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LIST OF ABBREVIATIONS

 

 

α                                   Alpha

 

ASA                                      American Society of Anaesthesiologists bpm                                              Beats per minute

DBP                         Diastolic Blood Pressure HR                         Heart rate

Inj                             Injection

 

iv                             Intravenous

 

kg                              Kilogram

 

L/hr                          litre/hour

 

MAC                        Minimum Alveolar Concentration MAP                        Mean Arterial Pressure

mcg                          Microgram.

 

mg                            Milligram

 

min                          Minute

 

ml                            Millilitre

 

pH                            Negative logarithm of hydrogen ion concentration pka                             Dissociation constant

PVC              -            Premature Ventricular Contraction SBP                          Systolic Blood Pressure

sec                           Second

 

SpO 2                        Oxygen saturation in blood.

Tab                          Tablet

 

yrs                             Years


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ABSTRACT

 

Laryngoscopy and tracheal intubation provoke cardiovascular, and autonomic responses. This response is primarily because of sympatho-adrenal stimulation that increases the myocardial oxygen demand, which may be detrimental in comorbid patients. Attenuation of significant increase in blood pressure and heart rate decreases the risk  of complications.

Many methods have been employed to blunt these responses and most commonly used being intravenous lignocaine and topical anaesthesia of pharynx, larynx and trachea.

In view of it, the present study was undertaken to evaluate and compare the effects of 2% Lignocaine 2mg/kg nebulization given 10 minutes and 2% Lignocaine 2mg/kg iv given 90 seconds before induction for the intubation response.

Materials & Methods:

 

90 ASA Grade I & II patients in the age group 18-45 years of either sex scheduled for elective surgeries under general anaesthesia were recruited for the study.

They were allocated into three groups, Group C, Group I, Group N with the sample size of 30 in each. Group I received 2% lignocaine 2mg/kg intravenous 90sec and Group N received nebulization with 2% lignocaine 2mg/kg 10 minute before induction.

In all patients general anaesthesia was administered. Heart rate, systolic and diastolic blood pressure and mean arterial pressure, SpO2, and ECG were recorded, basal values and subsequently at 1st, 2nd, 3rd, 5th, 7th, 9th, 11th and 15th minute after intubation. Inj Glycopyrrolate and Fentanyl iv for analgesia which was avoided earlier, so as to avoid their effects on intubation response was given after the recordings.


Results:

 

It was noted that, in control group, the rise of heart rate (HR), Systolic blood pressure (SBP), Diastolic blood pressure (DBP), Mean arterial in pressure (MAP) were found to be

23.4   bpm, 42.6 mm Hg, 25.36 mm Hg, 29.44 mm Hg respectively. Group I, the rise of HR, SBP, DBP, MAP were found to be 18 bpm, 20.54 mm Hg, 13.84 mm Hg, 16.1 mm Hg respectively. In Group N, the rise of HR, SBP, DBP, MAP were found to be 24.86 bpm, 32.26 mm Hg, 24.83 mm Hg, 27.3 mm Hg respectively.

Thus it was seen that use of lignocaine has suppressed heart rate and blood pressure changes to laryngoscopy and endotracheal intubation. In fact intravenous lignocaine has better suppressing property than nebulization of lignocaine

KEYWORDS: Laryngoscopy, endotracheal intubation; Cardiovascular response; Lignocaine, intravenous, nebulization.


CONTENTS

 

Sl.No.

 

Page no

1

INTRODUCTION

1

2

OBJECTIVES OF THE STUDY

3

3

ANATOMICAL ASPECTS

4

4

PHYSIOLOGY OF PRESSOR RESPONSE

11

5

PHARMACOLOGY OF LIGNOCAINE

15

6

REVIEWOF LITERATURE

22

7

METHODOLOGY

35

8

OBSERVATIONS AND RESULTS

40

9

DISCUSSION

54

10

CONCLUSION

65

11

SUMMARY

66

12

BIBLIOGRAPHY

68

13

ANNEXURES

 

PROFORMA MATER CHART

75


 

TABLE

No.

TITLE

PAGE

No.

1

Table showing Age distribution

41

2

Table showing Sex distribution

42

3

Table showing Weight distribution

43

4

Table showing Nature of Surgical procedures

44

5

Table showing changes in Mean Heart Rate

45

6

Table showing changes in Mean Systolic Blood Pressure (SBP)

47

7

Table showing changes in Mean Diastolic Blood Pressure (DBP)

49

8

Table showing changes in Mean Arterial Pressure (MAP)

51

9

Table showing changes in Mean Saturation of Oxygen (SpO2)

53


 

 

Figure No.

Details

Page No

1

Entrance to larynx (posterior view)

5

2

View of larynx during laryngoscopy

7

3

Sympathetic supply to heart and lungs

12

4

Photograph showing administration of Nebulization

39

5

Photograph showing CompAir Compressor Nebulizer NE-C28

 

and Injection Lignocaine 2%.

39

6

Graph showing Age distribution

41

7

Graph showing Sex distribution

42

8

Graph showing Weight distribution

43

9

Graph showing changes in Mean Heart Rate (HR)

45

10

Graph showing changes in Mean Systolic Blood Pressure (SBP)

47

11

Graph showing changes in Mean Diastolic Blood Pressure (DBP)

49

12

Graph showing changes in Mean Arterial Pressure (MAP)

51

13

Graph showing changes in Mean Saturation of Oxygen (SpO2)

53


 

INTRODUCTION

 

The major responsibility of an anaesthesiologist is the management of airway to provide adequate ventilation to the patient by securing airway during general anaesthesia. As such, no anaesthesia is safe unless diligent efforts are devoted to maintain an intact functional airway.

Endotracheal intubation is the overall accepted, “Gold standard of securing the airway and providing adequate ventilation.” However, endotracheal intubation requires time, a skilled anaesthesiologist, appropriate instruments and adequate  circumstances with respect to space and illumination

Direct laryngoscopy and endotracheal intubation following induction of anaesthesia is almost always associated with hemodynamic changes due to reflex sympathetic discharge caused by epipharyngeal and laryngopharyngeal stimulation.1 This increased sympatho-adrenal activity may result in hypertension, tachycardia and arrhythmias.2,3,4 This increase in blood pressure and heart rate are usually transitory, variable and unpredictable. Transitory hypertension and tachycardia are probably of no consequence in healthy individuals5 but either or both may be hazardous to patients with hypertension, myocardial insufficiency, penetrating eye injuries, intracranial lesion, or cerebrovascular diseases. This laryngoscopic reaction in such individuals may predispose to development of pulmonary oedema6 myocardial insufficiency7 and cerebrovascular accident.8 At least in such individuals there is a necessity to blunt these harmful laryngoscopic reactions.

Attenuation of pressor responses to manipulation of the airway has been practiced either by deepening the plane of anaesthesia,9,10 by the use of drugs known to obtund them or by using advanced airway devices.11,12


 

Many methods have been devised to reduce the extent of hemodynamic events including high dose of opioids,5,13 alpha and beta adrenergic blockers,14,15 calcium channel antagonist like diltiazem, verapamil16 and vasodilatation drugs like nitroglycerine.17 α2 agonist like Clonidine18 and Dexmedetomidine are used 19

Various studies have reviewed the effect of Lignocaine in forms like viscous lignocaine20 aerosols,21 oropharyngeal sprays 22 and intravenous23,24 route to blunt these responses.

Topical anaesthesia with lignocaine applied to the larynx and trachea in a variety of ways remains a popular method used alone or in combination with other techniques.

Intravenous lignocaine has been used to supress cough during tracheal intubation,25 laryngospasm and cough during extubation.26 It has also been used to suppress airway hyperactivity and mitigate bronchoconstriction after tracheal  intubation.27 In a study using intravenous and inhaled lignocaine, lignocaine in both the routes attenuated reflex bronchoconstriction significantly. Lignocaine plasma concentrations were significantly lower in the group where lignocaine was used via inhalational route.28

Intravenous lignocaine with its well established centrally depressant and anti- arrhythmic effect was found to be a more suitable alternate method to minimize this pressor response.23,24

The present study was undertaken to compare the effect of Intravenous lignocaine and nebulization of lignocaine on blunting the haemodynamic responses to endotracheal intubation.


 

 

OBJECTIVES OF THE STUDY

 

The main objectives of the present study are:

 

 

 

 

1.  To study the effect of 2% lignocaine 2mg/kg iv, on hemodynamic responses to laryngoscopy and endotracheal intubation.

2.  To study and compare effect of intravenous lignocaine with nebulization of 2% lignocaine 2mg/kg on hemodynamic responses to laryngoscopy and endotracheal intubation.

