Document Type : Original Article


1 Noncommunicable diseases Research Center, Fasa University of medical sciences, Fasa, Iran

2 Department of Anesthesiology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Plastic Surgery, Jahrom University of Medical Sciences, Jahrom, Iran

4 Research Center for Noncommunicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran


Introduction: Intraoperative hemorrhage is one of the most important complications of septorhinoplasty surgery. Many techniques and drugs are used to reduce this problem. Accordingly, the present study was conducted to investigate the effect of oral clonidine as a premedication on hemorrhage during septorhinoplasty surgery.
Methods: In this double-blind randomized clinical trial, 53 patients undergoing septorhinoplasty at Motahari Hospital in Jahrom were studied. Patients were randomly divided into oral clonidine and placebo groups. Intraoperative hemorrhage was measured based on the blood in the suction. The data were analyzed in SPSS-21 and both descriptive and inferential statistical tests were computed.
Results: Both groups were homogenous in terms of demographic variables of age, weight, gender and the level of fluid received during the surgery. Mean hemorrhage (P = 0.001) and total duration of surgery (P = 0.031) in the clonidine group were significantly lower than the control group.
Conclusion: The results of the present study revealed that oral clonidine as a premedication for anesthesia can reduce hemorrhage and the duration of septorhinoplasty surgery. It is recommended that future studies be performed with a larger sample size and compare with other drugs.

Graphical Abstract

Effect of Oral Clonidine as a Premedication on Hemorrhage during Septorhinoplasty: A Double-Blind Randomized Clinical Trial



Septorhinoplasty is considered as the most common plastic surgery in Iran [1]. The rate of septorhinoplasty in Iran is 180 cases per 100000 people [2], which is one of the highest rates of this surgery in the world [3]. One of the problems in the operating room for surgeons and anesthesiologists is intraoperative hemorrhage. Also, the surgeon needs a clear range of operation with minimum hemorrhage to perform delicate and sensitive operations. Additionally, the anesthesiologist wants to reduce intraoperative hemorrhage to maintain hemodynamic stability during the surgery [4]. Alpha-2 agonists have potentially beneficial effects. In addition to lowering blood pressure, they also have analgesic and sedative properties. They cause hemodynamic stability as a result of the central sympatholytic effect [5]. Clonidine is being used commonly as an adjunct in anesthesia in light of its sedative and anesthetic properties [6]. Also, its favorable effects on patient hemodynamics have been approved by anesthesiologists [7]. Clonidine is quickly absorbed in its oral administration, and its concentration reaches a maximum within 1.5 to 2 hours. Its half-life is about 8-12 hours [8]. Various studies have proven the effects of clonidine on reducing hemorrhage during septorhinoplasty [9-10]. Clonidine lowers arterial blood pressure without lowering postural blood pressure. It also reduces heart rate, reduces intraoperative hemorrhage in general, and reduces stress during surgery [11]. Since clonidine is one of the drugs studied extensively in recent years, the present study aimed to investigate the effect of oral clonidine as a premedication on hemorrhage during septorhinoplasty.

Material and Methods

Study design

The present study was a double-blind randomized clinical trial conducted over a three-month from February 2022 to April 2022 in patients who referred to the operating room of Motahari Hospital in Jahrom and underwent septorhinoplasty.

 Ethical considerations

Before entering the patients in this study, the research process was explained and informed consent was obtained from them. During the study, researchers adhered to the principles of the Helsinki Declaration and the confidentiality of patient information. All costs of the project were provided by the researchers and no additional costs were incurred by the patients. This study was approved by the ethics committee of Jahrom University of Medical Sciences under the code of ethics of IR.JUMS.REC.1400.072.


The statistical population of the present study included all patients undergoing septorhinoplasty surgery. The sample size was determined at 60 patient for each group assuming standard difference = 0.85 and 95% confidence level and power = 80% using the Altman nomogram and with considering 15% dropout in samples. Then, to have an equal chance of being in the intervention group or the control group, the samples were randomly assigned to study groups (30 patient in each group) using coin flipping.  Subjects were randomly divided into two groups of clonidine or control (placebo) based on the inclusion and non-exclusion criteria. Sampling was continued up to the stage where two groups were homogenized in terms of underlying characteristics (Figure 1).

