EVALUATION OF DEGREE OF HAEMODYNAMIC STRESS ATTENUATION PRODUCED BY COMBINATION OF LIDOCAINE AND ESMOLOL VERSUS LIDOCAINE OR
ESMOLOL ALONE DURING LARYNGOSCOPY AND INTUBATION
DISSERTATION SUBMITTED FOR DOCTOR OF MEDICINE
BRANCH X (ANAESTHESIOLOGY) APRIL 2019
THE TAMIL NADU DR.M.G.R MEDICAL UNIVERSITY CHENNAI
TAMIL NADU
CERTIFICATE BY GUIDE
INSTITUTE OF ANAESTHESIOLOGY AND CRITICAL CARE This is to certify that this dissertation entitled “EVALUATION OF DEGREE OF HAEMODYNAMIC STRESS ATTENUATION PRODUCED BY COMBINATION OF LIDOCAINE AND ESMOLOL VERSUS LIDOCAINE OR ESMOLOL ALONE DURING LARYNGOSCOPY AND INTUBATION” is a bonafide and genuine research work done by Dr.R.ANITHA in partial fulfillment of the requirement for the degree of MD in Anaesthesiology and Critical care.
Dr.M.RAJA M.D., Assistant Professor
Institute of Anaesthesiology Madurai Medical College Madurai-20
DR.M.KALYANASUNDARAM M.D., Professor
Institute of Anaesthesiology Madurai Medical College Madurai-20
Date:
Place: Madurai
CERTIFICATE BY HEAD OF THE DEPARTMENT
INSTITUTE OF ANAESTHESIOLOGY AND CRITICAL CARE This is to certify that this dissertation entitled “EVALUATION OF DEGREE OF HAEMODYNAMIC STRESS ATTENUATION PRODUCED BY COMBINATION OF LIDOCAINE AND ESMOLOL VERSUS LIDOCAINE OR ESMOLOL ALONE DURING LARYNGOSCOPY AND INTUBATION” is a bonafide and genuine research work done by Dr.R.ANITHA in partial fulfillment of the requirement for the degree of MD in Anaesthesiology and Critical care under the guidance of Prof.Dr.M.KALYANASUNDARAM M.D., Institute of Anaesthesiology and critical care.
Prof.DR.M. KALYANASUNDARAM M.D., Director I/C ,
Institute of Anaesthesiology,
Govt. Rajaji Hospital & Madurai Medical College, Madurai.
ENDORSMENT BY THE DEAN
GOVERNMENT RAJAJI MEDICAL COLLEGE AND HOSPITALS
This is to certify that this dissertation entitled “EVALUATION OF DEGREE OF HAEMODYNAMIC STRESS ATTENUATION PRODUCED BY COMBINATION OF LIDOCAINE AND ESMOLOL VERSUS LIDOCAINE OR ESMOLOL ALONE DURING LARYNGOSCOPY AND INTUBATION” is a bonafide and genuine research work done by Dr.R.ANITHA in partial fulfillment of the requirement for the degree of MD in Anaesthesiology and Critical care under the guidance of Prof.Dr.M.KALYANASUNDARAM M.D., Professor, Institute of Anaesthesiology and critical care.
Date:
DR.D. MARUTHUPANDIYAN M.S.,
Place: Madurai Dean
Govt. Rajaji Hospital Madurai Medical College Madurai.
DECLARATION
I, DR.R.ANITHA declare that the dissertation titled
“EVALUATION OF DEGREE OF HAEMODYNAMIC STRESS ATTENUATION PRODUCED BY COMBINATION OF LIDOCAINE AND ESMOLOL VERSUS LIDOCAINE OR ESMOLOL ALONE DURING LARYNGOSCOPY AND INTUBATION” has been prepared by me. This is submitted to the Tamil Nadu Dr. M.G.R Medical University, Chennai, in partial fulfillment of the requirement for the award of M.D. Degree Branch X (Anaesthesiology) to be held in APRIL 2019. I also declare that this dissertation, in part or full was not submitted by me or any other to any other university or board, either in India or abroad for any award, degree or diploma.
Place: Madurai
Date: DR.R.ANITHA
ACKNOWLEDGEMENT
I have great pleasure in expressing my deep sense of gratitude to PROF.DR.M.KALYANASUNDARAM M.D., Professor And Director, Institute Of Anaesthesiology, Government Rajaji Hospital and Madurai Medical College, Madurai for his kind encouragement and valuable guidance during the period of this study, with which this dissertation would not have materialized.
I would like to place on record my indebtedness to my Professors PROF.DR.R.SELVAKUMAR M.D, D.A, DNB, PROF.DR.S.PAPPIAH M.D., of the Institute Of Anaesthesiology, Madurai Medical College, Madurai for their whole hearted help and support in doing this study.
I express my sincere thanks to DR.D.MARUTHUPANDIAN M.S, THE DEAN, Madurai Medical College and Government Rajaji Hospital for permitting me to utilize the clinical materials of this hospital.
I express my profound thanks to assistant professor DR.M.RAJA M.D., for his valuable suggestions and technical guidance in doing this study.
Lastly, I am conscious of my indebtedness to all my patients for their kind cooperation during the course of study.
TABLE OF CONTENTS
S.NO TITLE PAGE NO.
1. INTRODUCTION 1
2. AIM OF THE STUDY 3
3. ANATOMY OF AIRWAY AND INNERVATION 4
4. PHYSIOLOGY OF AIRWAY REFLEX 9
5. ATTENUATION OF AIRWAY REFLEX 16
6. ESMOLOL 24
7. LIGNOCAINE 43
8. REVIEW OF LITERATURE 50
9.. MATERIALS AND METHODS 58
10 STATISTICAL ANALYSIS 62
11. RESULTS 74
12. DISCUSSION 76
13. CONCLUSION 79
14. BIBLIOGRAPHY 80
15. ANNEXURES PROFORMA MASTER CHART
ETHICAL CLEARANCE CERTIFICATE PLAGIARISM CERTIFICATE
82 85 103 104
1
INTRODUCTION
Direct laryngoscopy and endotracheal intubation frequently induces a cardiovascular stress response that is characterized by hypertension and tachycardia due to reflex sympathetic stimulation and an increase in serum catecholamines. The response is transient occurring 30 sec after intubation and lasting for less than 10 min. It may be hazardous in patients with hypertension, myocardial infarction, and other comorbidities. Various pharmacological approaches have been used to attenuate the pressure responses to laryngoscopy and tracheal intubation.
The sympathoadrenal response to laryngoscopy result in an increase in cardiac workload which in turn may culminate in perioperative myocardial infarction and acute heart failure in susceptible patients.
Perioperative myocardial infarction is one of the cause of postoperative morbidity and mortality due to hypertension and tachycardia. Control of the heart rate and blood pressure response to endotracheal intubation is essential in preventing adverse cardiovascular outcomes, as rate pressure product (RPP) acts as an indicator of oxygen demand by the heart at the onset of ischemia .