3.  To evaluate any side effects associated with the use of this drug in both routes.


 

ANATOMICAL ASPECTS29, 30

 

The relevant anatomy of the posterior surface of the tongue, the soft palate, epiglottis, larynx and trachea, with their nerve supply is explained briefly to understand the physiological effects of endotracheal intubation.

TONGUE:

 

It is a soft mobile organ which bulges upwards from the floor of the mouth. The posterior part of the tongue forms the anterior wall of the oropharynx. The dorsum of the tongue is long and extends from the tip to the base of the epiglottis and with it forms the glosso-epiglottic fold. It is separated into palatine and pharyngeal parts by a V shaped sulcus terminalis. The thick mucous membrane covering the tongue is posteriorly continuous with that on the anterior surface of epiglottis over the median and lateral glosso-epiglottic folds and the valleculae of the epiglottis between them.

EPIGLOTTIS:

 

It is likened to a leaf. It is attached at its lower tapering end to the back of the thyroid cartilage by means of the thyro-epiglottic ligament. Its superior extremity projects upwards and backwards behind the hyoid and the base of the tongue, and overhangs the inlet of the larynx. The posterior aspect of the epiglottis is free and bears a bulge, termed the tubercle, in its lower part. The upper part of the anterior aspect of the epiglottis is also free; it’s covering mucous membrane sweeps forward centrally onto the tongue and, on either side, onto the side walls of the oropharynx, to form, respectively, the median glosso-epiglottis and the lateral glosso-epiglottic folds.


 

The valleys on either side of the median glosso-epiglottic fold are termed the valleculae, The lower part of the anterior surface of the epiglottis is attached to the back of the hyoid bone by the hyoepiglottic ligament

SOFTPLATE:

 

Is a flexible muscular flap which extends postero-inferiorly from the posterior edge of the hard palate into the pharyngeal cavity. By varying its position, it can cut off the nasopharynx or the mouth from the remainder of pharynx. It is attached to the posterior edge of the hard palate and to the side walls of pharynx and has the uvula hanging down from the middle of its free posterior border. On each side, the posterior border is continuous with the palatopharyngeal arch.

LARYNX:

 


 

 

Figure 1: Entrance to larynx (posterior view)


 

The competent anaesthesiologist should have a level of knowledge of the anatomy of the larynx of which a laryngologist would not be ashamed. Evolutionally, the larynx is essentially a protective valve at the upper end of the respiratory passages; its development into an organ of speech is a much later affair. Structurally, the larynx consists of a framework of articulating cartilages, linked together by ligaments, which move in relation to each other by the action of the laryngeal muscles. It lies opposite the 4th, 5th and 6th cervical vertebrae, separated from them by the laryngopharynx; its greater part is easily palpable, since it is covered superficially merely by the investing deep fascia in the midline and by the thin strap muscles laterally.

The inlet of larynx is a large oblique shaped opening bounded antero-posteriorly by the epiglottis. It is bounded on each side by the aryepiglottic fold of mucous  membrane and postero-inferiorly by the inter-arytenoid fold of mucous membrane. Each aryepiglottic fold is a narrow and deep fold that extends posterior-inferiorly from the margin of the epiglottis to the arytenoid cartilage. It contains the aryepiglottic muscle and near its inferior ends two small pieces of cartilage which forms the cuneiform and corniculate tubercules in its free edge. The interarytenoid fold of mucous membrane passing between them forms the inferior boundary of inlet and encloses the muscle which pass between the posterior surfaces of the arytenoid cartilages.

Vocal cords are two folds of mucous membrane stretching antero-posteriorly from the vocal processes of the arytenoid cartilage to the posterior surface of the thyroid cartilage and enclosed within each of them is a band of fibroelastic tissue known as the vocal ligament. The opening between the two folds forms the glottis which is the narrowest portion of the airways in the adult.


 

LARYNGOSCOPIC ANATOMY

 


 

Figure 2: View of the larynx at laryngoscopy.

 

 

To view the larynx at direct laryngoscopy and then to pass a tracheal tube depends on getting the mouth, the oropharynx and the larynx into one plane. Flexion of the neck brings the axes of the oropharynx and the larynx in line but the axis of the mouth still remains at right angles to the others; their alignment is achieved by full extension of the head at the atlanto-occipital joint. This is the position, with the nose craning forwards and upwards.

At laryngoscopy, the anaesthesiologist first views the base of the tongue, the valleculae and the anterior surface of the epiglottis. The laryngeal aditus then comes into view bounded in front by the posterior aspect of the epiglottis, with its prominent epiglottic tubercle. The aryepiglottic folds are seen on either side running postero - medially from the lateral aspects of the epiglottis; they are thin in front but become thicker as they pass backwards where they contain the cuneiform and corniculate


 

cartilages. The vocal cords appear as pale, glistening ribbons that extend from the angle of the thyroid cartilage backwards to the vocal processes of the arytenoids. Between the cords is the triangular (apex forward) opening of the rima glottidis, through which can be seen the upper two or three rings of the trachea.

TRACHEA:

 

It is a wide tube of 13-15 mm diameter and 11- 14 cm in length. It commences at the larynx and terminates at the level of the fourth thoracic vertebra, where it divides into the two main bronchi. In new born the trachea is only 4 cm long. The tracheal architecture consists of a number of horizontal C shaped cartilages which are joined posteriorly by the trachealis muscle. Vertically these cartilages are joined to each other by fibroelastic tissue. This gives the trachea an appearance similar to that of tyres pilled one on top of the other, held together by elastic tissue and both covered by endothelium.

NERVE SUPPLY:

 

Glossopharyngeal nerve:

 

The ninth cranial nerve is a mixed nerve. Its motor fibres supply the stylopharyngeus muscle. The parasympathetics supply to the parotid glands is through glossopharyngeal nerve. It descends between the internal and external carotid arteries and after passing between superior and middle constrictors of pharynx, it branches into two terminal branches.

The pharyngeal branch consists of :

 

1.          One or two branches which supply the mucous membrane of the pharynx, posterior one third of the tongue, anterior surface of the epiglottis, glosso-epiglottic folds, valleculae and pyriform fossa are also supplied by this nerve.


 

2.           The larger branch accompanies the pharyngeal branches of the vagus to the pharyngeal plexus. One of its branches joins a branch of superior laryngeal nerve to form the carotid sinus nerve which supplies the carotid sinus and the carotid body.

Vagus nerve:

 

This is also a mixed cranial nerve. In the neck it descends vertically between the internal jugular vein and the internal carotid artery above and the common carotid artery below. All three structures are enclosed in the carotid sheath. It gives off numerous branches, three of which supply those areas of the pharynx and larynx stimulated by the endotracheal intubation.

1.          Pharyngeal branch: This branch forms the large part of the pharyngeal plexus to which are contributed branches of the glossopharyngeal nerve and fibres from the superior cervical sympathetic ganglion. This plexus supplies the muscles and mucous membrane of the pharynx.

2.          Superior laryngeal nerve: This branch divides into external and internal laryngeal nerves. The external branch descends on the anterior aspect of the thyroid cartilage to the crocothyroid muscle to which it supplies. The internal branch perforates the thyrohyoid membrane and lying in the submucous plane of  pyriform fossa. Supplies sensory branches to the larynx above the level of the glottis.

3.          Recurrent laryngeal nerve: on the right side leaves the vagus as the latter crosses the right subclavian artery; it then loops under the artery and ascends to the larynx in the groove between the oesophagus and trachea. On the left side, the nerve originates from the vagus as it crosses the aortic arch; the nerve then passes under


 

the arch to reach the groove between the oesophagus and the trachea. Once it reaches the neck, the left nerve assumes the same relationships as on the right. The recurrent laryngeal nerves provide the motor supply to the intrinsic muscles of the larynx apart from cricothyroid, as well as the sensory supply to the laryngeal mucosa inferior to the vocal cords.


 

PHYSIOLOGY OF PRESSOR RESPONSES30, 31

 

Direct laryngoscopy and endotracheal intubation following induction of anaesthesia is almost always associated with hemodynamic changes due to reflex sympathetic discharge caused by epipharyngeal and laryngopharyngeal stimulation. Here in with have explained briefly the physiology and effects of laryngoscopy and intubation to understand the haemodynamic changes.

SYMPATHETIC NERVOUS SYSTEM.

 

The sympathetic efferent nerve fibres originate from nerve cells in the lateral grey column of the spinal cord between the first thoracic and second lumbar segments (the thoracic outflow). Preganglionic fibres are myelinated. Ganglia are located either in the paravertebral sympathetic trunk or in prevertebral ganglia, such as the celiac ganglion. The sympathetic part of postganglionic fibres are long, non-myelinated sympathetic part of the system has a wide spread action on the body as the resulting preganglionic fibres synapsing on many postganglionic neurons and the suprarenal medulla releasing the sympathetic transmitters epinephrine and nor epinephrine. The sympathetic nervous system prepares the body for emergencies and severe muscular activity. There is no sympathetic out flow from cervical part of the cord nor from the lower lumbar and sacral parts. Those preganglionic fibres which are destined to synapse with cell bodies whose fibres are going to run with cervical nerves must ascend in the sympathetic trunk and those of lower lumbar and sacral nerves must descend in the trunk to lumbar and sacral ganglia.


