Effect of pain on autonomic nervous system indices derived from photoplethysmography in healthy volunteers.

BACKGROUND: Photoplethysmographic pulse wave amplitude (PPGA) and heart rate (HR) can be used to measure cold, nociception-induced autonomic responses, or both. The aim of our study was to correlate the intensity of experimental pain to changes in physiological variables reflecting the autonomic nervous system response to pain. METHODS: PPGA, HR, and subjective measurements of pain intensity were measured in 29 healthy male volunteers during two heat stimuli (43°C and 48°C) and the cold pressor test (CPT). Surgical pleth index (SPI), autonomic nervous system state (ANSS), and ANSS index (ANSSi) were calculated using PPGA and HR. RESULTS: Pain intensity scores increased on the average by 1.6, 3.5, and 8.1 for the 43°C, 48°C, and CPT stimuli, respectively. The pain intensity scores for all three stimuli groups were significantly different from each other (P<0.001). All three stimuli changed HR, PPGA, SPI, ANSS, and ANSSi values significantly from their respective baseline values (P<0.001 for all). Heat stimuli-induced pain intensity did not correlate with the magnitude of the respective changes in HR, PPGA, SPI, ANSS, and ANSSi. CPT-induced pain intensity correlated with the magnitude of the respective changes in HR, PPGA, SPI, ANSS, and ANSSi. PPGA, ANSSi, ANSS, and SPI differentiated between heat and cold stimuli-induced pain. CONCLUSIONS: All three thermal stimuli produced a significant change in photoplethysmograph-derived parameters. All photoplethysmograph-derived parameters appear to be suitable to study autonomic nervous system activation.

Effects of nitric oxide synthase inhibition on dexmedetomidine-induced vasoconstriction in healthy human volunteers.

BACKGROUND: This study aimed to assess the contribution of endothelial nitric oxide synthesis to the net responses of human peripheral blood vessels in vivo to the selective alpha(2)-adrenoceptor agonist dexmedetomidine. METHODS: Two groups of healthy young men were studied. In the first experiment, after brachial plexus block, the responses of digital arteries to systemically administered dexmedetomidine (target plasma concentration 1.2 ng ml(-1)) were studied using a photoplethysmograph (n=10) during i.a. infusions of saline and the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) (8 micromol min(-1)). In a separate experiment, after pre-treatment with acetylsalicylic acid, responses to increasing doses of dexmedetomidine (0.01-164 ng min(-1)) in the presence and absence of L-NMMA were compared in dorsal hand veins (DHV) (n=10) using linear variable differential transformers. RESULTS: L-NMMA significantly augmented dexmedetomidine-induced vasoconstriction of digital arteries as assessed by an increase in light transmission through a finger and by a decrease in finger temperature. The mean (95% confidence interval) extent of the additional effect of L-NMMA over the constrictor effect of dexmedetomidine alone was 19% (14-24) (P<0.0001). In DHV, L-NMMA had variable effects on the dexmedetomidine-constriction dose-response curve. In three subjects, the curve was shifted significantly to the left (with a >10-fold difference in ED(50)), but ED(50) was only marginally affected by L-NMMA in the other subjects (difference in ED(50)

Transcutaneous PO2 measurements in health and peripheral arterial occlusive disease.

Transcutaneous oxygen tensions (tcPO2) of the lower extremity were investigated in 24 control subjects and in 69 patients with various degrees of peripheral arterial occlusive disease. With a modified Clark-type oxygen electrode, tcPO2 was monitored from the right subclavicular region (position 1), upper calf (position 2), and dorsum of the foot (position 3). The tcPO2 was significantly lower in patients when compared to control subjects. The reproducibility of the method was determined from double determinations of the tcPO2 (position 2) in control subjects. The comparison of tcPO2 value between the right and left lower extremity showed no significant differences. The tcPO2 of the foot or leg showed an increase, when positioning the limb below the phlebostatic level. The response of the tcPO2 after transient arterial occlusion (4 minutes) was significantly delayed in patients compared to control subjects. Finally, preliminary results of 35 patients in whom amputations had been performed suggest that tcPO2 measurement may become a useful prognosticator for the determination of the optimal amputation level.

Effects of allopurinol on smoke inhalation in the ovine model.

