Anesthesia: Essays and Researches  Login  | Users Online: 201 Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
Home | About us | Editorial board | Ahead of print | Search | Current Issue | Archives | Submit article | Instructions | Copyright form | Subscribe | Advertise | Contacts

Table of Contents  
Year : 2013  |  Volume : 7  |  Issue : 1  |  Page : 29-33  

Premedication with clonidine versus fentanyl for intraoperative hemodynamic stability and recovery outcome during laparoscopic cholecystectomy under general anesthesia

1 Department of Anaesthesiology and Critical Care, N.S.C.B. Subharti Medical College, Swami Vivekananda Subharti University, Subhartipuram, NH-58, Meerut, Uttar Pradesh, India
2 Department of Radio diagnosis, Imaging and Interventional Radiology, N.S.C.B. Subharti Medical College, Swami Vivekananda Subharti University, Subhartipuram, NH-58, Meerut, Uttar Pradesh, India
3 Department of Surgery, N.S.C.B. Subharti Medical College, Swami Vivekananda Subharti University, Subhartipuram, NH-58, Meerut, Uttar Pradesh, India

Date of Web Publication26-Jun-2013

Correspondence Address:
Kumkum Gupta
108, Chanakyapuri, Shastri Nagar, Meerut - 250 004, Uttar Pradesh
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0259-1162.113984

Rights and Permissions

Background: Laparoscopic cholecystectomy under general anesthesia induced intraoperative hemodynamic responses which should be attenuated by appropriate premedication. The present study was aimed to compare the clinical efficacy of clonidine and fentanyl premedication during laparoscopic cholecystectomy for attenuation of hemodynamic responses with postoperative recovery outcome.
Subjects and Methods : In this prospective randomized double blind study 64 adult consented patients of either sex with ASA I and II, scheduled for elective laparoscopic cholecystectomy under general anesthesia and met the inclusion criteria, were allocated into two groups of 32 patients. Group C patients have received intravenous clonidine 1μg kg -1 and Group F patients have received intravenous fentanyl 2μg kg -1 5 min before induction. Anesthetic and surgical techniques were standardized. All patients were assessed for intraoperative hemodynamic changes at specific time and postoperative recovery outcome.
Results : Premedication with clonidine or fentanyl has attenuated the hemodynamic responses of laryngoscopy and laparoscopy. Clonidine was superior to fentanyl for intraoperative hemodynamic stability. No significant differences in the postoperative recovery outcome were observed between the groups. Nausea, vomiting, shivering and respiratory depression were comparable between groups.
Conclusion : Premedication with clonidine or fentanyl has effectively attenuated the intraoperative hemodynamic responses of laparoscopic cholecystectomy.

Keywords: Clonidine, fentanyl, hemodynamic response, laparoscopic cholecystectomy, laryngoscopy, pneumoperitoneum

How to cite this article:
Gupta K, Lakhanpal M, Gupta PK, Krishan A, Rastogi B, Tiwari V. Premedication with clonidine versus fentanyl for intraoperative hemodynamic stability and recovery outcome during laparoscopic cholecystectomy under general anesthesia. Anesth Essays Res 2013;7:29-33

How to cite this URL:
Gupta K, Lakhanpal M, Gupta PK, Krishan A, Rastogi B, Tiwari V. Premedication with clonidine versus fentanyl for intraoperative hemodynamic stability and recovery outcome during laparoscopic cholecystectomy under general anesthesia. Anesth Essays Res [serial online] 2013 [cited 2020 Aug 13];7:29-33. Available from:

   Introduction Top

Laparoscopic cholecystectomy provides substantial advantages of less postoperative pain with fewer pulmonary complications and more rapid convalescence. However the procedure is not risk free and insufflation of the abdominal cavity with carbon dioxide causes increased intra-abdominal pressure which predictably leads to increased hemodynamic responses. [1] The potential problem of hemodynamic response of pneumoperitoneum during laparoscopic surgery does need an optimal preoperative and intraoperative anesthetic care of patients. [2] Various pharmacological agents like nitroglycerine, beta blocker and opioids were used during anesthesia to provide hemodynamic stability during laryngoscopy and laparoscopy but with their own limitations. [3],[4],[5]

Clonidine, a α2 adrenergic agonist, has shown clinically useful drug profile due to its sympatholytic, hypnotic, sedative, anxiolytic, analgesic and anesthetic sparing effects without respiratory depression. [6],[7] In recent studies clonidine has shown attenuation of the pressor responses associated with laryngoscopy by reducing norepinephrine release.

