Published Online 2012 April 22 | DOI: 10.5812/aapm.2197
Effect of Clonidine Premedication on Blood Loss in Spine Surgery
Background: Blood loss in spine surgery is an important issue, even though it has been understudied compared with hip and knee arthroplasty.
Objectives: In this study, we evaluated the effect of oral clonidine as premedication on blood loss in lumbar spine fusion surgery under anesthesia with propofol and remifentanil.
Patients and Methods: In this double-blind, randomized clinical trial, 30 patients who were undergoing lumbar spine posterior fusion surgery due to traumatic fracture were allocated randomly into 2 groups. The study group (clonidine group) received a 200-μg oral clonidine tablet 60–90 minutes before anesthesia, and the control group received placebo at the same time. Induction and maintenance of anesthesia and the mean target arterial pressure for controlled hypotension with remifentanil were the same in the 2 groups. We compared the amount of intraoperative blood loss, dose of remifentanil/hour administered, need for nitroglycerine to reach the mean target arterial pressure when remifentanil was insufficient, duration of operation, and surgeon’s satisfaction of a bloodless field between groups.
Results: There was no statistically significant difference between groups in age (
Conclusions: As an oral premedication, clonidine can reduce surgical blood loss in lumbar spine posterior fusion surgery, even at the same levels of mean arterial pressure (MAP) with the control group. Its use can be studied in more complicated spine surgeries, such as scoliosis and spinal deformity surgeries.
Keywords: Clonidine; Anesthetics; Blood Loss, Surgical; Prevention and Control; Hypotension; Bloodless Medical and Surgical Procedures; Adrenergic Alpha-2 Receptor Agonists; Spinal Fractures
Spinal fusion surgery is often associated with major blood loss, which is sometimes significant, requiring the transfusion of blood or blood products (1). Blood loss can be an acute problem not only in major deformity surgery but also in less extensive fusion procedures. Decreasing bleeding is important to maintain a patient’s hemodynamic stability and improve the surgical field. In spine surgery, the latter aspect is especially important, due to the vicinity of major and highly fragile neurological structures. The surgeon’s comfort shortens the operating time, which further decreases bleeding (2). Decreased bleeding also reduces the need for the transfusion of blood products, thereby reducing the risk of complications, such as hemolytic and non-hemolytic reactions, acute lung injury, transmission of viral and bacterial infections, hypothermia, and coagulation disorders.
Blood-sparing techniques can be divided into two groups, based on their goals: they are aimed at decreasing the bleeding itself [hemodynamically (e.g., controlled hypotension, local vasoconstrictors, epidural blockade) or with chemical/biologicalagents (e.g., desmopressin, aprotinin, tranexamic acid, epsilon-aminocaproic acid, estrogens, bone wax, hemostatic “sponges,” fibrin sealants)] or at decreasing the need for homologous transfusion (e.g., acute hemodilution, planned autologous ransfusion, cell-saving systems, erythropoietin).
Controlled hypotension has been used with success in orthopedic surgery. It is applied widely in spine surgery, and several studies have demonstrated it to be useful in spine surgery (3–6). Agents that are used alone to induce controlled hypotension include inhalation anesthetics, sodium nitroprusside, nitroglycerin, trimethaphan, alprostadil (prostaglandin E1), adenosine, remifentanil, and agents that are used in spinal anaesthesia. Agents that can be used alone or as adjuvants include calcium channel antagonists (e.g., nicardipine), beta-adrenoceptor antagonists (e.g., propranolol, esmolol), and fenoldopam. Agents that are primarily used adjunctively include angiotensin converting enzyme (ACE) inhibitors and clonidine. The preferred technique is a combination of remifentanil with propofol or an inhalation agent (isoflurane, desflurane, or sevoflurane) (7–11). Alpha-2 adrenergic agonists (clonidine and dexmedetomidine) have been used successfully as adjuvants, oral premedication, and intravenous infusion during anesthesia to induce controlled hypotension (12–20). Clonidine is an alpha-2 adrenergic agonist, which has been used as a centrally acting antihypertensive drug. Recent studies have demonstrated it to have sedative, anxiolytic (21), analgesic, and anesthetic-sparing (it reduces the dose of anesthetic and analgesics used intra- and postoperatively) effects, and it stabilizes the circulatory system and reduces perioperative stress response (22–24).
In this study, we used clonidine as oral premedication and as an adjuvant to remifentanil to induce controlled hypotension during posterior fusion of the lumbar spine and compared its effects in reducing intraoperative bleeding with remifentanil alone.
3. Patients and Methods
Thirty patients were studied in 2 groups: clonidine (n = 15) and control (n = 15).
