European Journal of Cardiovascular Medicine

Induced hypotension is an anaesthetic technique intended to reduce surgical blood loss and aid visibility in the surgical field. Surgical patients under general anaesthesia have many potential sources of hypotension, including volatile anaesthetic, narcotics, and analgesics, such as opioids. Surgical bleeding and shifts in intravenous fluid resulting in third spacing also lead to intraoperative hypotension. One of the anaesthesiologists’ roles is to maintain proper induced hypotensive care under the guidance of haemodynamic parameters. Severe blood pressure fluctuations can lead to catastrophic complications, such as cardiac arrest, neurological deficit, myocardial ischemia or infarct, acute kidney injury, and unilateral or complete visual loss, particularly during spine surgeries in the prone position [1,2]. Due to the fatal complications of intraoperative hypotension, various monitors are used to avoid excessive fluctuations in vital signs.

Dexmedetomidine is a potent, highly selective α2-adrenoceptor agonist that may provide anti-sympathetic analgesia and sedation without respiratory depression [3], and it has been successfully used for controlled hypotension in other surgical procedures [4].

Clonidine is also a selective α-2 adrenergic agonist with some α-1 agonist properties and acts by decreasing the sympathetic nervous system output from the central nervous system. Various studies have found that preoperative administration of clonidine decreases mucosal bleeding, which improves surgical field visibility and reduces the duration of surgery. [5, 6, 7]

Dexmedetomidine and clonidine both have been used for blunting of haemodynamic response to laryngoscopy and tracheal intubation. [8,9] We designed this study to evaluate and compare the efficacy of dexmedetomidine and clonidine for producing controlled hypotension during orthopaedic/spinal surgeries. The primary objective of the study was to assess and compare the hypotensive effectiveness and haemodynamic stability of dexmedetomidine and clonidine in orthopaedic/spinal surgeries by comparing the haemodynamic parameters from the baseline at different time intervals within each group (intragroup) and between both the groups (intergroup). The secondary objectives were to assess and compare the quality of the intraoperative surgical field, emergence time, sedation score, visual analogue scale (VAS) score and time to first rescue analgesic demand in the post-operative period and to compare the proportion of cases with side effects.

This study was a prospective observational study was carried out prospectively in Department of Anaesthesiology in a tertiary care hospital after getting approval from ethical committee of institution during period May 2023-June 2024.

Sample size: The sample size was calculated to be 32 subjects for each of the two groups at an alpha error of 0.05 (95% confidence) and power of 80% expecting a minimum detectable difference of 4.96 ± 6.9 mmHg in mean arterial pressure in both groups from the baseline, at 15 min after intubation as per earlier studies. Further, the sample size was rounded off to 35 subjects in each group. Thus, a total of 70 patients were selected randomly amongst the patients posted for orthopaedic/spinal surgeries.

Inclusion criteria:

Adult patients of age 18-65 years, ASA grade I-II and weighing between 50 to 80kgposted for orthopaedic/spinal surgeries.

Exclusion criteria:

Contraindication to fluid challenge, defined as evidence of blood volume overload and/ or hydrostatic pulmonary edema prior to procedure, Active substance abuse (alcohol /tobacco products) and severe depression on medications, Patients with implantable cardiac pacemaker, defibrillator or dysrhythmia, Severe Heart Failure, MI > 30 Kg/m2.Allergy to drugs.

