A comparative study of clonidine versus a combination of diazepam and atropine for premedication in orthopaedic patients.SK Chaurasia, DG Kane, LS Chaudhari
Department of Anaesthesiology, Seth G. S. Medical College, Parel, Mumbai, India., India
Sixty patients in the age group of 18-60 years of A.S.A. Grade I/II risk, scheduled for elective orthopaedic surgeries under general anaesthesia were studied for pre-medication with either oral clonidine or with combination of effects of diazepam & atropine. Patients in Group A (clonidine group) received tablet clonidine 100 mcg (1 tablet) if less than 50 kg in weight and 200 mcg if weighing more than 50 kg two hours before surgery. Patients in Group B (Diazepam-atropine group) received one tablet of Diazepam (10 mg) orally two hours before surgery and injection atropine-sulphate 0.01 mg/kg half an hour preoperatively by intramuscular route. In our study, the sedative and anti-sialogogue effects of clonidine were comparable to those of diazepam-atropine combination, which are commonly used premedicants. The anti-anxiety effect of clonidine was found to be better than that of diazepam-atropine combination. Clonidine also proved to be a better agent for the attenuation of pressor response to laryngoscopy and intubation. Thus, oral clonidine is a better premedicant compared to atropine-diazepam combination. Also, it is a more acceptable agent because of its oral route of administration.
Keywords: Adjuvants, Anesthesia, Adolescent, Adult, Analgesics, Anti-Anxiety Agents, Benzodiazepine, Clonidine, Comparative Study, Diazepam, Drug Combinations, Human, Middle Age, Orthopedic Procedures, Preanesthetic Medication,
From the earliest times attempts have been made to relieve the pain of surgical intervention by oral administration of herbal preparations. The quest for better means to alleviate pain and anxiety, to induce amnesia and mental detachment has always led the pioneers to the discovery of newer drugs and techniques.
An ideal premedicant should have qualities like reduction of fear and anxiety, enabling the patient to face his operation with calm and confidence, potentiation of anaesthesia, diminishing the side effects of anaesthetic agents and techniques, reduction of unwanted reflex activity, production of amnesia, ensuring a smooth recovery and administration of concurrent medication for specific therapeutic effects.
This study was undertaken to evaluate the beneficial effects of oral clonidine as a premedicant in comparison with the commonly used combination of oral diazeparn and intramuscular atropine.
Our study consisted of sixty adult patients in the age group of 18-60 years of A.S.A. Grade I/II risk, scheduled for elective orthopaedic surgeries under general anaesthesia. The patients were allocated randomly into two groups. In one group, Group A (Clonidine group) of 30 patients, each patient received tablet Clonidine (Arkanene) 100 mcg (1 tablet) if less than 50 kg in weight and 200 mcg (2 tablets) if weighing more than 50 kg with sips of water, two hours pre-operatively. In the other group, Group B (Diazepam-atropine group) of 30 patients, each patient received one tablet Diazepam (10 mg) orally, two hours before surgery and injection atropine sulphate 0.01 mg/kg body weight half an hour pre-operatively by intramuscular route.
On the day of surgery, systolic and diastolic blood pressures and heart rates were measured before pre-medication and for two hours after. Scoring was done for sedation, antianxiety and antisialogoue effects two hours after pre-medication. The following scoring system was used.
Antisialogogue effect was scored by checking drying of mouth with a blotting paper by blotting the tongue and inner aspect of cheek for 30 seconds each.
After the above assessment, an intravenous access was secured and infusion of 5% dextrose started. ECG (lead II) and oxygen saturation were continuously monitored. Baseline haemodynamic criteria were assessed and recorded
All patients were pre-oxygenated with 100% oxygen for five minutes by a facemask. Anaesthesia was induced with sleep dose of 2.5% thiopentone sodium given intravenously. Endotracheal intubation was done after relaxation with succinyl choline in the dose of 1.5-2 mg/kg body weight. The patient was then ventilated with 60% nitrous oxide and 40% oxygen with a tidal volume of 10-12 ml/kg and a rate of 12-14 breaths per minute. Analgesia was provided with pentazocine 0.3 mg/kg administered intravenously. For maintenance of relaxation vecuronium bromide was administered according to body weight. Systolic, diastolic blood pressures and heart rate were monitored during induction and at one, three, five, ten, 15 and 30 minutes after intubation of the trachea. The rate pressure products were calculated at regular intervals. A sedative was not given routinely and was given only if deemed necessary on the basis of haemodynamic criteria. Extubation was done after reversal of the non-depolarising muscle relaxant. Post operatively all patients were enquired about awareness during the anaesthetic.