There was no statistically significant difference between groups with regard to age, sex, or ASA physical status (
The clonidine group had significantly less intraoperative blood loss (422.3 ± 139 mL;
Surgeon satisfaction for a bloodless field was good in 14 (93.3%) of patients in the clonidine group compared to 10 (66.7%) patients in the control group, but the difference was not statistically significant (
There was no episode of severe bradycardia that caused hemodynamic instability or was not reversible with atropine in either group.
There was no need for nitroglycerin to maintain controlled hypotension in either group.
Blood sparing in spine surgery is important, but its techniques have been understudied compared to other orthopedic and surgical fields, with the current practice based more on beliefs than evidence (2).
Controlled hypotension is among the most widely used techniques for reducing blood loss in various types of surgery, and remifentanil has been used successfully to induce controlled hypotension and reduce intraoperative blood loss in various types of surgery, including spine surgery (8–11). In our study, oral clonidine premedication as an adjunct to remifentanil resulted in significantly less blood loss during posterior spine fusion. Clonidine reduced intraoperative blood loss at the same levels of blood pressure as the control group, as the remifentanil dose was adjusted in both groups to the same target MAP of 60 to 70 mmHg. This finding is similar to results by Okuyama
The exact mechanism by which controlled hypotension decreases blood loss is still unclear. Some authors have hypothesized that hypotensive anesthesia gives rise to an ischemic wound, which then causes less blood loss. But few studies have attempted to measure blood flow through scientific measures, such as flowmetry (2). Lee
Factors other than blood pressure, postulated to affect intra-operative blood loss include intra-abdominal pressure (related to prone positioning), the number of spinal segments being operated on, body weight, the pathological entity of the disease necessitating surgery (spine surgery due to tumoral lesions is associated with more bleeding), and surgeon’s experience (32). In our study, all patients were operated due to traumatic fractures of the spine on 3 to 4 spinal segment levels and by the same surgical team. There was no significant difference in weight between the two groups, and all patients were positioned in the same way and by the same team. Thus, the effects of the above mentioned factors have been negated.
Our study shows that clonidine, as oral premedication at a dose of 3 μg/kg, is effective in reducing intraoperative blood loss in posterior spinal fusion. It is probably effective in more complicated spine surgeries, such as scoliosis surgery. Also, its effect in reducing blood loss appears to be in part independent of its hypotensive effects. Thus, it is possible that it has the same effect at higher blood pressure, which can obviate the need for hypotensive anesthesia.
We would like to acknowledge our patients who shared their experience and volunteered to participate in this study. We would also like to acknowledge the help of Mrs S. Zamani in collecting the data.
- Financial Disclosure: There is no finacial disclosure.
- Funding/Support: The study was supported by departmental resources.
- Please cite this paper as: Taghipour Anvari Z, Afshar-Fereydouniyan N, Imani F, Sakhaei M, Alijani B, Mohseni M. Effect of Clonidine Premedication on Blood Loss in Spine Surgery. Anesth Pain. 2012;1(4):252-6. DOI: 10.5812/AAPM.2197
- 1. Cole JW, Murray DJ, Snider RJ, Bassett GS, Bridwell KH, Lenke LG. Aprotinin reduces blood loss during spinal surgery in children. Spine (Phila Pa 1976). 2003;28(21):2482-5.
- 2. Szpalski M, Gunzburg R, Sztern B. An overview of blood-sparing techniques used in spine surgery during the perioperative period. Eur Spine J. 2004;13(Suppl 1):S18-27.
- 3. Grundy BL, Nash CL, Brown RH. Deliberate hypotension for spinal fusion: prospective randomized study with evoked potential monitoring. Can Anaesth Soc J. 1982;29(5):452-62.
- 4. Lee TC, Yang LC, Chen HJ. Effect of patient position and hypotensive anesthesia on inferior vena caval pressure. Spine (Phila Pa 1976). 1998;23(8):941-7.
- 5. Ullrich PF, Keene JS, Hogan KJ, Roecker EB. Results of hypotensive anesthesia in operative treatment of thoracolumbar fractures. J Spinal Disord. 1990;3(4):329-33.
- 6. Degoute CS. Controlled hypotension: a guide to drug choice. Drugs. 2007;67(7):1053-76.
- 7. Imani F, Jafarian A, Hassani V, Khan ZH. Propofol-alfentanil vs propofol-remifentanil for posterior spinal fusion including wake-up test. Br J Anaesth. 2006;96(5):583-6.
- 8. Okuyama K, Inomata S, Toyooka H. The effects of prostaglandin E1 or oral clonidine premedication on blood loss during paranasal sinus surgery. Can J Anaesth. 2005;52(5):546-7.
- 9. Park SH, Do SH, Kim CS, Ro YJ, Han SH, Kim JH. Controlling deliberate hypotension in hypertensive patients undergoing spinal surgery: a comparison between remifentanil and sodium nitroprusside. Anesth Pain Med. 2010;5(1):38-44.
- 10. Chillemi S, Sinardi D, Marino A, Mantarro G, Campisi R. The use of remifentanil for bloodless surgical field during vertebral disc resection. Minerva Anestesiol. 2002;68(9):645-9.