Procedure: Group A received dexmedetomidine 1 μg/kg in 10 ml of saline over 10 min followed by 1 μg/kg/h infusion. Group B received clonidine 2 μg/kg in 10 ml of saline over 10 min followed by 1 μg/kg/h infusion. The patient's fasting status and informed written consent were confirmed. After taking the patient into the operating room, all standard monitors were attached and an 18-G intravenous catheter was inserted. All patients were premedicated with inj. midazolam 0.02 mg/kg, inj. glycopyrrolate 4 μg/kg and inj. fentanyl 2 μg/kg intravenously and pre-oxygenated with 100% oxygen. Anaesthesia was induced with inj. thiopentone sodium 5 mg/kg and inj. succinylcholine 1.5 mg/kg and maintained on oxygen-nitrous oxide (40:60), isoflurane (0.4%–1%) and intermittent boluses of atracurium. Loading dose of study drug was given 10 min before induction of general anaesthesia (GA), and its maintenance dose infusion was started soon after induction of anaesthesia and continued intraoperatively until 5 min before the completion of surgery or stopped on the occurrence of hypotension below our target, whichever was earlier. Intraoperative haemodynamic parameters such as heart rate (HR), systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP) and oxygen saturation (SpO2) were recorded at baseline, after the loading dose, after induction, 1 min after intubation, 5 min after intubation and thereafter every 10 min until shifting of the patient to the recovery area. The surgical site was observed for the severity of bleeding and the need for frequent suctioning by using the average category scale proposed by Fromme and Boezaart.[10, 11] [score 0 = no bleeding; score 1 = slight bleeding, no suctioning of blood required; score 2 = slight bleeding, occasional suctioning required, surgical field not threatened; score 3 = slight bleeding, frequent suctioning required, bleeding threatens surgical field a few seconds after suction is removed; score 4 = moderate bleeding, frequent suctioning required, bleeding threatens surgical field directly after suction is removed; score 5 = severe bleeding, constant suctioning required, bleeding appears faster than can be removed by suction, surgical field severely threatened and surgery suspended]. Blood loss estimation was done by measuring suction canister volume minus irrigation fluid used in surgery. The number of small gauges soaked in blood was also counted and estimated accordingly. Patients were reversed with inj. neostigmine 0.05 mg/kg and inj. glycopyrrolate 0.01 mg/kg intravenously. Extubation was done when the patient was responding to verbal commands. Emergence time was defined as the time interval between discontinuation of anaesthetics to the response of eye opening to verbal commands. Post-operatively, patients were kept in the recovery room, monitored for 30 min and later shifted to the post-operative wards. Post-operative haemodynamic parameters, emergence time and sedation score were recorded every 30 min. Sedation was assessed by using Ramsay Sedation Score.[12] post-operative pain was assessed by VAS score every 15 min until the patient reached a VAS score of 3. Time to first rescue analgesia was noted and patients were allowed to receive intravenous diclofenac 75 mg as rescue analgesia. This was the endpoint of our study. Post-operative complications such as nausea, vomiting, shivering, dryness of mouth, hypotension and bradycardia were also recorded.

Hypotension was defined as MAP <65 mmHg and was treated by stopping hypotensive agent and giving fluid bolus and inj. me phentermine 6 mg bolus as per need. Bradycardia was defined as HR <50/min and treated with intravenous atropine 0.6 mg if not resolved by stopping study drug infusion. Inj. ondansetron 0.1 mg/kg was given to treat post-operative nausea/vomiting.

Statistics: SPSS 21, Microsoft Excel were used and unpaired student’s t test, chi square tests etc were applied. P < 0.05 was considered statistically significant.

Demographic data were statistically comparable in both groups [Table 1]. We observed that both HR and MAP were significantly decreased (P = 0.001) at all observation time points after giving a loading dose of study drugs in comparison to baseline in both the groups. The reduction in HR and MAP was more in group A as compared to group B, and the difference was statistically significant (P = 0.001) [Tables2 and 3]. The average category score for surgical field visibility ranged between 1 and 3 in group A and between 2 and 3 in group B. The difference in average category scale was statistically insignificant and surgical field visibility was comparable in both groups. Mean estimated blood loss was statistically comparable in both groups A and B (124.14 ± 6.45 ml vs 128.71 ± 6.75 ml) (P = 0.429). The mean emergence time was statistically significantly longer in group A (7.26 ± 0.60 min) in comparison to group B (6.52 ± 0.74 min) (P = 0.001). Mean sedation scores were statistically significantly higher in group A as compared to group B at all the time intervals post-operatively (P = 0.001) [Figure 1]. Although the sedation that occurred in group A was more than that in group B, the depth of sedation was such that it could be termed as conscious sedation (appeared to be asleep but readily arousable). The mean VAS score in group A was lower at different time intervals in comparison to group B [Figure 2]. Time to first rescue analgesia was significantly longer in group A (110.33 ± 11.27 min) as compared to group B (85.29 ± 10.08 min) (P = 0.001). Post-operative complications were statistically comparable between the two groups. The main side effect in group A was dry mouth (4/35 = 11.42% vs 1/35 = 2.85% in group B) while nausea and vomiting occurred more in group B (4/35 = 11.42% vs 1/35 = 2.85% in group A). Hypotension and bradycardia occurred in 3 (8.57%) patients in group A and in 2 (5.71%) patients in group B but reverted spontaneously after stopping infusion of study drug and giving fluids. None of the patients had severe adverse effects.

TABLE 1 showing distribution of patients.

TABLE 2 showing comparison of mean heart beats/min

TABLE 3 showing comparison of mean arterial pressure.

