|Year : 2022 | Volume
| Issue : 2 | Page : 263-267
Efficacy of intravenous clonidine premedication in the prevention of adverse hemodynamic changes during intubation in patients undergoing laparoscopic surgery in comparison with placebo
Sudhir S Rao, KN Vikas, K Rooparani, R Vinay
Department of Anaesthesiology, M. S. Ramaiah Medical College, Bengaluru, Karnataka, India
|Date of Submission||23-Jun-2022|
|Date of Decision||24-Aug-2022|
|Date of Acceptance||29-Aug-2022|
|Date of Web Publication||26-Sep-2022|
Dr. R Vinay
No. 356, 12th Main 6th Block, Rajaji Nagar, Bengaluru - 560 010, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Context: Laparoscopic surgeries involve the creation of pneumoperitoneum, which produces significant hemodynamic changes. Alpha-2 adrenergic receptor agonists like clonidine are used as adjuvants during aesthesia for analgesic, sedative, sympatholytic and cardiovascular stabilizing effects. Aims: This study aims to assess the efficacy of intravenous (i.v.) clonidine premedication in the prevention of adverse hemodynamic changes during intubation in a patient undergoing laparoscopic surgery in comparison with (normal saline) placebo. Settings and Design: Eighty patients undergoing elective laparoscopic surgery were randomly assigned into two groups to receive either clonidine 3 μg.kg-1 diluted in normal saline or an equivalent quantity of normal saline administered intravenously 20 min before surgery. Materials and Methods: The primary outcome was to compare the efficacy of clonidine premedication in the prevention of adverse hemodynamic changes during intubation in patients undergoing laparoscopic surgery. Other outcome parameters observed were requirements of induction agents and intraoperative analgesia and postoperative adverse effects. Statistical Analysis Used: Analysis of variance 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 a categorical scale between two or more groups. Results: Heart rate reduced significantly after 10 min 3 μg.kg−1 clonidine administration and the decrease persisted throughout induction and intubation. The fluctuations of systolic, diastolic, and mean arterial pressures were high in the control group when compared with the clonidine group, throughout induction and intubation. Conclusions: Premedication with i.v. clonidine is a relatively safe and effective method that provides stable hemodynamics and protection against stress responses induced during laryngoscopy and intubation in patients undergoing laparoscopic surgery.
Keywords: Clonidine, hemodynamic changes, intubation, laparoscopic surgery
|How to cite this article:|
Rao SS, Vikas K N, Rooparani K, Vinay R. Efficacy of intravenous clonidine premedication in the prevention of adverse hemodynamic changes during intubation in patients undergoing laparoscopic surgery in comparison with placebo. Anesth Essays Res 2022;16:263-7
|How to cite this URL:|
Rao SS, Vikas K N, Rooparani K, Vinay R. Efficacy of intravenous clonidine premedication in the prevention of adverse hemodynamic changes during intubation in patients undergoing laparoscopic surgery in comparison with placebo. Anesth Essays Res [serial online] 2022 [cited 2022 Dec 5];16:263-7. Available from: https://www.aeronline.org/text.asp?2022/16/2/263/357138
| Introduction|| |
Significant hemodynamic changes were observed in laparoscopic surgeries, which can have complications in hemodynamically disturbed patients. Pneumoperitoneum affects several homeostatic systems, leading to alteration in acid–base balance, cardiovascular and pulmonary physiology, and stress response. The cardiovascular changes associated with pneumoperitoneum include an increase in mean arterial pressure (MAP), decrease in cardiac output, and increase in systemic vascular resistance which in turn compromises tissue perfusion.
Clonidine inhibits the release of catecholamines and vasopressin and thus modulates the hemodynamic changes induced by pneumoperitoneum., Alpha-2 agonists like clonidine have been used extensively in the past for the attenuation of the sympathoadrenal response to tracheal intubation and surgery.
