Recovery from intracranial operations requires the anaesthesia method to ensure haemodynamic stability and fast recovery to allow immediate neurological evaluation. Airway irritation appearing during tracheal extubation may cause a cough or difficulties in breathing and may contribute to an increase in blood pressure (BP) [1,2]. Hypertension can cause an increase in brain oedema or haemorrhage, which may give rise to herniation . Many drugs and methods have been used in order to ensure stable haemodynamics. Attempts have been made to oppose the stress response by the use of drugs such as narcotic analgesics, deep anaesthesia induced by inhalation, local anaesthetics, adrenoreceptor blockers and vasodilator agents . Dexmedetomidine is a highly selective α-2 receptor agonist that has sedative, analgesic, anxiolytic and amnesic effects without significant respiratory depression [5-8]. It also has a sympatholytic effect through decreases in the concentration of norepinephrine. This in turn decreases the BP and the heart rate (HR) [9-11]. We hypothesized that dexmedetomidine with its sympatholytic effect might prevent hypertensive responses during extubation without delaying recovery after intracranial surgery. In this study, we used bolus dexmedetomidine immediately before extubation, and compared the effects on haemodynamic response and recovery to a standard anaesthetic regimen.
After obtaining approval from the Hospital Institutional Review Board (Ref. No: 07-04) and informed written consent from each patient, 40 patients, ASA I-III, aged 18-75 yr, undergoing intracranial operation were recruited. Any patient with arrhythmia, heart failure, kidney deficiency, allergy history, dementia, pregnancy or breast feeding, Glasgow Coma Score (GCS) < 15, HR below 60 min−1 or arterial pressure less than 100/60 mmHg were not included. The patients were randomly divided into two equal groups of 20 patients before the operations using a computer-generated randomization schedule.
Non-invasive electrocardiography (ECG), peripheral oxygen saturation (SPO2), systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressure monitoring were recorded by a Drager Primus Infinity Delta Monitor (Drager, Lübeck, Germany) and baseline values were noted for each patient. For induction, 2 μg kg−1 fentanyl, 5-7 mg kg−1 thiopental and 0.1 mg kg−1 vecuronium were used. Two minutes after induction, all the patients were intubated by the oral route and were ventilated with a semi-closed mechanical ventilator (Drager Primus). Tidal volume and respiration rate were regulated so as to obtain end-tidal CO2 30-32 mmHg throughout the operation. Isoflurane at 0.6-0.8% end-tidal concentration in 50% O2/N2O was used for anaesthesia maintenance and vecuronium 0.05 mg kg−1 h−1 infusion was used to maintain muscle relaxation. Central venous pressure was monitored by a three-lumen catheter placed in the right subclavian vein and direct arterial pressure monitoring with a 20-G cannula in the right radial artery. When the perioperative SAP exceeded the baseline value, the dose of inhalation anaesthetic was increased up to maximum of 1% end-tidal concentration and if an adequate decrease could not be obtained 50-100 μg nitroglycerin was administered. The patients who required nitroglycerin administration were excluded from the study. When the perioperative SAP was lower than the baseline values, colloid infusion was started and the dose of inhalation anaesthetic reduced by 0.2% intervals down to a minimum 0.4%. If the MAP was lower than 60 mmHg, 5 mg ephedrine was given. Those patients who required ephedrine were also excluded from the study. If the HR was lower than 50 beats min−1, 0.5 mg atropine was given and these patients were not included in the study as well.
The vecuronium infusion was stopped approximately 1 h before the end of the operation. Isoflurane concentration was reduced by 50% when there was 5 min left to the end of the procedure and in Group I 0.5 μg kg−1 dexmedetomidine was given intravenously (i.v.) over 60 s. In Group II, 0.9% NaCl was used instead of dexmedetomidine following the same schedule. The attending anaesthetists did not know whether dexmedetomidine or 0.9% NaCl was the content of the syringe. At the very last suture of the surgery, the inhalation anaesthetic was stopped completely and when patients had sufficient spontaneous respiration and a train-of-four >90%, they were extubated. The patients had 100% O2 inhalation through masks for 5 min following extubation. SAP, DAP and MAPs, HRs and SPO2 levels were recorded just before administrating dexmedetomidine or 0.9% NaCl i.v. at the end of the surgery, 1 min before extubation, during extubation and at 1, 3, 5, 10, 20 and 30 min after extubation. Time interval between cessation of volatile anaesthetics and extubation was recorded and time between cessation of volatile agent and adequate verbal and motor response to stimulus was recorded and accepted as recovery time. Five-point extubation quality scores were as follows: (1) no cough, easy breathing; (2) slight coughing (one or two), easy breathing; (3) moderate coughing (three or four); (4) heavy coughing, breathing hard; and (5) laryngospasm, severe coughing and hardly breathing.
SPSS (Statistical Package for social Sciences; SAS Institute Inc., Cary, NC, USA) for Windows 10.0 was used for analysis of the data. The sample size for the total number of the patients of the study was n = 38, Power 0.80, β: 0.20 and α: 0.05 when Δ: 13, SD: 20 for the MAP parameter. In addition to the descriptive statistical methods (mean ± SD), t-test was used for the comparisons among groups. Normality of the data was tested by the Kolomogorov-Smirnov method. Repeated measures data were analysed by ANOVA. Differences from the baseline values were analysed by Bonferroni's method, paired sample t-test. χ2-test was used for the quality parameters. P < 0.05 was accepted as significant.