We hypothesized that the pulmonary damage induced by smoke inhalation is the result of ischemic reperfusion injury. We determined the effect of allopurinol (xanthine oxidase inhibitor) on the pulmonary microvascular fluid flux in an ovine model after inhalation of cotton smoke (n = 13) and compared these data with those from untreated similarly smoke-injured (n = 7), as well as sham- (air, n = 9) smoked, animals and sheep given an equivalent dose of CO (n = 7). Smoke injury resulted in an increased lung lymph flow, lymph-to-plasma protein ratio, lung content of polymorphonuclear cells, and extravascular lung water (gravametric), in addition to histological evidence of tissue (pulmonary) edema and destruction. No significant difference was found in these variables between the sheep that were injured with smoke whether or not they were pretreated with allopurinol. The sham-smoked and CO-insufflated animals showed no significant changes in cardiopulmonary function or morphology. We conclude that there are few data to support a role of ischemic reperfusion injury in the pulmonary damage seen after smoke inhalation.

Positive end-expiratory pressure ventilation increases extravascular lung water due to a decrease in lung lymph flow.

Positive end-expiratory pressure (PEEP) is used to improve gas exchange, increase functional residual capacity, recruit air spaces, and decrease pulmonary shunt in patients suffering from respiratory failure. The effect of PEEP on extravascular lung water (EVLW), however, is still not fully understood. This study was designed as a prospective laboratory experiment to evaluate the effects of PEEP on EVLW and pulmonary lymph flow (QL) under physiologic conditions. Twelve adult sheep were operatively prepared to measure haemodynamics of the systemic and pulmonary circulation, and to assess EVLW In addition, the lung lymphatic duct was cannulated and a tracheostomy performed. The animals were then mechanically ventilated in the awake-state without end-expiratory pressure (PEEP 0). After a two-hour baseline period, PEEP was increased to 10 cmH2O for the duration of two hours, and then reduced back to 0 cmH2O. Cardiopulmonary variables, QL, and arterial blood gases were recorded intermittently; EVLW was determined two hours after each change in PEEP. The increase in PEEP resulted in a decrease in QL (7 +/- 1 vs 5 +/- 1 ml/h) and an increase in EVLW (498 +/- 40 vs 630 +/- 58 ml; P<0.05 each) without affecting cardiac output. As PEEP was decreased back to baseline, QL increased significantly (5 +/- 1 vs 10 +/- 2 ml/h), whereas EVLW returned back to baseline. This study suggests that institution of PEEP produces a reversible increase in EVLW that is linked to a decrease in QL.

Measurement of systolic blood pressure using pulse oximetry during helicopter flight.

OBJECTIVE: Monitoring of vital signs in critically ill patients during helicopter flight is difficult because of the noise and vibrations of the aircraft. We evaluated the use of a pulse oximeter to measure systolic BP intraflight. DESIGN: Systolic BP measured by pulse oximetry was compared with systolic BP measured by the direct intra-arterial and the arterial occlusion methods intraflight. Systolic BP by pulse oximetry was measured by observing the return of the plethysmographic waveform of the pulse oximeter as the BP cuff ipsilateral to the pulse oximeter probe was slowly deflated. Arterial occlusion pressure was measured by observing the return of the intraarterial waveform as the BP cuff ipsilateral to the arterial cannula was slowly deflated. SETTING: The study was performed during patient transport, intraflight. PATIENTS: Ten critically ill patients were studied. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Seventy-three sets of measurements were recorded. The best correlation (r2 = .99) was found between pulse oximetry and the arterial occlusion method. The indirect methods correlated better with each other than with direct intraarterial measurements. The noise and the vibrations of the helicopter did not significantly interfere with the operation of the pulse oximeter. CONCLUSIONS: We conclude that a pulse oximeter that displays a plethysmographic waveform can accurately measure systolic BP intraflight.

Amount of air infused to patient increases as fluid flow rates decrease when using the Hotline HL-90 fluid warmer.

