Effectiveness of Low Dose Dexmedetomidine for an Oligaemic Field in Middle Ear Surgery: A Randomised Control Trial
Correspondence Address :
Dr. Smriti Sinha,
312, Dahlia Block, Aashiyana Garden, Sonari, Jamshedpur, Jharkhand, India.
E-mail: firstname.lastname@example.org; email@example.com
Introduction: Microscopic middle ear surgeries are best done under hypotensive anaesthesia to provide an oligaemic field. Dexmedetomidine is an α2 agonist which produces hypotension by sympathetic response blockade.
Aim: To study the effectiveness of low dose dexmedetomidine in providing an oligaemic field. The additional requirement of inhalational agent required to maintain the oligaemic field in the control group, intubation response and postoperative analgesia were also assessed.
Materials and Methods: The randomised, placebo-controlled double-blind study was conducted by recruiting 48 patients in the study, who were divided into two groups i.e, study group (n=24) and placebo group (n=24). The study group received low dose dexmedetomidine infusion (0.5 μg/kg loading dose followed by 0.2 μg/kg/hr) and placebo group received weight-adjusted saline. The quality of the surgical field was assessed on a score of 0-5. The Minimum Alveolar Concentration (MAC) of inhalational agent needed, postoperative sedation score and pain score were noted. All the data were recorded in Statistical Package for Social Sciences (SPSS) software, version 22.0.
Results: The mean score of quality of the surgical field in the study group was 2.00±0.59, compared to 3.50±0.88 in the placebo group. The mean MAC of isoflurane was 1.32±0.31 in the placebo group and 0.85±0.23 in the study group (p-value=0.03). The study group had a Ramsay sedation score of 3.08±0.65 compared to 2.29±0.75 in the placebo group at 5 minutes after extubation (p-value <0.001). The mean pain score in the dexmedetomidine group in 10 minutes postoperative period was 1.83±2.25, while in placebo group it was 3.25±1.96 (p-value=0.025). However, over the next 20-60 minutes postoperative period the pain score between the two groups were comparable, with no significant difference in analgesia, postoperative shivering and other side-effects.
Conclusion: A low dose dexmedetomidine can effectively provide a bloodless field for middle ear microsurgical procedures.
Bloodless surgical field, Controlled hypotension, Hypotensive anaesthesia
The middle ear microsurgeries need a bloodless surgical field, attention to patient’s head positioning, airway management, facial nerve monitoring, avoidance of nitrous oxide, smooth and calm recovery, and prevention of postoperative nausea and vomiting (1). The bloodless surgical field is preferred for safe tympanic membrane and ossicular reconstruction as blood can obscure the surgical field. Various methods are employed including reverse Trendelenburg position, local infiltration with vasoconstrictors and pharmacological agents to provide controlled hypotension. Controlled hypotension is a method by which arterial blood pressure is decreased predictably and deliberately to decrease blood loss. The level of hypotension is determined by achieving a bloodless field within the safety limits of cerebral and coronary flow. This safety limit is not fixed and generally taken as Mean Arterial Pressure (MAP) as low as 50 mmHg or a 30% drop in MAP in American Society of Anaesthesiologists (ASA) physical status I subject (2). The safety limit of a chronic hypertensive patient will be different and they may not tolerate a drop of more than 25 % of the MAP, due to the shift of cerebral auto regulation limit towards higher blood pressure (2).
Dexmedetomidine is a centrally acting α 2A agonist. It acts by presynaptic activation of α-2 adrenoceptors, thus inhibiting the release of norepinephrine, terminating the propagation of pain signals and postsynaptic activation of α-2 adrenoceptors in the Central Nervous System (CNS), thus inhibiting sympathetic activity. Dexmedetomidine evokes a biphasic blood pressure response. At lower doses, the dominant action of dexmedetomidine is sympatholytic mediated by α-2A adrenergic receptor, and thus is used to provide controlled hypotension by decreasing blood pressure and heart rate, these actions have been put to use, as an infusion, for providing ideal condition for middle ear microsurgical procedure (3).
Under general anaesthesia, dexmedetomidine is commonly used to attenuate sympathoadrenal response, to provide analgesia by reducing the requirement of intraoperative and postoperative opioid requirement, emergence agitation prevention and reducing postoperative shivering (4). The doses used varies from 1 μg/kg to 0.5 μg/kg loading dose with the maintenance of 0.75-0.4 μg/kg/hr (3),(4).