A lot of studies have been undertaken in the past on oral clonidine; as a premedication drug, it has also been found a benefit in preventing adverse hemodynamic alterations in laryngoscopy and intubation.,,
Hence, this study is being conducted to assess the hemodynamic response to laryngoscopy and intubation and the need for an induction dose of thiopentone after a single dose of clonidine 3 μg.kg−1 intravenous (i.v.) given as an infusion over 20 min, as compared to placebo.
| Materials and Methods|| |
Ethical committee clearance was obtained from the institutional review board (285/IEC/RRMC/04-2020) on April 17, 2020, between July 2020 and December 2021; the Declaration of Helsinki, 1975 (as revised in 2013) in accordance with was taken; informed written consent was taken from the patient undergoing surgery, whoever is meeting eligible criteria. Patients aged between 20 and 60 years of either sex, belonging to the American Society of Anesthesiologists (ASA) PS class I or II scheduled for laparoscopic surgery.
Patients with a history of hypertension, diabetes, bronchial asthma, ischemic heart disease, aortic stenosis, left ventricular failure, atrioventricular block, decreased ejection fraction, difficult airway, and intubation time >20 s were excluded from the study. Lack of patient consent, drug dependence, patients allergic to clonidine, severe coronary insuffciency, recent myocardial infarction and patients on monoamine oxidase inhibitors or tricyclic antidepressants were also excluded from the study.
All patients received 5 mg diazepam orally on the previous night. After arriving at the operation theater, an 18-gauge i.v. cannula was done, and patients were preloaded with 500 mL of Ringer's lactate i.v. premedicated with 0.04 mg.kg-1 midazolam and 0.2 mg of glycopyrrolate. The closed envelope method was used to assign into one of the groups. Clonidine group (clonidine 3 μg.kg−1 in 20 mL normal saline), and control group (control – 20 mL normal saline). In the operating room baseline readings of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP were measured, and under the supervision of an anesthesiologist, the drug diluted in 20 mL of normal saline or control diluted in 20 mL of normal saline was injected to the patients. The vital parameters as stated above were recorded at intervals of 1, 3, and 5 min and recorded. i.v. induction was done with a 2.5% thiopentone 4–6 mg.kg−1. i.v. vecuronium 0.1 mg.kg−1 was administered intravenously to facilitate endotracheal intubation. Patients were intubated with the appropriate cuffed oral endotracheal tube within 20 s by an expert senior anesthetist. Patients were maintained with low-flow oxygen with air, isoflurane, and vecuronium in divided doses. Preemptive analgesia was given with i.v. fentanyl 1–1.5 μg.kg−1. Mechanical ventilation was done with pressure control mode to maintain end-tidal carbon dioxide level at near normal range. Pneumoperitoneum was induced by carbon dioxide insufflation. About 15 mmHg of intra-abdominal pressure was maintained during surgery. During the procedure, an increase in the MAP >20% was taken care of by nitroglycerin i.v. infusion of 0.5 μg.kg−1.min−1 initially, titrated according to blood pressure and increased maximum 5 μg.kg−1.min−1.
The vital parameters as abovestated were recorded at 1, 3, and 5 min after induction, 1, 3, and 5 min after intubation. At the end of the procedure, patients were adequately reversed with injection neostigmine (0.05 mg.kg−1) and injection glycopyrrolate (0.01 mg.kg−1) intravenously. After extubating, the patients were monitored.
Complications such as hypotension, hypertension, bradycardia, tachycardia, and shivering were noted intraoperatively and postoperatively and postoperative nausea and vomiting (PONV) was checked for 2 h during the postoperative period.
The sample size was based on keeping alpha and beta errors of 5% and 10% and the power of the study at 90%. Chi-square/Fisher's exact test has been used to find the significance of study parameters on a categorical scale between two groups with SPSS Software (Statistical Package for the Social Sciences) version 22.0 and R environment version 3.2.2 (IBM, New Orchard Road, Armonk, New York, USA). Significances were assessed at a 5% level of significance.
| Results|| |
Eighty adult patients were included in the study. The basic characteristics, namely, age, gender, ASA PS Classification, and body mass index (BMI) of the two groups are summarized in [Table 1]. There were no significant differences between the two groups with regard to gender, BMI, and ASA PS classification [Table 1].