In all, 40 patients were randomized and none of the patients dropped out. There were no significant differences regarding patient characteristics, duration of anaesthesia and the duration of surgery between groups (Table 1).
There was no significant difference in MAP among the groups with respect to the baseline values and regarding the values prior to the administration of their individual drugs.
MAP at the end of surgery, 1 min before extubation, at the time of extubation and at 1, 3, 5, 10 and 20 min after the extubation were significantly higher in Group II when compared with Group I (P < 0.01), but there was no difference 30 min after extubation (Fig. 1).
There was no significant difference among groups regarding the baseline values of HR and the HR values prior to the administration of their individual drugs. At the end of surgery, 1 min before extubation, at extubation and 1, 3, 5, 10, 15, 20 and 30 min after extubation the HR was significantly higher in Group II when compared with Group I (P < 0.01) (Fig. 2). There were no statistically significant differences between the groups with respect to extubation duration (Group I: 8 ± 0.9; Group II: 8 ± 1) and recovery time (Group I: 14 ± 0.8; Group II: 13 ± 1.2).
While all patients in Group I had an extubation quality score of 1, in Group II 35% of the patients had a score 1, 45% of the patients scored 2 and 20% had 3 for extubation quality. This difference was statistically significant (P < 0.001).
In the postoperative period, no patient needed treatment for bradycardia or hypotension and none of them exhibited nausea, vomiting, respiratory depression or desaturation.
In this study, we found that a single bolus of 0.5 μg kg−1 dexmedetomidine attenuated the increase in HR and BP after extubation, improved extubation conditions but did not prolong recovery in patients presenting for craniotomy.
In previous studies of other patient populations, dexmedetomidine has been found to significantly attenuate the BP and HR response to extubation [12,13].
Tanskanen and colleagues , in 54 patients undergoing surgery for supratentorial brain tumours demonstrated that the decrease in the hypertensive response to extubation was related to dexmedetomidine dose. Dexmedetomidine plasma target doses of 0.2 and 0.4 ng mL−1 were compared to placebo. Dexmedetomidine decreased the haemodynamic responses caused by stimuli during anaesthesia; a higher dose was more effective than a lower dose. However, in contrast to the latter study, which used a continuous infusion of dexmedetomidine throughout the procedure, we found that a single bolus at the end of the procedure was effective.
In a study on patients undergoing cataract surgery, dexmedetomidine was seen to significantly attentuate the cough reflex during extubation, improving the quality of extubation . In our study, cough, difficulty in breathing, laryngeal oedema and bronchospasm were not observed and extubation was superior in the dexmedetomidine group compared to the control group. It may be that the analgesic and sedative characteristics of dexmedetomidine contribute to a lower level of sensitivity to laryngeal stimulation during extubation.
It is important to perform neurological examination as early as possible in the postoperative period to determine the effect of the surgical intervention on the patient's clinical condition and to facilitate early diagnosis and treatment of possible complications. For these reasons, stable haemodynamics should be sustained with appropriate dosage and timing to make an early neurological examination possible. In our study, we noted that the extubation and recovery times did not change when 0.5 μg kg−1 dexmedetomidine was administered to patients undergoing intracranial operations.
Lawrence and colleagues  reported that in their study of patients receiving 2 μg kg−1 of dexmedetomidine, five of them had hypotension and six had bradycardia, which required treatment with ephedrine and atropine, respectively. In a study by Guler and colleagues , one patient had bradycardia and three had hypotension following 0.5 μg kg−1 dexmedetomidine. In our study, no bradycardia or hypotension that required treatment was observed in patients when volatile anaesthetic dosage was decreased by 50% and 0.5 μg kg−1 dexmedetomidine given 5 min before the end of the operation. We believe that these drug-related cardiovascular side-effects were related to dosage and the speed of administration of the drug and the duration and dosage of volatile anaesthetics. It is known that activation of α-2 receptors on smooth muscles of the vascular wall causes vasoconstriction. A period of hypertension can be observed following rapid dexmedetomidine infusion but BP then decreases when the drug reaches the central nervous system [6,16]. In our study, we observed similar results. Arterial pressure increased by 20 mmHg following 0.5 μg kg−1 infusion but it returned to normal values within 1 min. The believed sympatholytic effect appeared after the third minute.
Many studies have shown that dexmedetomidine, like all other α-2 adrenoceptor agonists, has very little effect on ventilation and there is no difference in respiratory function in patients who received dexmedetomidine compared to ones who received placebo following extubation [17-19]. We noted that spontaneous ventilation was present in the entire dexmedetomidine group and their extubation time was the same as that of the control group.
In conclusion, we found that a dexmedetomidine 0.5 μg kg−1 bolus administration ensured a reduced haemodynamic response to extubation and a quality of recovery comparable to the placebo group after intracranial surgery without causing a delay in extubation or recovery.
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Keywords:© 2008 European Society of Anaesthesiology
DEXMEDETOMIDINE; PRESSURE INTRACRANIAL; NEUROSURGERY, intracranial; INTUBATION INTRATRACHEAL, extubation; CARDIOVASCULAR PHYSIOLOGY