.

 

 

 

 

Abstract               Background: Clonidine is a centrally acting alpha-2 agonist and is used as an anti-hypertensive. Laryngoscopy and intubation are intense noxious stimuli leading to a surge in catecholamine release. This potentially has deleterious effects in patients with known cardiac compromise. Many drugs have been suggested by anaesthesiologists for inducing a hypotensive state during intubation and surgery in hypertensive patients. In our study we evaluated the efficacy of clonidine for attenuation of the pressor response during intubation and the effect on stress responses during anaesthesia1. Clonidine is also known to preserve heart rate variability2 throughout the surgery in addition to the sedative and analgesic properties. Materials and Methods: 60 hypertensive patients with optimally controlled hypertension, belonging to ASA grade II-III were included in the study. They were randomly divided into 2 groups. Study group was given Tab. Clonidine and Control group was given Tab. Alprazolam 90 minutes before the surgery. All the patients were given general anaesthesia. The pressor response and hemodynamic variability were assessed in both the groups. The sedative and analgesic properties of clonidine were also evaluated in addition to postoperative nausea and vomiting. Results: The heart rate, systolic and diastolic blood pressure were lower in the study group and this difference was statistically significant (P < 0.001) in contrast to the control group. The hemodynamic variability was significantly lesser in the study group compared to the control group (HR- P < 0.05, SBP- P < 0.001 and DBP- P < 0.05). Rescue analgesia was significantly prolonged in the study group compared to the control group (184 ± 30.4 v/s 98.40 ± 24.3 minutes). Nausea and vomiting were lesser in the study group. (P > 0.05). Conclusion: Oral clonidine premedication prevents the pressor response to endotracheal intubation, preserves intra-operative hemodynamic variability, sparing the requirement of other anaesthetics along with added advantages of sedation, analgesia and lesser postoperative nausea, vomiting.

Key Words: Clonidine, Hypertension, General Anaesthesia.

 

 

INTRODUCTION

The primary reasons for pre-medicating a patient before surgery are to relieve anxiety, induce sedation, promote hemodynamic stability, minimise the chances of aspiration, provide analgesia and improve post anaesthesia recovery. Patients about to undergo surgery maybe anxious and frightened. This anxiety is related to surgery, anaesthesia, hospital environment etc. Anxiety results in the stimulation of sympathetic nervous system with subsequent tachycardia, blood pressure changes and cardiac work. This phenomenon is more commonly seen in hypertensive patients leading to serious consequences. Alpha 2 adrenergic receptors are present at central and peripheral sites, and they serve to modulate a wide variety of physiological and behavioural functions including pain transmission and autonomic outflow. Activation of these receptors would reduce peripheral sympathetic outflow, inhibit the release of substance P from the primary afferents of dorsal horn, and suppress the noxiously evoked activity of wide dynamic range neurones which are important for the centripetal transmission of nociceptive impulses. Clonidine, an alpha 2 agonist, has a half-life around 8 to 12 hours and has been shown to reduce peripheral sympathetic discharge, post-operative pain and analgesic requirement in clinical use. These characteristics suggest that clonidine may be useful as a premedication in hypertensive patients who are subjected to general anaesthesia. In our study we assessed the effect of clonidine on perioperative hemodynamics in hypertensive patients. Clonidine has sedative and anxiolytic properties in addition to perioperative hemodynamic stability and analgesic action, thus improving post anaesthesia recovery. 

 

AIMS AND OBJECTIVES

To study the effect of oral clonidine premedication in hypertensive patients with controlled hypertension in view of: 

1. Anxiolysis and sedation.

2. Attenuation of pressor response to laryngoscopy and endotracheal intubation.

3. Intra operative hemodynamic stability throughout the surgery.

4. Postoperative recovery and analgesia.                

 