Figure 1: Mean sedation score

Figure 2: Mean VAS score

Induced hypotension is often needed to reduce bleeding in surgeries like orthopaedic/spinal surgeries. Dexmedetomidine causes a reduction in blood pressure, slowing of HR, sedation and analgesia. The fall in blood pressure is mainly due to inhibition of central sympathetic outflow and due to stimulation of presynaptic α-2 adrenoceptors decreasing norepinephrine release.[13] Dexmedetomidine has a very minimal respiratory depressant effect with potent sedative and analgesic effects compared with opioids and other sedatives. Controlled hypotension has a definitive role in orthopaedic/spinal surgeries as it reduces bleeding during surgery and improves visibility of the surgical field, which can decrease the duration of surgery and anaesthesia. There are not many studies comparing clonidine with dexmedetomidine in orthopaedic/spinal surgeries. Moreover, we used continuous infusion of dexmedetomidine or clonidine while previous studies used bolus doses. In the present study, we compared these two drugs in terms of haemodynamic parameters, mean average category scale, mean emergence time, mean sedation score, time to first rescue analgesic demand and adverse effects. We found that though induced hypotension was achieved with both the drugs, dexmedetomidine produced more stable haemodynamic with lower readings of MAP and HR along with more prolonged post-operative analgesia and conscious sedation in comparison to clonidine. Our results are similar to the study done by Suggala et al.[12], who compared dexmedetomidine and clonidine for controlled hypotension and concluded that dexmedetomidine provided more effective controlled hypotension and analgesia and thus allowed less nasal bleeding as well as comparable surgical field visibility. They also noted that the time to first rescue analgesic request was significantly prolonged in the dexmedetomidine group along with higher sedation scores as compared to clonidine.

In another study, Chhabra A, et al. [14] compared dexmedetomidine and magnesium sulphate for induced hypotension during FESS and found that haemodynamic were superior in the dexmedetomidine group. They also observed good post-operative analgesia and sedation. It produces analgesic effects by acting at α-2 receptors within the locus coeruleus and spinal cord. Dexmedetomidine also has the unique property of providing conscious sedation.[15]

We found that both the drugs have improved and comparable surgical field quality. These results were in line with those of the study done by Escamilla et al. [16] who, when comparing the efficacy of clonidine and dexmedetomidine to improve the quality of the surgical field by hypotensive anaesthesia in FESS, found no significant differences between clonidine and dexmedetomidine in the quality of surgical field. Soliman R, et al. [17] compared dexmedetomidine and magnesium sulphate and found that better operating condition was provided by dexmedetomidine but with more hypotension and bradycardia like our study. Kim et al.,[18] in a meta-analysis of randomised controlled trials comparing the perioperative administration of hypotensive agents, found dexmedetomidine to be a superior agent. They also concluded that systemic use of dexmedetomidine reduces intraoperative bleeding and operating time, provides relatively stable haemodynamic by alleviating stress response and reduces the fentanyl requirement significantly. Moshiri et al. [19] compared dexmedetomidine with propofol and found that the desired surgical field is made possible by reducing HR rather than vasoconstriction. In our study, the HR was comparatively lower and less fluctuating in the dexmedetomidine group, which is in favour of more stable haemodynamic and blunting of response to sympathomimetic stimuli by dexmedetomidine.

The limitation of our study is that we did not use a control group because it would have been unethical not to try to control bleeding in orthopaedic/spinal surgeries where surgical field visibility may be compromised due to bleeding. Invasive monitoring of blood pressure can also be done in hypotensive anaesthesia, but a recent retrospective study done by Lee et al. [20] concluded that it does not aid in achieving lower target blood pressures.

We conclude that both dexmedetomidine and clonidine can be used for controlled hypotension to improve surgical field quality in Orthopaedic/spinal surgeries. Dexmedetomidine provides more haemodynamic stability and an additional benefit of post-operative analgesia and conscious sedation

