Dexmedetomidine sedation for carotid endarterectomy
*Magdalena Sidorowicz1, Radosław Owczuk1, Barbara Kwiecińska1, Magdalena A. Wujtewicz1, Jacek Wojciechowski2, Maria Wujtewicz1
1Department of Anaesthesiology and Intensive Therapy, Medical University of Gdańsk
2Department of Cardiac and Vascular Surgery, Medical University of Gdańsk
- Table 1. Characteristics of patients
- Table 2. Drugs administered in premedication and during procedure – means (SD) or number of individuals
- Fig. 1. BIS changes in patient groups *p<0.05 compared with baseline value # p<0.05 compared with group A
- Fig. 2. MAP changes in patient groups (means and 95% confidence intervals) *p<0.05; ** p<0.005; *** p<0.0005; **** p<0.000005 compared with baseline values
- Fig. 3. HR changes in patient groups (means and 95% confidence intervals) *p<0.05; ** p<0.005; *** p<0.0005; **** p<0.0005 compared with baseline values
Background. General anaesthesia and deep sedation during endarterectomy exclude direct contact with the patient, required for safe performance of the surgery. The aim of the study was to assess sedation with dexmedetomidine and its cardiovascular effects.
Methods. Sixty-four adult patients, scheduled for internal carotid artery surgery under infiltration analgesia, were randomly divided to receive dexmedetomidine in the loading dose of 1 μg kg-1 over 10 min. followed by 0.2 μg kg-1 h-1 continuous infusion (group D) or placebo (group P). The BIS score, heart rate (HR) and mean arterial pressure (MAP) were noted.
Results. In the group D, mean BIS scores during carotid artery clamping (CAC) were lower, compared to the baseline and to the values recorded in the group P. The BIS scores in the group P did not differ from baseline. In the group D, we did not observe cardiovascular reactions that could be attributed to CAC; in the group P. MAP and HR increased during CAC, and returned to normal 10 min after clamp release. Significant decrease of HR was observed after 12 min of dexmedetomidine infusion, at 10 and 15 min after CAC in group D. Urapidil and fentanyl were administered more often in the placebo group.
Conclusions. The 0.2 μg kg-1h-1 dexmedetomidine infusion, administered during carotid endarterectomy, secured cardiovascular stability and reduced the need for additional analgesia.
Surgical management for carotid artery stenosis (CEA) prevents neurological deficit symptoms and ischaemic brain stroke. Patients with both symptomatic and asymptomatic stenosis are submitted to the procedure, the benefits of which were demonstrated in the NASCET and ECST trials [1, 2].
For CEA procedures, general or regional anaesthesia may be applied alongside with anaesthetic monitoring with or without sedation. In the light of current literature, none of these methods is significantly superior to others and none contributes to important decreases in intra- and perioperative morbidity [3, 4]. Each method should be targeted at sustaining the adequate blood and oxygen supply to the brain during the procedure and in the perioperative period. General anaesthesia and deep sedation hinder contact with patients and thus detection of neurological deficit symptoms; some surgeons prefer to operate patients who remain conscious or under shallow sedation with regional anaesthesia. These methods are uncomfortable for patients and may not guarantee haemodynamic stability; therefore the search for a new sedative agent continues so as to increase the patient`s safety and provide adequate comfort during surgery.
Dexmedetomidine belongs to the group of hypnotic, analgesic and sympatheticolytic drugs and was registered for 24-hours sedation [5, 6, 7, 8, 9, 10, 11]. Keeping verbal contact with the patient under adequate sedation is of the utmost importance . Although dexmedetomidine is administered mainly for sedation in ITUs [13, 14], there is an increasing number of reports concerning its application in other settings [15, 16, 17, 18].
The aim of the present study was to assess dexmedetomidine sedation for carotid endarterectomy, haemodynamic issues, in particular.
The study protocol was approved by the Ethical Committee of the Medical University of Gdansk, and patient informed consents for participation in the study were obtained. The study population included ASA II-III patients undergoing elective surgery due to symptomatic or asymptomatic internal carotid artery (ICA) stenosis. Severe ICA stenosis was diagnosed during Doppler ultrasound examinations when the ICA lumen was found to be narrowed by over 70-80%.
Before surgery, all the patients were premedicated with 1 mg kg-1 of intramuscular pethidine. On arrival to the operating room, monitoring was started with the three-lead ECG, pulse oximetry, and non-invasive blood pressure measurements. The cannula was introduced into a peripheral vein and the infusion of 0.9% sodium chloride solution was initiated. The facemask ventilation was applied with the oxygen flow of 6 L min-1.
