Effect of the Location of Tetanic Stimulation on Autonomic Responses: A Randomized Cross-Over Pilot Study.

Background: Tetanic stimuli are used as standardized noxious inputs to investigate nociception. Previous studies have applied tetanic stimuli to various anatomical locations without validating that the resulting physiological responses were independent of the location where tetanic stimuli were applied. Our aim was to investigate the effects of three anatomical tetanic stimulus application sites on physiological variables reflecting autonomic nervous system responses as measured by photoplethysmography (PPG). Methods: Under general anesthesia, a five second, 100 hertz, 70 milliamp tetanic stimulus was applied to the ulnar nerve, medial side of the tibia, and thorax (T5 dermatome) (N=12). The effect of tetanic stimuli on PPG-derived variables (AC, DC, and ACDC) and pulse rate at each stimulus location was determined using repeated-measures analysis of variance (ANOVA) followed by Dunnett's post hoc test. Maximum tetanic stimulus-induced changes in PPG-derived variables and pulse rates were compared among the three stimulus locations using ANOVA. Results: AC and ACDC values of PPG decreased, and the DC values of PPG increased in response to tetanic stimuli-induced vasoconstriction at each location (p<0.001 for all). The maximum changes in the AC, ACDC, and DC values did not differ between locations (p=NS). There were no significant changes in pulse rate (p=NS). Conclusion: The results showed that tetanic stimulation at either of these three locations provides the same autonomic nervous system responses, as measured by PPG. Clinical Trial Registration: ClinicalTrials.gov; NCT03648853.

Bilateral Superficial Trigeminal Nerve Blocks are not More Effective than a Placebo in Abolishing Post-operative Headache Pain in Pituitary Transsphenoidal Neurosurgery: A Prospective, Randomized, Doubleblinded Clinical Trial.

BACKGROUND: Pituitary neurosurgery executed via the transsphenoidal endonasal approach is commonly performed for pituitary adenomas. Reasons for prolonged hospital stay include postoperative headache and protracted nausea with or without vomiting. Bilateral superficial trigeminal nerve blocks of the supra-orbital V1 and infra-orbital V2 (SION) nerves performed intra-operatively as a regional anesthetic adjunct to general anesthesia were hypothesized to decrease 6 hours postoperative morphine PCA (patient-controlled analgesia) use by patients. METHODS: Forty-nine patients, following induction of general anesthesia for their transsphenoidal surgery, were prospectively randomized in a double-blinded fashion to receive additional regional anesthesia as either a block (0.5% ropivacaine with epi 1:200,000) or placebo/sham (0.9% normal saline). The primary endpoint of the study was systemic morphine PCA opioid consumption by the two groups in the first 6-hours postoperatively. The secondary endpoints included (1) pain exposure experienced postoperatively, (2) incidence of postoperative nausea and vomiting, and (3) time to eligibility for PACU discharge. RESULTS: Of the 49 patients that were enrolled, 3 patients were excluded due to protocol violations. Ultimately, there was no statistically significant difference between morphine PCA use in the 6 hours postoperatively between the block and placebo/sham groups. There was, however, a slight visual tendency in the block group for higher pain scores, morphine use p=0.046, and delayed PACU discharge. False discovery rate corrected comparisons at each time point and then revealed no statistically significant difference between the two groups. There were no differences between the two groups for secondary endpoints. CONCLUSION: It was found that a 6-hour postoperative headache after endoscopic trans-sphenoidal pituitary surgery likely has a more complicated mechanism involving more than the superficial trigeminovascular system and perhaps is neuro-modulated by other brain nuclei.

Electroencephalographic Arousal Patterns Under Dexmedetomidine Sedation.

