 and 2 was considered as acceptable.
All children were uniformly given inj. atropine 10ug/kg and inj. fentanyl 2ug/kg IV as premedication. Adequately preoxygenated and induced with inj.
propofol 2mg/kg , inj. atracurium 0.5mg/kg and intubated with appropriate sized endotracheal tubes. Maintained with O2/ N2O mixture at 4 litres of fresh gas flow at 50:50 ratio ,and sevoflurane 0.2-0.4%. Intraoperative haemodynamic parameters monitored every 15 minutes and recorded. At the end of surgery after adequate airway reflexes and adequate muscle power by reversal with inj. neostigmine 50ug/kg and inj. atropine 10ug /kg patient extubated in lateral position. Post operatively pulse rate ,blood pressure, oxygen saturation and respiratory rate was recorded every thirty minutes for two hours.
43
STATISTICAL ANALYSIS
Datas collected from the study were statistically analysed. The collected data was analysed with IBM SPSS 20 version. To describe about the data descriptive statistics frequency analysis used, percentage analysis were used for categorical variables and for continuous variables the mean and standard deviation were used.
To find the significance difference between the bivariate samples in paired groups paired sample t-test used for the normal data and for Independent variables between the groups ( Midazolam and Dexmedetomidine) unpaired sample t-test for the normal data was used.
For the multivariate analysis the repeated measures of two way Anova test was used. To find the significance in categorical data Chi-square test was used. In all the above statistical tools the probability value < 0.05 is considered as significant level.
OBSERVATION AND RESULTS P value ≤ 0.01 Highly Significant P value ≤ 0.05 Significant
P value ≥ 0.05 Not Significant
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tests - Means: Difference between two independent means (two groups) Analysis: A priori: Compute required sample size
Input: Tail(s) = One Effect size d = 0.51
α err prob = 0.05
Power (1-β err prob) = 0.80 Allocation ratio N2/N1 = 1
Output: Noncentrality parameter δ = 2.5243712 Critical t = 1.6608814
Df = 96
Sample size group 1 = 49 Sample size group 2 = 49 Total sample size = 98
Rounded the sample size into 50 in each groups.
45
DEMOGRAPHIC VARIABLES
Independent Samples Test
GROUP N Mean Std.
Deviation
Std. Error Mean
t Value
P Value
Age
DEXMEDETOMIDINE 50 3.8300 1.73679 .24562 0.831 0.408 MIDAZOLAM 50 4.1200 1.75418 .24808
P>0.05 No Difference in age in two groups
There is no statistical significant difference ( p > 0.05 ) between two groups in terms of age.
KEY WORDS IN CHART ; PR -PUSERATE, BP-BLOOD PRESSURE, RR-RESPIRATORY RATE, SPO2- OXYGEN SATURATION,
IOP-INTRAOPERATIVE PERIOD ,POP- POSTOPERATIVE PERIOD, T- TIME IN MINUTES.
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5
DEXMEDETOMIDINE MIDAZOLAM
3.83 4.12
Comparison of Age for Two groups
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Sex * GROUP Crosstabulation
GROUP Total
DEXMEDETO MIDINE
MIDAZOLAM
Sex
Male Count 37 36 73
% within GROUP 74.0% 72.0% 73.0%
Female Count 13 14 27
% within GROUP 26.0% 28.0% 27.0%
Total Count 50 50 100
% within GROUP 100.0% 100.0% 100.0%
Pearson Chi-Square=0.51 p=0.822
P>0.05 No statistical significant Difference in age in two groups
Among 50 children in group M 36 male and 14 females whereas in group D 37males and 13 females. There is no statistical significant difference between the two groups in gender distribution.
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
DEXMEDETOMIDINE MIDAZOLAM
74% 72%
26% 28%
Comparison of Gender for Two groups
Female Male
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Independent Samples Test
GROUP N Mean Std.
Deviatio n
Std.
Error Mean
t Valu
e
P Valu
e Weigh
t
DEXMEDETOMIDIN E
5 0
11.500
0 3.82393 .5407 9
0.604 0.547
MIDAZOLAM 5
0 12.000
0 4.43087 .6266 2
P>0.05 No statistical significant difference in Weight between the two groups.
0 2 4 6 8 10 12
DEXMEDETOMIDINE MIDAZOLAM
11.5 12
Comparison of Weight for Two groups
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Descriptive Statistics
GROUP Mean Std.
