Preanaesthetic medication forms an integral part of anaesthetic management and some form of premedication is universally administered before any anaesthesia. The ideal premedication should be effective and pleasant to be taken orally, have analgesic and non emetic properties,  should  not impair  cardiovascular  stability or depress respiration, should have  antisialagogue effect and should effectively alleviate apprehension of the patient.Alpha-2 adrenoceptor agonists have been used as premedicants because of their beneficial properties in anaesthesia. The clinically available alpha-2 adrenergic agonist is clonidine, which is mainly used as an anti hypertensive agent, but has many properties of ideal premedicant and also has beneficial effect on heamodynamics during stressful condition like laryngoscopy and endotracheal intubation 1(Dipak L. Raval, 2002).Circulatory stimulation during tracheal intubation results from both direct laryngoscopy and placement of the tube in the trachea. Pharmacological attempts to attenuate these blood pressure and heart rate elevations have included topical anaesthesia of the oropharynx, iv lidocaine, adrenergic blocking drugs, vasodialiting drugs, and deep anaesthesia 2 (stoelting, 1997).

Therefore this study was done to evaluate the effectiveness of oral clonidine in attenuating the haemodynamic responses associated with laryngoscopy  and  endotracheal  intubation in patients  already on antihypertensive drug treatment and comparing its effect with a placebo (oral ranitidine). Ranitidine is an H2-receptor antagonist routinely   used as a premedication. It competitively inhibits histamine binding to H2-receptors thereby reducing gastric acid output and raising gastric pH.

Approval from our institutionl ethical committe was obtained. Written informed consen twas taken. The present study was conducted on 100-adult patients of ASA Grade I and II of either sex, receiving antihypertensive treatment posted for a variety of elective surgical procedures in the Department of Anaesthesiology, Govt. Medical college & AGH, Kota. Patients were divided in 2 groups of 50 patients. Study – I: All patients in this group received oral tablet clonidine 150μg , 90 minutes before surgery. Placebo – II: All the patients in this group received oral tablet ranitidine 150mg 90 minutes before surgery. Unwilling Patients, Emergency Surgeries, Patients with ASA Grade III or higher, Patients with Neurological and endocrine abnormalities, Patients with renal impairment and hepatic disease, Patients with congestive heart failure, Valvular heart disease,Hypotension, IHD, diabetes mellitus, Patients on Psychotropic drugs or history of drug allergies, Patients with language or communication difficulties, Patients first time diagnosed for hypertension and did not receive antihypertensive drugs for minimum three days, Patients and in whom intubation took time more than 20 seconds was considered as exclusion criteria. A thorough preanaesthetic evaluation were done. Tab alprazolam 0.5 mg was administered to all patients on the night before day of surgery. Patients were kept nil per oral from midnight prior to surgery.On the day of surgery, morning dose of antihypertensive drugs were given to the patients in the morning (6-7am) as oral premedication Placebo – II control(tab ranitidine 150 mg)/ Group – I study drug(tab clonidine 150µg) orally 90 minute before laryngoscopy and intubation in preoperative period. On the day of surgery, systolic and diastolic blood pressures, and heart rate were measured during premedication and 90 minutes after premedication. Scoring was done for sedation, anxiolysis and antisialogogue effects 90 minutes after premedication in the preoperative room. Antisialogogue effect was scored by checking drying of mouth with a blotting paper at the tongue and inner aspect of cheek for 30 seconds each. Then in O.T. I.V..line secured and multiparamonitor attached. The baseline heart rate, oxygen saturation and electrocardiogram, systolic and diastolic arterial blood pressure were recorded. Pre anaesthetic medication with, inj.Nalbuphine 10 mg IV was given to all patients. Preoxygenation of all patients was done for 3 minutes. Induction of anaesthesia was done with inj. Propofol 2mg/kg IV slowly till the loss of eye reflex. Inj. Glycopyrrolate 0.2mg was given along with propofol. Inj. Succinylcholine was administered 1.5 – 2 mg/kg body weight intravenously after anaesthesia induction. Then after 60-90 seconds when complete relaxation is achieved, fasciculation passed away, laryngoscopy was done using rigid laryngoscope with standard Macintosh blade. Intubation was done with appropriate sized disposable, high volume low pressure cuffed plastic endotracheal tube. Maintenance of anaesthesia was started with 100% oxygen + 1.5 to 2% halothane. And inj. Vecuronium bromide was injected to all patients mechanically ventilated to maintain EtCO2 35 to 40mm of Hg. Rcord of vital parameters ie. Pulse, systolic BP and diastolic BP was kept at premedication, 90 min. after premedication, pre induction, post induction ,immediately after larygoscopy and intubation,then at 1min.,3 min, 5 min,10 min.30 min after intubation. Reversal with inj.Neostigmine 0.05-0.08 mg/kg IVand inj.Glycopyrrolate 0.02mg/kg was done after completion of surgical procedure.Thorough suction of oral cavity and pharynx was done. After regaining muscle power to maintain spontaneous respiration and adequate tidal volume, all the patients were extubated. After extubation oxygenation done for 5 minutes,shiting criteria followed. All recorded data were done expressed as mean ± S.D. The two groups as between study and placebo groups as between subjects factor (group) and the six measurements (during premedication, 90 min. After Premedication, preinduction, post induction, during laryngoscopy and after intubation) as the within subject factor (time) was considered. Paired sample t-test was used for comparision of two subsequent measurements in both groups.