OBJECTIVE: The intraoperative use of fluid warming devices has been recommended to avoid perioperative hypothermia and related adverse outcomes. To evaluate whether these devices might introduce risks of their own, we measured the volume of air escaping from a warmed intravenous solution that might be delivered to a patient. METHODS: In an operating room maintained at 19-19.5 degrees C, we tested an HL-90 Hotline fluid warmer with the L-70 fluid-warming set. One liter of lactated Ringer's solution was infused at flow rates of 150, 300, 500 and 3400 ml/h. The air that formed within the L-70 tubing during infusion was collected in a bubble trap placed at the end of the L-70 tubing. The volume of air in the bubble trap was measured. Twelve separate measurements were obtained at each flow rate. One additional study (n = 8) was performed using the L-10 Gas Vent to determine whether this equipment might reduce the volume of air infused when fluid flow rate was 300 mL/h. The volume of air collected at each flow rate was compared using ANOVA. RESULTS: Volume of air increased significantly from 1.0 +/- 0.2 mL to 2.9 +/- 0.4 ml as flow rate decreased from 3400 ml/h to 150 ml/h (p < 0.0001). The L-10 gas eliminator was ineffective in reducing the amount of air infused. CONCLUSIONS: We conclude that the use of the Hotline fluid warmer can result in infusion of air into the patient, introducing possible risk of air embolism.

Dose-response study of oral famotidine for reduction of gastric acidity and volume in outpatients and inpatients.

A relatively new H2-antagonist, famotidine, has become clinically available, but its effectiveness in decreasing gastric acidity and volume has not been compared in inpatients and outpatients. We reexamined the difference in gastric acidity and volume in inpatients and outpatients, and tested the effectiveness of different oral doses and dosage regimens of famotidine in reducing gastric acidity and volume in both groups of patients. Patients received either placebo or 20 mg or 40 mg of famotidine orally the night before surgery (HS) and on the morning of surgery (AM). One hundred forty-two inpatients and 180 outpatients were randomized to one of seven groups as follows: 1) placebo (HS)/placebo (AM); 2) 20 mg of famotidine (HS)/20 mg of famotidine (AM); 3) 20 mg of famotidine (HS)/placebo (AM); 4) placebo (HS)/20 mg of famotidine (AM); 5) 40 mg of famotidine (HS)/40 mg of famotidine (AM); 6) 40 mg of famotidine (HS)/placebo (AM); and 7) placebo (HS)/40 mg of famotidine (AM). We measured the gastric acidity and volume after induction of anesthesia and found no difference between the inpatients and outpatients, with or without famotidine. We found that famotidine given HS and AM or AM only was effective in reducing gastric acidity in both groups of patients, and that there was no difference between the 20-mg and 40-mg doses of famotidine. Gastric volume was not affected by any famotidine dose.

Effects of dexmedetomidine on hypoxia-evoked glutamate release and glutamate receptor activity in hippocampal slices.

BACKGROUND: The selective alpha(2) agonist dexmedetomidine may improve neurologic outcome after incomplete ischemia in animals when it is administered either before or after the start of the ischemic insult. To clarify further the mechanisms by which alpha(2) agonists may provide neuroprotective effects, the authors tested the hypotheses that dexmedetomidine decreases synaptic and extrasynaptic glutamate release stimulated by potassium chloride or hypoxia, and decreases postsynaptic glutamate receptor activity during aerobic or hypoxic conditions. METHODS: Glutamate released from brain slices (300-microns thick) from rat hippocampus was measured in a cuvette during two experimental stresses: (1) potassium chloride-evoked depolarization (30 mM) with and without 10 nM, 100 nM, or 1,000 nM dexmedetomidine; and (2) hypoxia (95% N2 - 5% CO2) with and without 100 nM dexmedetomidine. Glutamate release was quantified by fluorescence assay using 1 mM nicotinamide adenine dinucleotide, and 5 international units per ml glutamate dehydrogenase. The formation of nicotinamide dinucleotide reduced from nicotinamide adenine dinucleotide by glutamate dehydrogenase was measured fluorometrically (excitation light 340 nm, emission intensity 460 nm) in the solution above the slice. Glutamate receptor activity was determined by the change in cytosolic calcium concentration in CA1 neurons in the presence and absence of 100 nM dexmedetomidine during administration of N-methyl-D-aspartate (100 microM) and during simulated ischemic penumbra conditions (PO2 = 20 mmHg, glutamate 3 mM). Calcium concentration was measured using a microscope fluorometer in fura 2-loaded rat hippocampal brain slices. RESULTS: Dexmedetomidine attenuated potassium chloride-evoked glutamate release by 37%, 51%, (P = 0.03) and 27%, respectively, for the 10 nM, 100 nM, and 1,000 nM concentrations, and decreased (at 100 nM) the increase in glutamate release in response to hypoxia by 61% (P < 0.0001). Dexmedetomidine (100 nM) had no effect on N-methyl-D-aspartate or hypoxia plus 3 mM L-glutamate-mediated calcium changes. CONCLUSIONS: The selective alpha(2)-adrenergic agonist dexmedetomidine decreases evoked glutamate release from hippocampal rat brain slices during depolarization or hypoxic stress, but does not alter calcium changes mediated by the stimulation of glutamate receptors during aerobic or hypoxic conditions.

