bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of Propofol in Adult Patients Undergoing Coronary Revascularization
Authors: Bailey James M. , Mora Christina T. , Shafer Stephen L. 
Published: November 2003

Background
Propofol is increasingly used for cardiac anesthesia and for perioperative sedation. Because pharmacokinetic parameters vary among distinct patient populations, rational drug dosing in the cardiac surgery patient is dependent on characterization of the drug's pharmacokinetic parameters in patients actually undergoing cardiac procedures and cardiopulmonary bypass (CPB). In this study, the pharmacokinetics of propofol was characterized in adult patients undergoing coronary revascularization.

Methods
Anesthesia was induced and maintained by computer-controlled infusions of propofol and alfentanil, or sufentanil, in 41 adult patients undergoing coronary artery bypass graft surgery. Blood samples for determination of plasma propofol concentrations were collected during the predefined study periods and assayed by high-pressure liquid chromatography. Three-compartment model pharmacokinetic parameters were determined by nonlinear extended least-squares regression of pooled data from patients receiving propofol throughout the perioperative period. The effect of CPB on propofol pharmacokinetics was modeled by allowing the parameters to change with the institution and completion of extracorporeal circulation and selecting the optimal model on the basis of the logarithm of the likelihood. Predicted propofol concentrations were calculated by convolving the infusion rates with unit disposition functions using the estimated parameters. The predictive accuracy of the parameters was evaluated by cross-validation and by a prospective comparison of predicted and measured levels in a subset of patients.

Results
Optimal pharmacokinetic parameters were: central compartment volume = 6.0 l; second compartment volume = 49.5 l; third compartment volume = 429.3 l; Cl1 (elimination clearance) = 0.68 l/min; Cl2 (distribution clearance) = 1.97 l/min1; and Cl3 (distribution clearance) = 0.70 l/min. The effects of CPB were optimally modeled by step changes in V1 and Cl1 to values of 15.9 and 1.95, respectively, with the institution of CPB. Median absolute prediction error was 18% in the cross-validation assessment and 19% in the prospective evaluation. There was no evidence for nonlinear kinetics. Previously published propofol pharmacokinetic parameter sets poorly predicted the observed concentrations in cardiac surgical patients.

Conclusions
The pharmacokinetics of propofol in adult patients undergoing cardiac surgery with CPB are dissimilar from those reported for other adult patient populations. The effect of CPB was best modeled by an increase in V1 and Cl1. Predictive accuracy of the derived pharmacokinetic parameters was excellent as measured by cross-validation and a prospective test.
Comparison of the Effects of Etomidate, Propofol, and Thiopental on Respiratory Resistance after Tracheal Intubation
Authors: Eames Wendell O. , Rooke Alec G. , Sai-Chuen Wu Rick , Bishop Michael J. 
Published: November 2003

Background
Tracheal intubation frequently results in reversible bronchoconstriction. Propofol has been reported to minimize this response in healthy patients and in asthma patients, but may be unsuitable for hemodynamically unstable patients for whom etomidate may be preferable. The current study examined respiratory resistance after tracheal intubation after induction with either thiopental, etomidate, or propofol. A supratherapeutic dose of etomidate was used to test the hypothesis that the bronchoconstrictive response could be minimized by deep intravenous anesthesia.

Methods
Seventy-seven studies were conducted in 75 patients. Anesthesia was induced with either 2.5 mg/kg propofol, 0.4 mg/kg etomidate, or 5 mg/kg thiopental. Respiratory resistance was measured at 2 min after induction.

Results
Respiratory resistance at 2 min was 8.1 +/- 3.4 cmH2O.1(-1).s (mean +/- SD) for patients receiving propofol versus 11.3 +/- 5.3 for patients receiving etomidate and 12.3 +/- 7.9 for patients receiving thiopental (P < or = 0.05 for propofol vs. either etomidate or thiopental).

Conclusions
Respiratory resistance after tracheal intubation is lower after induction with propofol than after induction with thiopental or after induction with high-dose etomidate.
Thoracic Epidural Anesthesia Via the Lumbar Approach in Infants and Children
Authors: Blanco D. , Llamazares J. , Rincon R. , Ortiz M. , Vidal F. 
Published: November 2003

Background
In upper abdominal or chest surgery, the segmental approach to thoracic epidural space has the advantage of reducing the total dose of local anesthetic needed. This approach, however, is associated with greater risk of neurologic damage or dural puncture. The aim of this study was to assess the success and the degree of difficulty in advancing a 19-G catheter from the lumbar epidural space to the thoracic level in patients aged 0-96 months.