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The mechanical stimulation of four different areas of upper respiratory tract viz. nose, epipharynx, laryngopharynx and the tracheobronchial tree induces reflex cardiovascular responses . These stress responses are seen because of stimulation of epipharynx and laryngopharynx and least with tracheobronchial stimulation. The sensory afferents from the epipharynx and laryngopharynx are carried by glossopharyngeal nerve, while trigeminal and vagus nerves carry sensations from tracheobronchial tree. This results in enhanced neural activity in the cervical sympathetic afferent fibers. These afferent fibers activate vasomotor centre which ends in reflex cardiovascular responses in the form of tachycardia, hypertension and cardiac dysrrhythmias and laryngobronchial spasm. Laryngovagal stimulation causes bradycardia, laryngosympathetic stimulation leads to hypertension and tachycardia.
Laryngospinal stimulation leads to hypotension and splanchnic reflexes.
The aim is to protect the heart from noxious stimulation arising as a result of laryngoscopy and intubation. The normal patients usually tolerate this increased sympathetic response but patients having valvular heart disease, coronary artery disease, aortic aneurysms, recent myocardial infarction and cerebral aneurysms or intracranial hypertension require careful hemodynamic control during laryngoscopy, intubation, extubation, skin incision and surgical manipulations. The rise in heart rate, systolic and diastolic blood pressure, mean arterial pressure are highly undesirable in such patients.
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AIM OF THE STUDY
To evaluate the safety and efficacy of esmolol and lidocaine in attenuating the cardiovascular stress responses to laryngoscopy and intubation and to assess whether combination of drugs is more effective than either drug alone.
4
ANATOMY OF AIRWAY AND INNERVATION
Introduction:
Laryngoscopy, Endotracheal intubation and any airway manipulations like placement of LMA or oropharyngeal airway may induce drastic changes in physiology of cardiovascular system through the airway reflexes. But these changes are usually of short duration and does not lead to complications in healthy individuals. But these changes may cause serious problems in patients with reactive airways, coronary artery disease
& neurosurgery patients.
Anatomy of the airway:
The upper airway extends from nares and mouth to the glottis.
Cricoid cartilage is the landmark between the upper and lower respiratory tract.
Figure 1
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NERVE SUPPLY OF UPPER AIRWAY
Figure 2
6
Nerve supply of the airway:
Figure 3
This figure shows the course of Superior laryngeal nerve and recurrent laryngeal nerve.
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Airway innervation:
Figure 4
Oral cavity is innervated by the branches of trigeminal, facial, glossopharyngeal and hypoglossal nerve. Nasal cavity is innervated by anterior and posterior ethmoidal nerves. It is also supplied by anterior- superior alveolar branch and infra orbital branch of maxillary nerve.
8
Glossopharyngeal nerve supplies base of the tongue, upper part of epiglottis and pharyngeal wall. Superior laryngeal nerve supplies lower part of the epiglottis and supra glottic parts of the pharynx.
The larynx mucous membrane receives its nerve supply from the superior and recurrent laryngeal nerves.
Superior laryngeal nerve:
The superior laryngeal nerve arises from inferior ganglion of vagus but receives a small branch from the superior sympathetic ganglion. At the level of greater horn of hyoid it divides into an internal and external branch.
The internal branch is purely sensory. The upper branch supplies the mucous membrane of the lower part of the pharynx, epiglottis, vallecula and vestibule of the larynx. The lower branch supplies the aryepiglottic fold and mucous membrane of the posterior part of rima glottidis. The lower part of the larynx below the vocal cords is supplied by the recurrent laryngeal nerve. The external branch of superior laryngeal nerve supplies the cricothyroid muscle and all the rest of the muscles of larynx are supplied by recurrent laryngeal nerve.
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PHYSIOLOGY OF AIRWAY REFLEX
Lower part of pharynx, epiglottis and larynx contain numerous sensory receptors which respond to chemical, thermal and mechanical stimuli. The mechanoreceptors are rich in the lower pharynx, epiglottis and vocal cords areas.
Stimulation of these receptors will produce reflex responses like cough, hiccup, reflex sympathetic stimulation and cardiovascular pressor response.
The sensory unit consists of free nerve endings which lies between the mucosal cells of airway epithelium. Sensory units seems to be particularly more over the arytenoids cartilages and they are also found on the laryngeal side of epiglottis.
The superior laryngeal nerve carries large amount of small diameter myelinated fibres ( A-delta, B sensory fibres) which carry afferent impulses.
The recurrent laryngeal nerve carries sensory fibres from rapidly adapting receptors which are activated by light touch. These receptors are more on the inferior surface of vocal cords.
Afferent fibres in the laryngeal nerves lies centrally in the nucleus tractus solitarius, in particularly posterior and caudal parts. The central
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reflex site lies in medulla. The nucleus tractus solitarius terminate closely with the vasomotor centre.
Sympathetic activity originates in the reticular formation of the lower pons and upper part of medulla which are represented bilaterally. Together these two areas are referred as vasomotor centre. The vasomotor centre neurons are under continuous influence of afferent impulses that originates from mechanoreceptors located in the heart, arteries and lungs.
Every efferent sympathetic route is made of a pre-ganglionic neuron.
The pre-ganglionic neuronal cell bodies lie within the thoracic & upper lumbar spinal cord. These fibres pass from the spinal cord via anterior routes of each spinal nerve and then via the white ramus to synapse with post ganglionic cell bodies located within the ganglia of the sympathetic chains.
From these ganglia sympathetic post ganglionic fibers pass to effector organs. T8 to T12 pre-ganglionic fibers synapse with adrenal medulla.
Stimulation of these receptors can cause release of catecholamines into the circulation through adrenal medulla leading to pressor response of intubation.
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Cardiovascular response to intubation:
The cardiovascular responses to noxious airway manipulation are initiated by proprioceptors responding to tissue irritation in the supraglottic region and in the trachea. Located in close proximity to the airway mucosa, these proprioceptors consist of mechanoreceptors with small diameter myelinated fibers, slowly adapting stretch receptors with large-diameter myelinated fibers, and polymodal endings of nonmyelinated nerve fibers.
The glossopharyngeal and vagal afferent nerves transmit these
impulses to the brainstem, which in turn, causes widespread autonomic activation through the sympathetic and parasympathetic nervous systems.
Bradycardia, often elicited in infants and small children during laryngoscopy or intubation, is the autonomic equivalent of the laryngospasm response. Although seen rarely in adults, this reflex results from an increase in vagal tone at the sinoatrial node and is virtually a monosynaptic response to a noxious stimulus in the airway.
In adults and adolescents, the more common response to airway manipulation is hypertension and tachycardia mediated by the cardioaccelerator nerves and sympathetic chain ganglia.
This response includes widespread release of norepinephrine from adrenergic nerve terminals and secretion of epinephrine from the adrenal medulla. Some of the hypertensive response to endotracheal intubation also
12
results from activation of the renin angiotensin system, including release of renin from the
renal juxtaglomerular apparatus, which is innervated by β-adrenergic nerve terminals.
