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Biomedical subjects

J E Caldwell

Publications and source records attributed to J E Caldwell.

At least 19 recordsLinked to original sources
PubMed2001

Does discontinuation of desflurane at the time of neostigmine administration speed recovery from cisatracurium block compared to that with a propofol-based technique?

BACKGROUND: Volatile anaesthetics are known to influence the effect of neostigmine as an antagonist of neuromuscular block. The aim of the present study was to investigate whether discontinuation of desflurane at the time of neostigmine administration shortens reversal time from cisatracurium block, compared to that with a propofol-based anaesthesia. METHODS: Ten volunteers were studied twice. For one study, anaesthesia was induced with alfentanil and propofol and maintained with nitrous oxide 70% and propofol 150 microg. kg-1. min-1. For the other study, experimental conditions were replicated except that desflurane 6% was administered and the dose of propofol was only 50 microg. kg-1. min-1. The evoked mechanical response of the adductor pollicis to train-of-four (TOF) stimulation was recorded. Neuromuscular block was induced with cisatracurium 0.2 mg. kg-1. When the magnitude of the first TOF response (T1) had recovered to 10%, the block was antagonized with neostigmine 70 microg. kg-1. At this time, propofol was decreased to 50 microg. kg-1. min-1, or the desflurane was discontinued. RESULTS: There were no significant differences between the two techniques of anaesthesia in the rate of neostigmine-induced recovery of the TOF ratio. The times (mean+/-SD) to achieve TOF ratios of 0.7, 0.8, and 0.9 were (propofol first, desflurane second) 6.1+/-2.2 and 6.5+/-1.6 min; 10.4+/-4.2 and 9.6+/-2.7 min; 17.1+/-6.9 and 21.0+/-13.0 min, respectively. CONCLUSION: Discontinuing desflurane does not speed neostigmine-induced recovery from cisatracurium neuromuscular block, when compared to that during propofol-based anaesthesia.

Adult↗
PubMed2001

Hemoglobin desaturation after succinylcholine-induced apnea: a study of the recovery of spontaneous ventilation in healthy volunteers.

BACKGROUND: Because of the rapid recovery of neuromuscular function after succinylcholine administration, there is a belief that patients will start breathing sufficiently rapidly to prevent significant oxygen desaturation. The authors tested whether this belief was valid. METHODS: Twelve healthy volunteers aged 18-45 yr participated in the study. After preoxygenation to an end-tidal oxygen concentration greater than 90%, each subject received 5 mg/kg thiopental and 1 mg/kg succinylcholine. Oxygen saturation (SaO2) was measured at both a finger and an ear lobe (beat to beat). During the period of apnea and as they were recovering, the volunteers received continuous verbal reassurance by the investigators. If the SaO2 decreased below 80%, the volunteers received chin lift and, if necessary, assisted ventilation. The length of time the subject was apneic and level of desaturation were related by linear regression analysis. One hour after recovery and again 1 week later, subjects were asked a series of questions regarding their emotional experience. RESULTS: In six volunteers, SaO2 decreased below 95% during apnea; in four, SaO2 decreased below 80%, necessitating chin lift and assisted ventilation in three. Apnea time was significantly longer in volunteers who reached SaO2 less than 80% than in those who did not (7.0+/-0.4 and 4.1+/-0.3 min, respectively), and there was a significant correlation between the length of time the subject was apneic and the magnitude of desaturation. CONCLUSIONS: Spontaneous recovery from succinylcholine-induced apnea may not occur sufficiently quickly to prevent hemoglobin desaturation in subjects whose ventilation is not assisted.

Adolescent↗
PubMed2000

Rapid tracheal intubation with large-dose rocuronium: a probability-based approach.