MATERIAL AND METHODS

After obtaining approval from the ethical committee written informed consent was taken from all the hypertensive patients. In this randomised, double blind study, 60 patients were selected for planned, elective surgeries to be done under general anaesthesia requiring tracheal intubation. All the patients were in the age range of 30 to 70 years under ASA grade II-III with adequately controlled hypertension. These patients were regularly taking anti-hypertensive treatment and there were no defaulters. The patients were assigned to a Control group (n=30) and a Study group (n=30) randomly. All the patients received their respective morning dose of anti-hypertensive treatment at 6am on the day of surgery. The surgery was scheduled at 9 am for all the patients. Patients in the control group received tablet alprazolam 0.25 mg and patients in the Study group received tablet Clonidine 2 mcg/kg orally at 90 minutes prior to surgery. Alprazolam is a benzodiazepine and was given as an anxiolytic and sedative for patients in the Control group. The exclusion criteria included allergy or contraindication to any drug used, obese patients (body weight > 100 kg) difficult airway, congestive heart failure, severe coronary insufficiency, concomitant use of MAO inhibitors and/or opioids, respiratory, renal or cerebral disease and pregnancy. Significant change in the technique of anaesthesia in any of the patient was also excluded from the study. In the operating room and 18 gauge intravenous cannula was inserted in an appropriate antecubital vein and Ringer solution was started at 2- 4 ml /kg/hour throughout the surgery. During episodes of fluid challenge, fluid was given at the rate of 10ml/kg/hour. Monitoring included an automated BP cuff, ECG and pulse oximetry. All the patients received Inj. Glycopyrrolate 0.1mg/kg intramuscularly before the surgery. After 3 minutes of preoxygenation, the patient was ready for induction of anaesthesia. Inj. Thiopentone Na (5mg/kg) was administered intravenously and after the loss of consciousness, 0.16 mg/ kg of Inj. Vecuronium (muscle relaxant) was given. Laryngoscopy was done and the patient was intubated. Blood pressure and heart rate were measured and recorded at the following points: Baseline. pre-induction, post-induction, during laryngoscopy and intubation, 15 mins thereafter till the surgery got done and every 2 hours in the post-operative period up to 24 hours. Anaesthesia was maintained on O2, N20 and Isoflurane on Bain’s circuit on IPPV with Inj. Vecuronium as a muscle relaxant. In case of acute and severe hemodynamic fluctuations, medical intervention other than adjustment of isoflurane concentration alone was applied. If bradycardia (heart rate<40 beats/min) occurred Inj. Atropine 0.5 mg was given intravenously. Hypotension (BP<60 mm of Hg) was managed with increments of 3 mg of Inj. Ephedrine. Hypertension (BP>120mm of Hg) was treated with Inj. Esmolol 10 mg IV or Cap. Nifedepine 5 mg sublingually. After the surgery, reversal was done with IV Inj. Glycopyrrolate 10 mcg/kg and Inj. Neostigmine 0.04 mg/kg diluted in 20 ml of normal saline. After the conclusion of surgery, the patient was extubated and transferred to the recovery room. ECG, blood pressure, SPO2 and respiratory rate were monitored and recorded. Pain intensity was assessed using a Visual Analogue Scale (0 denoted no pain and 10 noted intolerably worst pain). Rescue analgesia was given to the patient with a VAS score of 6 or more. Different adverse events included nausea vomiting bradypnea and CO2 retention. VAS, Sedation score and adverse effects were recorded up to 24 hours after the surgery. Inj. Tramadol was offered when the patient complained of intolerable pain or the VAS was greater than 6. Time of rescue analgesia and the total requirement of analgesia up to 24 hours was recorded.

 

STATISTICAL ANALYSIS

The demographic data and hemodynamic parameters were analysed using Paired- T test. Rescue analgesia, total analgesic requirement up to 24 hours in the post-operative period, VAS and sedation score was analysed by Mann Whitney test. The sex was analysed by Chi- square test. Adverse effects were analysed by Fisher’s exact test.

RESULTS

Table 1: Demographic data (Mean ± SD)

 

Table 2: Comparison of Heart Rate between Control and Study Group (Mean ± SD)

NS: Not Significant           S: Significant       HS: Highly Significant

 

                                              Table 3: Comparison of Systolic BP between Control and Study Group (Mean ± SD)

NS: Not Significant           S: Significant       HS: Highly Significant

 

Table 4: Comparison of Diastolic BP between Control and Study Group (Mean ± SD)

NS: Not Significant           S: Significant       HS: Highly Significant

 

Table 5: Intra-operative Variability of Haemodynamic Parameters.

