Dexmedetomidine infusion during middle ear surgery under general anaesthesia to provide oligaemic surgical field: A prospective study.

BACKGROUND AND AIMS: Middle ear surgery requires bloodless surgical field for better operating conditions, deep level of anaesthesia and rapid emergence. Recent studies suggest that α2 agonists could provide desired surgical field, sedation and analgesia. The present study was aimed to evaluate the clinical effects of dexmedetomidine infusion as anaesthetic adjuvant during middle ear surgery using operating microscope.
METHODS: Sixty four adult patients aged 18-58 years, American Society of Anaesthesiologists Grades I and II, of both gender were randomised into two comparable equal groups of 32 patients each for middle ear surgery under general anaesthesia with standard anaesthetic technique. After induction of general anaesthesia, patients of Group I were given dexmedetomidine infusion of 0.5 μg/kg/h and patients of Group II were given placebo infusion of normal saline. Isoflurane concentration was titrated to achieve a systolic blood pressure 30% below the baseline value. All patients were assessed intra-operatively for bleeding at surgical field, haemodynamic changes, awakening time and post-operative recovery.
RESULTS: Statistically significant reduction was observed in the required percentage of isoflurane (0.8 ± 0.6%) to maintain the systolic blood pressure 30% below the baseline values in patients receiving dexmedetomidine infusion when compared to those receiving placebo infusion (1.6 ± 0.7%). Patients receiving dexmedetomidine infusion had statistically significant lesser bleeding at surgical field (P < 0.05). The mean awakening time and recovery from anaesthesia did not show any significant difference between the groups.
CONCLUSION: Dexmedetomidine infusion can be safely used to provide oligaemic surgical field for better visualization using operating microscope for middle ear surgery.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Middle ear surgery under general anaesthesia is revolutionised with the introduction of hypotensive anaesthesia that provides a relatively bloodless field while using an operating microscope. The primary methods to minimise blood loss during middle ear surgery included mild head elevation of 15°, and infiltration or topical application of epinephrine (1: 50,000 or 1: 200,000). Currently, many inhalational or intravenous anaesthesia techniques were evaluated to offer ideal intra-operative conditions for middle ear surgery with their advantages and disadvantages.[1234]

Numerous pharmacological agents effectively lower the systemic blood pressure for hypotensive anaesthesia techniques. Sodium nitroprusside and nitroglycerine precisely control the blood pressure due to their rapid onset and short duration of action, but intra-arterial blood pressure monitoring and electrocardiogram (ECG) with S-T segment analysis are mandatory. An infusion of 10 - 20 μg/kg/h remifentanil is also useful but is associated with side effect of hyperalgesia.

Dexmedetomidine, a potent and selective α2-adrenoceptor agonist, is used as adjuvant to general anaesthesia during surgery at pre-operative state (sedation), intra-operative state (analgesia and hemodynamic stability) and during post-operative period (no respiratory depression). It is valuable because of its anaesthetic and analgesic-sparing effects with predictable and dose-dependent haemodynamic effects.[56]

The present prospective double blind placebo control randomised study was aimed to evaluate the effects of dexmedetomidine infusion on the requirement of isoflurane concentration to lower systolic blood pressure below 30% of baseline values, quality of oligaemic surgical field, and awakening time in patients undergoing middle ear surgery.

METHODS

After approval from institutional Ethical Committee and written informed consent, 64 adult patients of American Society of Anaesthesiologists (ASA) physical status I and II of both genders, aged 18-58 years, weighing 45-65 kg, scheduled for elective middle ear surgery, were enrolled for this prospective double-blind placebo controlled randomised study. Exclusion criteria were presence of cardiac or respiratory disease, hypertension, obesity (body mass index > 26 kg/m2 ), hepatic or renal dysfunction, bleeding or coagulation disorders. Patients with a history of anticipated difficult airway, those on sedatives, hypnotics or antihypertensive medication or allergy to any anaesthetic medications were also excluded from the study. None of the patients had previous experience with general anaesthesia.

Patients were randomly divided into two groups of 32 patients each by computer generated random table number. Patients of Group I received infusion of dexmedetomidine 0.5 μg/kg/h and patients of Group II received placebo infusion of normal saline during middle ear surgery after induction of anaesthesia till 20 min before completion of surgery. The study drug solution was prepared by an anaesthesiologist who was blinded to study protocol and was not involved for intra-operative data collection. The surgeon and resident anaesthetist were also blinded to the treatment regimen.

All patients were admitted prior to the day of the surgery, and fasting of 6 h was ensured. On arrival to the operation theatre, the baseline systemic blood pressure, heart rate, peripheral oxygen saturation (SpO2) and ECG were recorded. After establishing the intravenous line, lactate Ringer solution was started and they were pre-medicated with palonosetron (75 μg), glycopyrrolate (0.2 mg), midazolam (2 mg) and fentanyl (2 μg/kg), 15 min before induction of anaesthesia.