Inclusion criteria were all subjects over 18 years of age, hemoglobin above 10, normal PT/ PTT/ INR, normal hemodynamics and heart rate above 60 beats per minute.

 Exclusion criteria were patients with coagulation disorders, coronary artery disease, stroke, venous thrombosis and clonidine sensitivity.


All patients who met the inclusion criteria at the time of study entered the study after obtaining their written consent and explaining the study conditions for them. They were randomly divided into clonidine and placebo groups by coin flipping method. Group A received oral clonidine at a dose of 0.2 Mg and Group B was treated with placebo. This study was designed in a double-blind method. It means that the patient, the person giving the drug to the patient and the data analyst were not aware of the type of drug. Both groups received the drugs orally (with a small amount of water) two hours before induction of anesthesia. Both groups of patients underwent septorhinoplasty by a surgeon. The level of intraoperative hemorrhage was estimated based on the rate of hemorrhage in the suction.


[1]. Ebrahimi A., Kalantar Motamedi M.H., Shams A., Nejadsarvari N., Health and social problems of rhinoplasty in Iran. World Journal of Plastic Surgery, 2016, 5:75 [Google Scholar]
[2]. Sari A.A., Babashahy S., Olyaeimanesh A., Rashidian A., Estimating the frequency and rate of first 50 common types of invasive procedures in iran healthcare system. Iranian Journal of Public Health, 2012, 41:60 [Google Scholar], [Publisher]
[3]. Rastmanesh R., Gluck M.E., Shadman Z., Comparison of body dissatisfaction and cosmetic rhinoplasty with levels of veil practicing in Islamic women. International Journal of Eatin 2009, 42:339 [Crossref], [Google Scholar], [Publisher]
[4]. Sadri B., Nadri S., Pousti S., Mahmoudvand H., Clonidine decreased intraoperative bleeding in rhinoplasty. 2007, 9:25 [Google Scholar] 
[5]. Maze M., Tranquilli W., Alpha-2 adrenoceptor agonists: defining the role in clinical anesthesia. The Journal of the American Society of Anesthesiologists, 1991, 74:581 [Google Scholar] 
[6]. Dahmani S., Brasher C., Stany I., Golmard J., Skhiri A., Bruneau B., Nivoche Y., Constant I., Murat I., Premedication with clonidine is superior to benzodiazepines. A meta analysis of published studies. Acta anaesthesiologica scandinavica, 2010, 54:397 [Crossref], [Google Scholar], [Publisher]
[7]. Sung C.S., Lin S.H., Chan K.H., Chang W.K., Chow L.H., Lee T.Y., Effect of oral clonidine premedication on perioperative hemodynamic response and postoperative analgesic requirement for patients undergoing laparoscopic cholecystectomy. Acta Anaesthesiologica Sinica, 2000, 38:23 [Google Scholar] 
[8]. Munoz M.C.S., De Kock M., Forget P., What is the place of clonidine in anesthesia? Systematic review and meta-analyses of randomized controlled trials. Journal of Clinical Anesthesia, 2017, 38:140 [Crossref], [Google Scholar], [Publisher]
[9]. Ghazipour A., Ahmadi K., Sarafraz M., Abshirini H., Akbari N., Can clonidine as a pre-anaesthetic drug decrease bleeding during rhinoplasty surgery?. Indian Journal of Otolaryngology and Head & Neck Surgery, 2013, 65:301 [Crossref], [Google Scholar], [Publisher]
[10]. Tabrizi R., Eftekharian H., Pourdanesh F., Khaghaninejad M.S., Does oral clonidine premedication decrease bleeding during open rhinoplasty?. Journal of Craniofacial Surgery, 2014, 25:1101 [Crossref], [Google Scholar], [Publisher]
[11]. Raghuwanshi S.K., Chakravarty N., Asati D.P., Bankwar V., Use of clonidine as an adjuvant to infiltration anaesthesia in tympanoplasty: a randomized double blind study. Indian Journal of Otolaryngology and Head & Neck Surgery, 2014, 66:57  [Crossref], [Google Scholar], [Publisher]