Paired student t-test' with modification was used for comparison of two normal distributions the significance of the difference between two values was determined.
The differences in the sedation scores and the anti-sialogogue effect scores in the two groups [Table - 1] were found to be statistically insignificant while the anxiolysis score was found to be significant (p<0.05). The clonidine group showed better score than diazepam-atropine group which means that patients in the clonidine group were more comfortable compared to diazepam -atropine group.
As shown in [Table - 2], there was an increase in heart rate during induction, with intubation and after intubation in both the groups
In the clonidine group, the peak of heart rate came down in 5 to 10 min and touched baseline value at the end of 15 min after intubation whereas in the diazepam-atropine group the peak lasted longer and the heart rate remained consistently higher even 30 minutes after intubation.
As shown in [Table - 3], the peak of systolic blood pressure in Group A i.e. clonidine group began to decrease within three to five minutes and touched its baseline at the end of 30 minutes after infiltration whereas in the diazepam atropine group the maximum increase in blood pressure was seen at five minutes and systolic blood pressure remained consistently higher even 30 minutes after intubation. The systolic blood pressure remained significantly higher in the diazepam-atropine group than in the other group.
The diastolic blood pressure in Group A returned to its baseline value at the end of 30 minutes after intubation whereas in Group B the diastolic blood pressure remained consistently higher even 30 minutes after intubation.
Rate Pressure Product
From a minimum value in both groups at baseline value (pre-induction) rate pressure product rose to its peak in diazepam-atropine group in five minutes and in clonidine group in three minutes. The rate pressure product fell to baseline value in the clonidine group within 30 minutes after endotracheal intubation but was consistently high ever at 30 minutes in the diazepam-atropine group.
In pre-anaesthetic days both wine and opium were given to mitigate the terrors of surgery. Claude Bernard first observed that the use of morphine before chloroform in a dog resulted in achieving anaesthesia in a smooth, rapid manner and with lesser dosage of chloroform. Ever since the realisation of the importance of giving drugs before the induction of anaesthesia, the search for an ideal premedicant has been going on. Among the many agents used as premedicants for their specific actions, benzodiazepines (especially diazepam), and atropine have been used for a long time. For nearly two decades, alpha-2 adrenergic agonists have been widely used by veterinarians to achieve dose-dependent sedation, analgesia and muscle relaxation in a variety of species. As regards sedation both the groups showed similar effects. There was no statistically significant difference between them.
Ghignone et al in a study on the effect of oral clonidine in comparison with diazepam as premedicant observed better sedation levels in the clonidine group. Our study showed sedative properties of clonidine comparable to diazepam. The sedative action of clonidine may be due to decreased tonic activity of the locus coeruleus, which modulates the stimuli arriving at the central nervous sytsem.
As regards anxiolysis, which is also one of the requirements of a good premedicant, our study showed better anxiolytic effect in the clonidine group then in diazepam-atropine group. Pouttu et al found no significant differences in sedative and anxiolytic effects between two group pre-medicated with diazepam or clonidine
The antisialogogue effect seen in the clonidine group in our study was as good as that seen in the control group. This finding is similar to that observed by Karhuvaara et al.
Dry mouth and significant sedation was also observed by Kriton et al in patients given either 2-2.5 mg/kg or 4-4.5 mg/kg of clonidine pre-medication orally in a study done in elderly patients to evaluate haemodynamic safety. In our study, clonidine proved to be better than diazepam- atropine combination as far as haemodynamic response to laryngoscopy and intubation were concerned.
The baseline values (measured about 2 hours after pre-medication) were found to be significantly lower in the clonidine group as compared to diazepam- atropine group. The heart rate, systolic and diastolic blood pressures and rate pressure products were all seen to increase after laryngoscopy and intubation and the rise was much more significant in diazepam-atropine group as compared to clonidine group. Also, the variables came down to near baseline values within 10-15 min in the clonidine group but were still significantly higher and did not come to baseline even after 30 minutes in the control group. Similar attenuation of sympatho-adrenal response to laryngoscopy and intubation was observed by Pouttu et al.
Oral clonidine pre-medication is seen to significantly lower the resting haemodynamic parameters and attenuate effectively the sympatho-adrenergic response to laryngoscopy and intubation in comparison to a premedicant combination of oral diazepam and intramuscular atropine. It also gives an equivalent sedative, anxiolytic and anti-sialogogue effect. Thus clonidine is a more desirable alternative as a premedicant. By avoiding a needle prick clonidine can also be considered a more acceptable premedicant as compared to a combination of atropine-diazepam.
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6], [Table - 7], [Table - 8]