Introduction

The pressor response to tracheal intubation resulting in tachycardia and hypertension, is well described as plasma concentrations of catecholamine are increased and may be associated with myocardial ischaemia ^(1,2,3). Haemodynamic responses may be attenuated by several methods, including administration of iv opioids, vasodilators,  blockers or by deepening anesthesia.

Benzodiazepines, opiates, barbiturates, histamine and  adrenoceptor antagonists as well as anticholinergic agents, have traditionally been used as preoperative medication to eliminate or to suppress the stress reaction to anesthesia and surgery. It has become evident that, ₂ adrenoceptor agonists may also be a useful class of drugs in conjunction with anesthesia ⁽²⁾. They simultaneously potentiate the effects of general anesthetic agents, reduce their dose requirements and attenuate sympathoadrenal responses to noxious stimuli encountered during anesthesia and surgery, thus providing improved haemodynamic, metabolic and hormonal stability ⁽³⁾.

Dexmedetomidine is a highly selective and potent ₂ adrenoceptor agonist. It is a pure ₂ adrenoceptor agonist in some pharmacological models in which clonidine has shown only partial agonistic activity.

The aim of the present study was to investigate the effects of two different doses of dexmedetomidine infusion on controlling haemodynamic response to tracheal intubation and the quality of intubation.

Materials and Methods

After obtaining approval from the Ethics Committee and written informed consent, we studied 60 ASA I or II patients aged 18-60 years undergoing elective gynecologic surgery. Patients whose physical characteristics suggested difficulties in intubation and those who had a previously documented failed intubation and the patients who had hypertension or cardiovascular disease and taking any medication were excluded. The patients were allocated randomly ( balanced randomisation using a computer program, block size 10 ) to receive either dexmedetomidine infusion 1 g.kg^-1 (n:30) in group I in ten minutes or 0,5 g.kg^-1 (n:30) in group II in five minutes before induction of anesthesia ( Lifecare 5000, Abbott, North Chicago, USA). The study was conducted in a double-blind fashion. Baseline measurements of arterial blood pressure, heart rate and O₂ saturation were performed in the operating room.

After arrival of the patients to the operating room, ECG and heart rate (Petaş KMA 100 monitor) were monitored continuously and non- invasive recordings of systolic, diastolic and mean arterial pressure at 5 min intervals were started with an automated oscillometric device. A vein in the dorsum of the left hand was cannulated for iv infusion ( 10 ml.kg^-1 0,9% NaCl ) and administration of drugs.

During the infusion of dexmedetomidine, patients were preoxygenated with 100% oxygen via a face mask (oxygen flow 6 lt.min^-1). 90 secondes after the infusion, thiopentane 5 mg.kg^-1 was given. Vecuronium 0,1 mg.kg^-1 was administered to produce neuromuscular block. Then the patient’s lungs were ventilated manually with 100% oxygen. 90 sec after vecuronium, laryngoscopy was attempted by the anesthetist. The anesthetist performing intubation assessed each patient for four variables: face mask ventilation, jaw relaxation, poısition of the vocal cords, reflex movement to tracheal intubation. The criteria used for ranking these variables were evaluated with the scoring system described by McNeil ⁽⁴⁾.

Anaesthesia was maintained with Sevoflurane 1% and N₂O-O₂ (66-34%). Measurements of SBP, DBP, MAP, HR and SpO₂ were performed 60 sec after dexmedetomidine infusion (t₁), 60 sec after induction (t₂), 60 sec after intubation (t₃) and 5 min after intubation (t₄). Hypotension (reduction in arterial pressure of 30% or more from the baseline) was treated primarily by increasing the i.v. infusion rate , and then reducing sevoflurane concentration or with 10 mg bolus dose of efedrine. Bradycardia ( definied as heart rate less than 45 beat.min^-1) was treated with 0.5 mg bolus dose of atropine.

Statictical evaluation was performed using GraphPad Prisma v.3 packed programme. Data were analysed with Newman Keuls test, chi-square test, student’s t test as appropriate. p<0,05 was considered statistically significant. The results were presented as means and SD.

Results

The two groups were comparable in patient characteristics (Table 1). SAP, DAP, MAP were significantly lower in group I at t₃ ( p<0,05, p<0,01) (Table 2). The two groups were comparable in heart rates (p>0,05), SpO₂ levels in group I at t₁ were significantly lower than group II (p<0,05) ( Table 3). The two groups were also comparable in reflex movement to intubation, jaw relaxation, position of the vocal cords and the total quality scores of tracheal intubation (p>0,05).

In group I, SBP, DBP, MAP levels at t₀ were significantly higher than t₂ and t₄, and significantly lower than t₃ period (Table 2). HR levels at t₀ were significantly higher than all the other periods, SpO₂ levels at t₀ were significantly lower than t₁, t₂, t₃, t₄ (p<0,05, p<0,01, p<0,001) (Table 3).