UNLABELLED: There are situations in anesthesia in which it may be desirable to achieve rapid tracheal intubation with perfect conditions, i.e., no coughing or straining. To determine the dose of rocuronium that gives a high probability of achieving perfect conditions for rapid (within 60 s) tracheal intubation, we administered a range of doses of rocuronium, some larger than used previously. Sixty adults, anesthetized with thiopental 4 mg/kg IV and alfentanil 10 microg/kg IV, received rocuronium 0.4 to 2.0 mg/kg IV. We used logistic regression to define the relationship of rocuronium dose to probability of achieving perfect intubation conditions. We estimated the doses giving 90% and 95% probability of achieving perfect intubation and used resampling to determine confidence limits for these estimates. Rocuronium 1.85 and 2.33 mg/kg gave, respectively, 90% and 95% probability of perfect intubation conditions. The confidence limits (5th and 95th percentile) for these estimates were 1.15 to 2.31 and 1.23 to 3.22 mg/kg, respectively. In conclusion, it is possible to achieve perfect intubation conditions with large doses of rocuronium, but the long duration of action and expense may limit the usefulness of the technique. IMPLICATIONS: We found that it is possible to have a 90% probability of achieving perfect conditions for rapid tracheal intubation with large (up to 2.0 mg/kg) doses of rocuronium. These large doses of rocuronium may be useful in, for instance, head trauma or open globe injuries if succinylcholine is contraindicated.

Adult↗
PubMed2000

The effects of clonidine on human digital vasculature.

Large concentrations of alpha(2) agonists cause vasoconstriction. However, the threshold of the vasoconstrictive effect in humans is not known. We studied seven volunteers to determine the lower limit of the vasoconstrictive effect of clonidine. Subjects were studied while they were awake, and they were anesthetized with propofol/alfentanil/N(2)O. Arterial blood pressure was continuously monitored via radial arterial catheter and vasoconstriction via finger volume plethysmography measuring infrared light transmitted through a fingertip (LTF). Clonidine was administered, targeting plasma clonidine concentrations of 0.3, 0.45, 0.68, 1.0, 1.5, and 2.25 ng/mL. The maximum change from preclonidine values for systolic blood pressure (SBP) and LTF was analyzed by using repeated measures analysis of variance. In awake subjects, clonidine (2.25 ng/mL) decreased LTF by 14%+/-13% and SBP from 141+/-7 to 110+/-15 mm Hg (P<0.0001). In contrast, clonidine (2.25 ng/mL) increased LTF in anesthetized subjects by 21%+/-16% and SBP from 91+/-7 to 106+/-19 mm Hg (P<0.0001). We conclude that the same dose of clonidine that decreased blood pressure and caused vasodilation in awake subjects had the opposite effect in anesthetized subjects with reduced sympathetic tone, increasing blood pressure and causing vasoconstriction in human digital vasculature. Our findings suggest that the lower threshold for clonidine-induced vasoconstriction in human digital vasculature is 1.0 ng/mL.

Adult↗
PubMed2000

Temperature-dependent pharmacokinetics and pharmacodynamics of vecuronium.

BACKGROUND: The authors evaluated the influence of temperature on the pharmacokinetics and pharmacodynamics of vecuronium because mild core hypothermia doubles its duration of action. METHODS: Anesthesia was induced with alfentanil and propofol and maintained with nitrous oxide and isoflurane in 12 healthy volunteers. Train-of-four stimuli were applied to the ulnar nerve, and the mechanical response of the adductor pollicis was measured. Volunteers were actively cooled or warmed until their distal esophageal temperatures were in one of four ranges: < 35.0 degrees C, 35.0-35.9 degrees C, 36.0-36.9 degrees C, and > or = 37.0 degrees C. With temperature stabilized, vecuronium was infused at 5 microg x kg(-1) x min(-1) until the first response of each train-of-four had decreased by 70%. Arterial blood (for vecuronium analysis) was sampled at intervals until the first response recovered to at least 90% of its prevecuronium level. Vecuronium, 20 microg x kg(-1) x min(-1), was then infused for 10 min, and arterial blood was sampled at intervals for up to 7 h. Population-based nonlinear mixed-effects modeling was used to examine the effect of physical characteristics and core temperature on vecuronium pharmacokinetics and pharmacodynamics. RESULTS: Decreasing core temperature over 38.0-34.0 degrees C decreases the plasma clearance of vecuronium (11.3% per degrees C), decreases the rate constant for drug equilibration between plasma and effect site (0.023 min(-1) per degrees C), and increases the slope of the concentration-response relationship (0.43 per degrees C). CONCLUSIONS: Our results show that reduced clearance and rate of effect site equilibration explain the increased duration of action of vecuronium with reducing core temperature. Tissue sensitivity to vecuronium is not influenced by core temperature.