Deviation
N
Baseline pulse rate[PR]
DEXMEDETOMID
INE 92.8000 7.53766 50
MIDAZOLAM 94.4200 6.21417 50
Total 93.6100 6.92076 100
Pre medication T[
time]15 PR
DEXMEDETOMID
INE 92.2600 7.04160 50
MIDAZOLAM 93.3800 6.08072 50
Total 92.8200 6.56957 100
Pre medication T30 PR
DEXMEDETOMID
INE 90.0600 6.81059 50
MIDAZOLAM 90.7000 5.35000 50
Total 90.3800 6.10147 100
Pre medication T45 PR
DEXMEDETOMID
INE 86.6000 6.93115 50
MIDAZOLAM 86.8800 5.39705 50
Total 86.7400 6.18179 100
IOP [
intraoperative]T0 PR
DEXMEDETOMID
INE 86.2200 6.98479 50
MIDAZOLAM 87.1200 5.35910 50
Total 86.6700 6.21021 100
IOP T30 PR
DEXMEDETOMID
INE 83.7400 7.04739 50
MIDAZOLAM 83.6000 5.82044 50
Total 83.6700 6.43076 100
IOP T45 PR
DEXMEDETOMID
INE 82.7400 7.15088 50
MIDAZOLAM 82.4400 5.28054 50
Total 82.5900 6.25566 100
IOP T60 PR
DEXMEDETOMID
INE 81.9400 6.97930 50
MIDAZOLAM 81.8400 5.62922 50
Total 81.8900 6.30840 100
IOP T90 PR
DEXMEDETOMID
INE 81.5800 6.95199 50
MIDAZOLAM 81.8600 5.56230 50
Total 81.7200 6.26531 100
IOP T120 PR DEXMEDETOMID
INE 82.2000 6.58694 50
49
MIDAZOLAM 81.8400 5.31213 50
Total 82.0200 5.95603 100
POP
[postoperative]T0 PR
DEXMEDETOMID
INE 82.6000 6.67618 50
MIDAZOLAM 82.3200 5.56021 50
Total 82.4600 6.11410 100
POP T30 PR
DEXMEDETOMID
INE 83.5800 6.37626 50
MIDAZOLAM 83.6200 5.05032 50
Total 83.6000 5.72254 100
POP T60 PR
DEXMEDETOMID
INE 84.8000 6.34710 50
MIDAZOLAM 83.8000 5.06287 50
Total 84.3000 5.73400 100
POP T90 PR
DEXMEDETOMID
INE 85.2600 6.19681 50
MIDAZOLAM 84.7600 5.04494 50
Total 85.0100 5.62731 100
POP T120 PR
DEXMEDETOMID
INE 85.9000 5.78263 50
MIDAZOLAM 85.3600 4.71974 50
Total 85.6300 5.25829 100
Tests of Within-Subjects Effects
Source Type III
Sum of Squares
df Mean
Square F Sig.
Time 21184.709 14 1513.194 274.941 p<0.001 Time * GROUP 173.557 4.436 39.128 2.252 .056 Error(Time) 7551.067 434.695 17.371
Note: There is no statistical significant difference in groups and timings. (p
>0.05)
50
Estimates
GROUP Time Mean Std.
Error
95% Confidence Lower Upper
DEXMEDETO MIDINE
Baseline PR 92.800 .977 90.861 94.739 Pre medication T15 92.260 .930 90.414 94.106 Pre medication T30 90.060 .866 88.341 91.779 Pre medication T45 86.600 .878 84.857 88.343 IOP T0 PR 86.220 .880 84.473 87.967 IOP T30 PR 83.740 .914 81.926 85.554 IOP T45 PR 82.740 .889 80.976 84.504 IOP T60 PR 81.940 .897 80.161 83.719 IOP T90 PR 81.580 .890 79.813 83.347 IOP T120 PR 82.200 .846 80.521 83.879 POP T0 PR 82.600 .869 80.876 84.324 POP T30 PR 83.580 .813 81.966 85.194 POP T60 PR 84.800 .812 83.189 86.411 POP T90 PR 85.260 .799 83.674 86.846 POP T120 PR 85.900 .746 84.419 87.381
MIDAZOLAM
Baseline PR 94.420 .977 92.481 96.359 Pre medication T15 93.380 .930 91.534 95.226 Pre medication T30 90.700 .866 88.981 92.419 Pre medication T45 86.880 .878 85.137 88.623 IOP T0 PR 87.120 .880 85.373 88.867 IOP T30 PR 83.600 .914 81.786 85.414 IOP T45 PR 82.440 .889 80.676 84.204 IOP T60 PR 81.840 .897 80.061 83.619 IOP T90 PR 81.860 .890 80.093 83.627 IOP T120 PR 81.840 .846 80.161 83.519 POP T0 PR 82.320 .869 80.596 84.044 POP T30 PR 83.620 .813 82.006 85.234 POP T60 PR 83.800 .812 82.189 85.411 POP T90 PR 84.760 .799 83.174 86.346 POP T120 PR 85.360 .746 83.879 86.841 Key words PR –pulse rate, IOP-intra operative period, POP –postoperative. T – time in minutes.