The present study was aimed to compare the clinical efficacy of premedication with clonidine versus fentanyl for intra-operative hemodynamic stability and postoperative recovery variables during laparoscopic cholecystectomy under general anesthesia.

   Subjects and Methods Top

After approval of Institutional Ethical Committee and written informed consent, 64 healthy adult patients of ASA physical status I and II of either sex aged 32 to 57 years, scheduled for elective laparoscopic cholecystectomy under general anesthesia from August 2011 to April 2012 were enrolled for this double blind prospective randomized study. Patients with hypertension, history of cardiac, pulmonary or renal disease, psychiatric disorder, and any drug therapy of beta blockers, methyldopa, and monoamine oxidase (MAO) inhibitors were excluded from the study. Other exclusion criterion were body mass index >25 and anticipated difficult airway. All patients were evaluated during pre-anesthesia checkup before enrollment. Drug preparation was done by the resident anesthesiologist who was blinded to the randomization schedule and the study protocol. The observer was also blinded about the group allocations and medication schedule.

Patient's group allocation was done by computer generated code based on a two way randomization. Group C patients (n0 = 32) received intravenous clonidine 1 μg kg -1 and Group F patients (n = 32) received fentanyl 2 μg kg -1 given over 10 minutes prior to induction of general anesthesia. These doses were considered appropriate to provide adequate and comparable clinical effects.

All patients were premedicated with oral alprazolam 0.25 mg and ranididine 150 mg night before surgery. On the day of surgery they received premedication of glycopyrrolate 0.2 mg intramuscularly 30 min prior to induction of anesthesia. On arrival to operation room routine hemodynamic monitoring of base line heart rate, systemic arterial pressure, arterial oxygen saturation (SpO 2 ), continuous ECG was performed. An intravenous infusion of ringer lactate was started in non-dominant arm. The premedication of clonidine 1 μg kg -1 or fentanyl 2 μg kg -1 was given over 10 minutes and 5 minutes prior to induction according to group allocation. After premedication heart rate, arterial blood pressure, respiratory rate and oxygen saturation were assessed and recorded.

All patients were given metoclopramide 10 mg and midazolam 2 mg intravenously and after preoxygenation for 3 min, the anesthesia was induced with propofol 2 mg kg -1 and tracheal intubation was facilitated by vecuronium 0.1mg kg -1 . Anesthesia was maintained with isoflurane 1-1.5% and 60% nitrous oxide in oxygen with supplementary fentanyl (50-100 μg) to maintain the heart rate and mean arterial pressure within 20% of preinduction values. The patient's lungs were initially ventilated with a tidal volume of 8 -1 , a respiratory rate of 12 breaths per minutes, and I:E ratio of 1:2 in volume controlled mode. Five minutes after securing the airway and abdominal insufflation, the lung mechanics were adjusted to maintain normocapnia (EtCO2 between 35-40 mm Hg). Vecuronium 0.05 was administered during surgery as required to maintain a train of four ratio of <25%.

Pneumoperitoneum was created and maintained by insufflation of carbon dioxide. The table was tilted to about 15 o reversed Trendelenburg position with left side rotation to facilitate exposure of the gall bladder. Intra-abdominal pressure was maintained between 12-15 mm Hg during the surgery. At the end of surgery, the surgeon administered 10 ml ropivacaine 0.75% in the peritoneum through the main trocar, the isoflurane and nitrous oxide were discontinued and residual neuromuscular block was antagonized with neostigmine (0.05 mg kg -1 ) and atropine (0.02 mg kg -1 ). The trachea was extubated when respiration was adequate in tidal volume and patient was able to obey simple commands.

All patients were assessed for changes in hemodynamic parameters of heart rate and mean arterial pressure prior to premedication, before induction, after laryngoscopy and intubation, after pneumoperitoneum, followed by every 5 min for 30 min thereafter every 15 min till end of surgery and after extubation. Criteria for tachycardia, bradycardia, hypotension and hypertension were any increase or decrease more than 20% from the baseline. The intraoperative bradycardia or tachycardia, hypotension or hypertension and any untoward incident requiring intervention was recorded and managed accordingly.

The patients were transferred to post anesthesia care unit and were monitored for any hemodynamic abnormalities, respiratory depression (respiratory rate < 8 breaths/min) or hypoxemia (SpO 2 < 94%), shivering, nausea and vomiting and were managed as required.