BACKGROUND: The depth of dexmedetomidine-induced sedation is difficult to assess without arousing the patient. We evaluated frontal electroencephalogram (EEG) as an objective measure of dexmedetomidine-induced sedation. Our aims were to characterize the response patterns of EEG during a wide range of dexmedetomidine-induced sedation and to determine which spectral power best correlated with assessed levels of dexmedetomidine-induced sedation. METHODS: Sedline EEG sensor was positioned on the forehead of 16 volunteers. Frontal EEG data were collected at 250 Hz using the Sedline monitor. A computer-controlled infusion pump was used to infuse dexmedetomidine to four 15-minute target plasma concentrations of 0.3, 0.6, 1.2, and 2.4 ng/mL. Arterial blood samples for dexmedetomidine plasma concentration and sedation (self-reported numerical rating scale) and arousal were measured at baseline and at the end of each infusion step. The EEG signal was used to estimate spectral power in sequential 4-second data segments with 75% overlap for 3 power bands: delta = 0.5-1.5 Hz, alpha = 9-14 Hz, beta = 15-24 Hz. We quantified the relationships among the plasma concentrations of dexmedetomidine, level of sedation, and various EEG parameters. RESULTS: EEG data at the end of the dexmedetomidine infusion steps show progressive loss of high frequencies (beta) and increase in alpha and delta powers, with increasing dexmedetomidine concentrations. Beta prearousal spectral power was best in predicting dexmedetomidine-induced level of sedation (R = -0.60, 95% CI, -0.43 to -0.75). The respective values for delta and alpha powers were R = 0.28 (95% CI, 0.03-0.45) and R = 0.16 (95% CI, -0.09 to 0.38). When the beta power has dropped below -16 dB or the delta power is above 15 dB, the subjects show moderate to deep levels of sedation. When awakening the subject, there is a reduction in power in the delta and alpha bands at the 0.6, 1.2, and 2.4 ng/mL dexmedetomidine target levels (P < .001 for all). In beta band, there is a rapid awakening-induced increase in power (P < .001) followed by a slow return toward baseline values. After arousing the subjects, the EEG powers returned toward baseline values significantly slower than our clinical observation of the subjects' wakefulness would have suggested. CONCLUSIONS: Using a wide range of dexmedetomidine doses, we found that frontal EEG beta power of less than -16 dB and/or a delta power of over 15 dB was associated with a state of moderate to deep sedation and that poststimulus return of EEG powers toward baseline values took significantly longer than expected from observation of the arousal response. It is unclear whether these observations are robust enough for clinical applicability.

Pharmacokinetics and pharmacodynamics of dexmedetomidine-induced vasoconstriction in healthy volunteers.

AIMS: Alpha-2 agonists are direct peripheral vasoconstrictors, which achieve these effects by activating vascular smooth muscle alpha-2 adrenoceptors. The impact of this response during dexmedetomidine infusion remains poorly quantified. Our goal was to investigate the pharmacokinetic (PK) and pharmacodynamic (PD, vasoconstriction) effects of a computer-controlled dexmedetomidine infusion in healthy volunteers. METHODS: After local ethics committee approval, we studied 10 healthy volunteers. To study the peripheral vasoconstrictive effect of dexmedetomidine without concurrent sympatholytic effects, sympathetic fibres were blocked with a brachial plexus block. Volunteers received a dexmedetomidine target-controlled infusion for 15 min, to a target concentration of 0.3 ng ml-1 . Arterial blood samples were collected during and for 60 min after dexmedetomidine infusion for PK analysis. Peripheral vasoconstriction (PD) was assessed using finger photoelectric plethysmography. PK/PD analysis was carried out using nonlinear mixed-effect models. RESULTS: We found that the computer-controlled infusion pump delivered mean concentrations greater than 0.3 ng ml-1 over the 15-min infusion duration. The peripheral vasoconstrictive effect correlated with dexmedetomidine plasma concentrations during and after the infusion. A three-compartment model provided a better fit to the data than a two-compartment model. CONCLUSIONS: We found that dexmedetomidine-induced vasoconstriction is concentration dependent over time. Dexmedetomidine PK were best estimated by a three-compartment model with allometric scaling. Our results may contribute to future modelling of dexmedetomidine-induced haemodynamic effects.

The Effect of Tracheal Intubation-Induced Autonomic Response on Photoplethysmography.

Introduction. Intraoperative stress responses and postoperative pain can be monitored using photoplethysmography (PPG). PPG signal has two components, AC and DC. Effects of noxious stimuli-induced stress responses have not been studied on the DC component of PPG. The aim of this study was to investigate the effect of a known noxious stimulus (endotracheal intubation) on both the AC and DC components of PPG. Methods. 15 surgical patients having general anesthesia were enrolled into this clinical study. PPG was recorded electronically from a pulse oximeter. Maximum changes in the AC and DC components of the PPG and pulse rate were determined in response to endotracheal intubation from high frequency (62.5 Hz) PPG recordings. Results. Endotracheal intubation-induced autonomic stress response resulted in a significant decrease in the AC component of the PPG and an increase in pulse rate in every subject (p < 0.05 for all). The decrease in the AC component of the PPG was 50 ± 12% (p < 0.05) and the increase in pulse rate was 26 ± 10 bpm (p < 0.05). The response of the DC component was variable (p = NS). Conclusion. Endotracheal intubation-induced stress response resulted in a significant and consistent change in the AC, but not the DC component of the PPG. This trial is registered with ClinicalTrials.gov Identifier NCT03032939.