Effect of dexmedetomidine, an alpha2-adrenoceptor agonist, on human pupillary reflexes during general anaesthesia.

AIMS: To test the hypothesis that the alpha2-adrenergic agonist, dexmedetomidine, dilates the pupil and does not alter the pupillary light reflex of anaesthetized patients. METHODS: Eight volunteers were administered general anaesthesia with propofol, nitrous oxide and alfentanil. One hour and 25 min after induction of anaesthesia, a 45 min infusion of dexmedetomidine was begun, targeting a plasma concentration of 0.6 ng x ml(-1). Pupil size, pupillary light reflex amplitude, light reflex recovery time, and reflex dilation were measured before and during dexmedetomidine infusion. RESULTS: Dexmedetomidine produced no change in pupil size and light reflex recovery time, increased the light reflex from 0.30 +/- 0.14 to 0.37 +/- 0.12 mm and significantly reduced pupillary reflex dilation by 72 +/- 62%. CONCLUSIONS: These pupillary effects of dexmedetomidine in humans are difficult to reconcile with the findings obtained in cats and rats that have demonstrated a direct inhibitory effect of alpha2-adrenergic agonists on the pupilloconstrictor nucleus. The increase in the magnitude of the light reflex in response to dexmedetomidine does not necessarily involve an anxiolytic mechanism.

Effects of intrathecally administered dexmedetomidine, MPV-2426 and tizanidine on EMG in rats.

BACKGROUND: When administered intrathecally, alpha-2 adrenergic agonists produce spinally mediated antinociception, but also rapidly redistribute to supraspinal sites. This investigation the compared EMG effects of intrathecally administered dexmedetomidine, MPV-2426 (fadolmidine), and tizanidine in Sprague-Dawley rats, which has not been previously described. METHODS: We studied electromyographic (EMG) responses of the head and gastrocnemius muscles, antinociception using the tail-flick test, and sedation by using observer assessment. Saline, dexmedetomidine (0.5 microg, 2.5 microg and 12.5 microg), MPV-2426 (2 microg, 10 microg and 50 microg) and tizanidine (2 microg, 10 microg and 50 microg) were administered intrathecally. RESULTS: Tizanidine 50 microg, MPV-2426 10 microg and 50 microg, and dexmedetomidine 2.5 microg and 12.5 microg, decreased EMG activity (P < 0.005). Dexmedetomidine 12.5 microg, MPV-2426 50 microg, and tizanidine 10 microg and 50 microg increased tail-flick latencies (P < 0.01). Dexmedetomidine alone significantly increased the magnitude of observer-assessed sedation (P < 0.0001). CONCLUSION: We conclude that in rats, intrathecally administered dexmedetomidine, MPV-2426 and tizanidine have dose-dependent effects on EMG. At antinociceptive doses, the EMG effects of these three alpha-2 adrenergic agonists differ (dexmedetomidine > MPV-2426 > tizanidine).

Does measurement of systolic blood pressure with a pulse oximeter correlate with conventional methods?

The pulse oximeter is commonly used in the operating room. We evaluated the use of a pulse oximeter to monitor systolic blood pressure in 20 healthy volunteers and 42 anesthetized patients. We compared the pulse oximeter method of measuring systolic blood pressure with the cuff methods using Korotkoff sounds and Doppler ultrasound as well as with direct pressure measurement through an intraarterial cannula. Systolic blood pressure values obtained by pulse oximeter correlated well with values obtained by other conventional methods. The best correlation was found with Doppler ultrasound (r = 0.996) and the worst with arterial cannulation (r = 0.880). We conclude that this method can be used intraoperatively to measure systolic blood pressure.