In addition to activation of the autonomic nervous system, laryngoscopy and endotracheal intubation result in stimulation of the central nervous system, as evidenced by increases in electroencephalographic (EEG) activity, cerebral metabolic rate, and cerebral blood flow (CBF). In patients with compromised intracranial compliance, the increase in CBF may result in elevated intracranial pressure (ICP), which, in turn, may result in herniation of brain contents and severe neurologic compromise.
Mediators of cardiovascular response:
a) Secretion of epinephrine from adrenal medulla
b) Release of norepinephrine from adrenergic nerve terminals c) Activation of Renin-Angiotensin-Aldosterone system
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Attenuation of Cardiovascular responses:
A) Technical considerations:
Gentle cricoid pressure
Laryngoscopy using Macintosh or McCoy blade compared to Miller blade cause less response
Insertion of LMA compared to ETT cause less hemodynamic disturbance
B) Topical Anaesthesia:
Topical laryngotracheal spray with lidocaine 2% to 4%
Regional nerve blocks of superior laryngeal nerve, glossopharyngeal nerve and transtracheal blocks
C) Inhalational Anaesthetics:
Inhalation agents at 2.5 to 3 MAC suppress the hemodynamic response to intubation.
D) Intravenous agents:
Opioids- Fentanyl, alfentanil, remifentanil
Local anaesthetics -Lidocaine
β adrenergic receptor antagonist- Esmolol Labetalol
Vasodilators-Nitroglycerine
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Sodium Nitroprusside Hydralazine
Centrally acting α agonist-Clonidine
α2 agonist- Dexmedetomidine
Calcium channel blockers
Upper Airway Reflexes
It is the upper airway that protects the respiratory gas exchange surface from noxious substances. It is appropriate to say that the nose, mouth, pharynx, larynx, trachea, and carina has lots of sensory nerve endings and reflex motor responses. Anaesthesiologists are especially familiar with the glottic closure reflex (laryngospasm), which is often encountered. The cough, sneeze and swallow reflexes are also other important upper airway reflexes.
Afferent pathways for laryngospasm and the hemodynamic responses to laryngoscopy and endotracheal intubation are initiated by the glossopharyngeal nerve when the stimulation is superior to the anterior surface of the epiglottis while it is initiated by the vagus nerve when the stimulation occurs from the level of posterior epiglottis down into the lower airway.
15
As the laryngeal closure reflex is mediated by vagal efferents to the glottis, it is a monosynaptic response, occurring mostly when a patient is not in deeper plane of anaesthesia as vagally innervated sensory endings in the airway are stimulated and conscious respiratory efforts by the patient cannot override the reflex.
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ATTENUATION OF AIRWAY REFLEX
The airway reflexes can be prevented by
Technical considerations
Topical anaesthesia
Regional nerve blocks
Intravenous agents
Inhalation agents
Choice of neuromuscular blocking drugs
Technical considerations:
Laryngoscopy itself is a moderately stimulating procedure and use of a straight blade (Miller blade) with elevation of the vagally innervated posterior aspect of the epiglottis results in significantly higher arterial BP than does use of a curved blade (Macintosh or Corazzelli–London–McCoy [CLM]).
Newer video and optical laryngoscopes, which do not require alignment of the laryngeal axes for adequate visualization of the vocal cord inlet and subsequent intubation, have the potential to minimize the pressor response to airway manipulation by reducing the amount of force needed to displace oropharyngeal tissues and limiting cervical spine motion .
17
Minimising the airway stimulation by using appropriate size blade.
Insertion of LMA is also considered as a highly stimulant procedure.
Appropriate dosage of propofol 2.5 mg/kg prior to LMA insertion can suppress the reflex laryngospasm.
Topical Anaesthesia:
The surfaces of the mouth and nose are easily anesthetized with topical anaesthetic sprays or gels. Lidocaine is equally effective as cocaine and less toxic; it can be combined with a vasoconstrictor to give equivalent intubating conditions. Administration of an antisialagogue 30 to 60 minutes before application of the topical anesthetic results in better anesthesia as well as better intubating conditions. The lack of secretions probably minimizes dilution of the applied anaesthetic and also results in better intubating conditions.
Using lignocaine spray prior to intubation also helps in preventing the laryngospasm.
Inflating the cuff with 5ml of 1% lignocaine, 1ml of 8.4% sodium bicarbonate and 5ml of sterile water helps in preventing the airway reflexes.
18
Regional Anaesthesia:
Regional nerve blocks helps in preventing the airway reflexes to intubation. The superior laryngeal nerve innervates the superior surface of the larynx, and the glossopharyngeal nerve innervates the oropharynx.
Depositing local anesthetic on each cornu of the hyoid bone can block the superior laryngeal nerve . Blockade of the glossopharyngeal nerve at the tonsillar pillars (sensory distribution above the level of the epiglottis) potentiates this effect by decreasing the stimulus of laryngoscopy.
The infraglottic larynx derives sensory innervation from the recurrent laryngeal nerves, which run along the posterolateral surfaces of the trachea. Again, topical anesthesia rather than nerve block is the method of choice for obtunding reflexes. Injection of several milliliters of 4%
lidocaine via the cricothyroid membrane routinely results in excellent blockade of sensation. With the preceding combination, awake patients exhibit little response as the ETT is inserted.
Intravenous agents:
I.V Lidocaine 1.5mg/kg suppresses airway reflexes to intubation like cough and laryngospasm.
Propofol in doses of 2.5mg/kg suppresses airway reflexes and facilitates LMA insertion.
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Propofol helps in achieving deeper planes of anaesthesia thereby preventing the airway reflexes.
Inhalation agents:
Inhaled β2-agonists (salbutamol, terbutaline)
Inhaled anticholinergics (ipratropium bromide)
Both can be given 30 to 60 minutes prior to induction helps in bronchodilation and preventing bronchospasm.
Sevoflurane is the inhalational anaesthetic agent of choice.
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BETA ADRENERGIC RECEPTOR ANTAGONIST INTRODUCTION:
Beta adrenergic receptor antagonist binds selectively to these receptors and interfere with the ability of catecholamines or
other sympathomimetics to provoke responses on the heart and smooth muscles of the airway and blood vessels. Propranolol is the standard β- adrenergic antagonist drug to which all other β -adrenergic antagonist are compared.
CLASSIFICATION:
β adrenergic receptor antagonist are classified as nonselective β1 andβ 2 receptors and cardio selective β1 receptor.
A. NONSELECTIVE (β1 , β2)
1.Without intrinsic sympathomimetic activity:
Propranolol , sotalol, timolol
2.With intrinsic sympathomimetic activity:
Pindolol
3.With additional α blocking property:
Labetalol, carvedilol
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B. CARDIOSELECTIVE(β1):
Metoprolol , Atenolol, Acebutalol , Bisoprolol, Esmolol, Betaxolol, Celiprolol, Nebivolol
ANOTHER SYSTEM OF CLASSIFICATION
First generation Second generation Third generation Propranolol
Timolol Sotatol Pindolol
Metoprolol Atenolol Acebutolol Bisoprolol Esmolol
Labetalol Carvedilol Celiprolol Nebivolol
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MECHANISM OF ACTION:
Acts by competitive inhibition, with selective affinity for β adrenergic receptors. β adrenergic receptors are G protein coupled receptors and their occupancy by agonist (norepinephrine,epinephrine) stimulates G protein which activates adenylate cyclase to produce cyclic adenosine monophospate. Protein kinases are activated by cAMP which phosphorylates proteins including L type voltage dependent calcium channels and troponin C in a variety of tissues.