A sample size was based on initial pilot observation which indicated that approximately 23 to 27 patients per group were needed to ensure power 0.80 for detecting clinically meaningful reduction by 20% in heart rate and mean arterial pressure. Assuming a 5% dropout rate, the final sample size was set at 64 patients. The results obtained in the study are presented as Mean ± SD in tabulated manner and Statistical analysis was done with SPSS software for windows using student t test and Chi square test. P < 0.05 was considered statistically significant and P < 0.001 was taken as highly significant.

   Results Top

A total of 64 patients were randomly assigned to two groups of 32 patients each. Both groups were comparable with respect to demographic and operational factors. No significant differences were found with respect to age, weight, gender, time between premedication to anesthetic induction, duration of laryngoscopy and surgical procedure. The anesthetic technique did not differ among the study groups [Table 1].
Table 1: Demographic profile of patients

Click here to view

There was no significant difference in the mean heart rate and arterial blood pressure values between groups before premedication. Though after induction, the hemodynamics was stable in both groups but heart rate increased immediately after laryngoscopy in fentanyl group and maximum increase was observed after 1 min of laryngoscopy whereas no such changes were observed in heart rate in clonidine group. It remained stabilized during intraoperative period in comparison to fentanyl group [Table 2].
Table 2: Mean heart rate changes during laparoscopic cholecystectomy

Click here to view

No significant difference was observed in the mean arterial pressure (MAP) before and after premedication in both groups. The attenuation of mean arterial blood pressure was observed in both groups. Clonidine group has shown more intraoperative stability of hemodynamic response during pneumoperitoneum [Table 3]. Hemodynamic variables recorded at specified timings during the study are shown in [Figure 1] and [Figure 2].
Figure 1: Showing changes in mean arterial blood pressure during laparoscopic cholecystectomy

Click here to view
Figure 2: Showing changes in heart rate during laparoscopic cholecystectomy

Click here to view
Table 3: Mean arterial blood pressure changes during laparoscopic cholecystectomy

Click here to view

During the intraoperative period, heart rate and mean arterial blood pressure values were close to preoperative values without requirement of any other medication and remained stabilized throughout the surgery. Rapid intravenous infusion was needed in 5 patients of Group C to treat hypotension. None of the patients had persistent or severe hypotension intra-operatively, thus vasoactive drugs were not used.

There were no significant differences between groups with respect to awakening and recovery times. All patients were well oriented and able to obey verbal commands in postoperative care unit. The premedication with fentanyl allows earlier cognitive recovery [Table 4].
Table 4: Recovery outcome from general anesthesia after premedication

Click here to view

Postoperative undesirable adverse events were comparable between groups and were manageable. The postoperative nausea and vomiting were found in both groups and was treated with ondansetron. Eleven patients (35.2%) of fentanyl group and five patients (7%) of clonidine group needed tramadol 50 mg for postoperative shivering. Bradycardia of 7 patients was treated with intravenous atropine. No significant complication has occurred after use of intravenous premedication of clonidine or fentanyl in our study [Table 5].
Table 5: Postoperative adverse events after laparoscopic cholecystectomy

Click here to view

   Discussion Top

The present study has evaluated the efficacy of intravenous premedication of clonidine versus fentanyl for intraoperative hemodynamic stability during laparoscopic cholecystectomy under general anesthesia. The hemodynamic pressor response was attenuated by clonidine and fentanyl effectively. The premedication with clonidine showed more intraoperative hemodynamic stability as compared to fentanyl premedication. Near stable hemodynamic values in the present study was an indication of adequate analgesia and sedation with clonidine or fentanyl premedication.

Clonidine, a α2 adrenergic agonist, possesses several properties such as sedation, analgesia, bradycardia and hypotension to make it a valuable premedicant to attenuate the hemodynamic response without any deleterious effect. The hemodynamic results of our study were in agreement with recent studies with clonidine and fentanyl. [8],[9],[10],[11]

Reid and Brace first described the hemodynamic response to laryngoscopy and intubation due to intense sympathetic discharges caused by stimulation of larynx. [12] These hemodynamic responses can be detrimental in elderly and hemodynamically compromised patients due to associated risk of myocardial ischemia or cerebral hemorrhage, therefore these should be attenuated. [13],[14],[15] Many pharmacological methods were evaluated either in premedication or during induction to attenuate these adverse hemodynamic responses with controversial results. The most important premedicants were lidocaine, esmolol, sodium nitroprusside and opioids. [3],[4],[16] Moreover numerous techniques have also been used to reduce the severity of the hemodynamic responses of laparoscopic surgery to counteract its detrimental effects.