Table 1: Mean of demografic profile, sedation score, anxiolysis score and antisialogogue score

Table 1: Mean of demografic profile, sedation score, anxiolysis score and antisialogogue score

Graph 1: Comparisons between Group I and Group II to find the increase in HR   from pre induction to post laryngoscopy

Graph 2: Comparison between Group I and Group II to find the increase in SBP from pre-med to post laryngoscopy

Graph 3: Comparison between Group I and Group II to find the increase in DBP

The degree of sedation was observed 90 minutes before surgery and at the time of induction (90 mins after premedication). Grading was based on a 4 point scoring system. In group I, 24% were moderately drowsy or sedated, 36% mildly sedated and 40 % were fully awake with no patient falling asleep, whereas in group II, sedation score was either 0 in 90% or score 1 in 10% of patients. No patient had a score of 2 with no patient falling asleep.

The degree of anxiolysis was observed 90 minutes before surgery and at the time of induction (90 mins after premedication). Grading was based on a 5 point scale. In group I  clonidine group, 64% were comfortable and 36% remained with uneasy. Whereas in group II  placebo no patients were comfortable, 14% remained uneasy, 52% were anxious and 24% were very upset or worried and 10% terrified. This was found statistically very significant showing clonidine with better anxiolysis scores than placebo.

Changes in the vital parameters were studied and analyzed. The basal heart ratechanged was  77.46 ± 8.10 to beats per minute in clonidine group  with peak value 89.64 ± 7.04at after intubation while in placebo group basal heart rate was it varied from 74.86 ± 7.35  with peak value of 106.48 ± 7.01at after intubation. Systolic blood pressure before premedication was 122.08 ± 9.98 mm Hg in clonidine group with peak 138.48 ± 16.84mmHg after laryngoscopy  whereas basal systolic B.P was it  125.96 ± 7.35 mm Hg in placebo group with peak 159.56  ±14.22mmHg after laryngoscopy.

Haemodynamic parameters recorded include heart rate, systolic and diastolic blood pressure during premedicaton, 90 min after premedication, preinduction, postinduction, during laryngoscopy  and after 1, 3, 5,10,15,30 minutes from the onset of laryngoscopy and intubation.