The sympatholytic effect of dexmedetomidine in adults was studied in previous research using dose of 1 μg/kg loading dose followed by 0.4-0.6 μg/kg/hr (5),(6),(7),(8). The adverse effects of dexmedetomidine are hypotension, hypertension, nausea, hypoxia, bradycardia, first and second-degree atrioventricular block as well as atrial fibrillation at higher doses (9). In an attempt to avoid adverse effects of higher doses, in the current study, dexmedetomidine was used at a low dose of 0.5 μg/kg intravenously over 10 minutes as a bolus dose and then infusion at the rate of 0.2 μg/kg/hr. The primary objective was to assess the effectiveness of test drug in lower doses to provide a bloodless field for middle ear microsurgical procedure. The secondary objectives were to assess haemodynamic response to laryngoscopy and intubation, the stress response of surgery by assessing heart rate and MAP and observe any other adverse effects postoperatively.
The randomised, placebo-controlled double-blinded study was conducted at the Bangalore Baptist Hospital, Bengaluru, Karnataka, India, from January 2013 to December 2013. The approval from Institutional Ethics Committee was taken (BBH/IRB/2012/019). The patients were explained about the procedure and informed consent was taken to include in the study.
Inclusion criteria: The patients scheduled for elective, middle ear surgeries under general anaesthesia in the age group of 16-55 years in American Society of Anesthesiologists (ASA) grade I and II were included in the study if they consented to it.
Exclusion criteria: Pregnant, lactating mothers, patients with renal impairment, hepatic dysfunction, history of allergic drug reactions and on antihypertensive medication with α-2 agonists, α methyldopa were excluded from the study. Patients in whom dexmedetomidine infusion was discontinued due to haemodynamic derangements during the study were also excluded from the study.
Sample size calculation: Based on a pilot study, the surgical field scoring (primary objective) was expected to lower by 30% in patients who received dexmedetomidine compared to the placebo group. The sample size was calculated as 48 (24 patients per group) with 80% power and a significance level of 0.05. The sample size was calculated by the application online “Sample size calculator” (10).
• Study group (n=24): Dexmedetomidine 0.5 μg/kg intravenously over 10 minutes as a bolus dose, and then infused at the rate of 0.2 μg/kg/hr (100 μg/50 mL syringe -2 μg/mL, diluted with normal saline) till the end of the surgery.
• Placebo group (n=24): Received weight-adjusted normal saline at the same volume (ml) and rate (ml/hr) as in study group (Table/Fig 1).
Allocation process: Patients were randomised by using the block randomisation process, with each size block of 4, to get equal numbers in both study as well as the placebo group. With a block size of 4, there were six possible ways to equally assign participants to a block. Allocation concealment included sequentially structured alphabets of 4 kept in a sealed opaque envelope. The patient and the investigator involved both were blinded. The infusion was prepared by an anaesthesiologist, not involved in the study.
Preoperative assessment was done for all the patients and nil per orally for 6 hours before surgery followed. All patients were pre-medicated with oral alprazolam 0.5 mg at night one day prior and in the morning of the surgery for anxiolysis. The monitors including non-invasive blood pressure monitor, pulse oxymeter, capnography and integrated anaesthetic gas analyser (Aspire 7900 with Philips IntelliVue MP40) were used intraoperatively to monitor Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP), Heart Rate (HR), oxygen saturation (SpO2), end-tidal CO2, and Minimum Alveolar Concentration (MAC) throughout the surgery. Two intravenous accesses were secured, one for fluid and the other one dedicated to study drugs. All the patients were pre oxygenated and premedication with glycopyrrolate 0.2 mg intravenously (i.v.) in the operation theatre. The induction of anaesthesia was done with a graded dose of propofol up to 2 mg/kg, fentanyl 2 μg/kg and atracurium 0.5 mg/kg i.v., followed by endotracheal intubation. Intraoperative analgesia was provided by morphine 0.1 mg/kg i.v. as a bolus. Maintenance of anaesthesia was with 50% oxygen, 50% air (FiO2 of 0.5) with low flow anaesthesia, 1% isoflurane and intermittent positive pressure ventilation. The target of induced hypotension was a 30% reduction of MAP from baseline, which was intraoperative done by titrating inhalational agents to the desired effect. Controlled hypotension was provided in all the patients and MAC of isoflurane needed was also noted. Intravenous atracurium 0.1 mg/kg was used for maintenance.
Surgical field: Quality of the surgical field was assessed at the end of the surgery by asking the operating surgeon to score on a scale of 0-5, where ‘0’ meant no bleeding, and ‘5’ stood for severe bleeding which needed continuous suctioning . The desired level was to achieve ≤2 (11).