Adult↗
PubMed1999

The effects of dexmedetomidine on neuromuscular blockade in human volunteers.

UNLABELLED: The neuromuscular effects of dexmedetomidine in humans are unknown. We evaluated the effect of dexmedetomidine on neuromuscular block and hemodynamics during propofol/alfentanil anesthesia. During propofol/alfentanil anesthesia, the rocuronium infusion rate was adjusted in 10 volunteers to maintain a stable first response (T1) in the train-of-four sequence at 50% +/- 3% of the pre-rocuronium value. Dexmedetomidine was then administered by computer-controlled infusion, targeting a plasma dexmedetomidine concentration of 0.6 ng/mL for 45 min. The evoked mechanical responses of the adductor pollicis responses (T1 response and T4/T1 ratio), systolic blood pressure (SBP), heart rate (HR), and transmitted light through a fingertip were measured during the dexmedetomidine infusion and compared with predexmedetomidine values using repeated-measures analysis of variance and Dunnett's test. Plasma dexmedetomidine levels ranged from 0.68 to 1.24 ng/mL. T1 values decreased during the infusion, from 51% +/- 2% to 44% +/- 9% (P < 0.0001). T4/T1 values did not change during the infusion. Plasma rocuronium concentrations increased during the infusion (P = 0.02). Dexmedetomidine increased SBP (P < 0.001) and decreased HR (P < 0.001) (5-min median values) during the infusion compared with values before the infusion. Dexmedetomidine increased the transmitted light through the fingertip by up to 41% +/- 8% during the dexmedetomidine infusion (P < 0.001).We demonstrated that dexmedetomidine (0.98 +/- 0.01 microg/kg) increased the plasma rocuronium concentration, decreased T1, increased SBP, and decreased finger blood flow during propofol/alfentanil anesthesia. We conclude that dexmedetomidine-induced vasoconstriction may alter the pharmacokinetics of rocuronium. IMPLICATIONS: We studied the effect of an alpha2-agonist (dexmedetomidine) on rocuronium-induced neuromuscular block during propofol/alfentanil anesthesia. We found that the rocuronium concentration increased and the T1 response decreased during the dexmedetomidine administration. Although these effects were statistically significant, it is unlikely that they are of clinical significance.

Adrenergic alpha-Agonists↗
PubMed1999

The influence of renal function on the pharmacokinetics and pharmacodynamics and simulated time course of doxacurium.