Republished: Society for Neuroscience in Anesthesiology and Critical Care expert consensus statement: Anesthetic management of endovascular treatment for acute ischemic stroke.

Literature on the anesthetic management of endovascular treatment of acute ischemic stroke (AIS) is limited. Anesthetic management during these procedures is still mostly dependent on individual or institutional preferences. Thus, the Society of Neuroscience in Anesthesiology and Critical Care (SNACC) created a task force to provide expert consensus recommendations on anesthetic management of endovascular treatment of AIS. The task force conducted a systematic literature review (up to August 2012). Because of the limited number of research articles relating to this subject, the task force solicited opinions from experts in this area. The task force created a draft consensus statement based on the available data. Classes of recommendations and levels of evidence were assigned to articles specifically addressing anesthetic management during endovascular treatment of stroke using the standard American Heart Association evidence rating scheme. The draft consensus statement was reviewed by the Task Force, SNACC Executive Committee and representatives of Society of NeuroInterventional Surgery (SNIS) and Neurocritical Care Society (NCS) reaching consensus on the final document. For this consensus statement the anesthetic management of endovascular treatment of AIS was subdivided into 12 topics. Each topic includes a summary of available data followed by recommendations. This consensus statement is intended for use by individuals involved in the care of patients with acute ischemic stroke, such as anesthesiologists, interventional neuroradiologists, neurologists, neurointensivists and neurosurgeons.

Society for Neuroscience in Anesthesiology and Critical Care Expert consensus statement: anesthetic management of endovascular treatment for acute ischemic stroke*: endorsed by the Society of NeuroInterventional Surgery and the Neurocritical Care Society.

Literature on the anesthetic management of endovascular treatment of acute ischemic stroke (AIS) is limited. Anesthetic management during these procedures is still mostly dependent on individual or institutional preferences. Thus, the Society of Neuroscience in Anesthesiology and Critical Care (SNACC) created a task force to provide expert consensus recommendations on anesthetic management of endovascular treatment of AIS. The task force conducted a systematic literature review (up to August 2012). Because of the limited number of research articles relating to this subject, the task force solicited opinions from experts in this area. The task force created a draft consensus statement based on the available data. Classes of recommendations and levels of evidence were assigned to articles specifically addressing anesthetic management during endovascular treatment of stroke using the standard American Heart Association evidence rating scheme. The draft consensus statement was reviewed by the Task Force, SNACC Executive Committee and representatives of Society of NeuroInterventional Surgery (SNIS) and Neurocritical Care Society (NCS) reaching consensus on the final document. For this consensus statement the anesthetic management of endovascular treatment of AIS was subdivided into 12 topics. Each topic includes a summary of available data followed by recommendations. This consensus statement is intended for use by individuals involved in the care of patients with acute ischemic stroke, such as anesthesiologists, interventional neuroradiologists, neurologists, neurointensivists, and neurosurgeons.

Enzyme-inducing anticonvulsants increase plasma clearance of dexmedetomidine: a pharmacokinetic and pharmacodynamic study.

BACKGROUND: Dexmedetomidine is useful during mapping of epileptic foci as it facilitates electrocorticography unlike most other anesthetic agents. Patients with seizure disorders taking enzyme-inducing anticonvulsants appear to be resistant to its sedative effects. The objective of the study was to compare the pharmacokinetic and pharmacodynamic profile of dexmedetomidine in healthy volunteers with volunteers with seizure disorders receiving enzyme-inducing anticonvulsant medications. METHODS: Dexmedetomidine was administered using a step-wise, computer-controlled infusion to healthy volunteers (n = 8) and volunteers with seizure disorders (n = 8) taking phenytoin or carbamazapine. Sedation and dexmedetomidine plasma levels were assessed at baseline, during the infusion steps, and after discontinuation of the infusion. Sedation was assessed by using the Observer's Assessment of Alertness/Sedation Scale, Ramsay Sedation Scale, and Visual Analog Scale and processed electroencephalography (entropy) monitoring. Pharmacokinetic analysis was performed on both groups, and differences between groups were determined using the standard two-stage approach. RESULTS: A two-compartment model was fit to dexmedetomidine concentration-time data. Dexmedetomidine plasma clearance was 43% higher in the seizure group compared with the control group (42.7 vs. 29.9 l/h; P = 0.007). In contrast, distributional clearance and the volume of distribution of the central and peripheral compartments were similar between the groups. No difference in sedation was detected between the two groups during a controlled range of target plasma concentrations. CONCLUSION: This study demonstrates that subjects with seizure disorders taking enzyme-inducing anticonvulsant medications have an increased plasma clearance of dexmedetomidine as compared with healthy control subjects.