The effect of β adrenergic stimulation is to produce positive chronotropic, ionotropic and dromotropic effects in heart.
Figure 5
23
Difference between β1 ,β2 ,β3 receptors
β1 β2 β3
Location Heart, JG cells in kidney
Bronchi, bloodvessels, uterus, liver, GIT, urinary tract, eye
Adipose tissue
Selective agonist
Dobutamine Salbutamol , terbutaline BRL37344
Selective antagonist
Metoprolol, Atenolol
Alpha methyl propranolol
CGP20712 A
Potency of Noradrenali ne as agonist
Moderate Weak Strong
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ESMOLOL
Esmolol is an ultra short-acting selective β1- adrenergic receptor antagonist administered intravenously. Esmolol is a useful drug for preventing or treating adverse systemic blood pressure and heart rate increases that occur intra operatively in response to noxious stimulation, as during tracheal intubation.
Esmolol has been used during resection of pheochromocytoma and may be useful in the perioperative management of thyrotoxicosis,
pregnancy-induced hypertension, and epinephrine- or cocaine-induced cardiovascular toxicity.
25
The β1 selectivity of esmolol may unmask β2-mediated vasodilation by epinephrine-secreting tumors. Administration of esmolol to patients chronically treated with βadrenergic antagonists has not been observed to produce additional negative inotropic effects. The reason for this observation is that esmolol, in the dose used, does not occupy sufficient additional βreceptors to produce detectable increases in β blockade.
Pharmacokinetics
Available for intravenous administration only. Esmolol is buffered to pH 4.5 to 5.5, which may be responsible for pain on injection.
The drug is compatible with commonly used intravenous solutions and non depolarizing neuromuscular blocking drugs. The elimination half- time of esmolol is about 9 minutes, reflecting its rapid hydrolysis in the blood by plasma esterases that is independent of renal and hepatic function. Less than 1% of the drug is excreted unchanged in urine, and about 75% is recovered as an inactive acid metabolite. Clinically insignificant amounts of methanol also occur from the hydrolysis of esmolol.
Plasma esterases responsible for the hydrolysis of esmolol are distinct from plasma cholinesterase, and the duration of action of succinylcholine
26
is not predictably prolonged in patients treated with esmolol. The heart rate returns to predrug levels within 15 minutes after discontinuing the drug. Poor lipid solubility limits transfer of esmolol into or across the placenta.
Side Effects
β-adrenergic antagonists exert their most prominent
pharmacologic effects as well as side effects on the cardiovascular system.
These drugs may also alter airway resistance, carbohydrate and lipid metabolism, and the distribution of extracellular ions.
β Adrenergic antagonists may cause hypoglycaemia
Gastrointestinal side effects include nausea, vomiting, and diarrhea.
Fever, rash, myopathy, alopecia, and thrombocytopenia have been associated with chronic β-adrenergic antagonist treatment.
Contraindication
preexisting atrioventricular heart block
cardiac failure not caused by tachycardia
hypovolemic patients with compensatory tachycardia
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chronic obstructive airway disease.
In patients with diabetes mellitus, there is the risk that β-adrenergic blockade may mask the signs of hyperglycemia and thus delay its clinical recognition.
1.Cardiovascular System β-Adrenergic antagonists
1. produce negative inotropic and chronotropic effects.
2. The rate of spontaneous phase 4 depolarization is decreased, exaggerating AV block.
3. Enhance the pressor effect of epinephrine (preventing the β 2 vasodilating effect &unopposed its α-adrenergic effect)
4. Causes development of cold hands and feet.
5. Precipitates heart failure in compensated states.
6. Produces bradycardia, low cardiac output, hypotension, and cardiogenic shock
7. Seizures and prolonged intraventricular conduction of cardiac impulses are thought to be the result of local anaesthetic properties of certain βadrenergic antagonists
8. Hypoglycemia produced by β-adrenergic antagonist overdose.
28
MANAGEMENT:
1. Atropine in incremental doses upto 3mg intravenously.
2. If atropine is ineffective, nonselective β-adrenergic agonist isoproterenol 2 to 25 mg per minute intravenously.
3. Pure β 1-adrenergic agonist : dobutamine is recommended (Dopamine is not recommended because α-adrenergic–induced vasoconstriction is likely to occur with the high doses required to overcome β blockade.)
4. Glucagon : The drug of choice to treat massive β adrenergic antagonist overdose, 1 to 10 mg IV followed by 5 mg per hour intravenously,
5. (Stimulates adenylate cyclase and increases intracellular cAMP concentrations independent of β -adrenergic receptors).
6. Calcium chloride, 250 to 1,000 mg intravenously.
7. Transvenous artificial cardiac pacemaker.
8. Hemodialysis to remove minimally protein-bound, renally excreted β -adrenergic antagonists in patients refractory to pharmacologic therapy
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2.Airway Resistance
Nonselective β -adrenergic antagonists will increase airway resistance because of bronchoconstriction due to blockade of β 2 receptors, which is exaggerated in patients with preexisting obstructive airway disease. Selective β 1- adrenergic antagonists such as metoprolol and esmolol are less likely to increase airway resistance.
3.Metabolism
β-Adrenergic antagonists alter carbohydrate and fat metabolism. Tachycardia a warning sign of hypoglycemia in insulin- treated diabetics, is blunted by β -adrenergic antagonists . Altered fat metabolism is evidenced.
4.Distribution of Extracellular Potassium
Distribution of potassium across cell membranes is influenced by sympathetic nervous system activity as well as insulin. Stimulation of β 2- adrenergic receptors causes movement of potassium intracellularly. β - adrenergic blockade increases concentration of extracellular potassium . But selective β 1-adrenergic antagonists would impair skeletal muscle uptake of potassium less than nonselective β -adrenergic antagonists.
30
5.Interaction with Anaesthetics
Myocardial depression produced by inhaled or injected anaesthetics could be additive with depression produced by β -adrenergic antagonists but not excessive. Additive cardiovascular effects are greatest with enflurane and least with isoflurane. Sevoflurane and desflurane, like isoflurane, do not seem to be associated with significant additive cardiovascular effects .
In the presence of anaesthetic drugs that increase sympathetic nervous system activity (ketamine), or when excessive sympathetic nervous system activity is present because of hypercarbia, the acute administration of a
β-adrenergic antagonist may unmask direct negative inotropic effects of concomitantly administered anaesthetics, with resulting decreases in systemic blood pressure and cardiac output.
5.Nervous System
β adrenergic antagonists may cross the blood–brain barrier.
Peripheral paresthesias have been described. Atenolol and nadolol are less lipid soluble with lower incidence of CNS effects.