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There is no significant statistical difference in terms of variability in pulse rate.
75 80 85 90 95 100
Baseline PR Pre medication T15 PR Pre medication T30 PR Pre medication T45 PR IOP T0 PR IOP T30 PR IOP T45 PR IOP T60 PR IOP T90 PR IOP T120 PR POP T0 PR POP T30 PR POP T60 PR POP T90 PR POP T120 PR Comparison of PR in two groups
DEXMEDETOMIDINE MIDAZOLAM
52
Comparison of Systolic blood pressure
Descriptive Statistics
GROUP Mean Std.
Deviation
N
Baseline
DEXMEDETOMID
INE 85.3800 11.97939 50
MIDAZOLAM 83.0400 11.31724 50
Total 84.2100 11.65349 100
premedication 15
DEXMEDETOMID
INE 85.3800 11.88017 50
MIDAZOLAM 83.5000 10.82750 50
Total 84.4400 11.34787 100
premedication 30
DEXMEDETOMID
INE 84.4600 11.29242 50
MIDAZOLAM 82.5200 10.50800 50
Total 83.4900 10.89574 100
premedication t45
DEXMEDETOMID
INE 82.9600 10.25583 50
MIDAZOLAM 79.6800 15.28563 50
Total 81.3200 13.05457 100
IOP T0
DEXMEDETOMID
INE 83.1600 10.32208 50
MIDAZOLAM 81.3000 9.29615 50
Total 82.2300 9.81738 100
IOP T15
DEXMEDETOMID
INE 82.6400 10.05649 50
MIDAZOLAM 81.0200 8.93626 50
Total 81.8300 9.49966 100
IOP T30
DEXMEDETOMID
INE 82.0600 9.43162 50
MIDAZOLAM 80.5000 8.22949 50
Total 81.2800 8.84100 100
IOP T45
DEXMEDETOMID
INE 81.7200 9.29569 50
MIDAZOLAM 79.3800 7.94340 50
Total 80.5500 8.68224 100
IOP T60
DEXMEDETOMID
INE 81.6600 9.47308 50
MIDAZOLAM 79.3200 7.76554 50
Total 80.4900 8.69749 100
IOP T90 DEXMEDETOMID
INE 81.5600 9.18553 50
53
MIDAZOLAM 79.5800 7.57571 50
Total 80.5700 8.43544 100
IOP T120
DEXMEDETOMID
INE 81.9600 9.40681 50
MIDAZOLAM 79.6200 7.85296 50
Total 80.7900 8.70074 100
POP T0
DEXMEDETOMID
INE 82.0400 9.43498 50
MIDAZOLAM 80.5200 7.92887 50
Total 81.2800 8.70398 100
POP T30
DEXMEDETOMID
INE 82.5600 9.31569 50
MIDAZOLAM 81.1600 8.06443 50
Total 81.8600 8.69694 100
POP T60
DEXMEDETOMID
INE 83.2800 9.03743 50
MIDAZOLAM 81.5000 8.24683 50
Total 82.3900 8.65371 100
POP T90
DEXMEDETOMID
INE 83.9200 9.30183 50
MIDAZOLAM 81.8000 8.37635 50
Total 82.8600 8.87058 100
POP T120
DEXMEDETOMID
INE 84.4800 9.39005 50
MIDAZOLAM 82.3000 8.05149 50
Total 83.3900 8.77081 100
Tests of Within-Subjects Effects Source Type III Sum
of Squares df Mean Square F Sig.
Time 2531.378 15 168.759 15.631 p<0.00
1
Time * GROUP 78.700 15 5.247 .486 .949
Error(Time) 15871.048 1470 10.797
Note: There is no statistical significant difference in groups(p>0.05).
Key words ; IOP-intra operative period, POP –postoperative period. T –time in minutes.