Monitoring patients during helicopter flight.

In 11 patients being transported via helicopter we monitored heart rate, arterial oxygen saturation, and systolic blood pressure with a pulse oximeter. We were able to obtain vital signs in 10 of 11 patients. The pulse oximeter was a useful tool in monitoring vital signs intraflight.

Effects of reduced sympathetic activity on myocardial metaiodobenzylguanidine (MIBG) washout.

1. Increase in myocardial sympathetic activity contributes markedly to the pathophysiology of conditions such as congestive heart failure and is also associated with myocardial infarction. However, measurement of myocardial sympathetic activity in vivo is difficult. 2. The present study assesses the effectiveness of metaiodobenzylguanidine (MIBG) imaging to characterize modulation of sympathetic activity, as induced by dexmedetomidine, a highly specific alpha-2 adrenoceptor agonist. 3. We imaged washout of [125I]-MIBG from rabbit heart before and during two consecutive 45-min intravenous infusions of dexmedetomidine (10 microg kg(-1) followed by 16 microg kg(-1)) (n=9) or of saline (n=9). 4. Heart rate (HR), and mean blood pressure (BP) were measured before and at the end of each study period. Plasma noradrenaline (NA) was measured before and after study drug infusion. The hearts were then excised and biopsied for MIBG tissue concentration [MIBG] (% kg-dose g(-1)). 5. Relative to saline controls, dexmedetomidine significantly decreased HR, BP, plasma NA and MIBG washout. There was an inverse correlation between MIBG washout and residual [MIBG] in the myocardium (r= -0.75, P < 0.01). 6. These data suggest that a reduction of sympathetic nervous system activity causes a decrease in myocardial MIBG washout in vivo in rabbits, and confirms the usefulness of MIBG scintigraphy as a non-invasive tool to measure changes in myocardial sympathetic activity.

Sevoflurane increases lumbar cerebrospinal fluid pressure in normocapnic patients undergoing transsphenoidal hypophysectomy.

BACKGROUND: The data on the effect of sevoflurane on intracranial pressure in humans are still limited and inconclusive. The authors hypothesized that sevoflurane would increase intracranial pressure as compared to propofoL METHODS: In 20 patients with no evidence of mass effect undergoing transsphenoidal hypophysectomy, anesthesia was induced with intravenous fentanyl and propofol and maintained with 70% nitrous oxide in oxygen and a continuous propofol infusion, 100 microg x kg(-1) x min(-1). The authors assigned patients to two groups randomized to receive only continued propofol infusion (n = 10) or sevoflurane (n = 10) for 20 min. During the 20-min study period, each patient in the sevoflurane group received, in random order, two concentrations (0.5 times the minimum alveolar concentration [MAC] and 1.0 MAC end-tidal) of sevoflurane for 10 min each. The authors continuously monitored lumbar cerebrospinal fluid (CSF) pressure, blood pressure, heart rate, and anesthetic concentrations. RESULTS: Lumbar CSF pressure increased by 2+/-2 mmHg (mean+/-SD) with both 0.5 MAC and 1 MAC of sevoflurane. Cerebral perfusion pressure decreased by 11+/-5 mmHg with 0.5 MAC and by 15+/-4 mmHg with 1.0 MAC of sevoflurane. Systolic blood pressure decreased with both concentrations of sevoflurane. To maintain blood pressure within predetermined limits (within+/-20% of baseline value), phenylephrine was administered to 5 of 10 patients in the sevoflurane group (range = 50-300 microg) and no patients in the propofol group. Lumbar CSF pressure, cerebral perfusion pressure, and systolic blood pressure did not change in the propofol group. CONCLUSIONS: Sevoflurane, at 0.5 and 1.0 MAC, increases lumbar CSF pressure. The changes produced by 1.0 MAC sevoflurane did not differ from those observed in a previous study with 1.0 MAC isoflurane or desflurane.

Desflurane and isoflurane increase lumbar cerebrospinal fluid pressure in normocapnic patients undergoing transsphenoidal hypophysectomy.

