{'fraction_non_alphanumeric': 0.03215754705222485, 'fraction_numerical': 0.019942664838589058, 'mean_word_length': 5.439807383627608, 'pattern_counts': {'":': 0, '<': 3, '<?xml version=': 0, '>': 1, 'https://': 0, 'lorem ipsum': 0, 'www.': 1, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Blunting effect of dexmedetomidine on transient cardiovascular changes induced by inhalation of desflurane: a randomized controlled trial

Background: A rapid increase in desflurane concentration has been demonstrated to induce transient sympathetic hyperactivity and lead to increases in blood pressure and heart rate (HR). Additionally, the use of dexmedetomidine as an anesthetic adjunct has been reported to attenuate intraoperative sympathetic responses. We examined the hemodynamic effects of dexmedetomidine infusion before anesthetic induction on desflurane-induced cardiovascular changes. Methods: Patients were randomly divided into three groups. They received either normal saline (NS) (group 1, only NS) or dexmedetomidine solution diluted in 50 ml NS (group 2, 0.5 m g/kg; group 3, 1.0 m g/kg) for 10 minutes with a syringe pump before anesthetic induction. Desflurane was administered at a vaporizer dial setting of 8% for 5 minutes by manual ventilation. Results: In group 1, the HR significantly increased above the baseline during the entire 5 minutes after desflurane inhalation and the mean blood pressure (MBP) significantly increased above the baseline at 1, 2, and 3 minutes after desflurane inhalation. How-ever, in groups 2 and 3, the increases in HR and MBP induced by desflurane inhalation were significantly suppressed. The HR and MBP in group 2 remained closer to the baseline than in group 3. Conclusions: A loading infusion of dexmedetomidine for 10 minutes before induction of general anesthesia effectively attenuates the transient cardiovascular stimulation induced by desflurane inhalation, without significant hemodynamic side effects. The HR and MBP remained closer to the baseline after administration of 0.5 m g/kg dexmedetomidine than after administration of a dose of 1.0 m g/kg.

Dexmedetomidine is a highly selective a 2 adrenergic receptor agonist indicated for sedation and analgesia in both critical care and perioperative settings [8]. The use of dexmedetomidine as an anesthetic adjunct has been reported to attenuate intraoperative sympathetic tone and the hemodynamic response to endotracheal intubation [9][10][11][12]. This character of dexmedetomidine arises from the inhibition of sympathetic outflow at the a 2 adrenergic receptor in postsynaptic neurons of the central nervous system [8]. Kersten et al. [13] reported that pretreatment with dexmedetomidine decreased the hemodynamic effects induced by desflurane in a canine model. However, there has been limited research on dexmedetomidine that focuses on the attenuation of the hemodynamic effects induced by desflurane in humans.
Therefore, we conducted this investigation to examine the hemodynamic effects of dexmedetomidine infusion before anesthetic induction on desflurane-induced cardiovascular changes.

Patients
This was a randomized control study conducted at a tertiary teaching hospital. We obtained approval for our study from the Institutional Review Board (IRB) and Ethics Committee (IRB no. 2016-06-308-005), registered our study at www.clinicaltrials.gov (ID. KCT0002157), enrolled a total of 60 patients of American Society of Anesthesiologists physical status classification I and II (age ≥ 19 and < 65 years), and scheduled elective surgery for them at our hospital between August and December 2016 under general anesthesia. We obtained written informed consent from all participants. They were randomly assigned into three groups, and each group of 20 patients received an allocated intervention, respectively ( Fig.   1). The following patients were excluded: those who did not provide informed consent; those with histories of asthma, habitual abuse of hypnotics or sedatives, anemia, or hematocrit levels < 24%; those who required pre-anesthetic medication; those with uncontrolled hypertension (systolic blood pressure (SBP) ≥ 160 mmHg), pre-induction SBP ≤ 90 mmHg, pre-induction HR ≥ 100 or ≤ 45 beats/min, or uncontrolled diabetes (long-lasting blood glucose over 200 mg/dl); those with a risk of aspiration; those who were judged by the investigator unfit for our study; and pregnant women.
The patients enrolled in this study were randomly allo- Finally, all data values were analyzed for comparison among the three groups.

Statistical analysis
All data were expressed as mean ± standard deviation (SD).
Referring to existing literature that evaluated the hemodynamic effect of remifentanil in desflurane anesthesia [7], we performed a pilot study.

RESULTS
There were no significant differences in the baseline demographic and clinical characteristics among the three groups.
In addition, the mean end-tidal concentration of desflurane  (vol%) showed no significant differences among the groups (  There were several adverse events during this study. The incidence of hypertension (SBP ≥ 190 mmHg) was 30% (n = 6), 5% (n = 1), and 10% (n = 2) in groups 1, 2, and 3, respectively, and 1 patient in group 1 presented with tachycardia (HR > 130 beats/min) during desflurane inhalation. Meanwhile, 2 patients in group 3 presented with bradycardia (HR < 40 beats/min) during the first 10-minute drug infusion. However, among the three groups, there were no severe hemodynamic collapses or significant differences in the incidences of these adverse effects (Table 2).

DISCUSSION
Our hypothesis was that dexmedetomidine, a potent selective a 2 adrenergic receptor agonist, may suppress the transient sudden increases in BP and HR when desflurane concentration is rapidly increased over 1 MAC during anesthetic induction [14]. Our study showed that intravenous (IV) administration of dexmedetomidine over 10 minutes prior to anesthetic induction had blunting effects on transient cardiovascular changes induced upon inhalation of desflurane.
In previous studies, transient sympathetic stimulation effects of desflurane developed 1-2 minutes after inhalation and continued for 3-4 minutes [2,7]. Our study showed the same results, and dexmedetomidine infusion before anesthetic induction blunted these cardiovascular changes in our study.
Our study compared two different loading doses of dexme- Many studies have shown increases in plasma catecholamine concentrations after anesthetic induction with inhalation of desflurane [19,20]. These increases in plasma catecholamine concentrations are inhibited by dexmedetomidine [13,19,20]. It has been reported that the central a 2 adrenoceptor located in medullary nuclei is the main sympathetic catecholamine outflow inhibition site [21,22]. It has been reported that a lower HR is associated with decreased myocardial ischemia and improved long-term outcomes in patients undergoing major vascular surgery [23]. In addition, dexmedetomidine attenuates the hemodynamic and neuroendocrinal response of surgical trauma during heart surgery of high-risk adults and children as well [9,10,15,24]. In many studies, sympathetic stimulation by volatile agents has been shown to be related to cardiac ischemia in patients of cardiovascular disease [4]. In our study, decreases in HR compared with that of the control group suggested that suppression of sympathetic activation by perioperative dexmedetomidine seems to specifically beneficial in patients with ischemic heart disease to prevent myocardial infarction [4,25]. The side effects of dexmedetomidine in high-risk patients or during surgery are severe hypotension and bradycardia requiring immediate treatments. In other studies in patients undergoing heart surgery, there were no significant differences in the incidences of such adverse events [9,10].
There are several limitations to this study. First, we com- adults. Therefore, we could not know whether the outcomes were improved in patients with ischemic heart disease.
In conclusion, our randomized, prospective study demonstrates that infusion of dexmedetomidine for 10 minutes before general anesthetic induction has blunting effects on the transient cardiovascular changes induced by desflurane inhalation during the induction period.