Clonidine has been used as anesthetic adjuvant during balanced anesthetic regimen. Its anesthetic sparing effects are well established. The clonidine premedication attenuates the intraoperative hemodynamic response by reducing the nociceptive transmission and decrease norepinephrine concentration in serum. In our study, clonidine 1 μg/kg given intravenously has attenuated the hemodynamic response of laryngoscopy and laparoscopy effectively.

Recent studies with oral clonidine (150 μg) given 90 minutes before induction of general anesthesia have shown the attenuated hemodynamic response during laparoscopic surgery. Hayashi, et al. [9] and Sung, et al. [17] have concluded that clonidine provided perioperative hemodynamic stability during laparoscopic cholecystectomy. Laisalmi, et al. [18] has also reported that clonidine premedication blunts the stress response of surgery and reduces the requirement of narcotics and anesthetic agent.

In the present study, clonidine has caused intraoperative and postoperative bradycardia and subsequent use of atropine, suggesting that an anticholinergic drug should be used routinely as premedicants. Salivary and tracheobronchial mucus secretion further necessitates prophylactic administration of an antisialagogue agent. Thus, glycopyrrolate was the rationale choice in the present study.

The incidence of nausea and vomiting after general anesthesia has been reported to be as high as 24% and after laparoscopy it is as high as 42% due to rapid peritoneal distension. Metoclopramide has been shown to be effective and safe antiemetic for both prevention and treatment of nausea and vomiting. [19] In the present study, the metoclopramide was used in premedication as it increases the tone of lower esophageal sphincter and speeds gastric emptying. Decreased incidence of postoperative nausea and vomiting were found in the present study.

The mechanism of shivering in patients recovering from anesthesia though poorly understood, but volatile anesthetic agents are usually associated with altered temperature regulation. Regardless of its cause, shivering increases oxygen consumption, hence postoperative supplemental oxygen therapy helped to prevent hypoxemia. Clonidine group patients showed decreased incidence of postoperative shivering when compared to fentanyl group. [20]

Clonidine also plays a significant role in the treatment of hypertension, delirious syndrome and withdrawal syndromes of opioids, alcohol and nicotine addiction. It is also used in intensive care units to facilitate weaning from long term mechanical ventilation. [21],[22]

   Conclusion Top

Premedication with intravenous Clonidine or Fentanyl have effectively attenuated the hemodynamic responses during laparoscopic cholecystectomy under general anesthesia. Postoperative undesirable adverse events were comparable and manageable. The intraoperative hemodynamic stability with clonidine or fentanyl premedication might enable laparoscopic cholecystectomy in obese, hypertensive and cardiac compromised patients.