6.Fetus
β-Adrenergic antagonists can cross the placenta and cause bradycardia, hypotension, and hypoglycaemia in newborn. Also secreted in breast milk.
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7. Withdrawal Hypersensitivity
Acute discontinuation of β-adrenergic antagonist therapy can result in excess sympathetic nervous system activity that manifests in 24 to 48 hours.
Perioperative b-Adrenergic Receptor Blockade Recommended for patients
1. At risk for myocardial ischemia (known coronary artery disease, positive preoperative stress tests, left ventricular hypertrophy) 2. During high-risk surgery (vascular surgery, thoracic surgery,
intraperitoneal surgery, anticipated large blood loss) .
Perioperative myocardial ischemia is the single most important potentially reversible risk factor for mortality and cardiovascular complications after noncardiac surgery. Esmolol is an acceptable drug to achieve β-adrenergic receptor blockade during surgery and postoperatively in the intensive care unit where continuous intravenous infusions can be monitored.
Possible Explanations for Cardio protective Effects Produced by Perioperative β -Adrenergic Receptor Blockade:
1. Decreased myocardial oxygen consumption and demand
2. Less stress on potentially ischemic myocardium owing to decreased heart rate and myocardial contractility
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3. Attenuation of effects of endogenous catecholamines
4. Redistribution of coronary blood flow to ischemic areas .Increased coronary blood flow owing to increased diastolic time.
5. Plaque stabilization owing to decrease in shear forces.
6. Cardiac antidysrhythmic effects .
Esmolol hydrochloride was evaluated as the preferable agent to attenuate the stress response due to laryngoscopy and intubation for the following reasons.
1. It is a cardioselective β-1 antagonist, without any intrinsic sympathomimetic effect or membrane stabilising property.
2. Its lack of action on β-2 receptors, makes it the β-blocker of choice in patients having bronchial asthma.
3. Its onset of action being within a minute it can produce the required haemodynamic stability soon after its administration.
4. Its metabolism is not influenced by renal or hepatic function. It is rapidly hydrolysed by cytoplasmic esterases in hepatic cells and RBC. Patients with deficient plasma cholinesterase do not show prolonged effect of esmolol.
5. Its action is similar to other beta blockers. Decreasing cardiac output by reducing heart rate and force of contraction. Cardiac work and
33
oxygen consumption are reduced. These qualities are beneficial in angina patients and in hypertensives.
6. Its peak haemodynamic effects are produced within 6-10 min of administration.
7. It is an ultrashort acting beta-blocker with a short elimination half life of approximately 9 min (range 5-16 min).
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PHARMACOLOGY OF LOCAL ANESTHETICS:
The basic structure of local anaesthetics consists of lipophilic (aromatic) end, hydrophilic (amine) end, and a link between this two ends.
This link may be either amino ester or a amino amide bond which lead to classification of local anaesthetics into amino ester –linked local anaesthetic or amino amide-linked local anaesthetic.
By adding carbon atoms to either end of structure or to the link increases lipid solubility , protein binding, duration of action and toxicity and influences bio transformation of the molecule. There is positive correlation between intrinsic local anaesthetic potency and lipid solubility of local anaesthetics.
Local anaesthetics have a tertiary amine on hydrophilic end. This tertiary amines have positive charge (cation) or uncharged (base). The ratio of cation to base is determined by pKa of local anaesthetic and pH of solution in to which it is injected. The state of amine determines percentage of local anaesthetic molecules move through biological membranes. The unchanged forms pass readily through cell membranes, and hence speed of onset of local anaesthetic block theoretically suggesting that by increasing the concentration of uncharged local anaesthetic molecules injected.
35
Ester group:
Benzocaine
Clorprocaine
Cocaine
Cyclomethycaine
Dimethocaine
Piperocaine
Propoxycaine
Procaine
Tetracaine
Proparacaine Amide group:
Articaine
Bupivacaine
Dibucaine
Etidocaine
Levobupivacaine
Lignocaine
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Mepivacaine
Prilocaine
Ropivacaine
Trimecaine
Local anesthetics produce a rapid, reversible depression of nerve conduction, particularly with regard to sensory nerves, by binding to sodium channels and interfering with their function, thereby preventing propagation of action potentials.
Most local anesthetics are weak bases; they are formulated as chloride salts by combining them with acids to maximize their solubility. In plasma, they remain largely in the ionized or protonated form (BH+) before converting to the non-ionized (lipophilic) form to penetrate the nerve. The proportion of the drug in non-ionized form depends on its acid dissociation constant (pKa): the lower the pKa (i.e., the closer to pH 7.4), the more “free base” (B) available to enter the nerve cell, and more rapid the action. This relationship is defined by the
Henderson- Hasselbalch equation:
log[BH+]/[B] = pKa – pH
37
PHARMACOKINETICS :
Absorption
Systemic absorption of injected local anaesthetic from the site of administration is determined by several factors, including dosage, site of injection, drug-tissue binding, local tissue blood flow, use of a vasoconstrictor (eg, epinephrine), and the physicochemical properties of the drug itself. Anaesthetics that are more lipid soluble are generally more potent, have a longer duration of action, and takes longer time to achieve their clinical effect. Extensive protein binding also serves to increase the duration of action.
Distribution 1. Localized
As local anaesthetic is usually injected directly at the site of the target organ, distribution within this compartment plays an essential role with respect to achievement of clinical effect. For example, anaesthetics delivered into the subarachnoid space will be diluted with cerebrospinal fluid (CSF) and the pattern of distribution will be dependent upon a host of factors, among the most critical being the specific gravity relative to that of cerebrospinal fluid and the patient’s position. Solutions are termed hyperbaric, isobaric, and hypobaric, and will respectively descend, remain
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relatively static, or ascend, within the subarachnoid space due to gravity when the patient sits upright.
Determinants of spread of local anesthetic in CSF can be broadly classified as characteristics of the anaesthetic solution, CSF constituents, patient characteristics, and techniques of injection
2. Systemic :
The peak blood levels achieved during major conduction anesthesia will be minimally affected by the concentration of anaesthetic or the speed of injection. The disposition of these agents can be well approximated by a two-compartment model. The initial alpha phase reflects rapid distribution in blood and highly perfused organs ( brain, liver, heart, kidney), characterized by a steep exponential decline in concentration. This is followed by a slower declining beta phase reflecting distribution into less well perfused tissue ( muscle, gut), and may assume a nearly linear rate of decline. The potential toxicity of the local anaesthetics is affected by the protective effect afforded by uptake by the lungs, which serve to attenuate the arterial concentration, though the time course and magnitude of this effect have not been adequately characterized.