After pre-oxygenation for 3 min, anaesthesia was induced with propofol (2 mg/kg) till loss of verbal command and tracheal intubation was facilitated with vecuronium 0.1 mg/kg. Anaesthesia was maintained with 60% nitrous oxide in oxygen and isoflurane dial concentration was titrated to achieve a systolic blood pressure 30% below the baseline values. Patients were mechanically ventilated to maintain the end-tidal concentration (EtCO2) between 30 and 35 mm Hg.

Intra-operatively, the heart rate, arterial blood pressure, ECG, EtCO2 and peripheral pulse oximetry (SpO2) were monitored and recorded at 5 min intervals till end of surgery. Concentration of isoflurane was recorded in percentage every 15 min till conclusion of surgery. Hypotension was treated by decreasing the dial concentration of isoflurane or rate of infusion and bradycardia was treated with intravenous atropine.

During procedure the bleeding at surgical site was assessed by the surgeon as Grade 0-no bleeding-excellent surgical conditions; Grade I-minimum bleeding, sporadic suction needed; Grade II-diffuse bleeding, repeated suction needed; and Grade III-considerable, troublesome bleeding, and continuous suction was needed.

After surgery, the residual neuromuscular blockade was antagonized with neostigmine (0.05 mg/kg) and glycopyrrolate (0.008 mg/kg). Patients were extubated after observing adequate motor recovery and spontaneous breathing efforts. Awakening time following reversal of neuromuscular blockade was recorded. This duration of awakening time comprised from administration of reversal of neuromuscular blockade till sustained eye opening on command.

Patients were transferred to post-anaesthesia care unit for observation of any respiratory depression, haemodynamic changes, nausea/vomiting or any other drug-induced side-effects or complications.

The sample size was based on previous studies in which 28 patients were required to detect 20% decrease in bleeding in the dexmedetomidine group with type 1 error of 0.01 and power of 90%.[7] Assuming 5% drop out rate, the final sample size was set at 64 patients. The recorded data were tabulated and expressed in mean ± standard deviation. Statistical analysis was performed using Microsoft Excel and Stat graphics Centurion® for windows. The demographic data for categorical variables were compared using Chi-square test and statistical significance in time related variables were analysed using Student's t-test. P < 0.05 was considered as statistically significant.

RESULTS

The present study evaluated the clinical effects of dexmedetomidine infusion during middle ear surgery using operating microscope under general anaesthesia. It was successfully completed on 64 adult consenting patients, and all patients were included in the data analysis. The demographic data of age, sex, weight, ASA physical status and duration of surgery were comparable between the groups [Table 1].

Table 1

Patient demographic characteristics

The baseline values of mean heart rate and systolic blood pressure were comparable between the groups with no statistical significance. Though mean heart rate values were comparable during intra-operative period between the groups but bradycardia (heart rate < 54 beats/min) was observed in two patients of Group I which promptly responded to intravenous atropine. The mean heart rate was found to be higher in patients of Group II after the extubation while patients of Group I did not show much variation in their mean heart rate values [Table 2].

Table 2

Changes in heart rate during anaesthesia

The required percentage of isoflurane concentration was significantly less (P < 0.05) to maintain the mean systolic blood pressure 30% below baseline values in patients of Group I who received intra-operative dexmedetomidine infusion [Table 3].

Table 3

Comparison of mean percentage of isoflurane requirement to reduce systolic blood pressure 30% below control value

The operating microscope was used throughout the middle ear surgery and surgeons observed Grade I bleeding (minimum bleeding with sporadic suction) at surgical site in majority of patients of Group I and none of the patients had bleeding of Grade III [Table 4]. None of the patients of Group II had significant reduction in bleeding at surgical site, thus it is evident that patients receiving dexmedetomidine infusion had a better surgical field as compared to patient of Group II (P < 0.05). The difference in bleeding at surgical site was statistically significant between the groups.

Table 4

Assessment of intra-operative bleeding by surgeon (n: 64 patients)

All patients were able to obey the commands, and the duration of awakening time and recovery were comparable between the groups. Post-operative respiratory rate and peripheral SpO2 were comparable with no episode of desaturation at any time. No side effect of dexmedetomidine infusion was observed during the study period.