Patients were randomly assigned to two groups: D – dexmedetomidine group, and P – placebo group (0.9% NaCl). The solution of 200 µg of dexmedetomidine in 50 mL isotonic saline was prepared in an automatic syringe (final concentration - 4 µg mL-1). Before the initiation of surgery, patients in group D were given the loading dose of 1µg kg-1 min-1 dexmedetomidine in the continuous infusion over 10 min, followed by the maintenance dose of 0.2 µg kg-1h-1. Patients in group B received 0.9% NaCl solution.
The surgeon gave the infiltration anaesthesia with 1% lignocaine to the operated site. The patient`s neurological status was assessed before the initiation of the agent or placebo, before and after carotid artery clamping. The state of consciousness, verbal responses to commands and motor function of the upper extremity contralateral to the operation side were assessed. When no neurological symptoms were noted, endarterectomy with direct closure of the vessel was performed at 3 min after internal and external carotid artery clamping.
The analysed haemodynamic parameters included indirect measurement of SAP, MAP and DAP, continuous ECG and HR. The following measurement points were chosen: 0 – onset of dexmedetomidine or placebo infusion; 2, 4, 6, 8, 10 min after initiation of the dexmedetomidine loading dose or at 12 min of infusing the maintenance dose of the agent or placebo; Cx – ICA closure; C+5, C+10, C+15 – 5, 10 and 15 min after ICA closure, respectively; Dx – ICA clamp release, D+5, D+10, D+20 – 5, 10 and 20 min after ICA clamp release. The level of sedation was monitored using bispectral analysis.
During the procedure, in cases of MAP decrease below 80 mm Hg, intravenous ephedrine was administered in fractionated doses 12.5 mg until MAP normalisation, with blood pressure measurements every minute. Patients with MAP increase over 150 mm Hg were administered intravenous urapidil fractionated doses 12.5 mg until the return of mean pressure values below 150 mm Hg, with blood pressure monitoring every minute. The decrease in HR below 40 min-1 was treated with 0.5 mg intravenous atropine. Surgery-related pain was alleviated with intravenous fentanyl fractions of 0.05 mg until adequate analgesia.
Data normal distribution was verified with the Shapiro-Wilk’s W test and homoscedasticity with the Levene’s test. Both parametric (Student’s t) and nonparametric tests (?2 with Yates’ correction) were employed. Multiple comparisons were performed using the ANOVA test for repeated measurements and, when necessary, the post-hoc LSD Fisher’s test. Statistical significance was assigned at p<0.05.
The study included 64 patients. There were no significant differences between the two groups as for age, body weight, the operated side, ASA classification and arterial hypertension. In group D, surgery was abandoned in 3 cases due to loss of consciousness before ICA clamping (one analogous case in group P); general anaesthesia and carotid artery shunting were necessary in one patient due to high excitement (two cases in group P, respectively). Demographic data of patients are presented in Table 1.
The duration of procedures did not differ significantly between the groups (p=0.37). In group D, dexmedetomidine infusions lasted 65.9±24.8 min.
The detailed data concerning the drugs administered are presented in Table 2. There were no differences in total pethidine doses and those calculated for body weight. During the surgery, intravenous urapidil (p=0.001) and fentanyl (p=0.001) were more commonly administered in group P. Ephedrine was administered significantly more often in the dexmedetomidine group (p=0.0035).
Variations in BIS scores in the two groups are presented in Figure 1. In group D, BIS scores were significantly lower compared to baseline values and to group P at carotid artery clamping, at 5, 10 and 15 min after clamping and at ICA clamp release. In group P, there were no significant BIS score changes compared to baseline values.
There were no cases of blood pressure fluctuations related to ICA clamping in group D, except for decreases in MAP 10 min after clamping, 10 and 20 min after unclamping and arterial flow restoration as compared to baseline values. In group P, there was a significant MAP increase at ICA closure, which persisted for the entire period of clamping and until 10 min after artery clamp release (Fig. 2).
Figure 3 depicts variations in HR values in both groups. Patients given placebo developed HR changes similar to the MAP ones. There was a significant increase in HR from the time of ICA clamping until the last measurement point. A significant decrease in HR was observed in group D at 12 min of dexmedetomidine infusion as well as at 10 and 15 min after ICA closure.
The study findings demonstrate that administration of the lowest maintenance dose (0.2 µg kg-1 h-1) of dexmedetomidine during the ICA desobliteration results in greater haemodynamic stability compared to placebo.