Methods
In 39 patients undergoing abdominal surgery, the cutaneous distance between the L4-L5 and T10-T11 interspaces was measured, and an appropriate length of 19-G catheter was inserted into the epidural space through an 18-G Tuohy needle with bevel directed cephalad. The intent was to advance the full length of catheter measured to reach the objective. The tips were observed radiologically, and all those positioned cephalad to the T12 level were considered well placed. The degree of difficulty in advancing the catheter was classified as easy, difficult, or impossible. Complications reported were vascular and/or spinal puncture and difficulty removing the catheter.

Results
The catheter tip reached T10-T12 in 7 patients, L2 in 1, L3 in 8, and L4-L5 in 23. Forty-eight percent of the catheters described as easily advanced remained at the L4-L5 level, and only 22% reached the desired level. Difficult insertions occurred in eight patients, in whom the objective was never reached. One case of intravascular insertion was reported. All catheters were removed without difficulty.

Conclusions
The 19-G catheter is inappropriate for use in reaching the thoracic epidural space by the lumbar approach. Easy entrance of a catheter is not a reliable sign of having reached the desired level.
Concentration-Effect Relationships of Eltanolone Given as a Bolus Dose or Constant Rate Intravenous Infusion to Healthy Male Volunteers
Authors: Wessen Arne , Parivar Kourosh M. , Widman Marianne , Nilsson Anders , Hartvig Per 
Published: November 2003

Background
The primary purpose of this study was to evaluate concentration-effect relationships of the new steroid anesthetic eltanolone during recovery from a bolus dose and constant rate intravenous infusion in healthy male volunteers.

Methods
Ten subjects received a bolus dose of 0.75 mg/kg eltanolone over 20 s. A 2-h constant rate intravenous infusion of eltanolone was given to five subjects at a rate of 2 mg.kg-1.h-1 and to another five subjects at a rate of 3.5 mg.kg-1.h-1. Recovery performance was assessed as the time required to reach different end-points and by means of three different psychomotor tests.

Results
A low interindividual variability was found in the serum concentration of eltanolone at the pharmacodynamic end-points during recovery. The Cp50 value for "eye opening" was 382 micrograms/L (95% confidence interval, 285-489) after a bolus dose corresponding to a median time of 16 min (range 8-25). After eltanolone infusion, the Cp50 value for "eye opening" was 507 micrograms/L (95% confidence interval, 425-605) and the corresponding median time was 21 min (range 8-25) in the low-dose group and 49 min (range 31-66) in the high-dose group. The Cp50 values at the same effect end-points in the bolus group were less than those in the infusion groups, probably because of insufficient equilibration time between serum and the effect compartment.

Conclusions
Recovery characteristics of eltanolone were predictable because of a relatively low interindividual variability in serum concentrations but with a slow blood:effect compartment equilibration.
Reduction in the Shivering Threshold Is Proportional to Spinal Block Height
Authors: Leslie Kate , Sessler Daniel I 
Published: November 2003

Background
Hypothermia is nearly as common, and may be as severe, during spinal and epidural anesthesia as during general anesthesia. The authors have proposed that thermoregulatory failure results when regional anesthesia increases apparent leg skin temperature to a level far exceeding actual leg skin temperature. Extensive dermatomal blocks will alter thermal input to the hypothalamus from a greater skin-surface area more than less extensive ones and thus might be expected to impair central thermoregulatory control more. Accordingly, they tested the hypothesis that reduction in the shivering threshold is directly related to the number of dermatomes blocked during spinal anesthesia.

Methods
Eleven men, aged 62 +/- 6 yr (mean +/- SD), undergoing urologic surgery were studied. Ice-cold lactated Ringer's solution was administered intravenously before spinal blockade and the shivering threshold (triggering core temperature) was established. Spinal anesthesia then was induced using a randomly assigned dose of 0.5% bupivacaine (2-4 ml). Again, sufficient cold lactated Ringer's solution was given to induce shivering. Tympanic membrane, ambient and skin temperatures were measured, and extent of block was defined by loss of temperature discrimination. Presence of shivering was evaluated by a blinded observer. Mean upper-body skin and ambient temperatures, cooling rates and intravenous fluid volumes at the two thresholds were compared using paired, two-tailed t tests (P < 0.05). Linear regression defined the relationship between reduction in shivering threshold and the number of dermatomes blocked.