BACKGROUND: Rapid emergence from anesthesia makes desflurane an attractive choice as an anesthetic for patients having neurosurgery. However, the data on the effect of desflurane on intracranial pressure in humans are still limited and inconclusive. The authors hypothesized that isoflurane and desflurane increase intracranial pressure compared with propofol. METHODS: Anesthesia was induced with intravenous fentanyl and propofol in 30 patients having transsphenoidal hypophysectomy with no evidence of mass effect, and it was maintained with 70% nitrous oxide in oxygen and a continuous 100 micrograms.kg-2.min-1 infusion of propofol. Patients were assigned to three groups randomized to receive only continued propofol infusion (n = 10), desflurane (n = 10), or isoflurane (n = 10) for 20 min. During the 20-min study period, each patient in the desflurane and isoflurane groups received, in random order, two concentrations (0.5 minimum alveolar concentration [MAC] and 1.0 MAC end-tidal) of desflurane or isoflurane for 10 min each. Lumbar cerebrospinal fluid (CSF) pressure, blood pressure, heart rate, and anesthetic concentrations were monitored continuously. RESULTS: Lumbar CSF pressure increased significantly in all patients receiving desflurane or isoflurane. Lumbar CSF pressure increased by 5 +/- 3 mmHg at 1-MAC concentrations of desflurane and by 4 +/- 2 mmHg at 1-MAC concentrations of isoflurane. Cerebral perfusion pressure decreased by 12 +/- 10 mmHg at 1-MAC concentrations of desflurane and by 15 +/- 10 mmHg at 1-MAC concentrations of isoflurane. Heart rate increased by 7 +/- 9 bpm with 0.5 MAC desflurane and by 8 +/- 7 bpm with 1.0 MAC desflurane, and by 5 +/- 11 bpm with 1.0 MAC isoflurane. Systolic blood pressure decreased in all but the patients receiving 1.0 MAC desflurane. To maintain blood pressure within predetermined limits, phenylephrine was administered to six of ten patients in the isoflurane group (range, 25 to 600 micrograms), two of ten patients in the desflurane group (range, 200 to 500 micrograms), and in no patients in the propofol group. Lumbar CSF pressure, heart rate, and systolic blood pressure did not change in the propofol group. CONCLUSION: Desflurane and isoflurane, at 0.5 and 1.0 MAC, increase lumbar CSF pressure.

Postoperative pharmacokinetics and sympatholytic effects of dexmedetomidine.

UNLABELLED: Dexmedetomidine is a selective alpha2-adrenoceptor agonist with centrally mediated sympatholytic, sedative, and analgesic effects. This study evaluated: 1) pharmacokinetics of dexmedetomidine in plasma and cerebrospinal fluid (CSF) in surgical patients; 2) precision of a computer-controlled infusion protocol (CCIP) for dexmedetomidine during the immediate postoperative period; and 3) dexmedetomidine's sympatholytic effects during that period. Dexmedetomidine was infused postoperatively by CCIP for 60 min to eight women, targeting a plasma concentration (Cp) of 600 pg/mL. Before, during, and after infusion, blood was sampled to determine plasma concentrations of norepinephrine, epinephrine, and dexmedetomidine, and CSF was sampled to determine dexmedetomidine concentrations (C[CSF]). Heart rate and arterial blood pressure were measured continuously from 5 min before until 3 h after the end of infusion. During the infusion, Cp values generally exceeded the target value: median percent error averaged 21% and ranged from -2% to 74%; median absolute percent error averaged 23% and ranged from 4% to 74%. After infusion, C(CSF) was 4% +/- 1% of Cp. Because C(CSF) barely exceeded the assay's limit of quantitation, CSF pharmacokinetics were not determined. During the infusion, norepinephrine decreased from 2.1 +/- 0.8 to 0.7 +/- 0.3 nmol/L; epinephrine decreased from 0.7 +/- 0.5 to 0.2 +/- 0.2 nmol/L; heart rate decreased from 76 +/- 15 to 64 +/- 11 bpm; and systolic blood pressure decreased from 158 +/- 23 to 140 +/- 23 mm Hg. We conclude that infusion of dexmedetomidine by CCIP using published pharmacokinetic parameters overshoots target dexmedetomidine concentrations during the early postoperative period. Hemodynamic and catecholamine results suggest that dexmedetomidine attenuates sympathetic activity during the immediate postoperative period. IMPLICATIONS: We studied the pharmacokinetic and sympatholytic effects of dexmedetomidine during the immediate postoperative period and found that during this period, the published pharmacokinetic data slightly overshoot target plasma dexmedetomidine concentrations. We also found that heart rate, blood pressure, and plasma catecholamine concentrations decrease during dexmedetomidine infusion.