Carotid artery interventions are characterised by a high risk of adverse cardiovascular events, which may result in perioperative incidents of brain ischaemia and exacerbation of coronary heart disease including myocardial infarction . Therefore, irrespective of the type of anaesthesia during restoration of ICA patency, all measures should be taken to maintain haemodynamic stability, thus providing adequate brain and systemic blood supply.
There were numerous attempts to characterise methods of anaesthetic management best suited for both adequate anaesthesia/sedation and reduced incidence of adverse cardiovascular reactions associated with the carotid artery manipulation. Sedation and systemic analgesia were applied to patients under regional anaesthesia [19, 20]. Moreover, different systemic analgesics were studied [21, 22] as was lidocaine injected into the carotid sinus area  and alpha-2-mimetics for sedation and modulation of the autonomic nervous system function during CEA procedures [17, 24].
In the present study, dexmedetomidine, the alpha-2-mimetic of the highest specificity, was administered in the lowest dose (with the maintenance dose range of 0.2–0.7 µg kg-1 h-1). Noteworthy, haemodynamic parameters were stable both before ICA clamping (during dissection of tissues in the neck) and afterwards in patients administered the maintenance dose of 0.2 µg kg-1 h-1 of dexmedetomidine. This finding is important since higher maintenance doses of this agent may cause pressure drops or transient hypertension related to activation of alpha-2b receptors . Neither blood pressure increases nor decreases are desirable during carotid artery surgeries due to the risk of brain ischaemia or formation of haemorrhagic foci. Stable heart rate, herein observed in the group receiving dexmedetomidine, is undoubtedly beneficial for patients with abnormal coronary blood flow, who are at risk of increased oxygen deficits of the heart muscle in cases of tachycardia. Moreover, low doses of dexmedetomidine did not cause bradycardia and atropine was not required. Therefore, dexmedetomidine seems safe in patients with atropine contraindications and who constitute the majority of candidates for CEA procedures due to their advanced age. McCutcheon and co-workers  used half the initial loading dose of dexmedetomidine administered in our study and the same maintenance dose, which they compared to conventional sedation (fentanyl and midazolam). They observed statistically lower incidences of intraoperative interventions due to tachycardia and/or hypertension in the dexmedetomidine group yet found no differences in the number of interventions related to these two types of cardiovascular incidents. On the other hand, Bekker and others  compared dexmedetomidine and placebo in carotid artery operations and demonstrated that patients receiving alpha-2-mimetics less often needed intraoperative beta-blockers and their plasma catecholamine levels were lower.
In the present study, there were no decreases in BIS scores after the loading dose and during the infusion of dexmedetomidine. Hall and colleagues  administered dexmedetomidine and placebo to volunteers. Contrary to our findings, they showed that low doses of dexmedetomidine (the maintenance dose applied in one subgroup was identical to the one used in our study) caused significant decreases in BIS values and increased the level of sedation as compared to placebo. It should be emphasised, however, that they used a markedly higher loading dose (6 µg kg-1 min-1), which could have resulted in the differences observed.
In our study, BIS values decreased significantly only after carotid artery clamping, compared to baseline values and to the placebo group. ICA clamping in patients under general anaesthesia is known to reduce BIS scores , although no significant BIS score variations in patients presenting symptoms of CNS ischaemia during awake endarterectomy were observed . In our study, BIS score variations after ICA clamping in patients receiving dexmedetomidine seem to be related to overlapping of two factors potentially affecting the CNS electrical activity: drug administration and decreased blood flow after artery clamping. Lack of BIS changes in the placebo group could implicate greater relevance of the former factor.
Analgesia is a beneficial effect of dexmedetomidine administration. Although pain scores were not assessed in the present study, significantly lower numbers of fentanyl administrations required indicate indirectly a beneficial analgesic action of dexmedetomidine. High incidences of opioid administration in the placebo group may result from inadequate regional infiltration anaesthesia. This technique is commonly mentioned among methods of regional anaesthesia for carotid artery interventions yet at the same time it is described as slow, inconvenient and poorly tolerated by some patients . Therefore, the analgesic action of dexmedetomidine seems of the utmost importance in infiltration anaesthesia.
The maintenance dose of 0.2 µg kg-1 h-1 dexmedetomidine seems useful for carotid artery surgery due to its beneficial haemodynamic profile during the procedure and reduced consumption of hypotensive and analgesic drugs.
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Department of Anaesthesiology and Intensive Therapy
Medical University of Gdansk
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tel.: 0-58 349 24 06, fax: 0-58 346 11 82 e-mail: firstname.lastname@example.org Received: 20.01.2009