Hemodynamic stability after intraarterial injection of verapamil for cerebral vasospasm.

BACKGROUND: Vasospasm after subarachnoid hemorrhage is a common and potentially life-threatening complication. Treatment of vasospasm may include intraarterial (IA) injections of verapamil into the cerebral vasculature. Clinical experience suggests that the average patient experiences an acute reduction in systemic blood pressure after IA verapamil. Our study objective was to (1) identify the effects of IA injection of verapamil on mean arterial blood pressure (MAP) and heart rate (HR) in patients with cerebral vasospasm and (2) determine the effect of verapamil dose on change in MAP and HR. We hypothesized that (1) selective IA injection of verapamil for treatment of cerebral vasospasm is associated with a reduction in MAP and an increase in HR and (2) the change in MAP and HR are linearly related to the dose of verapamil administered. METHODS: We prospectively studied subjects with vasospasm scheduled for cerebral angiography with possible IA injection of verapamil. All subjects were given a general anesthetic. Invasive arterial blood pressure and HR were monitored continuously and recorded at 10-second intervals throughout the procedure. We identified the lowest MAP and highest HR before and after verapamil injection. The association between IA verapamil and change in MAP and HR was determined using repeated-measures multivariate regression analysis, adjusting for potential confounding factors (weight, preoperative vasopressor use, and preinjection MAP). Data are reported as adjusted coefficients and 95% confidence intervals (CI). RESULTS: We included 20 subjects who underwent a total of 46 injections of IA verapamil. On the basis of our multivariate model, on average, each 5 mg of IA verapamil was associated with a 3.5 mm Hg reduction in MAP (95% CI -5.0 to -2.0, P < 0.001). HR was not significantly altered by IA verapamil on both unadjusted and adjusted analyses (nonsignificant increase of 0.4 beats per minute for each 5 mg of IA verapamil, 95% CI -1.6 to 2.4, P = 0.70). CONCLUSIONS: Under general anesthesia, injection of IA verapamil into cerebral arteries reduces MAP but does not change HR in the average patient. Further research is required to determine the clinical significance of these results.

The effects of sympathectomy on finger photoplethysmography and temperature measurements in healthy subjects.

BACKGROUND: Photoplethysmography uses light transmission to measure changes in tissue volume. The resulting photoplethysmogram is composed of AC and DC components. Limited data are available on the effects of vasodilation on the AC and the DC components of the photoplethysmograph signal. The aims of our study were (1) to investigate the effects of sympathectomy on different components of the photoplethysmogram, and (2) to compare sympathectomy-induced changes in the photoplethysmogram with changes in peripheral temperature. METHODS: In 10 healthy subjects, sympathectomy-induced peripheral vasodilation was achieved using an axillary brachial plexus block. The nonblocked arm served as control. We obtained measurements of bilateral continuous measurements of finger blood volume (by photoplethysmography) and finger temperature. We separated the finger photoplethysmogram into its AC and DC components. In addition, we calculated the ratio of AC to DC (AC/DC). All data were recorded until 30 minutes after the end of brachial plexus block. Repeated-measures analysis of variance followed by the Dunnett post hoc test determined the effect of brachial plexus block on the finger photoplethysmogram and finger temperature. RESULTS: The DC component of the finger photoplethysmogram decreased (vasodilation) significantly (P < 0.0001) after brachial plexus block in the blocked arm starting 2.7 minutes after the block. Average decrease in DC values was -51% ± 19% (95% confidence interval: -61% to -42%) at 30 minutes after the block. None of the other photoplethysmogram components changed significantly from preblock baseline values. On average, the finger temperature increased significantly (P < 0.0001) starting 5.7 minutes after brachial plexus block in the blocked arm. Average increase in temperature was 7.1°C ± 3.8°C (95% confidence interval: 5.1°C-9.0°C) 30 minutes after the block. The DC component of the photoplethysmogram had the highest sensitivity and specificity to predict a successful block. CONCLUSIONS: This study characterizes sympathectomy-induced changes in the AC and DC components of the finger photoplethysmogram. In this experimental model, we found the DC component to be most sensitive in detecting peripheral vasodilation.