Metabolism and Excretion
The amide local anaesthetics are converted to more water-soluble metabolites in the liver (amide type) or in plasma (ester type), which are
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excreted in the urine. Since local anaesthetics in the uncharged form diffuse readily through lipid membranes, little or no urinary excretion of the neutral form occurs. Acidification of urine promotes ionization of the tertiary amine base to the more water-soluble charged form, leading to more rapid elimination. Ester-type local anaesthetics are hydrolyzed very rapidly in the blood by circulating butyrylcholinesterase to inactive metabolites. For example, the half-lives of procaine and chloroprocaine in plasma are less than a minute. However, excessive concentrations may accumulate in patients with reduced or absent plasma hydrolysis secondary to atypical plasma cholinesterase. The amide local anesthetics undergo complex biotransformation in the liver, which includes hydroxylation and N –dealkylation by liver microsomal cytochrome P450 isozymes. There is
considerable variation in the rate of liver metabolism of individual amide compounds, with prilocaine (fastest) > lidocaine > mepivacaine >
ropivacaine ≈ bupivacaine and levobupivacaine (slowest). As a result, toxicity from amide-type local anaesthetics is more likely to occur in patients with hepatic disease. For example, the average elimination half- life of lidocaine may be increased from 1.6 hours in normal patients to more than 6 hours in patients with severe liver disease. Many other drugs used in anaesthesia are metabolized by the same P450 isozymes, and concomitantadministration of these competing drugs may slow the hepatic metabolism of the local anaesthetics. Decreased hepatic elimination of
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local anesthetics would also be anticipated in patients with reduced hepatic blood flow. For example, the hepatic elimination of lidocaine in patients anesthetized with volatile anaesthetics (which reduce liver blood flow) is slower than in patients anaesthetized with intravenous anesthetic techniques. Delayed metabolism due to impaired hepatic blood flow may likewise occur in patients with congestive heart failure.
MECHANISM OF ACTION:
The primary mechanism of action of local anaesthetics is blockade of voltage-gated sodium channels. When progressively increasing concentrations of a local anaesthetic are applied to a nerve fiber, the threshold for excitation increases, impulse conduction slows, the rate of rise of the action potential declines, action potential amplitude decreases, and, finally, the ability to generate an action potential is completely abolished. These progressive effects result from binding of the local anesthetic to more and more sodium channels.
If the sodium current is blocked over a critical length of the nerve, propagation across the blocked area is no longer possible. In myelinated nerves, the critical length appears to be two to three nodes of Ranvier. At the minimum dose required to block propagation, the resting potential is not significantly altered.
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The blockade of sodium channels by most local anesthetics is both voltage and time dependent: Channels in the rested state, which predominate at more negative membrane potentials, have a much lower affinity for local anaesthetics than activated (open state) and inactivated channels, which predominate at more positive membrane potentials.
Therefore, the effect of a given drug concentration is more marked in rapidly firing axons than in resting fibers.
Between successive action potentials, a portion of the sodium channels will recover from the local anaesthetic block. The recovery from drug-induced block is 10–1000 times slower than the recovery of channels from normal inactivation. As a result, the refractory period is lengthened and the nerve conducts fewer action potentials.
Elevated extracellular calcium partially antagonizes the action of local anesthetics owing to the calcium-induced increase in the surface potential on the membrane (which favors the low-affinity rested state).
Conversely, increases in extracellular potassium depolarize the membrane potential and favor the inactivated state, enhancing the effect of local anaesthetics.
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Local anaesthetics are usually effective topically on airway mucosa.
The clinical effect is to reduce airway reactivity. At the same time, there is a reduction in airway caliber and a reduction in the reflexes that protect against aspiration.
Topicalization of the upper airway is a common technique in the
“awake” management of a difficult airway and it is also used during general anesthesia to facilitate upper airway instrumentation when neuromuscular blocking drugs agents are being deliberately avoided.
Topical local anesthesia is also used as an adjunct to general anesthesia in both upper airway and lower airway surgery.
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LIGNOCAINE
Lignocaine is an amide group synthetic local anesthetic .Its is the most common local anaesthetic used. It is available in various forms and various concentration.
Molecular weight of lignocaine- 234 pKa 7.6- 7.8 weak base.
T1/2 distribution- 10 min T1/2 elimination- 1.6 hours
Volume of distribution at steady state - 91 L Clearance - 0.95 L/min
MECHANISM OF ACTION
Lidocaine blocks the fast voltage-gated sodium channels and alters signal conduction in the neuronal cell membrane responsible for signal conduction. The local anesthetics are present in both ionized and
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unionized forms whose relative concentration depends on the pKa of the solution. The ionized form is the active one where as the unionized form only diffuses across the lipid membrane as they are only lipophilic.
The drug diffuses across the membrane and acts on the sodium channel from inner surface and keeps them in inactivated state. This keeps them persistently depolarized and inhibits action potential propogation.
The postsynaptic membrane will not depolarize in the presence of the local anesthetic and will thus fail to transmit an action potential. This creates the anaesthetic effect by not just preventing pain signals from propagating to the brain, but also by stopping them before they begin.
The same principle applies for this drug's actions in the heart.
Blocking sodium channels in the conduction system, as well as the muscle cells of the heart, raises the depolarization threshold, making the heart less likely to initiate or conduct early action potentials that may cause an arrhythmia.
METABOLISM AND EXCRETION
Its metabolized in liver by oxidation and de alkylation to monoethyl glycinexylidide. This undergoes further hydrolysis to become xylidide. Its metabolism is highly flow dependent that is depends on the hepatic blood
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flow. 75% of xylidide is excreted in urine as 4- hydroxyl2,6 dimethylaniline.
PHARMACODYNAMICS Local actions -
It acts locally causing loss of pain, touch and temperature sensation. Motor power and vasomotor tone is also lost in the region supplied by the nerves blocked.
SYSTEMIC ACTIONS:
Its action depends on the site/route {intravenous} of administration.
Cardiovascular system:-
It stabilizes the myocardial cell membrane. It depresses myocardial automaticity by inhibiting the action potential and reducing the duration of effective refractory period. At higher concentration, cardiac conductivity and contractility are depressed. Lignocaine causes blocked of sodium channels in cardiac muscle leading to membrane changes and cardiac toxicity. It suppresses ectopic foci by stabilizing membrane of damaged and excitable cells.
Vascular smooth muscle:
It acts on vascular smooth muscle producing vasodilatation.
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Respiratory system:
Lignocaine depresses the ventilatory drive to low PaO2 (Hypoxic drive).
Direct exposure of local anaesthetic to higher centres like medulla or peripheral nerves (intercostals, phrenic nerve) causes respiratory depression. Lignocaine has the property of relaxing bronchial smooth muscles. Intravenous lignocaine is shown to be effective in reducing the reflex broncho constriction that can occur following airway manipulation.
Central nervous System:
Lignocaine causes a sequence of stimulation followed by depression.
It causes sedation on intravenous administration. Sympathetic stimulation associated with airway manipulation leads to increased cerebral blood flow and increase in intra cranial pressure. Intravenous administration of lignocaine blunts the sympathetic surge and attenuates these responses.
Lignocaine injection is capable of reducing the Minimal Alveolar Concentration of volatile Anaesthetics by 40%.
Musculo –skeletal:
Lignocaine causes lytic degeneration, necrosis and edema of muscle.
Hematological :
Lignocaine causes fibrinolysis and may prolong clotting time.