[Table 2] shows the increase in mean SBP in the placebo group was statistically significant when compared to the increase in mean SBP in the clonidine group (P < 0.05).
|Table 2: Comparison of systolic blood pressure (mmHg) in two groups (n=80)|
Click here to view
[Table 3] shows in the clonidine group, the basal value of mean DBP was 77.88 mmHg ± 5.77 mmHg and in the placebo group, 79.45 mmHg ± 5.33 mm Hg. Evaluation between the groups showed that the increase in mean DBP observed in the placebo group was statistically significant when compared to the increase in mean DBP in the clonidine group (P < 0.005).
|Table 3: Comparison of diastolic blood pressure (mmHg) in two groups (n=80)|
Click here to view
There was a significant decrease in the dose of thiopentone required for loss of eyelash reflex during induction of anesthesia in the clonidine group (P < 0.05).
There was a significant decrease in the dose of fentanyl required during induction of anesthesia in the clonidine group (P < 0.05).
| Discussion|| |
This study was done on 80 adult patients to evaluate the effect of single i.v. dose of clonidine in attenuating hemodynamic response to laryngoscopy and intubation, in comparison with placebo.
Heart rate response
In our study in the clonidine group, the HR fell from the baseline value of 94.02 ± 9.85–74.00 ± 7.47, whereas in the placebo group, the HR reduced from 80.83 ± 7.53 to 80.75 ± 6.86 [Table 4]. When the groups were compared, the HR fall was significant in the clonidine group when compared to the placebo group. This is in agreement with the studies done by Aho et al., Das et al. Joris, et al. and Yu HP et al. studied and found clonidine significantly reduced the MAP and HR, and increase in systemic vascular resistance. In our study, we found an increase in HR in response to laryngoscopy and intubation from the value of 80.75 bpm ± 6.86 bpm to 102.30 bpm ± 9.83 bpm at 1 min after intubation, 112.55 bpm ± 9.71 bpm at 3 min, and 104.58 bpm ± 8.05 bpm at 5 min after intubation in the placebo group and in the clonidine group, the HR increased from 74.00 bpm ± 7.47 bpm to 73.58 bpm ± 7.81 bpm during 1 min after intubation, 74.53 bpm ± 7.74 bpm at 3 min, and 77.10 bpm ± 7.71 bpmat 5 min. An increase in HR in response to laryngoscopy and intubation was statistically significant at 1 min, 3 min, and 5 min after intubation in the placebo group compared with the clonidine group.
|Table 4: Comparison of mean arterial pressure (mmHg) in two groups (n=80)|
Click here to view
In our study, the results obtained were compared with the results of studies conducted by Laisalmi M et al., Keniya et al., Aho et al., Scheinin et al., Yildiz et al., Karthekeyan et al., Singh S., et al. and Málek J., et al.
Systolic blood pressure
The baseline value of SBP fell from 122.58 ± 16.85 to 100.45 ± 13.62 in the clonidine group and in the control group, we observed changes from the baseline value of 127.40 ± 6.88 to 135.65 ± 7.26 at 1 min after intubation. This shows that there was a significant fall in SBP in the clonidine group when compared with the control group.
This is in agreement with Aho et al., Joris et al., and Das et al., who used i.v. clonidine.
Diastolic blood pressure
The baseline value of DBP fell from 77.88 ± 5.77 to 61.85 ± 9.49 in the clonidine group and in the control group, we observed changes from the baseline value of 79.45 ± 5.33 to 91.65 ± 7.27, at 1 min after intubation. This shows that there was a significant fall in DBP in the clonidine group when compared with the control group.
This is in agreement with Aho et al., Joris et al., and Das et al., who used i.v. clonidine.