Subthalamic nucleus deep brain stimulator placement using high-field interventional magnetic resonance imaging and a skull-mounted aiming device: technique and application accuracy.

OBJECT: The authors discuss their method for placement of deep brain stimulation (DBS) electrodes using interventional MR (iMR) imaging and report on the accuracy of the technique, its initial clinical efficacy, and associated complications in a consecutive series of subthalamic nucleus (STN) DBS implants to treat Parkinson disease (PD). METHODS: A skull-mounted aiming device (Medtronic NexFrame) was used in conjunction with real-time MR imaging (Philips Intera 1.5T). Preoperative imaging, DBS implantation, and postimplantation MR imaging were integrated into a single procedure performed with the patient in a state of general anesthesia. Accuracy of implantation was assessed using 2 types of measurements: the "radial error," defined as the scalar distance between the location of the intended target and the actual location of the guidance sheath in the axial plane 4 mm inferior to the commissures, and the "tip error," defined as the vector distance between the expected anterior commissure-posterior commissure (AC-PC) coordinates of the permanent DBS lead tip and the actual AC-PC coordinates of the lead tip. Clinical outcome was assessed using the Unified Parkinson's Disease Rating Scale part III (UPDRS III), in the off-medication state. RESULTS: Twenty-nine patients with PD underwent iMR imaging-guided placement of 53 DBS electrodes into the STN. The mean (+/- SD) radial error was 1.2 +/- 0.65 mm, and the mean absolute tip error was 2.2 +/- 0.92 mm. The tip error was significantly smaller than for STN DBS electrodes implanted using traditional frame-based stereotaxy (3.1 +/- 1.41 mm). Eighty-seven percent of leads were placed with a single brain penetration. No hematomas were visible on MR images. Two device infections occurred early in the series. In bilaterally implanted patients, the mean improvement on the UPDRS III at 9 months postimplantation was 60%. CONCLUSIONS: The authors' technical approach to placement of DBS electrodes adapts the procedure to a standard configuration 1.5-T diagnostic MR imaging scanner in a radiology suite. This method simplifies DBS implantation by eliminating the use of the traditional stereotactic frame and the subsequent requirement for registration of the brain in stereotactic space and the need for physiological recording and patient cooperation. This method has improved accuracy compared with that of anatomical guidance using standard frame-based stereotaxy in conjunction with preoperative MR imaging.

Recent advances in pulse oximetry.

Conventional pulse oximetry uses two wavelengths of light (red and infrared) transmitted through a finger and a photodetector to analyze arterial hemoglobin oxygen saturation and pulse rate. Recent advances in pulse oximetry include: extended analysis of the photo plethysmographic waveform; use of multiple wavelengths of light to quantify methemoglobin, carboxyhemoglobin and total hemoglobin content in blood; and use of electronic processes to improve pulse oximeter signal processing during conditions of low signal-to-noise ratio. These advances have opened new clinical applications for pulse oximeters that will have an impact on patient monitoring and management.

Dexmedetomidine does not reduce epileptiform discharges in adults with epilepsy.

There are limited data on the effect of dexmedetomidine on epileptiform electroencephalogram (EEG). The aim of this study was to investigate if dexmedetomidine will abolish epileptiform discharges in patients with medically refractory seizure disorders who were candidates for surgery to resect foci of epileptic activity. With approval from the Institutional Review Board and written informed consent, we enrolled 5 patients with medically intractable seizures who were undergoing continuous video/EEG monitoring. EEG and hemodynamic values were recorded from 15 minutes before, during, and for 60 minutes after a 60-minute dexmedetomidine infusion. Epileptiform discharges were counted for each 15-minute epoch during the study. Two of the 5 patients had a discrete spike focus in each hemisphere. Thus, we analyzed the activity of 7 distinct foci. Epileptiform activity did not decrease in any individual focus during dexmedetomidine infusion. Although dexmedetomidine did not have a statistically significant effect on interictal epileptiform activity for the group as a whole, the activity of 4 foci increased during dexmedetomidine infusion. Dexmedetomidine did not reduce seizure focus activity and thus may be a suitable anesthetic adjunct during seizure surgery.