 

 

 

 

Figure 3: Sympathetic supply to heart and lungs Afferent sympathetic fibres

All the afferent fibres have their cell bodies in the posterior root ganglia of spinal nerves. The afferent fibres reach the spinal nerve in the white ramus communicants. Central processes enter the spinal cord by posterior nerve root. From there they ascend through the cord to brain stem.


 

Afferent sympathetic fibres

 

         Hypothalamus

 

Transmits signals through preganglionic cell bodies located in lateral horn cells of thoracic and upper two lumbar segments.

 

Post ganglionic cell bodies in ganglia in peripheral nervous system either in the sympathetic or in autonomic plexuses.

 

Causes massive sympathetic discharge

 

THE CARDIOVASCULAR REFLEXES

 

The cardiovascular responses to noxious airway manipulation are initiated by proprioceptors responding to tissue irritation in the supraglottic region and 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 superficial location of the proprioceptors and their nerves is the reason that topical local anaesthesia of the airway is such an effective means of blunting cardiovascular responses to airway interventions. The glossopharyngeal and vagal afferent nerves transmit these impulses to the brain stem, which, in turn, causes widespread autonomic activation through both the sympathetic and parasympathetic nervous systems.


 

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.

In addition to activation of the autonomic nervous system, laryngoscopy and endotracheal intubation result in stimulation of the central nervous system (CNS), as evidenced by increases in electroencephalographic activity, cerebral metabolic rate, and cerebral blood flow (CBF).


 

PHARMACOLOGY OF LIGNOCAINE31, 32, 33

 

 

Lignocaine was synthesised in 1943 in Sweden by Lofgren, it was introduced into clinical practice by Gordh in the year 1948.

PHARMACOLOGY

 

Clinically lignocaine is an amino-amide of xylidine-de-ethyl amino 2:6 dimethyl acetanilidine.

STRUCTURAL FORMULA:

 

 

 


 

PHYSICAL PROPERTIES:

 

It is very stable, not decomposed by boiling, acids or alkalies and withstands repeated autoclaving. The pKa of lignocaine is 7.72. At the normal tissue pH of 7.4 approximately 65% of lignocaine exists in the charged cationic form, whereas 35% exists in the uncharged base form.

Lipid solubility: Determination of partition co-efficient by means of n-heptane/pH 7.4 buffer system has given a value of 2.9.

Plasma protein binding: At a concentration of 2mcg/ml approximately 65% is bound to plasma proteins. Lignocaine is a local anaesthetic of moderate potency and duration, with good penetrative powers and rapid onset of action. It is effective by all routes of administration. Lignocaine sometimes causes vasodilation. Adrenaline as adjuvant


 

prolongs the duration of lignocaine as it reduces the rate of systemic absorption. With repeated injections, tachyphylaxis often occurs.

The hydrochloride salt in water has a pH of 6.5. Hepatic extraction ratio 65-70%.

Plasma half life 1.6 hrs.

 

Volume of distribution – 1.3 L/hr.

 

PREPARATIONS OF LIGNOCAINE

 

1.   Topical forms:

 

Topical spray 4% and 10% solution

 

Gel: 2% or 2.5%

 

Solution: 2% or 4% or 5%

 

2.   Parenteral forms: 0.5%, 1% .2%, or 4% as lignocaine hydrochloride.

 

Lignocaine is stored at temperature < 25ºC protected from light. Lignocaine is also available along with adrenaline in 1: 1 lakh or 1: 2 lakh concentrations.

PHARMACODYNAMICS

 

A.  Local effects:

 

Lignocaine blocks the conduction of impulses in the nerve fibres at the site of injection by closing sodium channels.

Sensory and motor fibres are inherently equally sensitive to lignocaine.

 

Smaller fibres and nonmyelinated nerve fibres are blocked more easily than longer and myelinated fibres.

Autonomic fibres are more susceptible than somatic fibres. Among somatic fibres order of blockade are pain-temperature-touch-deep pressure sense.

Addition of vasoconstrictor like Adrenaline (1:50,000 to 1:2 lakh) can


 

1.  Prolong the duration of action of lignocaine by decreasing the rate of removal from the local site of injection in to the circulation

2.  Reduces the systemic toxicity; of lignocaine by decreasing the rate of absorption and keeping the plasma concentration lower.

It is very effective surface analgesic causing rapid absorption from mucosal surface. The peak blood concentration is achieved within 4 to 15 minutes after  instillation. Given intravenously, peak blood levels are achieved immediately.

B.  Systemic effects

 

Cardiovascular system

 

Heart: Lignocaine is placed under classification of class 1- B anti-arrhythmic drugs classification.

It suppresses the automaticity in ectopic foci by antagonizing phase IV depolarization in Purkinje fibres and ventricular muscles by blocking sodium channels.

It does not depress SA node automaticity.

 

The rate of phase-0 depolarization is not decreased except in presence of hyperkalaemia.

Lignocaine markedly decreases the action potential duration and effective refractory period in Purkinje fibres and ventricular muscles.

Conduction velocity is not decreased.

 

It has practically no effect on action potential duration and effective refractory period of atrial fibres. Atrial re-entry is not affected.

It can suppress the re-entrant ventricular arrhythmias either by abolishing one way block or by producing two way blocks. At therapeutic plasma concentration of 3- 5mcg/ml, it causes little depression of cardiac contractility. There are no significant autonomic actions. All cardiac effects are direct actions.


 

Lignocaine is widely used in the management of ventricular dysrhythmias in a dose of 1 to 2 mg/kg bolus intravenously and 2.4 mg/min as infusion. It acts by its membrane stabilizing effect and depression of automaticity at atrio-ventricular node. It has been used effectively in the management of ventricular arrhythmias following myocardial infarction and cardiac surgery.

Vascular smooth muscle.

 

Lignocaine exists in two isomers, and the ability to produce vasoconstriction appears vested in one of the isomers. Hence lignocaine produces vasoconstriction with low doses and vasodilation at higher doses, very large doses cause circulatory collapse as a result of medullary depression and direct vasodilation.

At doses > 75mcg/kg/min with plasma concentration of > 10-20mcg/ml  lignocaine causes asystole and cardiovascular collapse.

Central nervous system

 

It readily crosses blood brain barrier causing central nervous system stimulation followed by depression with higher doses. The severity of the central nervous system effect correlates with plasma concentration. Central nervous system is more susceptible to toxic effects than the cardiovascular system. Mild toxic effects may cause drowsiness and sedation. Objective signs of central nervous system toxicity are usually excitatory in nature and may cause shivering, muscular tithing and convulsions. It has been shown to possess analgesic properties when given intravenously. Reduction of MAC of inhalational anaesthetic agents is used as an index of its central analgesic property. Higher serum levels produce a central stimulant effect and this is due to initial blockade of inhibitory pathway at limbic or higher centres in the cerebral cortex.


 

Neuromuscular junction

 

It can affect transmission at the neuromuscular junction and hence potentiate the effect of the depolarizing and non-depolarizing muscle relaxants.

Metabolism

 

It is metabolised by the liver microsomal enzymes, oxidases and amidases. The main pathway in man appears to be due to oxidative de-ethylation of lignocaine to monoethyl glycinexuylidide followed by subsequent hydrolysis of monoethyl glycinexylidide to xylidine. Excretion occurs through the kidneys.

Dosage

 

The safe dose limit for lignocaine has been much disputed. The factors governing the dosage are the weight of the patients and the different absorption rates from various sites and injections. The maximum safe dose is to 4.5 mg/kg without epinephrine and 7 mg/kg with epinephrine.

A concentration of 0.25-5% of lignocaine hydrochloride is used for infiltration. If extensive block is required then 0.5% with epinephrine is used. 0.5% lignocaine without adrenaline is used for intravenous regional anaesthesia. 1% lignocaine is usually sufficient for most nerve blocks. In dentistry, 2% lignocaine with adrenaline 12.5 mcg/ml (1:80,000) is useful. A concentration of 1.5-2% solution of lignocaine is used for epidural analgesia and sometimes with the addition of adrenaline 5 mcg/ml 1:200,000). For surface application, lignocaine solution in a concentration of (4%) for spraying or for application using wool pledgets.

It is used in a concentration of 2% as a lubricating gel in urethral surgery and for lubricating endotracheal tubes. In the management of cardiac dysrhythmias it is used in the dose of 1-2 mg/kg iv as a bolus dose followed by 2-4 mg/min (20-60 mcg/kg/min) as


 

infusion and then the dose is reduced. Caution must be exercised in the presence of low cardiac output and after cardiac surgery and a slow infusion rate must be maintained.