UNLABELLED: Doxacurium's clearance (C1) is markedly decreased in patients with renal failure undergoing kidney transplantation. However, no studies have determined the influence of renal function (as assessed by creatinine clearance [CrCl]) on its pharmacokinetics in patients without renal failure. We studied 53 patients aged 19-59 yr. During N2O/isoflurane anesthesia, doxacurium was infused over 10 min, plasma was sampled for up to 6 h, and twitch tension was measured. A three-compartment model was fit to plasma concentration data and an effect compartment model to twitch data. Mixed-effects modeling was used to determine the influence of covariates, including CrC1, on doxacurium's pharmacokinetic/pharmacodynamic parameters. Obesity decreased both doxacurium's Cl (1.1% per percent above ideal body weight [IBW]) and its neuromuscular junction sensitivity (0.4% per percent above IBW). Cl increased 0.6% per mL/min increase in CrCl. In addition, the rate constant for equilibration between plasma concentration and effect decreased 46% per 1% increase in isoflurane, central compartment volume decreased 86% per 1% increase in isoflurane concentration, and slow distributional Cl decreased 69% per mg/ 100 mL increase in serum albumin. Simulations showed that the latter two covariates influence the time course of bolus doxacurium administration minimally. Both obesity and renal dysfunction prolong doxacurium's recovery markedly. When dosing is based on IBW, effects of CrCl on neuromuscular recovery are smaller compared with dosing based on actual weight. Therefore, obese patients should be dosed based on IBW. No further dosage adjustment is necessary for patients with renal dysfunction; however, recovery will take longer in patients with moderate-to-severe renal dysfunction. IMPLICATIONS: We examined the factors influencing doxacurium's pharmacokinetic and pharmacodynamic characteristics. Both creatinine clearance and obesity significantly influence its time course. The effect of obesity is minimized if patients are dosed based on ideal body weight.

Adult↗
PubMed1999

Influence of renal failure on the pharmacokinetics and neuromuscular effects of a single dose of rapacuronium bromide.

BACKGROUND: Because renal function affects the elimination of muscle relaxants, each new muscle relaxant must be evaluated in patients with renal failure. Accordingly, the neuromuscular effects and pharmacokinetics of rapacuronium were identified in patients with renal failure. METHODS: Rapacuronium (1.5 mg/kg) was administered to 10 healthy volunteers and 10 patients with renal failure who were undergoing non-transplant surgery, were 18-45 yr old, and were anesthetized with propofol. The adductor pollicis muscle twitch tension was monitored. Plasma samples were obtained frequently for a period of 8 h to measure the concentrations of ORG9487 and its metabolite, ORG9488. Pharmacokinetic parameters were determined using mixed-effects modeling. RESULTS: One patient was excluded from analysis because he was taking phenytoin chronically. Twitch depression at 1 min was less in patients than in healthy volunteers (median values: 92% in patients, 99% in volunteers). The times to 90% and peak twitch depression; to 10%, 25%, and 75% twitch recovery; and to 70% and 80% train-of-four ratios were similar in volunteers and patients. Rapacuronium's clearance was 32% less in patients with renal failure; in both groups, clearance decreased 0.909% per year of age compared with the value in a 30 yr old. The steady state distribution volume was 14% less in women than in men and 16% less in patients than in volunteers. For ORG9488, clearance was 85% less in patients than in volunteers. CONCLUSIONS: The neuromuscular effects of a single dose of rapacuronium are affected minimally by renal failure. However, the decreased clearance of rapacuronium and its potent metabolite in renal failure suggests that repeated dosing of rapacuronium may lead to prolonged effects in patients with renal failure.

Adolescent↗
PubMed1999

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.

Anesthetics, Inhalation↗
PubMed1999

Rapid tracheal intubation with rocuronium: a probability approach to determining dose.

BACKGROUND: Rapid tracheal intubation with rocuronium has not been studied using a probability-based approach. The authors aimed to predict doses of rocuronium giving 90% and 95% probability of in intubation within 60 s and to estimate their durations of action. METHODS: After premedication with midazolam, 2 mg, anesthesia was induced in 80 subjects with fentanyl, 2 microg/kg, followed 3 min later by propofol, 2 mg/kg. Patients received randomly rocuronium, 0.0, 0.4, 0.8, or 1.2 mg/kg (n = 20/ dose). Laryngoscopy began 40 s later, aiming for intubation at 60 s, and conditions were graded perfect, acceptable, or unacceptable, with the first two conditions being successful intubation. Anesthesia was maintained with isoflurane 0.5-1.0% (end-tidal) and fentanyL Duration of action was time until reappearance of the first tactile train-of-four response. The dose versus fraction of patients with successful intubation was analyzed by logistic regression. Doses giving 90% and 95% (D90 and D95) probability of successful intubation were calculated. RESULTS: intubation was successful in 7, 11, 18, and 19 patients in the 0.0, 0.4, 0.8, and 1.2 mg/kg groups, respectively. The D90 and D95 doses (95% confidence limits in parentheses) were 0.83 (0.59-1.03) and 1.04 (0.76-1.36) mg/kg, respectively. Estimated time until first tactile train-of-four response after D90 and D95 doses was 32 and 46 min, respectively. CONCLUSIONS: After induction with fentanyl and propofol, rocuronium, 1.04 mg/kg gives 95% probability of successful intubation at 60 s.