Sedation score: The sedation score was assessed by Ramsay sedation score recorded preoperatively, after the bolus infusion, before induction and at 30 min postoperatively (12).
Any hypertension and tachycardia more than 20% from preoperative value with MAC level of 1 was considered as inadequate analgesia and i.v. fentanyl 1 μg/kg was given.
• Hypotension (MAP <60 mmHg) was treated with intravenous fluids and IV ephedrine 6 mg.
• Severe bradycardia (HR<40/min) was treated by atropine 0.6 mg IV. At the end of the surgery, ondansetron 0.1 mg/kg IV was administered to all patients, residual neuromuscular block was reversed with neostigmine 0.05 mg/kg and glycopyrrolate 0.01 mg/kg IV.
Postoperative period: During the postoperative period nausea, vomiting, respiratory depression, shivering, Visual pain analogue (VAS) scores (0=no pain, 10=worst pain), sedation (Ramsay sedation score) and vitals were recorded.
Recovery: The recovery of all the patients was assessed by Aldrete’s score and shifting from the postoperative ward was done after achieving satisfactory recovery (13).
All the data were recorded in Statistical Package for Social Sciences (SPSS) software (version 22.0). The primary objective, quality of the surgical field was compared by the Mann-Whitney U test. Results on continuous measurements like vitals were presented as Mean±SD (Minimum-Maximum), and an independent student t-test was used to compare between the groups. Significance was assessed at a 5 % level of significance.
The basic characteristics including, age, gender, weight and ASA grade were comparable between the two groups (Table/Fig 2).
The quality of the surgical field was better in the study group (Table/Fig 3). The mean MAC of isoflurane was 1.32±0.31 in the placebo group and 0.85±0.23 in the study group, with p-value of 0.03.
The effect on stress response of intubation assessed by change in HR and MAP at 30 seconds after intubation and the increase in HR was more in placebo group compared to study group. This was statistically significant (p-value <0.001). The MAP in the study group decreased compared to baseline after 30 seconds of intubation while increase in MAP was noted in placebo group. From 30 seconds postintubation to postoperative period, there was a significant difference between the two groups in HR and MAP (Table/Fig 4), (Table/Fig 5).
The SpO2 and EtCO2 did not show significant changes except at 45 minutes and 15 minutes, respectively. The baseline SpO2 was lesser in the study group but not clinically significant (Table/Fig 6).
The Ramsay sedation score was higher in the study group after 10 minutes of bolus dose and immediately postextubation postoperatively (p-value <0.001). After 30 minutes postextubation sedation scores were comparable in both the groups. All the patients in the study group were arousable, comfortable and maintained normal oxygen saturation on room air in Post Anaesthesia Care Unit (PACU) (Table/Fig 7).
The mean VAS pain score was lower in the study group in the immediate postoperative period. However, over the next 20-60 min postoperative period the pain score between the two groups were comparable.
The hypotension and bradycardia were not found in any patient throughout the study, while the incidence of shivering and postoperative nausea and vomiting (PONV) were similar in both groups (Table/Fig 8).
The present study was designed to study the effect of low dose dexmedetomidine in middle ear surgeries, which was found to provide an oligaemic surgical field without clinically significant adverse effects of higher doses. The blunting of intubation response and prolongation of postoperative analgesia was not found with low doses of dexmedetomidine.
Controlled hypotension and oligaemic surgical field: In current study, oligaemic surgical field could be achieved with 0.5 μg/kg loading dose followed by 0.2 μg/kg/hr of dexmedetomidine in middle ear surgery. In children for cochlear implant surgery and nasal surgery, to optimize the surgical field, dexmedetomidine was used in low doses of 0.5 μg/kg followed by 0.2-0.5 μg/kg/hr. Out of 35 patients, 33 patients had bleeding score ≤ 2 in cochlear surgery (14). For nasal surgery in pediatric patients, 97% of patients attained an intraoperative surgical field score of ≤ 2 (15). In another study, a loading dose of 1 μg/kg of dexmedetomidine followed by 0.4-0.8 μg/kg/hr helped in achieving intraoperative surgical field score of ≤2 in Functional Endoscopic Sinus Surgery (FESS) surgery (16). A randomised control trial, conducted with dexmedetomidine with loading dose of 1 μg/kg followed by 0.4-0.8 μg/kg/hr for endoscopic surgery, concluded similar findings of lower Besant’s scale score of intraoperative blood loss (17). Another study by Durums M et al., using dexmedetomidine 1 μg/kg for 10 minutes followed by 0.5 μg/kg/hr, in tympanoplasty surgeries found significantly low blood loss in patients who received dexmedetomidine compared to placebo (5). Other than ENT surgeries, research was done on scoliosis patients where dexmedetomidine was used in a dose of 1 μg/kg followed by 0.2-0.5 μg/kg/hr for spine deformity correction surgery. They concluded that the blood loss was significantly low (18). In the current study, low dose of dexmedetomidine as bolus and maintenance was found to be effective in achieving oligaemic surgical field.