DISCUSSION

Middle ear surgeries require good surgical field visibility with no post-operative nausea and vomiting. In the present study, the dexmedetomidine infusion was used to produce oligaemic surgical field during middle ear surgery using operating microscope. It is evident from the study that the patient receiving dexmedetomidine infusion has oligaemic surgical field and better visibility when compared to patient receiving placebo. These findings can be attributed to the fact that dexmedetomidine reduces sympathetic activity, resulting in lower blood pressure and reduced heart rate thereby decreasing blood loss at the surgical site to improve the quality of the surgical field.

Dexmedetomidine is a highly selective α2 adrenergic agonist and used as adjuvant in anaesthesia to reduce the intra-operative anaesthetic and analgesic requirement. It regulates the autonomic and cardiovascular systems by acting on blood vessels and inhibiting norepinephrine release at sympathetic terminals, thereby attenuating the heart rate and blood pressure responses to intra-operative stressful events of anaesthesia. It effectively minimises the surgical blood loss and improves the surgical field visibility. Its haemodynamic effects are predictable and dose-dependent.[8910]

Currently, many inhalational or intravenous anaesthesia techniques were evaluated to offer ideal intra-operative conditions for middle ear surgery. Jellish et al. judged that the intravenous anaesthesia technique provided better haemodynamic control, less movement, and faster emergence during middle ear surgery.[1] Short acting inhalational anaesthetics such as desflurane and isoflurane produced excellent operating conditions for otological surgery.[111213]

Even small amount of blood can obscure the microscopic operating field and decreasing the extravasation of blood may improve the results of surgical procedures. Different techniques, to minimise intra-operative blood loss during middle ear surgery are used. The conventional techniques of electively lowering the blood pressure are positive pressure ventilation and administration of hypotensive drugs.

In the study of Bekker et al., patients received an initial loading dose of 1 μg/kg of dexmedetomidine over 10 min, followed by a continuous infusion of 0.5 μg/kg/h and they determined that intra-operative dexmedetomidine infusion was effective for blunting the perioperative haemodynamic responses with no incidence of hypotension or bradycardia.[14] Our present study was in accordance with their study as all patients were haemodynamically stable, and none of them required vasopressor support or bolus administration of fluid to maintain haemodynamic status.

A meta-analysis of previous studies showed that the incidence of bradycardia requiring intervention was increased when maintenance dosages of dexmedetomidine were used in excess of 0.7 μg/kg/h. In our study, no patients suffered from bradycardia as dexmedetomidine infusion was given in dose of 0.5 μg/kg/h and loading dose of dexmedetomidine was not given.

The result of the present study indicates that the use of dexmedetomidine infusion reduced the percentage of isoflurane concentration to maintain a systolic blood pressure 30% below baseline values. These findings confirm with a previous study of Khan et al. which also showed that use of dexmedetomidine reduces the requirement of inhalational anesthetic.[15] Aho et al.[16] and Aantaa et al.[17] also reported a reduction of isoflurane requirement in their study, thus confirm the synergism between isoflurane and dexmedetomidine.

Dexmedetomidine was well tolerated, and none of the patients developed any drug-related side-effects or complications in the perioperative period. The dexmedetomidine infusion did not affect the awakening time or delay the recovery from anaesthesia.

Coughing on the tracheal tube during awakening will increase venous pressure and may cause post-operative bleeding, so deep extubation with sooth recovery is preferable. Guler et al. found that the increase in blood pressure and heart rate during extubation is decreased, and the quality of extubation is improved by dexmedetomidine.[18] Our findings were in accordance to their study.

Ebert et al. did not observe any apnoea, airway obstruction and hypoxemia with bolus doses of dexmedetomidine in their study, and they reported that the depression of respiration may be seen due to deep sedation.[19] In our study, none of the patients suffered from respiratory depression as we did not use dexmedetomidine in high doses.

Ear surgery may cause post-operative dizziness (vertigo), nausea and vomiting as inner ear is intimately involved with a sense of balance. Induction with propofol decreases the post-operative nausea and vomiting in patients undergoing middle ear surgery. Prophylaxis with palonosetron, a 5-hydroxytryptamine 3 receptor blocker in premedication was considered for the present study and none of the patients suffered from post-operative nausea and vomiting.

During surgery, middle ear is open to the atmosphere, and there is no pressure build up. Once the tympanic membrane graft is placed, the middle ear becomes a closed space. If nitrous oxide is allowed to diffuse into this space, middle ear pressure will rise and may interfere with tympanic membrane reconstruction. Therefore, nitrous oxide is either entirely avoided or discontinued prior to graft placement. Withdrawing nitrous oxide 10–20 min before placement of graft is the usual technique used in our institution.

CONCLUSION

Dexmedetomidine infusion was safe to provide oligaemic surgical field for better visualisation under operating microscope for middle ear surgery keeping the haemodynamic variations within the physiological range. It also reduced the requirement of isoflurane and recovery from anaesthesia was complete and smooth.