Adult↗
PubMed1999

Comparison of the intubation conditions provided by rapacuronium (ORG 9487) or succinylcholine in humans during anesthesia with fentanyl and propofol.

BACKGROUND: Currently, the only approved muscle relaxant with a rapid onset and short duration of action is succinylcholine, a drug with some undesirable effects. Rapacuronium is an investigational nondepolarizing relaxant that also has a rapid onset and short duration and consequently should be compared with succinylcholine in its ability to facilitate rapid tracheal intubation. METHODS: This prospective, randomized clinical trial involved 336 patients. Anesthesia was induced with fentanyl and propofol and either 1.5 mg/kg rapacuronium or 1.0 mg/kg succinylcholine. The goal was to accomplish tracheal intubation by 60 s after administration of the neuromuscular blocking drug. Endotracheal intubation was performed, and conditions were graded by a blinded investigator. Recovery of neuromuscular function was assessed by electromyography. RESULTS: Intubation conditions were evaluated in 236 patients. Intubation by 60 s after drug administration occurred in 100% of patients with rapacuronium and in 98% with succinylcholine. Intubation conditions were excellent or good in 87% of patients with rapacuronium and in 95% with succinylcholine (P < 0.05). The time (median and range) to the first recovery of the train-of-four response was 8.0 (2.8-20.0) min with rapacuronium and 5.7 (1.8-17.7) min with succinylcholine (P < 0.05). The overall incidence of adverse effects was similar with both drugs. CONCLUSIONS: A 1.5-mg/kg dose of rapacuronium effectively facilitates rapid tracheal intubation. It can be considered a valid alternative to 1.0 mg/kg succinylcholine for this purpose.

Adolescent↗
PubMed1998

Solution structure of the thermostable sweet-tasting protein brazzein.

The fruit of Pentadiplandra brazzeana Baillon contains a small, sweet-tasting protein named brazzein. The structure of brazzein in solution was determined by proton nuclear magnetic resonance spectroscopy at pH 5.2 and 22 degrees C. The brazzein fold, which contains one alpha-helix and three strands of antiparallel beta-sheet, does not resemble that of either of the other two sweet-tasting proteins with known structures, monellin and thaumatin. Instead, the structure of brazzein resembles those of plant gamma-thionins and defensins and arthropod toxins. Sequence comparisons predict that members of a newly-identified family of serine proteinase inhibitors share the brazzein fold.

Amino Acid Sequence↗
PubMed1998

Do the pharmacokinetics of vecuronium change during prolonged administration in critically ill patients?

Neuromuscular blocking drugs may be administered over several days to patients in the intensive care unit (ICU), but their pharmacokinetics have been studied at only one point in time, or assumed to be constant throughout the period of administration. We sought to determine if, in individual patients, the pharmacokinetics of vecuronium changed over the course of its administration in the ICU. In six critically ill patients, we measured plasma vecuronium concentrations during two periods: first, during initial administration of vecuronium and second, after its administration continuously for 3-6 days. A pharmacokinetic model was fitted to these plasma concentration data, and its parameters permitted to vary between the periods to determine if they had altered. Individual clearance values during the study ranged from 1.4 to 4.4 ml kg-1 min-1. During prolonged administration, vecuronium clearance increased in three and decreased in two patients. This change ranged from a 61% decrease to a 58% increase, and was not linked to any clinical factor. The steady-state volume of distribution (range 368-1765 ml kg-1; median 494 ml kg-1) did not change in any patient during the study. The change in clearance of vecuronium during its prolonged administration in critically ill patients suggests that future studies of neuromuscular blocking drugs in the ICU should take account of their changing pharmacokinetics over the course of administration.