Toxicity

 

The appearance of toxic symptoms is due to two factors. The toxicity of the drug and its serum levels.

Toxic symptoms may occur at plasma levels of 5mcg/ml in an awake patient, while levels of 10mcg/ml are toxic in the anaesthetised patient. Plasma levels depend on the speed with which lignocaine enters the circulation, which in turn depends on the dosage and rate of absorption of the drug from various sites. Peak blood levels are attained in 1 minute after intravenous administration and start decreasing by 3-4 minutes. Following laryngotracheal administration, peak blood levels are attained in 9-15 minutes. Alveolar absorption occurs at a faster rate than absorption from bronchial and bronchiolar mucosa. It is thought that, mucosal absorption simulate intravenous administration. However, systemic absorption of lignocaine may be slowed through larynx and tracheal mucosa as it is diluted with secretions lining the upper airway, impeding systemic absorption. Hence laryngotracheal administration is associated with delayed peak levels that are lower but more sustained. The peak blood levels after epidural injection follow a similar pattern to those seen after intra-muscular injection (average 18 minutes for plain lignocaine and after 23 minutes for lignocaine with adrenaline)

Side effects

 

Commonest side effects are nausea, drowsiness, and dizziness. At a higher levels shivering, muscular twitching, tremors and convulsions, bradycardia, decreased respiration with hypoxia can occur. Circulatory collapse may occur with very high dosage.


 

Hypersensitivity

 

This is due to an antigen-antibody reaction. Hypersensitivity to local anaesthetics is more common with ester-linked drugs than with amide group of drugs. This is more commonly seen in atopic individuals and can manifest as local oedema, urticaria, or angioneurotic oedema. Dermatitis may be encountered as a result of skin application. Anaphylaxis occurs less commonly. Although amide agents appear to be relatsively free from allergic type reactions, solution may contain preservatives like paraben and methylparaben whose chemical structure is similar to that of para-aminobenzoic acid.


 

REVIEW OF LITERATURE

 

HISTORICAL REVIEW

 

Endotracheal intubation has become an integral part of the anaesthetic management and critical care. It has been practised following its description by Rowbottam and Magill in 1921.32 Laryngoscopy and endotracheal intubation are attended by significant hypertension, tachycardia and arrhythmias. These hemodynamic responses were first recognised as early as in 1940 by Reid and Brace et al.34 They postulated that the disturbances in cardiovascular system were reflex in nature and mediated by the vagus nerve which originated in the, trachea, larynx, bronchi, or lungs and effects by sudden increase in the vagal tone. These reflexes were termed ‘vagovagal’ since both the efferent and afferent paths of the reflex were assumed to be vagus nerve. But in 1950 Burstein and co-workers,2 had a different conclusion that attributed the effects of laryngoscopy and tracheal intubation on ECG changes and suggested the pressor response as consequences of an increase in sympathetic and sympathoadrenal activity and also observed that deep anaesthesia minimizes ECG incident to tracheal intubation. In 1951 King BD and co-workers35 observed that during light general anaesthesia, direct laryngoscopy or tracheal intubation, uncomplicated by cough, anoxia, hypercarbia is capable of producing decided circulatory effects characterised by rise in blood pressure and increase in heart rate.

These responses being transitory are well tolerated by normal individuals but are more deleterious in patients with hypertension, myocardial insufficiency and cerebrovascular diseases which result in potentially dangerous effects like ventricular arrhythmias,4 myocardial ischemia,7 pulmonary oedema,6 left ventricular failure,6 and


 

cerebrovascular accidents.8 This hemodynamic stimulus is associated with increase in plasma nor-adrenaline concentrations parallel with the increase in blood pressure.36

Many methods and strategies have been employed and advocated to minimize and nullify the hemodynamic responses to laryngoscopy and intubation which work on the reflex arc.33

1.          By blocking the peripheral sensory afferent inputs – topical application and infiltration of superior laryngeal nerve.

2.          Block of central mechanism of integration of sensory inputs – morphine, fentanyl.

 

3.          Block of the efferent pathway effector sites – calcium channel blockers, intravenous lignocaine, esmolol.

Increasing the depth of anaesthesia with the use of inhalational agent like cyclopropane,9 trichloroethylene,37 chloroform and ethyl chloride38 for attenuation had been practised, but with the drawback of stormy induction. Halothane and enflurane10 had an advantage of smooth and rapid induction, non-inflammable but was associated with hypotension, bradycardia and myocardial ischemia which are deleterious in patients with coronary insufficiency and hypertension.

Laryngoscopy and tracheal intubation causes a reflex increase of sympathetic and sympathoadrenal system by irritation and stimulation of the laryngeal and pharyngeal tissues, anaesthetising using local anaesthetics like lignocaine at the site of stimulation was studied. And various studies have reviewed the effects of lignocaine in the form of viscous,20 aerosol, 21 spraying,22 and intravenous 23, 24 routes for blunting the response.

As early as in 1960, alpha adrenergic blocker, phentolamine14 was used to attenuate the laryngoscopic reactions. However, these drugs had long duration of action and the authors observed exaggerated fall in blood pressure during perioperative period,


 

because of their property of extensive vasodilation requiring rapid transfusion it was not used.

Beta adrenergic blockers were extensively studied for their negative chronotropic effects for blunting the hemodynamic responses to laryngoscopy and intubation like proctolol15 and labetalol.39 but had a delayed onset and longer duration of action which caused perioperative bradycardia and hypotension, hence a search for shorter acting beta blockers like esmolol40 was started.

The investigators used low doses of opioids as premedicants for blunting the laryngoscopic responses during 1970 and observed significant reduction in the hemodynamic responses to laryngoscopy and intubation. Use of morphine5 and fentanyl13 effectively reduced the tachycardia and hypertension associated with laryngoscopy and intubation but these agents were associated with respiratory depression, chest wall rigidity and in addition they prolonged the recovery time.10 The availability of synthetic narcotics like alfentanyl41 and sufentanyl42 with short duration and rapid onset of action helped the investigators to overcome the problems associated with the use of above mentioned drugs.

Calcium channel blockers like nicardipine, verapamil and diltiazem16 were studied widely to suppress the hemodynamic responses to laryngoscopy and intubation. Calcium ions exert a major role in the release of catecholamines from the adrenal gland and adrenergic nerve endings, which affects plasma catecholamine concentrations, in  response of sympathetic stimulation. The investigators reported that calcium channel blockers interfere with catecholamine release after tracheal intubation.

Directly acting vasodilators like sodium nitroprusside43 and nitroglycerine17 were tried but set back being that they caused reflex tachycardia being deleterious in patients

with co morbidities and requirement of invasive arterial monitoring.


 

Laryngoscopy and tracheal intubation are also employed for non-anaesthetic purposes. Diagnostic purposes for direct laryngoscopy and flexible bronchoscopy.44 Endotracheal intubation may be required for prevention of aspiration and protection of airway. Hence blunting the response becomes important as these patients come as for emergency procedures or critically ill.

CLINICAL REVIEW

 


Mounir N. Abou-Madi et al


21

conducted a study on cardiovascular responses to


 

laryngoscopy and tracheal intubation following nebulization of lignocaine.

 

20 patents scheduled for various procedures were selected for the study and were divided into two groups.

Pre-treated group: received inhalation of 6-8ml of mixture of 1/3rd of 2% viscous lignocaine + 2/3rd of 4% aqueous lignocaine

Control group: nebulized with saline instead of lignocaine in stage II, 10% lignocaine was nebulized instead of saline prior to intubation.

A standard premedication with Pentobarbitone 2mg/kg intramuscular was given one and half an hour before the surgery.

In the pre-treated group

 

Stage I – Pre operative observation period

 

ECG and BP was recorded, arterial blood drawn for gases, serum potassium and lignocaine levels was done

Stage II – Aerosol nebulization was administered.

 

Stage III - Post aerosol observation period. Blood samples drawn and parameters were recorded.


 

Stage IV - Anaesthesia induced with Thiopentone sodium 4mg/kg, anaesthesia continued with nitrous oxide, oxygen and halothane for 5 – 10 min.

Stage V – Steady state

 

For 2 minutes tracing of readings was done Stage VI – Laryngoscopy

Intubation facilitated with Inj. Succinylcholine 1.0mg/kg Stage VII – Intubation

Intubation performed, tracing done for 2min.

 

Stage VIII – Final observation period Was continued till end of procedure

Three stages were taken for statistical analysis

 

1.          Steady state

 

2.          Post laryngoscopy

 

3.          1minute after intubation

 

The authors observed heart rate, systolic blood pressure, diastolic blood pressure and ECG changes following laryngoscopy and intubation.