Dose of thiopentone and fentanyl
In the present study, the total dose of thiopentone required for induction was 240 mg (4.52 mg.kg−1) in the placebo group; it was 130 mg (2.82 mg.kg−1) in the clonidine group and the difference was found to be statistically significant (P < 0.001).
In the studies conducted by Keniya et al., Scheinin et al., Basar et al., and Aantaa et al. showed that there was a reduction in the dose of thiopentone required to induce the patient.
Patients in all the study groups were observed for bradycardia, hypotension, hypotension and bradycardia, shivering, PONV, tachycardia, and hypertension. About 17.5% of the patients had PONV in the control group, whereas in the clonidine group, the patients did not have PONV [Table 5].
In the other study, Javaherfroosh et al. used 0.2 mg tablet clonidine and observed the incidence of postoperative nausea – 21% and vomiting – 16% when compared to the control group nausea – 44% and vomiting – 34%.
Eva Oddby-Muhrbeck et al. used 2 μg.kg−1 of clonidine intravenously in breast cancer surgery and observed a significant reduction in the incidence of nausea and vomiting when compared to the control group.
Passi et al. used 150 μg of oral clonidine in laparoscopic cholecystectomy and observed fewer incidences of nausea and vomiting in the study group.
| Conclusions|| |
Conclusions that can be taken from this study are in the clonidine group patients, clonidine in the dose of 3 μg.kg−1 i.v. given over 20 min before intubation, effectively attenuated the HR response and also arterial pressure response to laryngoscopy and intubation. Clonidine also affords an added advantage of the reduction in requirements of induction agents and requirements of intraoperative analgesia and also brings down the incidence of postoperative complications such as nausea, vomiting, and shivering. Hence, it was concluded from the study conditions that clonidine can be employed to attenuate the hemodynamic response to laryngoscopy and intubation in a patient undergoing laparoscopic surgery. They also reduce the increase in blood pressure and HR occurring in response to the noxious stimuli during laparoscopic surgery.
The author would like to thank the Department of Anesthesiology, Rajarajeshwari Medical College and Ramaiah Medical College.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Joris JL. Anaesthesia for Laparoscopic Surgery. Miller's Anaesthesia. 6th
ed., Vol. 57. Philadelphia: Elsevier Churchill Livingstone 2285-2306; 2005. p. 2290-92.
Dhoste K, Lacoste L, Karayan J, Lehuede MS, Thomas D, Fusciardi J. Haemodynamic and ventilatory changes during laparoscopic cholecystectomy in elderly ASA III patients. Can J Anaesth 1996;43:783-8.
Hong JY, Chung KH, Lee YJ. The changes of ventilatory parameters in laparoscopic colecystectomy. Yonsei Med J 1999;40:307-12.
Cunningham AJ, Turner J, Rosenbaum S, Rafferty T. Transoesophageal echocardiographic assessment of haemodynamic function during laparoscopic cholecystectomy. Br J Anaesth 1993;70:621-5.
Joris J, Chiche JD, Lamy M. Clonidine reduced haemodynamic changes induced by pneumoperitoneum during laparoscopic cholecystectomy. Br J Anaesth 1995;74 Suppl:A124.
Joris JL, Chiche JD, Canivet JL, Jacquet NJ, Legros JJ, Lamy ML. Hemodynamic changes induced by laparoscopy and their endocrine correlates: Effects of clonidine. J Am Coll Cardiol 1998;32:1389-96.
Ghignone M, Quintin L, Duke PC, Kehler CH, Calvillo O. Effects of clonidine on narcotic requirements and hemodynamic response during induction of fentanyl anesthesia and endotracheal intubation. Anesthesiology 1986;64:36-42.
Raval DL. Oral clonidine premedication for the attenuation of haemodynamic response to laryngoscopy and intubation. IJA 2002;46:124-9.
Das AK, Rudra R. Clinical efficacy of oral clonidine as preanaesthetic medicant. IJA 1995;43:708-12.