Results
There were no significant differences between mean upper-body skin and ambient temperatures, cooling rates or intravenous fluid volumes at the control and spinal shivering thresholds. Spinal anesthesia reduced the shivering threshold in direct relation to the number of dermatomes blocked: delta threshold = 0.74 - 0.06 (dermatomes blocked); r2 = 0.58, P < 0.006.

Conclusions
Extensive spinal blockade impairs central thermoregulatory control more than less extensive blockade. Clinicians can thus anticipate more core hypothermia during extensive than during restricted spinal blockade.
Induction, Recovery, and Safety Characteristics of Sevoflurane in Children Undergoing Ambulatory Surgery
Authors: Lerman Jerrold , Davis Peter J. , Welborn Leila G. , Orr Rosemary J. , Rabb Mary , Carpenter Rob , Motoyama Etsuro , Hannallah Rafaat , Haberkern Charles M. 
Published: November 2003

Background
Sevoflurane is an inhalational anesthetic with characteristics suited for use in children. To determine whether the induction, recovery, and safety characteristics of sevoflurane differ from those of halothane, the following open-labeled, multicenter, randomized, controlled, phase III study in children undergoing ambulatory surgery was designed.

Methods
Three hundred seventy-five children, ASA physical status 1 or 2, were randomly assigned in a 2:1 ratio to receive either sevoflurance or halothane, both in 60% N2O and 40% O2. Anesthesia was induced using a mask with an Ayre's t piece or Bain circuit in four of the centers and a mask with a circle circuit in the fifth center. Maximum inspired concentrations during induction of anesthesia were 7% sevoflurane and 4.3% halothane. Anesthesia was maintained by spontaneous ventilation, without tracheal intubation. End-tidal concentrations of both inhalational anesthetics were adjusted to 1.0 MAC for at least 10 min before the end of surgery. Induction and recovery characteristics and all side effects were recorded. The plasma concentration of inorganic fluoride was measured at induction of and 1 h after anesthesia.

Results
During induction of anesthesia, the time to loss of the eyelash reflex with sevoflurane was 0.3 min faster than with halothane (P < 0.001). The incidence of airway reflex responses was similar, albeit infrequent with both anesthetics. The total MAC.h exposure to sevoflurane was 11% less than the exposure to halothane (P < 0.013), although the end-tidal MAC multiple during the final 10 min of anesthesia was similar for both groups. Early recovery as evidenced by the time to response to commands after sevoflurane was 33% more rapid than it was after halothane (P < 0.001), although the time to discharge from hospital was similar for both anesthetics. The mean ( +/- SD) plasma concentration of inorganic fluoride 1 h after discontinuation of sevoflurane was 10.3 +/- 3.5 microM. The overall incidence of adverse events attributable to sevoflurane was similar to that of halothane, although the incidence of agitation attributable to sevoflurane was almost threefold greater than that attributable to halothane (P < 0.004).

Conclusions
Sevoflurane compared favorably with halothane. Early recovery after sevoflurane was predictably more rapid than after halothane, although this was not reflected in a more rapid discharge from the hospital. The incidence of adverse events was similar for both anesthetics. Clinically, the induction, recovery, and safety characteristics of sevoflurane and halothane are similar. Sevoflurane is a suitable alternative to halothane for use in children undergoing minor ambulatory surgery.
Magnetic Resonance Imaging of Cerebrospinal Fluid Volume and the Influence of Body Habitus and Abdominal Pressure
Authors: Hogan Quinn H. , Prost Robert , Kulier Alexander , Taylor Mary Lou , Liu Spencer , Mark Leighton 
Published: November 2003

Background
Although the cerebrospinal fluid (CSF) is the pathway of anesthetic delivery and the diluent for neuraxially administered drugs, little is known about its volume, including variability among individuals, longitudinal distribution, or influence of body habitus. Models made to investigate subarachnoid anesthetic distribution lack valid dimensions. CSF volume was measured in volunteers, and the effect of obesity and abdominal compression on CSF volume was evaluated using magnetic resonance imaging.