In group II, SBP, DBP, MAP levels at t₀ were significantly higher than t₂ and t₄ and significantly lower than t₃ (Table 2). HR levels at t₀ were significantly higher than t₁, t₂, t₃ and t₄, SpO₂ levels at t₀ were significantly lower than t₁, t₂, t₃ and t₄ (p<0,005, p<0,01, p<0,001) (Table 3).

No patient required efedrine or atropine. Any side effect wasn’t seen due to the infusion of dexmedetomidine.

Figure 1

Table 1: Patient characteristics

Figure 2

Table 2: SBP, DBP and MAP levels of the patients

Figure 3

Table 3: HR and SpO levels of the patients

Discussion

The ₂ receptors are involved in regulating the autonomic and cardiovascular systems. ₂ receptors are located on blood vessels, where they mediate vasoconstriction, and on sympathetic terminals where they inhibit norepinephrine release. ₂ receptors are also located within the central nervous system and their activation leads to sedation, a reduction of tonic levels of sympathetic outflow and an augmentation of cardiac-vagal activity. This can result in a decrease in heart rate and cardiac output. The use of ₂ agonists in the perioperative period has been associated with reduced anesthetic requirements and attenuated heart rate and blood pressure responses to stressfull events. In addition, ₂ receptors within the spinal cord modulate pain pathways, thereby providing some degree of analgesia ^(5,6,7).

It was observed that dexmedetomidine used in premedication supresses the sympathetic activation which is due to the endotracheal intubation ⁽⁸⁾. Güler et al. found that the increase in blood pressure and heart rate during the extubation is decreased and the quality of extubation is increased by dexmedetomidine ⁽⁹⁾.

It was found in the study by Jaakola et al. that , during the intubation blood pressure and heart rate is significantly reduced by 0.6 μg.kg^-1 dexmedetomidine ⁽¹⁰⁾. In Scheinin’s study these parameters were also reduced by equal doses of dexmedetomidine ⁽¹¹⁾. In the other study which was done by Tezer et al. it is concluded that sympathetic responses during laryngoscopy and intubation were effectively reduced by dexmedetomidine 1 μg.kg^-1h^-1 and esmolol 250 μg.kg^-1min^{-1 (12)}. Khan et al. demonstrated that heart rate, sistolic and diastolic blood pressure were reduced by dexmedetomidine ⁽¹³⁾. In another study on the patients undergoing vascular surgery , it was observed that in the recovery period dexmedetomidine infusion led to supression on heart rate and plazma cathecholamine levels ⁽¹⁴⁾.

In this study dexmedetomidine 1 μg.kg^-1 and 0.5 μg.kg^-1 SAP, DAP, MAP and HR levels were significantly lower at 60 sec after induction and 5 min after intubation than baseline levels. But these levels were significantly higher 60 sec after tracheal intubation. It was found that dexmedetomidine 1 μg.kg^-1 is effective to suppress haemodynamic responses to tracheal intubation but dexmedetomidine 0.5 μg.kg^-1 hasn’t the same effect.

In some studies it is observed that mean arterial pressure was decreased by low doses of dexmedetomidine ( 0.25-1 μg.kg^-1 ) and mean arterial pressure was increased transiently and heart rate was decreased significantly by high doses of (1-4 μg.kg^-1) dexmedetomidine ^(6,7). Scheinin et al reported that the use of ₂ agonist leads to bradycardia ⁽¹¹⁾. Belleville et al found that dexmedetomidine which is given in two minutes the doses of 1-2 μg.kg^-1 causes irregular ventilation and apnea episodes ⁽¹⁵⁾. Ebert et al. didn’t observe any apnea, airway obstruction and hypoxemia with bolus doses of dexmedetomidine in their study and they reported that depression of respiration may be seen due to deep sedation, for the reason that ₂ adrenergic agonists don’t have active role on the respiration center ⁽⁷⁾.

In another study in which the infusion of opioid and ₂ adrenergic agonists were compared, it was concluded that dexmedetomidine doesn’t cause significant respiratuar depression and it decreases the risk of apnea ⁽¹⁶⁾. Hofer et al reported that dexmedetomidine seems to be a good choice in the critical patients in whom ventilation can be depressed with narcotics ⁽¹⁷⁾.

In the study which was done by Bekker et al patients in the dexmedetomidine group received an initial loading dose of 1 μg.kg^-1 of dexmedetomidine over ten min, followed by a continuous infusion of 0.5 μg.kg^-1.h^-1. They determined that intraoperative dexmedetomidine infusion was effective for blunting the increases in SBP perioperatively and it did not increase the incidence of hypotension or bradycardia ⁽¹⁸⁾.

In this study any hypotension or bradycardia, were seen and any medical intervention, was required. Also significant respiratory depression, apnea, muscle rigidity or decrease in SpO₂ were seen in any patient.

In assessing the quality of intubation, there was no difference between the groups in means of jaw relaxation, position of the vocal cords, reflex movement to intubation and total score of intubation quality.

In summary, these results suggest that to controll haemodynamic responses to tracheal intubation, dexmedetomidine 1 μg.kg^-1 is more effective than dexmedetomidine 0.5 μg.kg^-1 without any side effect.