Dexmedetomidine does not alter the sweating threshold, but comparably and linearly decreases the vasoconstriction and shivering thresholds.

BACKGROUND: Clonidine decreases the vasoconstriction and shivering thresholds. It thus seems likely that the alpha2 agonist dexmedetomidine will also impair control of body temperature. Accordingly, the authors evaluated the dose-dependent effects of dexmedetomidine on the sweating, vasoconstriction, and shivering thresholds. They also measured the effects of dexmedetomidine on heart rate, blood pressures, and plasma catecholamine concentrations. METHODS: Nine male volunteers participated in this randomized, double-blind, cross-over protocol. The study drug was administered by computer-controlled infusion, targeting plasma dexmedetomidine concentrations of 0.0, 0.3, and 0.6 ng/ml. Each day, skin and core temperatures were increased to provoke sweating and then subsequently reduced to elicit vasoconstriction and shivering. Core-temperature thresholds were computed using established linear cutaneous contributions to control of sweating, vasoconstriction, and shivering. The dose-dependent effects of dexmedetomidine on thermoregulatory response thresholds were then determined using linear regression. Heart rate, arterial blood pressures, and plasma catecholamine concentrations were determined at baseline and at each threshold. RESULTS: Neither dexmedetomidine concentration increased the sweating threshold from control values. In contrast, dexmedetomidine administration reduced the vasoconstriction threshold by 1.61 +/- 0.80 degrees C x ng(-1) x ml (mean +/- SD) and the shivering threshold by 2.40 +/- 0.90 degrees C x ng(-1) x ml. Hemodynamic responses and catecholamine concentrations were reduced from baseline values, but they did not differ at the two tested dexmedetomidine doses. CONCLUSIONS: Dexmedetomidine markedly increased the range of temperatures not triggering thermoregulatory defenses. The drug is thus likely to promote hypothermia in a typical hospital environment; it is also likely to prove an effective treatment for shivering.

The effect of clonidine on cerebral blood flow velocity, carbon dioxide cerebral vasoreactivity, and response to increased arterial pressure in human volunteers.

BACKGROUND: Because patients may be taking clonidine chronically or may be receiving it as a premedication before surgery, the authors investigated its effect on cerebral hemodynamics. METHODS: In nine volunteers, middle cerebral artery mean blood flow velocity (Vm) was measured using transcranial Doppler ultrasonography (TCD). CO2 vasoreactivity was measured before clonidine administration (preclonidine), 90 min after clonidine, 5 microg/kg orally, then following restoration of mean arterial pressure (MAP) to the preclonidine level. In addition, Vm was measured after a phenylephrine-induced 30-mmHg increase in MAP. RESULTS: After clonidine administration, Vm decreased from 62 +/- 9 to 48 +/- 8 cm/s (P < 0.01), and MAP decreased from 86 +/- 10 to 63 +/- 5 mmHg (P < 0.01; mean +/- SD). Clonidine decreased the CO2 vasoreactivity slope from 2.2 +/- 0.4 to 1.2 +/- 0.5 cm x s(-1) x mmHg(-1) (P < 0.05); restoring MAP to the preclonidine level increased the slope to 1.60 +/- 0.5 cm x s(-1) x mmHg(-1), still less than the preclonidine slope (P < 0.05). CO2 vasoreactivity expressed as a percentage change in Vm, decreased after clonidine, 3.5 +/- 0.8 versus 2.4 +/- 0.8 %/mmHg (P < 0.05); this difference disappeared after restoration of MAP, 3.1 +/- 1.2 %/mmHg. With a 30-mmHg increase in MAP, Vm increased by 13% before and after clonidine (P < 0.05). CONCLUSIONS: Clonidine, 5 microg/kg orally, decreases Vm and slightly attenuates cerebral CO2 vasoreactivity, therefore decreased cerebral blood flow and mildly attenuated CO2 vasoreactivity should be anticipated.