In control group

 

Heart rate increased by 38.8% (28 bpm), systolic blood pressure increased by 56% (60 mm Hg) and diastolic blood pressure raised by 66.0% (37 mm Hg) above the steady state values after 1minute post intubation .


 

ECG changes: had serious new arrhythmias. The incidence was highest in patients who had suffered the most acute rise in blood pressure.

Blood levels: after intubation the average blood level was 0.4 mcg/ml at 2min and at the end of study it was 0.3 mcg/ml

In Pre-treated group

 

Heart rate increased by 16.8% (17 bpm), systolic blood pressure by 10.3% (12 mm Hg) and diastolic blood pressure by 16.4% (11 mm Hg) above the steady state values after 1min post intubation.

ECG changes: There were no new arrhythmias or ECG changes.

 

Blood levels: The average lignocaine levels following nebulization was 1.4mcg/ml at 2min and 1.2mcg/ml at the end of the study.

The authors concluded,

 

1.          Topical anaesthesia applied immediately before intubation is ineffective.

 

2.          Systemic absorption of lignocaine probably accounts for the absence of arrhythmia in pre-treated group.

3.          Incidence of post intubation arrhythmias and hypertension is marked in patients with arteriosclerotic heart diseases.

They believed that inhalation of lignocaine aerosol is a safe, simple, effective, and generally acceptable method.

Mounir N. Abou-Madi et al23 conducted a study on cardiovascular responses to laryngoscopy and tracheal intubation following small and large intravenous doses of lignocaine.


 

Thirty male patients scheduled for various surgical procedures were selected for the study and were divided into three comparable groups A, B and C

Group A – received normal saline iv and served as control Group B – received 1% lignocaine 0.75 mg/kg iv

Group C – received 2% lignocaine 1.5 mg/kg iv

 

All the patients were pre-medicated with Inj. Meperidine 1 mg/kg and Inj. Atropine 0.4 mg/kg intramuscular one hour before surgery. Anaesthesia was induced with Inj. Thiopentone 4 mg/kg and intubation was facilitated with Inj. succinylcholine 1.0 mg/kg. Endotracheal intubation was carried out within 2-3 min of injection of test drug.

Changes in heart rate, systolic blood pressure and diastolic blood pressure in all the three groups were observed following laryngoscopy and intubation.

In control group, heart rate increased by 15.3% (14 bpm), systolic blood pressure increased by 30.3% (42 mm Hg) and diastolic blood pressure raised by 38.7% (31 mm Hg) above the pre- induction value .

In group B, (Lignocaine 0.75 mg/kg), heart rate increased by 26% (21.1 bpm), systolic blood pressure by 11,9% (17.6 mm Hg) and diastolic blood pressure by 25.2% (20 mm Hg) above the pre-induction value.

In group C, (Lignocaine 1.5 mg/kg) heart rate increased by 8.5% (8.5 bpm), systolic blood pressure increased by 21.5% (30.4 mm Hg) and diastolic blood pressure by 22.3% (21.8 mm Hg) above the pre-induction value.

The authors concluded that 1.5 mg/kg iv Lignocaine given 3 min before laryngoscopy and intubation provides protection against both tachycardia and hypertension. They also discussed the possible modes of action

Direct myocardial depressant action and indirect dose stimulant effect but with predominance depressant effect during induction.


 

Central stimulant effect (indirect, dose dependent stimulant action)

 

A peripheral vasodilating effect and an effect on the synaptic transmission

 

Suppress the cough reflex.

 

The authors also concluded that pre-induction aerosol topical analgesia of the upper airways would still be their method of choice to minimise post intubation cardiovascular reactions in patients with poor myocardial reserve and severe hypertension.

 

 

Robert K Stoelting3 compared the clinical effects of intravenous lignocaine 1.5 mg/kg given 30 sec before intubation and laryngotracheal viscous lignocaine 2 mg/kg given 10 min before intubation in 24 patients scheduled for elective coronary artery bypass graft operations.

Anaesthesia was induced with thiamylal 4 mg/kg and intubation was facilitated with succinylcholine 1.5 mg/kg. The duration of laryngoscopy was averaged less than 15 sec.

The authors observed no significant changes in heart rate following laryngoscopy and intubation in both the groups. However, in control group, mean arterial pressure raised by 17 mm Hg in viscous lignocaine group, by 14 mm Hg and in intravenous lignocaine group, mean arterial pressure increased by 22 mm Hg, above the pre-induction value.

The authors did not make any comment on changes in diastolic or systolic pressures. Mean arterial pressure decreased spontaneously and reached pre-induction levels by 2 min after intubation.

They concluded that a short duration direct laryngoscopy combined with laryngotracheal lignocaine before tracheal intubation minimises the pressor responses and ensures a spontaneous return of mean arterial pressure and heart rate towards awake


 

levels following intubation. Viscous or intravenous lignocaine is not helpful when laryngoscopy of short duration

Robert F. Bedford, et al45 compared the reduction in intracranial pressure following intravenous administration of bolus lignocaine at 1.5mg/kg with Thiopentone. Lignocaine significantly reduced the ICP with minimum changes in arterial pressure without altering the cerebral perfusion. Rise in ICP due to intubation and surgical stimulation is blunted  by it.

James F. Hamill, et al46 they observed that in a light barbiturate–nitrous oxide anaesthesia, topical laryngotracheal administration of 4ml of 4% lignocaine prior to laryngoscopy and tracheal intubation causes a significant increase in ICP, heart rate, and mean arterial pressure. 1.5mg/kg lignocaine intravenous administered 1minute before intubation prevents both rise in ICP, and was useful in blunting the hemodynamic response to laryngoscopy and endotracheal intubation. Cerebral perfusion was well maintained and it decreased CMRO2 and cerebral blood flow. Laryngotracheal topical application took 4-15 min for achieving plasma level of 1 - 2.7mcg/ml when compared with intravenous route.

Bahaman Venus,47 conducted a study on cardiovascular responses to laryngoscopy and tracheal intubation following nebulization of lignocaine

Study included 19 ASA class I and II adult patients scheduled for general anaesthesia for wide excision and extremity amputation procedures were divided into two groups.

Group I: 10 patients received of solution A (normal saline, 6ml) Group II: 9 patients received of solution B (4% lignocaine, 6ml) both groups were aerosolized with their


 

respective solutions 5 minute during pre-oxygenation before induction. A contoured breathing mask with attached nebulizer was used to deliver the aerosol.

All patients were pre-medicated with, atropine 0.05mg/10kg and morphine 1mg/10kg 1hour before the induction. Baseline measurements of blood pressure, heart rate and ECG recordings were noted. A standard technique for administration of general anaesthesia was followed and laryngoscopy and endotracheal intubation was performed in both the groups. The time and duration of each manoeuvre were recorded until 5 min after placement of endotracheal tube. Blood gas analysis was done.

They observed that the pressor response and tachycardia following laryngoscopy and endotracheal intubation in the control group I was clinically significant. The patients in aerosolized group maintained significantly lower pressor response and heart rate. 4 patients among the group I developed PVC and none in group II.

They concluded that

 

1.          The underlying mechanism is probably of reflex origin to mechanical stimulation of the larynx and trachea, as the arterial blood gas analysis was within the normal limits excluding the possible causes of hypercarbia and hypoxia.

2.          Aerosolization of lignocaine is a simple and effective technique for intubating patients with borderline cardiovascular status.

Stanley Tam, et al24 studied the optimal time of lignocaine injection before tracheal intubation, to prevent the pressor response. Seventy patients were divided into five groups with 14 patients in each group. Group 1, Group II, Group III and Group IV, received 1.5 mg/kg of lignocaine intravenously 1, 2, 3 and 5 minutes respectively. Group V received normal saline and served as control. All the patients received morphine 0.1 mg/kg and perphenazine, 0.05 mg/kg intramuscular before induction of anaesthesia. Patients were


 

given d-tubocurarine 0.04 mg/kg 5 min before intubation followed by thiopentone 4 mg/kg and suxamethonium 1.5 mg/kg before intubation. Heart rate, mean arterial pressure, systolic and diastolic pressure were monitored throughout the procedure.

The mean increase in heart rate in group I was 28 bpm, in group II it was 24 bpm, in group III it was 12 bpm and in group IV it was 22 bpm and in group V it was 25 bpm.

The mean increase in systolic blood pressure in group 1 is 32 mm Hg, in group II 29 mm Hg, in group III 12 mm Hg, in group IV 31 mm Hg and in group V it was 38 mm Hg.

The mean increase in diastolic blood pressure in group I was 29 mm Hg, in group II 29 mm Hg, in group III 9 mm Hg, in group IV 22 mm Hg and in group V it was 26 mm Hg.

The mean increase in mean arterial pressure in group I was 30 mm Hg. In group II 27 mm Hg, in group III 11 mm Hg, in group IV 27 mm Hg and in group V 32 mm Hg.