Effect of peripheral vasoconstriction on pulse oximetry.

OBJECTIVE: We tested the hypothesis that peripheral vasodilation has an effect on arterial oxygen saturation measurements by pulse oximetry, independent of temperature. METHODS: Study 1 compared finger arterial oxygen saturation values (SpO(2)), before and after peripheral vasoconstriction while temperature was kept constant. This was achieved by administering dexmedetomidine (peripheral vasoconstrictor) to 16 volunteers given general anesthesia. Study 2 compared SpO(2) before and after peripheral vasodilation (brachial plexus block) in a neurally denervated left hand and a neurally innervated right hand in ten awake volunteers. In both studies measurements were also made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmission through a finger (LTF), finger temperature and of hemodynamic variables. RESULTS: In Study 1, systolic blood pressure, SpO(2) and LTF values increased (vasoconstriction) during dexmedetomidine infusion, (P<0.0001 for all) while there were no changes in finger temperature. In Study 2, in the left hand (axillary block), temperature increased by 1.9 +/- 1.6 degrees C (P=0.004), SpO(2) decreased by 2.5 +/- 1.0 % (P<0.0001) and LTF values decreased (vasodilation) by 42 +/- 8 % (P<0.0001) after axillary block. Simultaneously, the axillary block did not induce any changes in temperature, SpO(2) or LTF values in the neurally innervated right hand. CONCLUSIONS: Our results demonstrate that finger pulse oximeter SpO(2) measurements can be affected by peripheral vascular tone independent of temperature. The mechanism for this effect remains speculative and unproven.

Placement of deep brain stimulator electrodes using real-time high-field interventional magnetic resonance imaging.

A methodology is presented for placing deep brain stimulator electrodes under direct MR image guidance. The technique utilized a small, skull-mounted trajectory guide that is optimized for accurate alignment under MR fluoroscopy. Iterative confirmation scans are used to monitor device alignment and brain penetration. The methodology was initially tested in a human skull phantom and proved capable of achieving submillimeter accuracy over a set of 16 separate targets that were accessed. The maximum error that was obtained in this preliminary test was 2 mm, motivating use of the technique in a clinical study. Subsequently, a total of eight deep brain stimulation electrodes were placed in five patients. Satisfactory placement was achieved on the first pass in seven of eight electrodes, while two passes were required with one electrode. Mean error from the intended target on the first pass was 1.0 +/- 0.8 mm (range = 0.1-1.9 mm). All procedures were considered technical successes and there were no intraoperative complications; however, one patient did develop a postoperative infection.

Alpha-2B adrenoceptor polymorphism and peripheral vasoconstriction.

OBJECTIVES: Alpha-2B adrenoceptors (AR) mediate vasoconstriction in the mice. A human alpha-2B AR deletion (D) variant has been associated with loss of short-term agonist-promoted receptor desensitization, which may lead to increased vasoconstriction upon alpha-2 AR activation. This study tested the hypothesis that alpha-2 AR activation will induce enhanced vasoconstriction in carriers of the alpha-2B AR DD genotype, compared to carriers of the II or the DI genotypes. METHODS: We administered 1 microg/kg dexmedetomidine (an alpha-2 agonist) intravenously to 80 surgical patients in whom sympatholytic effects of the drug were attenuated by general anesthesia. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmission through a finger (LTF) and of hemodynamic variables. RESULTS: Dexmedetomidine increased LTF (vasoconstriction), induced an initial increase in systolic blood pressure and decreased heart rate in all genotype groups (P<0.0001 for all). Three min after the start of dexmedetomidine infusion, the increase in LTF was more pronounced (P=0.014) in the DD group compared to the DI and II groups. There were no significant differences in LTF values between the groups at the end of or 5 min after dexmedetomidine infusion. There were no differences in systolic blood pressure or heart rate values between the groups during or after the dexmedetomidine infusion. CONCLUSIONS: The results of this study confirm that the alpha-2 agonist dexmedetomidine induced marked peripheral vasoconstriction. Subjects with the alpha 2B DD genotype had an enhanced vasoconstrictive response at the beginning of dexmedetomidine infusion. However, this enhanced vasoconstrictive response was not sustained throughout or after the 15-min dexmedetomidine infusion.