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INDICATIONS Nerve blocks
Topical applications, infiltration Intravenous regional anesthesia Spinal and epidural anaesthesia
Lignocaine as ANTIARRYTHMIC
It has cardiac membrane stabilising properties thus useful as ntiarrythmic.
In anti arrhythmic classification its classified under CLASS Ib Uses-
treatment of ventricular tachycardia
arrhythmia during cardiac surgey
digitalis toxicity
other USES-
attenuates pressor response during laryngoscopy and endotracheal intubation.
suppresses noxious reflex and sympathetic stimulation during suctioning and intubation
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intravenous lignocaine is used as adjuvant analgesic and supplements general anesthesia
It is used in chronic pain states
CONTRAINDICATION
Hypersensitive allergic individuals
Stoke Adams syndrome
severe heart blocks
TOXICITY :
SYMPTOM BLOOD LEVELS
Light headedness, tinnitus, circumoral numbness
4 mcg/ml
Visual disturbance 6mcg/ml
Muscle twitching 8 mcg/ml
Convulsion 10 mcg/ml
Unconsciousness 12mcg/ml
Respiratory arrest 20mcg/ml
Cardiac arrest 26mcg/ml
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Mainly due to systemic absorbtion of large doses used during nerve blocks and inadvertent intravascular injection. Main system affected is central nervous system
MANAGEMENT 100% oxygen
Airway management- intubation and ventilation
Convulsions managed with barbiturates and benzodiazepines Ventricular fibrillation treated with cardiac defibrillation
Maintain hemodynamic stability with I.V fluids and vasopressors and ionotropes
Treat electrolyte abnormality if any Adverse effects
ALLERGIC reactions- the preservative methyl paraben present in lignocaine causes most of the allergic reaction.
Intravenous lignocaine is devoid of preservative
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REVIEW OF LITERATURE
1. Sanjeev Singh, Edwin Ferguson Laing et al conducted a study’
‘ Comparison of esmolol and lidocaine for attenuation
of cardiovascular stress response to laryngoscopy and endotracheal intubation”
Anesthesia: Essays and Researches, 7(1), 83.
https://doi.org/10.4103/0259-1162.114008
In this study 120 patients of ASAI &II undergoing elective surgeries were divided into 3 groups C,L and E. ‘C’ received no drugs as placebo group ‘L’ received 1.5 mg/kg lidocaine and group ‘E’ received esmolol 2mg/kg 2 minutes before intubation. After induction of general anaesthesia with thiopental 6mg/kg and vecuronium0.12mg/kg test solution was infused two minutes before intubation. Changes in heart rate(HR), systolic blood pressure(SBP), diastolic blood pressure(DBP), mean arterial pressure(MAP) & rate pressure product(RPP) were measured before induction of general anaesthesia (baseline),1,3 & 5 minutes after tracheal intubation.
Percentage change in hemodynamic variables in groupC,L,Eareasfollows:HR=30.45,26.00&1.50%;MAP=20.80,15.85&10 .20%;RPP=61.44,40.86&11.68% respectively .They concluded prophylactic therapy with esmolol 2mg/kg is more effective and safe for
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attenuating cardiovascular responses to laryngoscopy and tracheal intubation in black population.
2 .Christoph H. Kindler,Philippe G. Schumacher et al conducted a study “Effects of Intravenous Lidocaine and/or Esmolol on
Hemodynamic Responses to Laryngoscopy and Intubation: A Double-Blind, Controlled
clinical Trial” Journal of Clinical Anesthesia, 8(6), 491–496.
https://doi.org/10.1016/0952-8180(96)00109-2
Department of Anaesthesia, University of Basel, Basel, Switzerland It is a randomized prospective double blind, placebo- controlled study to evaluate the efficacy of intravenous lidocaine , two doses of esmolol and combination of drugs at different dosage for attenuating cardiovascular responses to laryngoscopy.
90 ASA status I & II normotensive women scheduled for elective gynaecological procedure with general anaesthesia were divided into 6 groups. The first group received lidocaine 1.5 m&kg (Group LD); the second and third groups received esmolol 1mg/kg and 2 mg/kg, respectively (Groups El and E2, respectively); the fourth group received lidocaine 1.5 mg/kg and esmolol 1 mg/kg (Croup LID-El); the fifth group received lidocaine 1.5 mg/kg and esmolol 2 mg/kg (Croup LIDE2); the sixth group received saline as a placebo (Group PLAC). Systolic blood
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pressure and heart rate (HR) were recorded before induction, before injection of the first test drug, immediately before layngoscopy and 1,2 &5 minutes following intubation.
The proportion of patients with a maximum HR exceeding 90 beats/mt was significantly higher in the placebo group than in both esmolol groups .Systolic blood pressure values after tracheal intubation did not differ among groups except for those receiving the combinations of lidocaine and esmolol.
They Concluded Esmolol 1 to 2 mg/kg is reliably effective in attenuating HR response to tracheal intubation. Neither of the two doses of esmolol tested nor that of lidocaine affected the BP response. Only the combination of lidocaine and esmolol attenuated both HR and BP responses to tracheal intubation.
3.Harbhej Singh, Phongthara Vichitvejpaisal et al conducted a study
“Comparative Effects of Lidocaine, Esmolol, and Nitroglycerin in Modifying the Hemodynamic Response to Laryngoscopy and Intubation”
Journal of Clinical Anesthesia, 7(1), 5–8.
https://doi.org/10.1016/0952-8180(94)00013-T
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Department of Anesthesiology and Pain Management, University of Texas In this study 40 ASA I & II patients were randomly allocated to receive either5 ml of unknown solution , lidocaine 1.5 mg/kg, esmolol 1.4 mg/kg, nitroglycerine 2 microgm/kg after induction of anesthesia with thiopental sodium 5 mg/kg, and intubation was facilitated with vecuronium 0.15 mg/kg. Isoflurane (0.5% to 1 %) and 50% nitrous oxide in oxygen were used for maintenance of anesthesia. Mean arterial pressure (AP) and heart rate (HR) were recorded every minute for 20 minutes following induction of anesthesia.
Following laryngoscopy and intubation, MAP increased significantly in all four treatment groups (control 49% +- 19%, lidocaine 55% +- 26%, esmolol 25% +- 11%, nitroglycerin 45%+ -21%) compared with preinduction baseline values. In the esmolol pretreated patients, the increase in HR was significantly lower (20% +- 3 %) compared with the nitroglycerin (37% +-8%), lidocaine (52% +- 8%), and control (29% +- 4%) groups.
They concluded Esmolol 1.4 mg/kg IV was significantly more effective than either lidocaine or nitroglycerin in controlling the HR response to laryngoscopy and intubation .Esmolol also was significantly more effective than lidocaine in minimizing the increase in MAP (25% vs.
55%).