The results of the study showed that the mean increase in heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure in group III, where lignocaine was given in the dose of 1.5 mg/kg iv 3 min before laryngoscopy and intubation were comparatively less than the other groups, when compared with the base line values.

The authors concluded that intravenous lignocaine at 1.5 mg/kg attenuated increase in heart rate and arterial blood pressure, only when given 3 min before intubation. And it offers no protection against post-intubation changes when given at 1, 2 and 5 min before intubation.

Splinter et al48 studied the haemodynamic response to laryngoscopy and tracheal intubation in geriatric patients with thiopentone alone or in combination with 1.5mg/kg lignocaine and with 1.5mg/kg or 3mcg/kg fentanyl were measured. They observed that both the drugs decreased the rise in heart rate and blood pressure changes with fewer


 

haemodynamic fluctuations in case of fentanyl. Lignocaine treated patients had fewer cardiac dysrhythmias.

C D Miller and S J Warren49 studied the effect of intravenous lignocaine on the cardiovascular responses to laryngoscopy and tracheal intubation.

The study population consisted of 45 Chinese patients of ASA Grade I and Grade II, posted for elective thoracic surgery. The patients were divided into four groups.

Group I – Received normal saline 4 ml iv over 30 sec, 3 min before laryngoscopy and intubation and served as control

Group II – Received 1.5 mg/kg of lignocaine iv 3 min before laryngoscopy and intubation.

Group III – Received 1.5 mg/kg of lignocaine iv 2 min before laryngoscopy and intubation.

Group IV – Received 1.5 mg/kg of lignocaine iv 1 min before laryngoscopy and intubation.

The patients were premedicated with morphine 0.2 mg/kg and hyoscine 40mcg/kg intramuscular one hour before induction. Anaesthesia was induced with thiopentone 5 mg/kg 2.5 minutes before laryngoscopy. Neuromuscular block was produced with 1.5 mg/kg of suxamethonium iv given 1.5 min before laryngoscopy and subsequent tracheal intubation were performed using standard Macintosh laryngoscope and cuffed Portex endotracheal tube. Heart rate, Systolic and Diastolic pressures were recorded and the Mean arterial pressure and rate-pressure product were calculated.

The results of the study showed that, in control group the heart rate increased by a maximum of 27 bpm, systolic blood pressure increased by 31 mm Hg, diastolic blood pressure increased by 28 mm Hg. Group III and Group IV, where lignocaine 1.5 mg/kg iv was given 2 and 1 minutes before laryngoscopy and intubation, also showed that, statistically significant increase in heart rate, systolic and diastolic blood pressure. The


 

authors concluded that, lignocaine 1.5 mg/kg given intravenously within 3 min of laryngoscopy and intubation failed to attenuate cardiovascular responses.

Wilson IG, et al50 studied the effect of varying the time of prior doses of intravenous lignocaine 1.5mg/kg on the cardiovascular response and catecholamine responses to tracheal intubation. Forty healthy patients were given intravenous lignocaine 2, 3, and 4 min prior to intubation. When compared with placebo there was significant increase in heart rate in all groups, but no significant rise in mean arterial pressure in all groups given lignocaine. Placebo group showed rise in mean arterial pressure of 19% compared to basal values.

M.J.L.   Bucx, et al51 worked on the relationship between forces applied during laryngoscopy and haemodynamic changes. This helps in to differentiate between cardiovascular effect of laryngoscopy and tracheal intubation. There was no significant relationship between forces applied during laryngoscopy and cardiovascular changes. It is the tracheal intubation more than laryngoscopy that caused changes in routine uncomplicated and laryngoscopy and subsequent tracheal intubation.

Sklar BZ et al52 conducted a study to assess the effect of lignocaine inhalation at a dose of 40mg and 120mg and control group with intravenous lignocaine 1mg/kg and on stress response to laryngoscopy and intubation. They observed that heart rate response to intubation with inhalation was dose dependent and at a dose of 120mg rise in blood pressure was least compared to rest of the study groups. Hence concluded that inhalation of lignocaine prior to induction of anaesthesia is a safe and convenient method.


 

METHODOLOGY

 

A Study entitled Comparative study of lignocaine nebulization with intravenous lignocaine on stress response to laryngoscopy and tracheal intubation was undertaken in Victoria hospital and Bowring and Lady Curzon hospitals, Bangalore during November 2008 to October 2010. Ethical clearance was obtained for the study.

The study was conducted on 90 ASA grade I and II patients in the age group of 18 to 45 years of either sex scheduled for elective surgeries done under general anaesthesia.

Patients were allocated into three groups with the sample size of 30 each. Group C (n=30) received no drug, as control.

Group I (n=30) received 2% Lignocaine 2mg/kg slow intravenous. Group N (n=30) received 2% nebulization of Lignocaine 2mg/kg. Exclusion criteria:

1.      Patients    with    chronic   obstructive   lung disease,    cerebrovascular disease, cardiovascular diseases, psychiatric illness and liver disorders.

2.      Patients having known allergy either to Lignocaine or its preservatives

 

3.      Patients coming for emergency surgical procedure.

 

4.      Patients with history of laryngeal, tracheal surgery or any pathology.

 

A detailed pre-anaesthetic evaluation including history of previous illness, previous surgeries, general physical examination, and detailed examination of Cardiovascular system, Respiratory system and other relevant systems were done. Baseline investigations were carried out and recorded in the proforma.


 

The following investigations were done in all patients

 

1.       Haemoglobin estimation

 

2.       Bleeding time and clotting time

 

3.       Urine examination for albumin, sugar and microscopy

 

4.       Blood sugar, FBS/PPBS

 

5.       Blood Urea and Serum Creatinine

 

6.       Standard 12- lead electrocardiogram

 

7.       X-ray of Chest

 

An informed and written consent was taken after explaining the anaesthetic procedure in detail. All the patient were pre-medicated with Tab. Diazepam 10mg to allay anxiety and Tab. Ranitidine 150 mg on the night before surgery

Patient arrived to the preoperative room 30 minutes before surgery and preoperative basal heart rate, non-invasive blood pressure readings, SpO2, cardiac rate and rhythm were also monitored from a continuous visual display of electrocardiogram from lead II were recorded.

The patient in group N were nebulized with 2% lignocaine 2mg/kg body weight using a simple fitting face mask with CompAir Compressor Nebulizer NE-C28 model of OMRON healthcare, 10min before induction. On operating table intravenous line was secure with 18G cannula and ringer lactate 500ml infusion started. Patients were connected to non-invasive monitoring with 5 lead electrocardiograph (ECG), pulseoximeter, and non-invasive sphygmomanometer. All patients were pre-medicated with Inj Midazolam 1mg iv. All patients were pre-oxygenated with 100% oxygen for 3 minutes by a face mask.


 

Patients in Group C being the control did not receive any drug.

 

Patients in Group I received 2% lignocaine 2mg/kg body weight 90 sec before induction. Patient in group N were nebulized with 2% lignocaine 2mg/kg body weight 10 min before induction.

INDUCTION OF ANAESTHESIA

 

Anaesthesia was induced with Inj. Thiopentone 5mg/kg as 2.5 % solution, after loss of eye lash reflex and confirmation of adequacy of mask ventilation endotracheal intubation was facilitated with succinylcholine 1.5 mg/kg iv. Laryngoscopy was performed using Machintosh laryngoscope, under visualization of vocal cords a  lubricated (2% lignocaine jelly) cuffed endotracheal tube of appropriate size was passed. After confirming bilateral equal air entry, the endotracheal tube was secured.

Anaesthesia was maintained using 66% nitrous oxide and 33% of oxygen and Halothane 1%. After the patients recovered from succinylcholine further neuromuscular blockade was maintained with non-depolarizing muscle relaxants vecuronium.

MONITORING

 

The following cardiovascular parameters were recorded in all patients:

 

  Heart rate (HR) in beats per minutes (bpm)

 

  Systolic blood pressure (SBP) in mm Hg

 

  Diastolic blood pressure (DBP) in mm Hg

 

  Mean arterial pressure (MAP) in mm Hg

 

The above cardiovascular parameters were noted as below

 

1.          Basal before giving any study drugs and premedication

 

2.          One minute interval for 5 min after laryngoscopy and intubation

 

3.          Every two minutes interval for next 10 min.


 

After the recordings were obtained all patients received 0.2mg Glycopyrrolate iv and 3mcg/kg of Fentanyl iv for analgesia which was avoided earlier, so as to avoid their effects on intubation response. At the end of the procedure patients were reversed with Neostigmine 0.05 mg/kg iv and Glycopyrrolate 0.01 mg/kg iv and extubated after recovery of adequate muscle power and consciousness.