Nasreen F et al., conducted a study in middle ear surgery, intending to maintain a 30% reduction in MAP, comparing dexmedetomidine 1 μg/kg for 10 minutes followed by 0.4 μg/kg/hr with placebo, concluded lower percentage of halothane use in dexmedetomidine group (6). Gupta K et al., also conducted a study in patients requiring middle ear surgery with the goal of a 30% reduction in MAP for the oligaemic surgical field. They used dexmedetomidine in a dose of 0.5 μg/kg/hr, which was started after induction of anesthesia and used isoflurane as an inhalational agent (7). The mean dose of isoflurane in the placebo group was 1.6%, while, in the dexmedetomidine group mean was 0.8%. The use of an inhalational agent to produce controlled hypotension is standard practice, but the anticipated effect to decrease blood loss is controversial as the vasodilation produced by higher doses of inhalational agents can increase the blood loss (19). At a higher concentration of inhalational agents, vasodilatation can increase cerebral circulation and in effect lead to increased intracranial pressure. The cerebral auto regulation gets impaired at higher concentrations of isoflurane (20). In the current study, to achieve oligaemic field in the placebo group, higher MAC of the inhalational agent (isoflurane) was needed, which was comparable to the previous study (7).
The low dose dexmedetomidine decreases the requirement of isoflurane and is an effective adjuvant to decrease blood loss in safer doses of isoflurane. More than 1.3 MAC of isoflurane was found to be MAC of burst suppression which will not be required with dexmedetomidine as an adjuvant (21).
Intubation response: Dexmedetomidine is known to prevent intubation response in a dose of 1 μg/kg and 0.75 μg/kg effectively (22),(23). The lower dose of 0.5 μg/kg used in the current study was effective in preventing any change in MAP, while in HR there was an almost 4% increase. The sympathetic response was prevented but complete abolition was not there.
Sedation, postoperative analgesia and side-effects: In the present study, hypotension and bradycardia were not found in any patient. The oxygen saturation and EtCO2 remained well preserved in both the groups, the difference in sedation score was highly significant between the two groups after the bolus infusion and in the immediate postoperative period. The patients in dexmedetomidine were asleep but arousal in the immediate postop period. These findings were in line with a previous study (24).
Intraoperative dexmedetomidine helps in providing postoperative analgesia and decreasing postoperative shivering (25). These effects were found to be more prominent after loading dose of 0.75μg/kg and 1 μg/kg than 0.5 μg/kg (26). In current study, the mean pain score in dexmedetomidine group was low only in the immediate postoperative period. Any prolonged effect was not noted. In the recovery area, the incidence of PONV and shivering were similar in both groups and comparable. The postoperative effects of dexmedetomidine in form of prolonged analgesia and decrease in shivering (two patients in both groups) were not found with low dose in the current study.
The sample population consisted only adult patients who were relatively healthy (ASA physical status grade I and II). It needs to be determined whether the present findings can be generalised to other age group and ASA status as well.
Dexmedetomidine 0.5 μg/kg bolus infusion over 10 minutes before induction followed by 0.2 μg/kg/hr maintenance infusion can be recommended for all patients of ASA status I and II undergoing middle ear microsurgeries for providing controlled hypotension and better surgical field for the Ear, Nose and Throat surgeon. This technique could also be used for patients undergoing any other surgical procedure safely where the operating field has to be clear and to reduce blood loss.
Date of Submission: Oct 20, 2021
Date of Peer Review: Nov 20, 2021
Date of Acceptance: Apr 26, 2022
Date of Publishing: Sep 01, 2022
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA
PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Oct 23, 2021
• Manual Googling: Mar 30, 2022
• iThenticate Software: Jul 07, 2022 (16%)
ETYMOLOGY: Author Origin
- Emerging Sources Citation Index (Web of Science, thomsonreuters)
- Index Copernicus ICV 2017: 134.54
- Academic Search Complete Database
- Directory of Open Access Journals (DOAJ)
- Google Scholar
- HINARI Access to Research in Health Programme
- Indian Science Abstracts (ISA)
- Journal seek Database
- Popline (reproductive health literature)