   References Top

1.Cunningham AJ, Brull SJ. Laparoscopic cholecystectomy: Anesthetic implications. Anesth Analg 1993;76:1120-33.  Back to cited text no. 1
2.Jean IJ. Anaesthesia for laparoscopic surgery. In: Miller RD. editor. Anesthesia. 7 th ed. New York: Churchill Livingstone; 2010. p. 2185-202.  Back to cited text no. 2
3.Singh H, Vichitvejpaisal P, Gaines GY, White PF. Comparative effects of lidocaine, esmolol, and nitroglycerin in modifying the hemodynamic response to laryngoscopy and intubation. J Clin Anesth 1995;7:5-8.  Back to cited text no. 3
4.Chung KS, Sinatra RS, Halevy JD, Paige D, Silverman DG. A comparison of fentanyl, esmolol, and their combination for blunting the haemodynamic responses during rapid-sequence induction. Can J Anaesth 1992;39:774-9.  Back to cited text no. 4
5.Casati A, Fanelli G, Albertin A, Deni F, Danelli G, Grifoni F, et al. Small doses of remifentanil or sufentanil for blunting cardiovascular changes induced by tracheal intubation: A double-blind comparison. Eur J Anaesthesiol 2001;18:108-12.  Back to cited text no. 5
6.Tryba M, Gehling M. Clonidine: A potent analgesic adjuvant. Curr Opin Anaesthesiol 2002;15:511-7.  Back to cited text no. 6
7.Jamadarkhana S, Gopal S. Clonidine in adults as a sedative agent in the intensive care unit. J Anaesthesiol Clin Pharmacol 2010;26:439-45.  Back to cited text no. 7
[PUBMED]  Medknow Journal  
8.Tripathi DC, Komal SS, Dubey SR, Doshi SM, Rawal PV. Hemodynamic stress response during laparoscopic cholecystectomy: Effect of two different doses of intravenous clonidine premedication. J Anesth Clin Phar 2011;27:475-80.  Back to cited text no. 8
9.Mrinmoy D, Manjushree R, Gauri M. Hemodynamic changes during laparoscopy cholecystectomy: Effect of oral clonidine premedication. Ind J Anesth 2007;51:143-7.  Back to cited text no. 9
10.Feld JM, Hoffman WE, Stechert MM, Hoffman IW, Ananda RC. Fentanyl or dexmedetomidine combined with desflurane for bariatric surgery. J Clin Anesth 2006;18:24-8.  Back to cited text no. 10
11.Martin DE, Rosenberg H, Aukburg SJ, Bartkowski RR, Edwards MW Jr, Greenhow DE, et al. Low-dose fentanyl blunts circulatory responses to tracheal intubation. Anesth Analg 1982;61:680-4.  Back to cited text no. 11
12.Reid LC, Brace DE. Irritation of the respiratory tract and its reflex effect on heart. Surg Gynae Obstet 1940;70:157-62.  Back to cited text no. 12
13.Shribman AJ, Smith G, Achola KJ. Cardiovascular and catecholamine responses to laryngoscopy with and without tracheal intubation. Br J Anaesth 1987;59:295-9.  Back to cited text no. 13
14.Saif GM, Singh V, Kumar A, Wahal R, Bhatia VK. A study of cardiovascular response during laryngoscopy and intubation and their attenuation by ultra-short acting beta-blocker esmolol. Ind J Anaesth 2002;46:104-6.  Back to cited text no. 14
15.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.  Back to cited text no. 15
16.Mi WD, Sakai T, Takahashi S, Matsuki A. Haemodynamic and electroencephalograph responses to intubation during induction with propofol or propofol/fentanyl. Can J Anaesth 1998;45:19-22.  Back to cited text no. 16
17.Sung CS, Lin SH, Chan KH, Chang WK, Chow LH, Lee TY. Effect of oral clonidine premedication on perioperative hemodynamic response and postoperative analgesic requirement for patients undergoing laparoscopic cholecystectomy. Acta Anaesthesiol Sin 2000;38:23-9.  Back to cited text no. 17
18.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.  Back to cited text no. 18
19.Wilson EB, Bass CS, Abrameit W, Roberson R, Smith RW. Metoclopramide versus ondansetron in prophylaxis of nausea and vomiting for laparoscopic cholecystectomy. Surg Endosc 2001;15:1331-5.  Back to cited text no. 19
20.Nicolaou G, Chen AA, Jonton CE, Kenny GP, Bristow GK, Giesbrecht GG. Clonidine decrease vasoconstriction and shivering threshold without affecting the sweating threshold. Can J Anaesth 1997;44:636-42.  Back to cited text no. 20
21.Ise T, Yamashiro M, Furuya H. Clonidine as a drug for intravenous conscious sedation. Odontology 2002;90:57-63.  Back to cited text no. 21
22.Gillison M, Fairbairn J, McDonald K, Zvonar R, Cardinal P. Clonidine use in the intensive care unit of a tertiary care hospital: Retrospective analysis. Can J Hosp Pharm 2004;57:83-9.  Back to cited text no. 22


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

This article has been cited by
1 Influence of the perioperative administration of magnesium sulfate on the total dose of anesthetics during general anesthesia. A systematic review and meta-analysis
Laura Rodríguez-Rubio,Eduardo Nava,Julián Solís García del Pozo,Joaquín Jordán
Journal of Clinical Anesthesia. 2017; 39: 129
[Pubmed] | [DOI]
2 Attenuation of pneumoperitoneum-induced hypertension by intra-peritoneal lidocaine before pneumoperitoneum in laparoscopic cholecystectomy
Sun Ok Song,Hae Mi Lee,Sung Soo Yun,Hwarim Yu,Soo Young Shim,Heung Dae Kim
Yeungnam University Journal of Medicine. 2016; 33(2): 90
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
   Subjects and Methods
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded285    
    Comments [Add]    
    Cited by others 2    

Recommend this journal