 

 

 

Figure 4:Photograph showing administration of Nebulization


Figure 5:Photograph showing CompAir Compressor Nebulizer NE-C28 and Injection Lignocaine 2%.


 

OBSERVATION AND RESULTS

 

STATISTICAL METHODS.

 

Descriptive statistical analysis has been carried out in the present study. Results on continuous measurements are presented on Mean  SD (Min-Max) and results on categorical measurements are presented in Number (%). Significance is assessed at 5 % level of significance. Analysis of variance (ANOVA) has been used to find the significance of study parameters between three or more groups of patients, Chi-square/ Fisher Exact test has been used to find the significance of study parameters on categorical scale between two or more groups. Kruska Wallis test has been used to find the significance of SPO2 between three groups

Significant figures

 

+ Suggestive significance (P value: 0.05<P<0.10)

 

* Moderately significant (P value: 0.01<P    0.05)

 

** Strongly significant (P value: P 0.01)

 

Statistical software: The Statistical software namely SAS 9.2, SPSS 15.0, Stata 10.1, MedCalc 9.0.1, Systat 12.0 and R environment ver.2.11.1 were used for the analysis of the data and Microsoft word and Excel have been used to generate graphs, tables etc.


 

1.   AGE DISTRIBUTION

 

Table 1 : Table showing Age distribution

 

 

 

Age in years

Group C

Group I

Group N

No

%

No

%

No

%

18-20

4

13.3

2

6.7

6

20.0

21-30

6

20.0

10

33.3

8

26.7

31-40

8

26.7

10

33.3

6

20.0

41-50

12

40.0

8

26.7

10

33.3

Total

30

100.0

30

100.0

30

100.0

Mean ± SD

34.80±9.97

34.13±8.72

32.97±10.06

 

 

 

50

 

45

 

40

 

35

 

Text Box: Percentages30

 

25

 

20

 

15

10                                                                                                  Group C

Group I

5                                                                                                Group N


 

0

18-20                  21-30


31-40                  41-50


Age in years

 

 

Figure 6: Graph showing Age distribution.

 

Samples are age matched with p=0.756

 

There was no significant difference in age distribution in the three groups.


 

2.   SEX DISTRIBUTION

 

Table 2 : Table showing Sex distribution

 

 

Gender

Group C

Group I

Group N

No

%

No

%

No

%

Male

11

36.7

12

40.0

8

26.7

Female

19

63.3

18

60.0

22

73.3

Total

30

100.0

30

100.0

30

100.0

 

 

100

 

90

 

80

 

70


 

Text Box: Percentages60

 

50

 

40

 

30

 

20

 

10

 

0

Group C


 

 

 

 

 

 

 

 

 

 

 

Group I


 

 

 

 

 

 

 

 

 

 

 

Group N


 

 

Gender

 

Male Female


 

 

 

 

Figure 7: Graph showing Sex distribution.

 

 

Samples are gender matched with p=0.527

 

There was no significant difference in sex distribution in the three groups.


 

3.   WEIGHT DISTRIBUTION

 

Table 3 : Table showing Weight distribution

 

 

Weight (kg)

Group C

Group I

Group N

No

%

No

%

No

%

38-40

1

3.3

3

10.0

2

6.7

41-50

8

26.7

7

23.3

8

26.7

51-60

7

23.3

10

33.3

10

33.3

61-70

6

20.0

7

23.3

8

26.7

71-80

7

23.3

3

10.0

2

6.7

Total

30

100.0

30

100.0

30

100.0

Mean ± SD

60.63±12.93

57.00±11.70

56.00±10.10

50

 

45

 

40

 

35

 

Text Box: Percentages30

 

25

 

20

15                                                                                                  Group C

Group I

10                                                                                                  Group N

5

 

0

38-40             41-50             51-60            61-70             71-80

 

Weight (kg)

 

Figure 8: Graph showing Weight distribution.

 

 

Samples are weight matched with P=0.273

 

There was no significant difference in body weight distribution in the three groups.


 

4.   NATURE OF SURGICAL PROCEDURES

 

Table 4: Table showing nature of Surgical procedure

 

Surgery done

Group C

Group I

Group N

HEAD        AND        NECK SURGERIES

10

11

6

ABDOMINAL SURGERIES

4

10

7

LAPROSCOPIC SURGERIES

5

2

10

BREAST SURGERIES

2

3

3

SPINE        AND        LIMB SURGERIES

8

2

3

OTHERS

1

2

1

TOTAL

30

30

30


 

5.   CHANGES IN MEAN HEART RATE

 

Table 5

 

Table showing changes in Mean Heart Rate

 

 

HR (bpm)

 

Group C

 

Group I

 

Group N

Significant value

Group C-

Group I

Group C-

Group N

Group I-

Group N

Basal

85.50±10.30

86.13±10.27

86.97±11.24

0.971

0.854

0.950

Post

intubations

 

 

 

 

 

 

1 min

108.90±14.13

104.13±11.85

111.83±15.91

0.392

0.699

0.092+

2 min

104.87±14.73

103.53±12.42

109.73±15.34

0.930

0.385

0.215

3 min

100.10±13.93

101.03±15.07

105.87±16.47

0.969

0.310

0.438

4 min

95.80±12.79

93.63±13.34

100.8±15.39

0.818

0.348

0.119

5 min

95.07±10.85

93.60±11.79

95.93±14.81

0.894

0.962

0.754

7 min

94.57±11.48

89.47±10.17

92.30±14.94

0.252

0.758

0.650

9 min

91.33±12.12

87.00±7.72

91.60±14.71

0.338

0.996

0.296

11 min

89.13±10.95

87.27±12.4

88.33±12.57

0.819

0.964

0.937

13 min

87.57±8.53

86.00±9.87

85.53±12.50

0.830

0.732

0.984

15 min

85.13±9.36

84.20±12.53

86.63±12.04

0.946

0.867

0.687

 

 

120

 

110

 

Text Box: HR (bpm)100

 

90

 

80

 

70

 

60

Basal      1 min    2 min     3 min     4 min    5 min     7 min     9 min 11 min 13 min 15 min

Post intubations

 

Figure 9: Graph showing changes in Mean Heart Rate (HR)


 

 

In the control group, the basal HR was 85.50 bpm. One minute after intubation, it was 108.90, representing a rise of 23.4bpm. Subsequently, the elevated heart rate started settling down by 9 min By 3and 5 min it was 100 and 95.07 bpm respectively. The increase in HR at 1 minute after intubation compared.

In group I, the basal HR was 86.13 bpm, 1 minute after intubation, it was 104.13 representing a rise of 18 bpm. Subsequently, the elevated heart rate started settling down 9minute. By 3 and by 5 minutes it was 101.03 and 93.6 bpm respectively.

In group N, the basal HR was 86.97 bpm, 1 minute after intubation, it was 111.83 representing a rise of 24.86 bpm. Subsequently, the elevated heart rate started settling down by 11 minute. By 3 and by 5 minutes it was 105.87 and 95.93 bpm respectively.

When mean change in heart rate in first minute in group I and group N were compared with control (group C) group independently, there was no clinical or statistical significance.( group C v/s group I P = 0.392 , group C v/s group N p = 0.699 )

Intergroup comparison of change in heart rate in first minute between the study groups (group N & group I) showed no clinical or statistical significance (p = 0.092).


 

6. CHANGES IN THE MEAN SYSTOLIC BLOOD PRESSURE (SBP) Table 6 : Table showing changes in Mean Systolic Blood Pressure (SBP)

SBP            (mm Hg)

 

Group C

 

Group I

 

Group N

Significant values

Group C-

Group I

Group C-

Group N

Group I-

Group N

Basal

121.73±15.84

119.23±11.62

123.17±10.84

0.736

0.904

0.471

Post

intubations

 

 

 

 

 

 

1 min

164.33±22.17

139.77±13.40

155.43±14.89

<0.001**

0.119

0.002**

2 min

156.63±24.57

139.70±17.54

149.37±17.29

0.004**

0.345

0.155

3 min

148.00±18.20

130.13±19.53

138.40±18.67

0.001**

0.124

0.210

4 min

143.63±19.25

125.60±20.92

133.07±19.67

0.002**

0.106

0.321

5 min

139.63±17.58

125.73±18.84

129.67±15.63

0.007**

0.074+

0.657

7 min

134.73±15.30

126.53±15.25

127.47±13.65

0.085+

0.143

0.967

9 min

130.53±14.57

122.57±12.67

127.97±12.44

0.057+

0.735

0.261

11 min

128.63±12.95

124.67±11.24

125.37±10.53

0.387

0.524

0.970

13 min

130.60±13.64

124.20±13.12

128.00±12.51

0.147

0.723

0.502

15 min

127.50±13.37

125.60±13.41

128.60±11.25

0.832

0.940

0.633

 

 


 

200

 

190


Group C Group I Group N


180

 

Text Box: SBP (mm Hg)170

 

160

 

150

 

140

 

130

 

120

 

110

 

100

Basal      1 min    2 min     3 min     4 min    5 min     7 min     9 min 11 min 13 min 15 min

Post intubations

 

Figure 10: Graph showing changes in Mean Systolic Blood Pressure (SBP)


 

In the control group the basal value of SBP was 121.73 mm Hg, 1 minute following intubation, the SBP increased by 164.33 mm Hg, representing a rise of 42.6 mm Hg. This elevated pressure started coming down by 3 minutes. By 3 minutes and by 5 minutes it was 148 mm Hg and 139.63mm Hg respectively.