Methods
Low thoracic and lumbosacral axial magnetic resonance images of 25 healthy volunteers were obtained at 8-mm intervals by fast spin-echo sequence, which highlights CSF. A repeat image series was performed in 15 subjects during external abdominal compression. In two subjects, images were obtained without compression for the entire vertebral column. Dural sac and spinal cord areas were determined in a blinded fashion for each image using video/digital analysis. Area of the sac minus area of the cord constituted area of CSF and roots ("CSF/root"); this area multiplied by 8 mm resulted in CSF/root volume per section.

Results
There is great interindividual variability in CSF/root volume. From the T11-T12 disc to the sacral terminus of the dural sac, the mean volume for all subjects is 49.9 +/- 12.1 ml (mean +/- SD; range 28.0-81.1 ml). This volume was significantly less in relatively obese subjects (42.9 +/- 9.5 ml) than in nonobese subjects (53.5 +/- 12.9 ml). Abdominal compression decreased CSF/root volume by 3.6 +/- 3.2 ml. Sections through intervertebral foramina showed the biggest decrease with abdominal compression, with a lesser change in sections with veins and no change in the absence of these anatomic features. Total vertebral CSF/root volume in two subjects was 94.84 and 120.01 ml, respectively.

Conclusions
CSF volume is widely variable between individuals. The decreased CSF volume that results from increased abdominal pressure, such as with obesity or pregnancy, may produce more extensive neuraxial blockade through diminished dilution of anesthetic. The mechanism by which increased abdominal pressure decreases CSF volume is probably inward movement of soft tissue in the intervertebral foramen, which displaces CSF.
Cardiovascular Responses during Sedation after Coronary Revascularization
Authors: Wahr Joyce A. , Plunkett Jerill J. , Ramsay James G. , Reeves John , Jain Uday , Ley Catherine , Wilson Robert , Mangano Dennis T. 
Published: November 2003

Background
Propofol sedation offers advantages for titration and rapid emergence in the critically ill patient, but concern for adverse hemodynamic effects potentially limits its use in these patients. The current study compares the cardiovascular effects of sedation with propofol versus midazolam during the first 12 h after coronary revascularization.

Methods
Three hundred fifty-one patients undergoing coronary revascularization were anesthetized using a standardized sufentanil/midazolam regimen, and assigned randomly to 12 h of sedation with either propofol or midazolam while tracheally intubated. The incidence and characteristics of hemodynamic episodes, defined as heart rate less than 60 or greater than 100 beats/min or systolic blood pressure greater than 140 or less than 90 mmHg, were determined using data electronically recorded at 1-min intervals. The presence of myocardial ischemia was determined using continuous three-channel Holter electrocardiography (ECG) and of myocardial infarctions (MI) using 12-lead ECG (Q wave MI, Minnesota Code) or creatine kinase isoenzymes (CK-MB) analysis (non-Q wave MI, peak CK-MB > 70 ng/ml, or CK-MB > 70 IU/I).

Results
Ninety-three percent of patients in both treatment groups had at least one hemodynamic episode during the period of postoperative sedation. Propofol sedation resulted in a 17% lower incidence of tachycardia (58% vs. 70%, propofol vs. midazolam; P = 0.04), a 28% lower incidence of hypertension (39% vs. 54%; P = 0.02), and a greater incidence of hypotension (68% vs. 51%; P = 0.01). Despite these hemodynamic effects, the incidence of myocardial ischemia did not differ between treatment groups (12% propofol vs. 13% midazolam; P = 0.66), nor did its severity, as measured by ischemic minutes per hour monitored (8.7 +/- 5.8 vs. 6.2 +/- 4.6 min/h, propofol vs. midazolam; P = 0.19) or ischemic area under the curve (6.8 +/- 4.0 vs. 5.3 +/- 4.2; P = 0.37). The incidence of cardiac death (one per group), Q wave MI (propofol, n = 7; midazolam, n = 3; P = 0.27), or non Q wave MI (propofol, n = 16; midazolam, n = 18; P = 0.81) did not differ between treatment groups.