[12]. Bonnet C., Roche B., d'Athis F., Du Cailar J., Nicardipine vs trinitrin for controlled hypotension in maxillo-facial surgery. Cahiers D'anesthesiologie, 1992, 40:171 [Google Scholar], [Publisher]
[13]. Pasch T., Pingel I., Deliberate hypotension during rhinosurgery using labetalol, a combined alpha-and beta-adrenoceptor antagonist (author's transl). Anasthesie, Intensivtherapie, Notfallmedizin, 1982, 17:74  [Google Scholar], [Publisher]
[14]. Nassery W., Rhinoplasty using controlled hypotension. Zeitschrift fur Plastische Chirurgie, 1981, 5:117 [Google Scholar], [Publisher]
[15]. Maune S., Carbon dioxide laser diverticulostomy: a new treatment for Zenker diverticulum. The American Journal of Medicine, 2003, 115:172 [Crossref], [Google Scholar], [Publisher]
[16]. Ensinger H.E.R.M.A.N.N., Weichel T.H.O.M.A.S., Lindner K.H., Grünert A., Ahnefeld F.W., Effects of norepinephrine, epinephrine, and dopamine infusions on oxygen consumption in volunteers. Critical Care Medicine, 1993, 21:1502 [Crossref], [Google Scholar], [Publisher]
[17]. Roizen M.F., Should we all have a sympathectomy at birth? Or at least preoperatively? Anesthesiology and the Heart Springer, Dordrecht. 1990 [Crossref], [Google Scholar], [Publisher]
[18]. Dorman B.H., Zucker J.R., Verher E.D., Gartman D.M., Slachman F.N., Clonidine improves perioperative myocardial ischemia, reduces anesthetic requirement, and alters hemodynamic parameters in patients undergoing coronary artery bypass surgery. Journal of Cardiothoracic and Vascular Anesthesia, 1993, 7:386  [Crossref], [Google Scholar], [Publisher]
[19]. Bertram G., katzung. Adrenoreceptor activating and other sympathomometic drugs. Basic and clinical pharmacology. 1998 [Google Scholar]
[20]. Zangouei A., Zahraei S.A.H., Karbasy S.H., Rahmanifar M., Zangoue M., Comparison of the Effects of Clonidine, Promethazine, and Morphine on Bleeding During Rhinoplasty Surgery: A Triple-blind Clinical Trial Study, 2019, 9:555752 [Google Scholar]
[21]. Nadri S., Kazami S., Moradi M., Mahmoudvand H., Ahmadi Rokn abadi R., Papi O. A., The effect of oral clonidine pre-medication prior to anesthesia on bleeding during tympanoplasty. Yafte, 2014, 16:43 [Google Scholar], [Publisher]
[22]. Asgarian‐omran S., Mohseni M., Ebneshahidi A., The effect of oral clonidine premedication on blood loss and thequality of the surgical field during endoscopic sinus surgery: aplacebo-controlled clinical trial. Anesthesiology and Pain, 2012, 3:152 [Google Scholar], [Publisher]
[23]. Marchal J.M., Gomez‐Luque A., Martos‐Crespo F., Sanchez De La Cuesta F., Martinez‐Lopez M.C., Delgado‐Martinez A.D., Clonidine decreases intraoperative bleeding in middle ear microsurgery. Acta Anaesthesiologica Scandinavica, 2001, 45:627 [Crossref], [Google Scholar], [Publisher]
[24]. Sadri B., Nadri S., Pousti S., Mahmoudvand H., Clonidine decreased intraoperative bleeding in rhinoplasty. Yafte. 2007, 9:25 [Google Scholar] 
[25]. Jafarieh A., Hajimohammadi F., Etemadi A.A.A., Behzadi,M., Salavatipour A., Rojati M., The efficacy of clonidine on intraoperative bleeding in middle ear microsurgery.The Iranian Journal of Otorhinolaryngology. 2009, 31:48 [Google Scholar] 
[26]. Cardesin A., Pontes C., Rosell R., Escamilla Y., Marco J., Escobar M.J., Bernal-Sprekelsen M., A randomised double blind clinical trial to compare surgical field bleeding during endoscopic sinus surgery with clonidine-based or remifentanil-based hypotensive anaesthesia. Rhinology, 2015, 53:107 [Crossref], [Google Scholar], [Publisher]
[27]. Jab A.M., Hashemi J., Hashemi M., Soltani H., Oral clonidine premedication decreases intraoperative bleeding in patients undergoing endoscopic sinus surgery. Journal of Research in Medical Sciences, 2005, 1:25 [Google Scholar]