In group I the basal value of SBP was 119.23 mm Hg, 1 minute following intubation, the SBP increased by 139.77 mm Hg, representing a rise of 17.54 mm Hg. This elevated pressure started coming down by 3 minutes. By 3 minutes and by 5 minutes it was 130.13 mm Hg and 125.73 mm Hg respectively.

In group N the basal value of SBP was 123.17 mm Hg, 1 minute following intubation, the SBP increased by 155.43 mm Hg, representing a rise of 32.26 mm Hg. This elevated pressure started coming down by 3 minutes. By 3 minutes and by 5 minutes it was 138.40 mm Hg and 129.67 mm Hg respectively.

Statistical evaluation between the groups showed that the increase in SBP observed in control group was statistically highly significant when compared to increase in SBP in group I and N.

The increase in SBP in group C and group I were statistically highly significant compared to increase in SBP in group N(p < 0.001) and remained significant even up to 5minute post intubation.

Between group C and group N was no statistical significance.

 

Between group I and group N, the increase in SBP in group N was statistically significant compared to increase in SBP in group I (p < 0.002).


 

7. CHANGES IN THE MEAN DIASTOLIC BLOOD PRESSURE (DBP) Table 7 : Table showing changes in Mean Diastolic Blood Pressure (DBP)

DBP (mm Hg)

 

Group C

 

Group I

 

Group N

Significant values

Group C-

Group I

Group C-

Group N

Group I-

Group N

Basal

78.27±8.75

77.93±9.72

78.87±7.89

0.988

0.962

0.912

Post

intubations

 

 

 

 

 

 

1 min

103.63±11.71

91.77±11.12

103.70±11.21

<0.001**

1.000

<0.001**

2 min

96.63±14.44

89.17±14.47

97.27±12.2

0.095+

0.983

0.064+

3 min

90.83±12.09

85.03±13.04

89.57±10.65

0.152

0.912

0.312

4 min

89.57±12.01

81.93±14.68

85.2±11.75

0.062+

0.392

0.590

5 min

88.00±11.06

79.63±11.91

83.47±12.05

0.018*

0.294

0.415

7 min

84.80±11.13

82.40±12.59

83.30±10.21

0.692

0.866

0.949

9 min

85.60±8.63

80.30±11.20

84.83±11.01

0.122

0.956

0.212

11 min

83.97±9.13

81.70±8.38

82.73±7.62

0.551

0.837

0.883

13 min

86.03±8.89

81.83±14.07

82.37±9.22

0.305

0.403

0.981

15 min

84.03±8.05

81.57±12.18

83.83±7.41

0.572

0.996

0.624

 

 

110

 

100

 

Text Box: DBP (mm Hg)90

 

80

 

70

 

60

 

50

Basal      1 min     2 min    3 min     4 min     5 min     7 min     9 min 11 min 13 min 15 min

Post intubations

 

Figure 11: Graph showing changes in Mean Diastolic Blood Pressure (DBP)


 

 

In control group the basal value of DBP was 78.27 mm Hg, at I minute following intubation, the DBP increased by 103.63 mm Hg, representing a rise of 25.36 mm Hg. This elevated pressure started coming down by 3 minutes. By 3 minutes and by 5 minutes it was 90.83 mm Hg and 88.00 mm Hg respectively.

In group I the basal value of DBP was 77.93 mm Hg, at 1 minute following intubation, the DBP increased by 91.77 mm Hg, representing a rise of 13.84 mm Hg. This elevated pressure started coming down by 3 minutes. By 3 minutes and by 5 minutes it was 85.03 mm Hg and 79.63 mm Hg respectively.

In group N the basal value of DBP was 78.87 mm Hg, at 1 minute following intubation, the DBP increased by 103.70 mm Hg, representing a rise of 24.83 mm Hg. This elevated pressure started coming down by 3 minutes. By 3 minutes and by 5 minutes it was 89.57 mm Hg and 83.47 mm Hg respectively.

Statistical evaluation between the groups showed that the increase in DBP observed in control group was statistically highly significant when compared to increase in DBP in group I but not group N.

The increase in DBP in group C and group I were statistically highly significant compared to increase in DBP in group N (p < 0.001).

Between group C and group N there was no statistical significance.

 

Between group I and group N, the increase in DBP in group N was statistically significant compared to increase in DBP in group I (p < 0.001).


 

8. CHANGES IN THE MEAN ARTERIAL PRESSURE (MAP)

 

Table 8 : Table showing changes in Mean Arterial Pressure (MAP)

 

MAP (mm Hg)

 

Group C

 

Group I

 

Group N

Significant values

Group C-

Group I

Group C-

Group N

Group              I-

Group N

Basal

92.73±9.85

91.70±9.40

93.63±8.07

0.900

0.923

0.692

Post

intubations

 

 

 

 

 

 

1 min

122.17±15.39

107.80±10.59

120.93±11.64

<0.001**

0.925

<0.001**

2 min

116.60±14.96

106.03±14.67

114.67±12.83

0.014*

0.858

0.053+

3 min

109.90±11.91

100.13±13.86

105.87±12.44

0.011*

0.442

0.196

4 min

107.67±12.64

96.60±16.09

101.13±13.71

0.009**

0.182

0.436

5 min

105.27±11.54

94.97±13.28

98.90±12.43

0.005**

0.123

0.442

7 min

101.43±11.65

97.07±12.46

98.03±10.4

0.312

0.491

0.944

9 min

100.57±9.70

94.80±10.14

99.20±10.58

0.077+

0.861

0.219

11 min

98.83±9.20

96.00±7.82

96.87±7.9

0.389

0.633

0.914

13 min

100.93±8.79

95.93±12.57

97.60±9.07

0.150

0.425

0.806

15 min

98.50±8.71

96.17±11.12

98.83±7.72

0.596

0.989

0.510

 


 

150

 

140


Group C Group I Group N


130

 

Text Box: MAP (mm Hg)120

 

110

 

100

 

90

 

80

 

70

 

60

 

50

Basal      1 min     2 min    3 min     4 min     5 min     7 min     9 min 11 min 13 min 15 min

Post intubations

 

Figure12: Graph showing changes in Mean Arterial Pressure (MAP)


 

In the control group the basal value of MAP was 92.73 mm Hg, at 1 minute following intubation, the MAP increased by 122.17 mm Hg, representing a rise of 29.44 mm Hg. This elevated pressure started coming down by 3 minutes. By 3 minutes and by 5 minutes it was 109.90 mm Hg and 105.27mm Hg respectively.

In group I the basal value of MAP was 91.70 mm Hg, at 1 minute following intubation, the MAP increased by 107.80 mm Hg, representing a rise of 16.1 mm Hg. This elevated pressure started coming down by 3 minutes. By 3 minutes and by 5 minutes it was100.13 mm Hg and 94.97 mm Hg respectively.

In group N the basal value of MAP was 93.63 mm Hg, at 1 minute following intubation, the MAP increased by 120.93 mm Hg, representing a rise of 27.3 mm Hg. This elevated pressure started coming down by 3 minutes. By 3 minutes and by 5 minutes it was 105.87mm Hg and 98.90 mm Hg respectively.

Statistical evaluation between the groups showed that the increase in MAP observed in control group was statistically highly significant when compared to increase in MAP in group I but not group N.

The increase in MAP in group C and group I were statistically highly significant compared to increase in MAP in group N (p < 0.001).

Between group C and group N there was no statistical significance.

 

Between group I and group N, the increase in MAP in group N was statistically significant compared to increase in MAP in group I (p < 0.001).


 

9.    CHANGES IN THE MEAN SATURATION OF OXYGEN (SpO2) Table 9 : Table showing changes in Mean Saturation of Oxygen.

SpO2(%)

Group C

Group I

Group N

P value

Basal

98.13±0.51

98.57±0.57

98.43±0.5

NS

Post intubations

 

 

 

 

1 min

100.00

100.00

100.00

NS

2 min

100.00

100.00

100.00

NS

3 min

100.00

100.00

100.00

NS

4 min

100.00

100.00

100.00

NS

5 min

100.00

100.00

100.00

NS

7 min

100.00