S: Significant       HS: Highly Significant

 

There was no statistical difference in both the groups regarding age, sex, weight, ASA grading and duration of the surgery. There was no statistical difference between the two groups in the baseline values of heart rate, systolic blood pressure and diastolic blood pressure. After swallowing the tablet, all the three hemodynamic parameters were considerably decreased in the control group. This difference was statistically significant (P < 0.001) from induction up to 24 hours in the post-operative period between the two groups (Table 2,3,4). The variability of the hemodynamic parameters was assessed intraoperatively. There was a statistically significant difference (P < 0.05) for heart rate and diastolic blood pressure between the two groups. Also, there was a highly significant difference (P < 0.001) for systolic blood pressure between the two groups (Table 5). There was no statistically significant difference in the VAS and sedation scores till 2 hours post-operatively. Rescue analgesia was given when the patient complained of pain and demanded pain relief. Rescue analgesia was significantly prolonged in the study group compared to the control group (184 ± 30.4 v/s 98.40 ± 24.3 minutes). Patients in the control group required 2 or more than 2 doses of Inj. Pethidine in contrast to the study group (68% v/s 28%, P < 0.05). Incidence of nausea and vomiting was less in the study group compared to the control group (30% v/s 50%, P > 0.05). Bradycardia and hypotension were seen in the study group but this observation was statistically insignificant. No other side effects were seen.

DISCUSSION

Clonidine has been used successfully as an adjunct for hypotensive techniques^3-5. The present study demonstrated the efficacy of clonidine on perioperative hemodynamics in hypertensive patients. Endotracheal intubation is a noxious stimulus which increases the blood pressure and heart rate. Stone DJ et al⁶ has suggested that hemodynamic changes during airway management have little consequences in otherwise healthy young adults. However, patients with certain co-morbidities such as hypertension may not tolerate such hemodynamic fluctuations. Profound hypertension and tachycardia are noticed in these patients. Clonidine, an alpha 2 agonist has been shown to reduce the sympathetic outflow. Maze M et al⁷ defined the role of alpha-2 adrenoceptor agonists in clinical anaesthesia. Our study demonstrates that clonidine can be a useful adjunct in maintaining the hemodynamic stability of hypertensive patients during intubation and intra-operative period. Ghignone M et al^8,9 studied the effect of clonidine on perioperative hemodynamics and isoflurane requirements and concluded that pre-operative treatment with clonidine reduces the total anaesthetic requirement to maintain the blood pressure in the target range. Clonidine premedication effectively blunted the cardiovascular response to intubation and surgical stress. Chun Sung et al¹⁰ studied the effect of oral clonidine on perioperative hemodynamic response and postoperative analgesic requirement. Clonidine decreased the anaesthetic requirement to maintain the peri-operative hemodynamics within the defined range and spared the use of isoflurane and reduced the requirement of postoperative analgesia leading to a smoother postoperative recovery. Entholzner et al¹¹ showed that premedication with clonidine resulted in a synergistic effect on the central nervous system which corelated with the defined depth of anaesthesia. Benhamou D et al¹² and Park J et al¹³ highlighted that Clonidine cannot be used as a pure analgesic alone but it has been shown to enhance analgesia. The post-operative analgesic effect of clonidine in our study corelates with the research done by Mikawa et al¹⁴. He studied the efficacy of oral clonidine for postop pain relief in children. Samso E et al¹⁵ studied the comparative assessment of anaesthetic and analgesic effect of intramuscular and epidural clonidine in humans. Sedation is a well-known side effect of clonidine which was advantageous for us before induction and intubation. Postoperatively, we frequently assessed the sedation scores in our patients but there was no statistical difference between the two groups. Nausea and vomiting were lesser in the study group. Zhao H et al¹⁶ studied the effect of clonidine on nausea and vomiting. He concluded that clonidine premedication is effective for preventing shivering and nausea after general anaesthesia combined with epidural anaesthesia. Handa F et al¹⁷ studied the efficacy of oral clonidine premedication in the prevention of postoperative vomiting and found it to be useful in children following strabismus surgery. The anti-emetic property of clonidine needs further investigation.

 

CONCLUSION

We conclude that oral premedication with clonidine prevents the pressor response to endotracheal intubation, reduces intra-operative hemodynamic variability, sparing the requirement of other anaesthetics and maintaining circulatory parameters in the post-operative period. With an easy oral route of administration, it offers adequate sedation, good post-operative analgesia, less nausea vomiting and a high margin of safety. Thus, clonidine can be used as an ideal premedication in hypertensive patients undergoing general anaesthesia.

 

REFERENCES