Adult↗
PubMed1997

Venous bleeding during transsphenoidal surgery: its association with pre- and intraoperative factors and with cavernous sinus and central venous pressures.

Venous bleeding during transsphenoidal surgery for resection of pituitary tumors is a common problem that interferes with the performance of the surgical procedure. In this study, data were collected prospectively from 50 patients to determine whether there were pre- or intraoperative factors (e.g., patient demographics, type and grade of pituitary tumor, intraoperative hemodynamics) associated with venous bleeding which might be used to predict its occurrence. In addition, central venous pressure (CVP), and cavernous sinus pressure (CSP) were measured in 13 patients to evaluate the relationship of these pressures to each other and to the severity of venous bleeding. During resection of the pituitary tumor, the severity of venous bleeding was graded as minimal, moderate, or severe, the latter two grades requiring therapeutic intervention. Moderate bleeding requiring intervention occurred in 15 of the 50 patients, and resolved in all cases. Moderate bleeding was not related to CSP or CVP, and no specific associated factor was observed. CSP was not correlated with CVP, and was higher than that predicted from the CVP and the position of the patient or the hydrostatic gravitational pressure gradient. These results suggest that it is not possible to predict in advance which patients will have problems with venous bleeding, but that simple therapeutic maneuvers are effective.

Adult↗
PubMed1997

Improving the design of muscle relaxant studies. Stabilization period and tetanic recruitment.

BACKGROUND: The results from studies of muscle relaxants show wide variations among institutions. The authors hypothesized that some of this variability could be explained by differences in duration of nerve stimulation before drug administration (stabilization period). METHODS: Train-of-four stimulation was applied every 12 s to both ulnar nerves and adductor pollicis twitch tension was measured in anesthetized participants given 30 micrograms/kg vecuronium. In phase 1, the stabilization period was > 30 min for both extremities. In phase 2-4, stabilization period was 20 min for one extremity and 2 min for the other. In addition, in phase 3, a 2-s 50-Hz tetanus initiated the 2-min stimulation period; in phase 4, duration of tetanus was 5 s. Twitch recovery was recorded until stable for more than 15 min. Time to 25% recovery (clinical duration) was calculated based on two indices: predrug and final (recovery) twitch tension. Values for onset and clinical duration were compared by paired parametric and nonparametric tests. RESULTS: In phase 1, predrug and recovery twitch tension were similar in each extremity, and onset and clinical duration did not differ between extremities, permitting paired comparisons in remaining studies. In phase 2, onset was more rapid with 20-min of prestimulation. With 20-min prestimulation, predrug and recovery twitch tension were similar; with 2-min prestimulation, recovery twitch tension exceeded predrug values. When referenced to predrug twitch tension, clinical duration was shorter with 2-min, that with 20-min prestimulation. Initiating stimulation with 2-s or 5-s 50-Hz tetani (phases 3, 4) abolished differences between extremities in onset and recovery. CONCLUSIONS: With only train-of-four stimulation (no tetani), onset and clinical duration vary with duration of prestimulation, suggesting that a brief period of predrug stimulation is inadequate. However, lengthy prestimulation may be impractical in clinical studies. Tetanic stimulation for 2 or 5 s obviates the need for prolonged stabilization during studies of muscle relaxants.

Adult↗
PubMed1997

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.

Adrenergic alpha-Agonists↗