- 11. Frank T, Wehner M, Heinke W, Schmadicke I. [Clonidine vs. Midazolam for premedication - comparison of the anxiolytic effect by using the STAI-test]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2002;37(2):89-93.
- 12. Marchal J, Gómez-Luque A, Martos-Crespo F, Sanchez De La Cuesta F, Martínez-López MC, Delgado-Martinez AD. Clonidine decreases intraoperative bleeding in middle ear microsurgery. Acta Anaesthesiol Scand. 2001;45(5):627-33.
- 13. Hajymohammadi F, Farad F, Taheri A, Hoozan B. [Clonidine decreases intra operative bleeding in endoscopic surgery]. Tehran Univ Med J. 2002;60(5):378-82.
- 14. Jabalameli M, Hashemi S, Soltani H, Hashemi S. Oral clonidine premedication decreases intraoperative bleeding in patients undergoing endoscopic sinus surgery. J Res Med Sci. 2005;10(1):25-30.
- 15. Welfringer P, Manel J, Garric J. [Clonidine premedication and isoflurane anesthesia to reduce bleeding in otologic surgery]. Ann Fr Anesth Reanim. 1992;11(2):125-31.
- 16. Lee J, Lovell AT, Parry MG, Glaisyer HR, Bromley LM. I.v. clonidine: does it work as a hypotensive agent with inhalation anaesthesia? Br J Anaesth. 1999;82(4):639-40.
- 17. Durmus M, But AK, Dogan Z, Yucel A, Miman MC, Ersoy MO. Effect of dexmedetomidine on bleeding during tympanoplasty or septorhinoplasty. Eur J Anaesthesiol. 2007;24(5):447-53.
- 18. Ayoglu H, Yapakci O, Ugur MB, Uzun L, Altunkaya H, Ozer Y. Effectiveness of dexmedetomidine in reducing bleeding during septoplasty and tympanoplasty operations. J Clin Anesth. 2008;20(6):437-41.
- 19. Toivonen J, Kaukinen S. Clonidine premedication: a useful adjunct in producing deliberate hypotension. Acta Anaesthesiol Scand. 1990;34(8):653-7.
- 20. Degoute CS, Ray MJ, Manchon M, Dubreuil C, Banssillon V. Remifentanil and controlled hypotension; comparison with nitroprusside or esmolol during tympanoplasty. Can J Anaesth. 2001;48(1):20-7.
- 21. Striebel HW, Koenigs D, Heil T. [The role of clonidine in anesthesia]. Anaesthesist. 1993;42(3):131-41.
- 22. Fidzianska-Dlugosz E. [Use of clonidine for perioperative therapy]. Przegl Lek. 1998;55(5):284-7.
- 23. Morin AM, Geldner G, Schwarz U, Kahl M, Adams HA, Wulf H. Factors influencing preoperative stress response in coronary artery bypass graft patients. BMC Anesthesiol. 2004;4(1):7.
- 24. Lee TC, Buerkle H, Wang CJ, Liang CL, Lu K, Huang PL. Effect of isoflurane versus nicardipine on blood flow of lumbar paraspinal muscles during controlled hypotension for spinal surgery. Spine (Phila Pa 1976). 2001;26(1):105-9.
- 25. Sivarajan M, Amory DW, Everett GB, Buffington C. Blood pressure, not cardiac output, determines blood loss during induced hypotension. Anesth Analg. 1980;59(3):203-6.
- 26. Brodsky JW, Dickson JH, Erwin WD, Rossi CD. Hypotensive anesthesia for scoliosis surgery in Jehovah’s Witnesses. Spine (Phila Pa 1976). 1991;16(3):304-6.
- 27. Fornai F, Blandizzi C, del Tacca M. Central alpha-2 adrenoceptors regulate central and peripheral functions. Pharmacol Res. 1990;22(5):541-54.
- 28. Tanaka M, Nishikawa T. Effects of clonidine premedication on the pressor response to alpha-adrenergic agonists. Br J Anaesth. 1995;75(5):593-7.
- 29. Nishikawa T, Kimura T, Taguchi N, Dohi S. Oral clonidine preanesthetic medication augments the pressor responses to intravenous ephedrine in awake or anesthetized patients. Anesthesiology. 1991;74(4):705-10.
- 30. Tanaka M, Nishikawa T. Enhancement of pressor response to ephedrine following clonidine medication. Anaesthesia. 1996;51(2):123-7.
- 31. Talke PO, Lobo EP, Brown R, Richardson CA. Clonidine-induced vasoconstriction in awake volunteers. Anesth Analg. 2001;93(2):271-6.
- 32. Raw DA, Beattie JK, Hunter JM. Anaesthesia for spinal surgery in adults. Br J Anaesth. 2003;91(6):886-904.