1. Dutton R.P. Controlled hypotension for spinal surgery. Eur. Spine J. 2004;13((Suppl. S1)):S66–S71.
2. Lehman L.W., Saeed M., Moody G., Mark R. Hypotension as a Risk Factor for Acute Kidney Injury in ICU Patients. Comput. Cardiol. 2010;37:1095–1098.
3. Chrysostomou C, Schmitt CG. Dexmedetomidine: sedation, analgesia and beyond. Expert Opin Drug MetabToxicol. 2008;4(5):619–627.
4. Snidvongs K, Tingthanathikul W, Aeumjaturapat S, Chusakul S. Dexmedetomidine improves the quality of the operative field for functional endoscopic sinus surgery: systematic review. J Laryngol Otol. 2015;129(Suppl 3):S8–13.
5. Jiwanmall M, Joselyn AS, Kandasamy S. Intravenous clonidine as a part of balanced anaesthesia for controlled hypotension in functional endoscopic sinus surgery: A randomisedcontroled trial. Indian J Anaesth. 2017;61:418–23.
6. Ramchandani S, Lakra AM, Shah PJ, Lalwani J, Sahare KK. Effect of intravenous clonidine premedication for the bloodless surgical field in patients undergoing middle ear or nasal surgery: A comparison of three different doses. Anesth Essays Res. 2015;9:397–400.
7. Bajwa SJ, Kaur J, Kulshrestha A, Haldar R, Sethi R, Singh A. Nitroglycerine, esmolol and dexmedetomidine for induced hypotension during functional endoscopic sinus surgery: A comparative evaluation. J Anaesthesiol Clin Pharmacol. 2016;32:192–7.
8. Kumar NR, Jonnavithula N, Padhy S, Sanapala V, Naik VV. Evaluation of nebulised dexmedetomidine in blunting haemodynamic response to intubation: A prospective randomised study. Indian J Anaesth. 2020;64:874–9.
9. Choudhary S, Sharma S, Kumari I, Kalluraya S, Meena K, Dave T. Comparative evaluation of oral melatonin and oral clonidine for the attenuation of haemodynamic response to laryngoscopy and tracheal intubation–A prospective randomiseddouble blind study. Indian J Anaesth. 2020;64:696–703.
10. Fromme GA, MacKenzie RA, Gould AB, Jr, Lund BA, Offord KP. Controlled hypotension for orthopaedic/spinal AnesthAnalg. 1986;65:683–6.
11. Boezaart AP, van der Merwe J, Coetzee A. Comparison of sodium nitroprusside- and esmolol-induced controlled hypotension for functional endoscopic sinus surgery. Can J Anaesth. 1995;42:373–6.
12. Suggala KK, Kishan Rao B, Nagrale MH. Comparison of dexmedetomidine, with clonidine-based anaesthesia for controlled hypotension in functional endoscopic sinus surgery. J Evid Based Med Healthc. 2020;7:782–6.
13. Giovannitti JA, Jr, Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists: A review of current clinical applications. Anesth Prog. 2015;62:31–9.
14. Chhabra A, Saini P, Sharma K, Chaudhary N, Singh A, Gupta S. Controlled hypotension for FESS: A randomised double-blinded comparison of magnesium sulphate and dexmedetomidine. Indian J Anaesth. 2020;64:24–30.
15. Guven DG, Demiraran Y, Sezen G, Kepek O, Iskender A. Evaluation of outcomes in patients given dexmedetomidine in functional endoscopic sinus surgery. Ann OtolRhinolLaryngol. 2011;120:586–92.
16. Escamilla Y, Cardesín A, Samara L, López S, Izquierdo A, Fradera M, et al. Randomized clinical trial to compare the efficacy to improve the quality of surgical field of hypotensive anesthesia with clonidine or dexmedetomidine during functional endoscopic sinus surgery. Eur Arch Otorhinolaryngol. 2019;276:3095–104.
17. Soliman R, Fouad E. The effects of dexmedetomidine and magnesium sulphate in adult patients undergoing endoscopic transnasal transsphenoidal resection of pituitary adenoma: A double-blind randomised study. Indian J Anaesth. 2017;61:410–7.
18. Kim DH, Lee J, Kim SW, Hwang SH. The efficacy of hypotensive agents on intraoperative bleeding and recovery following general anesthesia for nasal surgery: A network meta-analysis. Clin Exp Otorhinolaryngol. 2021;14:200–9.
19. Moshiri E, Modir H, Yazdi B, Susanabadi A, Salehjafari N. Comparison of the effects of propofol and dexmedetomidine on controlled hypotension and bleeding during endoscopic sinus surgery. Ann Trop Med Public Health. 2017;10:721–5.
20. Lee YL, Thangavelautham S, Harikrishnan S, Karthekeyan R, Kothandan H. Is hypotensive anaesthesia guided by invasive intraarterial monitoring required for orthopaedic/spinal – A retrospective review of anaesthetic practice and intraoperative blood loss in orthopaedic/spinal  surgery in a tertiary hospital? Indian J Anaesth. 2021;65:525–32.