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4.M. Vucevic, G. M. Purdy And F. R. Ellis conducted a study on
“Esmolol Hydrochloride for the management of cardiovascular responses to laryngoscopy and tracheal intubation”
British Journal of Anaesthesia 1992; 68: 529-530
In this study30 ASAI /II Patients were randomly allocated to receive either esmolol 500mcg/kg/min as loading dose for 2 min followed by 100mcg/kg/min maintenance infusion 10 min prior to tracheal intubation and continued for 5 min or normal saline. Heart rate ,systolic, diastolic and mean arterial pressure were recorded . These measurements were made at 1-min. intervals during the infusion period, and at 30-s intervals during laryngoscopy and intubation.
Both groups developed similar and significant increases in heart rate but the maximum heart rates in the study group were significantly less than those recorded in the control group. In addition, the maximum pressures recorded in the control group were significantly greater than those recorded in the study group.
They concluded that a continuous i.v. infusion of esmolol hydrochloride is a safe and effective technique for suppressing the cardiovascular stress response associated with laryngoscopy and intubation.
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5.Andrew Livett & Graham M. Dresden conducted a study on
“The Efficacy of Esmolol versus Lidocaine to Attenuate the Hemodynamic Response to Intubation in Isolated Head Trauma Patients" Academic Emergency Medicine, 8(1), 19–24.
https://doi.org/10.1111/j.1553-2712.2001.tb00541.x
It was a prospective, double-blind, randomized study, performed in 30 patients with isolated head trauma. Each underwent a standardized intubation protocol including esmolol or lidocaine, both at 2 mg/ kg.
Esmolol was used in 16 patients and lidocaine in 14. Mean Glasgow Coma Scale (GCS) score was 7.9 +-6 4.0 SD. Cranial computed tomography (CT) hemorrhagic findings included 9 subdural/epidural hematomas, 6 cortex hemorrhages, and 2 multi-hemorrhages. Eleven patients received surgical intervention: 9 patients received a craniotomy, and 2 ventricular catheter.
The 2-minute time interval around intubation was used to assess each drug’s efficacy. The mean difference change between groups for heart rate was 4.0 beats/min (95% CI = 217.7 to 9.7 beats/min), for systolic blood pressure was 1.3 mm Hg (95% CI = 227.8 to 30.4 mm Hg), and for diastolic blood pressure was 2.6 mm Hg (95% CI = 227.1 to 21.9 mm Hg). The power of this study was 90% to detect a 20-beat/min difference in heart rate, a 35-mm Hg difference in systolic blood pressure, and a 20-mm Hg difference in diastolic blood pressure.
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They concluded Esmolol and lidocaine have similar efficacies to attenuate moderate hemodynamic response to intubation of patients with isolated head trauma.
6. Tamaskar, Bhargava et all conducted a study on
“Effect of Esmolol hydrochloride on attenuation of stress response during laryngoscopy and intubation in ear, nose and throat (ENT) procedures”
British Journal of Anaesthesia3(11), 1370–1377.
In this study two groups of 25 patients each were taken as control group and Esmolol group and Esmolol 1.5 mgs per kg IV as bolus dose was administered to Esmolol group 3 minutes prior to induction of anaesthesia followed by laryngoscopy and intubation. The vital parameters were recorded every minute for five minutes. There were no significant differences in the basal parameters in both the groups before giving Esmolol and with respect to age, sex and ASA grading. There was significant reduction in heart rate (6.4%) at the time of induction as compared to rise of heart rate (15.16%) in control group. This was highly significant. Same way – there was fall in systolic blood pressure (7.69%) in esmolol group in comparison to a rise of 14.28% in control group.
Diastolic blood pressure in esmolol group showed a fall of 2.9% as compared to a rise of 21.2% in control group. The RPP was found to decrease by 13.1% in esmolol group in comparison to a rise of 31.2 % in
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control group which was also highly statistically significant. They concluded Esmolol hydrochloride is proved to be a very effective drug, ultrashort acting rapid onset and offset of action, easily titrable, so highly useful in reducing the stress response of laryngoscopy and intubation.
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MATERIALS AND METHODS
A double blinded prospective randomized study involving 3 study groups was planned and the institutional ethical committee approval for the study was obtained. The informed written consent was obtained from the patients participating in the study.
Sample Size:
In order to detect a 10% difference in heart rate and blood pressure, with beta error of 80% (0.8), the sample size was calculated as 30 in each group with a total of 90.
Based on inclusion and exclusion criteria, 90 patients who gave written consent were included in this study.
Selected patients were divided randomly by computer based randomized number into into three groups – either to receive lignocaine 1.5 mg/kg (n=30) or esmolol 2mg/kg (n=30) or lignocaine 1mg/kg and esmolol 1mg/kg (n=30)
DESIGN OF STUDY: Prospective Randomized double blinded Study
DURATION OF THE STUDY: One year
INCLUSION CRITERIA:
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a) Elective surgeries under general anaesthesia b) Both sexes
c) Age :18-45 years d) ASA I& II
EXCLUSION CRITERIA:
1. Patients with contraindications to beta blockers like bronchial asthma, COPD
2. Basal heart rate <60 bpm
3. Basal systolic blood pressure < 100 mmHg 4. Heart block ,any ECG abnormalities
5. Acute decompensated heart failure 6. Peripheral vascular disease
7. Patients on respiratory or cardiac medications 8. Patients with uncontrolled systemic illness 9. Patients with significant organ dysfunction 10. Patients with respiratory compromise
11. Patients with known allergies to local anaesthetics
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METHODOLOGY
90 Patients were randomly assigned by computer based randamozised number into three groups, esmolol group(group E), lidocaine group(group L) and combination group (group LE).In the operation theatre ,all the patients were secured with 18 G IV line and started on intravenous fluids. Standard monitors were attached. Pulse rate, Blood pressure and SpO2 were recorded continuously. All patients received premedication Inj.
Glycopyrolate 0.2mg & Inj. Fentanyl 2mcg/kg. Induction was with Inj.
Thiopentone sodium 5mg/kg and paralysed with Inj. Vecuronium 0.5mg/kg. Group E received normal saline 5ml 3 minutes prior & esmolol 2mg/kg made as 10ml 90 seconds prior to intubation. Group L received lidocaine 1.5mg/kg made into 5ml 3minutes prior & normal saline 10 ml 90seconds prior to intubation. Group LE received lidocaine 1mg/kg as 5ml 3minutes prior & esmolol 1mg/kg as 10ml 90 seconds prior to intubation.
Intubation was done in all patients by third year MD postgraduate. After 15 minutes of intubation anaesthesia was maintained with 1 MAC sevoflurane and 50% nitrous oxide and skin incision was made 5 minutes later.
PARAMETERS TO BE MONITORED:
The following parameters are assessed:
• Mean heart rate
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• Systolic BP
• diastolic BP
• Mean arterial pressure
• Rate pressure product index
The recorded parameters were entered in master chart and compiled in Microsoft Excel.
STATISTICAL TOOLS TO BE APPLIED:
The information collected regarding all the selected cases were recorded in a Master Chart. Data analysis was done with the help of computer by using SPSS 16 software.
Using this software, 'p' values were calculated through One way ANOVA and chi square test for consolidated data to test the significance of difference between variables.