Conclusions
Hemodynamic episodes occur frequently in the first 12 h after coronary revascularization. Compared with a standard sedation regimen (midazolam), propofol sedation appears to modulate postoperative hemodynamic responses by reducing the incidence and severity of tachycardia and hypertension and increasing the incidence of hypotension. Both sedation regimens appear similarly safe with respect to myocardial ischemia. These findings indicate that propofol infusion provides effective sedation without deleterious hemodynamic effects in patients recovering from cardiac surgery.
Rapid Rewarming Causes an Increase in the Cerebral Metabolic Rate for Oxygen that Is Temporarily Unmatched by Cerebral Blood Flow
Authors: Enomoto Sakae , Hindman Bradley J. , Dexter Franklin , Smith Tom , Cutkomp Johann 
Published: November 2003

Background
Jugular venous hemoglobin desaturation during the rewarming phase of cardiopulmonary bypass is associated with adverse neuropsychologic outcome and may indicate a pathologic mismatch between cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2). In some studies, rapid rewarming from hypothermic cardiopulmonary bypass results in greater jugular venous hemoglobin desaturation. The authors wished to determine if rewarming rate influences the temperature dependence of CBF and CMRO2.

Methods
Anesthetized New Zealand white rabbits, cooled to 25 degrees C on cardiopulmonary bypass, were randomized to one of two rewarming groups. In the fast group (n = 9), aortic blood temperature was made normothermic within 4 min. In the slow group (n = 9), aortic blood temperature was made normothermic over 25 min. Cerebral blood flow (microspheres) and CMRO2 (Fick) were determined at baseline (25 degrees C), and at brain temperatures of 28 degrees, 31 degrees, 34 degrees, and 37 degrees C during rewarming.

Results
Systemic physiologic variables appeared similar between groups. At a brain temperature of 28 degrees C, CMRO2 was 47% greater in the fast rewarming group than in the slow group (2.2 +/- 0.5 vs. 1.5 +/- 0.2 ml O2.100 g-1. min-1, respectively; P = 0.01), whereas CBF did not differ (48 +/- 18 vs. 49 +/- 8 ml.100 g-1.min-1, respectively; P = 0.47). Throughout rewarming, CBF increased as a function of brain temperature but was indistinguishable between groups. Cerebral metabolic rate for oxygen differences between groups decreased as brain temperatures increased.

Conclusions
Cerebral venous hemoglobin desaturation with rapid rewarming is caused by an increase in CMRO2 that is temporarily greater than the increase in CBF. This mismatch may indicate a transient abnormality in flow-metabolism coupling, or the effect of temperature gradients on oxygen transfer from hemoglobin to brain.
Prolonged Regional Nerve Blockade
Authors: Curley Joanne , Castillo Jenny , Hotz Joyce , Uezono Megumi , Hernandez Sonia , Lim Jeong-Ok , Tigner Joseph , Chasin Mark , Langer Robert , Berde Charles 
Published: November 2003

Background
Biodegradable microspheres are a useful method of drug delivery because they are both injectable and biodegradable, eliminating the need for surgical implantation or removal. Previous work has characterized implantable preparations of local anesthetics in polymer pellets for prolonged regional anesthesia. In this article, the authors characterize injectable suspensions of bupivacaine-polymer microspheres and examine whether they can produce prolonged blockade of the sciatic nerve in rats.

Methods
Microspheres were prepared using polylactic-co-glycolic acid polymers loaded with 75% w/w bupivacaine by a solvent evaporation method. Bupivacaine release from microspheres was determined in vitro by ultraviolet spectroscopy and scintillation counting. Sensory and motor blockade of the rat sciatic nerve were assessed in vivo after injection of microsphere suspensions.

Results
Depending on the type of microspheres, the dose, and the additive used, mean duration of sciatic nerve block ranged from 10 h to 5.5 days. Incorporation of 0.05% w/w dexamethasone into the microspheres resulted in significant prolongation of block (up to 13-fold), and only preparations that contained dexamethasone produced blocks lasting beyond 1 day. Bupivacaine was released in a controlled manner in vitro. Dexamethasone does not substantially slow bupivacaine release from microspheres in vitro.

Conclusions
Prolonged percutaneous blockade of peripheral nerves is feasible. The recovery from blockade is complete, and plasma bupivacaine levels are far below the range associated with systemic toxicity. The mechanisms underlying the dexamethasone block-prolonging effect are under investigation.