Rudra A, Das AK, Chaudhri S. Evaluation of clonidine as premedicant during ketamine anaesthesia. J Anaesthesiol Clin Pharmacol 1994;11:123-7.
Aho M, Lehtinen AM, Laatikainen T, Korttila K. Effects of intramuscular clonidine on hemodynamic and plasma beta-endorphin responses to gynecologic laparoscopy. Anesthesiology 1990;72:797-802.
Das M, Ray M, Gauri M. Haemodynamic changes during laparoscopic cholecystectomy: Effect of clonidine premedication. IJA 2007;51:205-10.
Yu HP, Hseu SS, Yien HW, Teng YH, Chan KH. Oral clonidine premedication preserves heart rate variability for patients undergoing larparoscopic cholecystectomy. Acta Anaesthesiol Scand 2003;47:185-90.
Laisalmi M, Koivusalo AM, Valta P, Tikkanen I, Lindgren L. Clonidine provides opioid-sparing effect, stable hemodynamics, and renal integrity during laparoscopic cholecystectomy. Surg Endosc 2001;15:1331-5.
Keniya VM, Ladi S, Naphade R. Dexmedetomidine attenuates sympathoadrenal response to tracheal intubation and reduces perioperative anaesthetic requirement. Indian J Anaesth 2011;55:352-7.
] [Full text]
Aho M, Lehtinen AM, Erkola O, Kallio A, Korttila K. The effect of intravenously administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements in patients undergoing abdominal hysterectomy. Anesthesiology 1991;74:997-1002.
Scheinin B, Lindgren L, Randell T, Scheinin H, Scheinin M. Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone and peroperative fentanyl. Br J Anaesthesia 1992;68:126-31.
Yildiz M, Tavlan A, Tuncer S, Reisli R, Yosunkaya A, Otelcioglu S. Effect of dexmedetomidine on haemodynamic responses to laryngoscopy and intubation: Perioperative haemodynamics and anaesthetic requirements. Drugs R D 2006;7:43-52.
Sulaiman S, Karthekeyan RB, Vakamudi M, Sundar AS, Ravullapalli H, Gandham R. The effects of dexmedetomidine on attenuation of stress response to endotracheal intubation in patients undergoing elective off-pump coronary artery bypass grafting. Ann Card Anaesth 2012;15:39-43.
] [Full text]
Singh S, Arora K. Effect of oral clonidine premedication on perioperative haemodynamic response and postoperative analgesic requirement for patients undergoing laparoscopic cholecystectomy. Indian J Anaesth 2011;55:26-30.
] [Full text]
Málek J, Knor J, Kurzová A, Lopourová M. Adverse hemodynamic changes during laparoscopic cholecystectomy and their possible suppression with clonidine premedication. Comparison with intravenous and intramuscular premedication. Rozhl Chir 1999;78:286-91.
Basar H, Akpinar S, Doganci N, Buyukkocak U, Kaymak C, Sert O, et al
. The effects of preanesthetic, single-dose dexmedetomidine on induction, hemodynamic, and cardiovascular parameters. J Clin Anesth 2008;20:431-6.
Aantaa R, Kanto J, Scheinin M, Kallio A, Scheinin H. Dexmedetomidine, an alpha 2-adrenoceptor agonist, reduces anesthetic requirements for patients undergoing minor gynecologic surgery. Anesthesiology 1990;73:230-5.
Javaherfroosh F, Raza Pipelzadeh M, Namazi M. Clonidine reduces post operative nausea and vomiting in laparoscopic gynecological surgery. Pak J Med Sci 2009;25:782-5.
Oddby-Muhrbeck E, Eksborg S, Bergendahl HT, Muhrbeck O, Lönnqvist PA. Effects of clonidine on postoperative nausea and vomiting in breast cancer surgery. Anesthesiology 2002;96:1109-14.
Passi Y, Raval B, Rupakar VB, Chadha AI. Effect of oral clonidine premedication on haemodynamic response during laparoscopic cholecystectomy. J Anaesth Clin Pharmacol 2009;25:329-32.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]