In clonidine group very highly significant and consistent attenuation of sympathetic responses was noted. Heart rate increased  at during laryngoscopy   with a gradual return to near basal levels of heart rate at 3 minute. Systolic B.P.  during laryngoscopy showed increase above premedication by mean value of 16.40±11.88 mmHg in clonidine group whereas in placebo group by 33.60±15.96mmHg. Diastolic B.P. during laryngoscopy showed  increase above premedication  by mean value of 6.04±7.06 mmHg in clonidine group whereas in placebo group by 13.76±7.63mmHg

Laryngoscopy and intubation is associated with a rise in heart rate, blood pressure and incidence of cardiac arrhythmias. Although these responses of blood pressure and heart rate are transient and short lived, they may prove to be detrimental in high risk patients especially in those with cardiovascular disease, increased intracranial pressure and anomalies of the cerebral blood vessels. These potentially dangerous changes disappear within 5 minutes of laryngoscopy ,3,4.

The most significant laryngoscopic factor influencing cardiovascular responses is found to be the duration of laryngoscopy5. A linear increase in heart rate and mean arterial pressure during the first 45 seconds has been observed. Further prolongation has little effect. As the duration of laryngoscopy is normally less than 30 seconds, the results of studies in which it takes longer than this have less clinical relevance. The force applied during laryngoscopy has only minor effect5.In our study the duration of laryngoscopy and intubation was limited to 20 seconds in first attempt.

For nearly two decades, α2 adrenergic agonists have been widely used by veterinarians to achieve dose- dependent sedation, analgesia and muscle relaxation in a variety of species. Clonidine though an antihypertensive has been increasingly used as premedication6,7 since it reduces anaesthetic requirements, improves haemodynamic stability especially during laryngoscopy and intubations and also potentiates post operative analgesic regimens.

In this anaesthetic technique  the drugs administered did not have any significant effect on heart rate or blood pressure. Both groups were similarly premedicated regarding anxiolysis.

The preinduction values of arterial blood pressure and heart rate were considerably lesser than the resting values before premedication. Whereas in control group I they were nearly same or slightly higher.

None of the patients in the clonidine group suffered from bradycardia and hypotension.

The effect of clonidine on the haemodynamic responses may be attributable to its overall inhibitory action on the catecholaminergic areas of the lower brain, as stated by Aho et al in 1990.

Wright et al. in 1990 stated that clonidine acts on the receptor sites at the medulla oblongata and presynaptically at peripheral nerve terminals causing a reduction in the activity of the sympathetic nervous system

Unwarranted fear and anxiety which hinders the patient to face his operation with calm and confidence has led to search for an ideal premedicant. A search has been constantly on for mitigating this response by employing many agents among which clonidine has been one of the drugs to come under a lot of scrutiny in the recent years. Clonidine further enjoyed our approval for this study because of the added advantages it offered like its efficacy in mitigating the sympathetic response to laryngoscopy and intubation, its effect on reducing anxiety, its ability to reduce overall anaesthetic requirements and its property of potentiating post operative analgesic regimens. It was seen that the decrease in anxiety was highly significant in the clonidine group as compared to the placebo group. Clonidine has significant effects on sedation score 0, awake and talkative in 40% patients when compared to placebo (oral ranitidine) in whom sedation score 0 was in 90% patients which is a commonly used premedicant. Oral clonidine has got significant antisialogogue effect. Clonidine also proved to be a better agent for the attenuation of pressor response to laryngoscopy and intubation. Mean systolic B.P. in control group was 159.56 mmHg whereas in study group who received oral clonidine was 138.48 mmHg after laryngoscopy. In placebo group – II this rise in systolic B.P.was observed up to 30 minuts after intubation. Whereas in clonidine group – I up to 10 minute only. Thus oral clonidine 150μg given 90 minute before laryngoscopy and intubation is a better premedicant . Also it is a more acceptable agent because of its oral route of administration.

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5  . Bucx MJL, Van Geel RTM, Scheck PAE and Stijnen T. Cardiovascular effects of forces applied during laryngoscopy. Anaesthesia 1995; 50:17-22.

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