ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundThis single-blind randomized study in general surgery evaluated the efficacy of perflubron emulsion (PFC) as an artificial oxygen carrier being used to augment preoperative acute normovolemic hemodilution to reduce and avoid transfusion of both allogeneic erythrocytes and erythrocytes from preoperative autologous donation compared with standard of care.MethodsSubjects (N = 492) with hemoglobin concentrations of 12–15 g/dl undergoing noncardiac surgical procedures with 20 ml/kg or greater expected blood loss were randomized into two groups. Control patients were transfused intraoperatively at a hemoglobin concentration less than 8.0 ± 0.5 g/dl or at protocol-defined, physiologic triggers. PFC-treated patients first underwent acute normovolemic hemodilution to hemoglobin of 8.0 ± 0.5 g/dl, followed by dosing with perflubron emulsion (1.8 g/kg). When hemoglobin reached less than 6.5 ± 0.5 g/dl, an additional 0.9-g/kg dose was given. PFC patients were transfused at hemoglobin less than 5.5 ± 0.5 g/dl or at predefined physiologic triggers. After surgery, hemoglobin was maintained at 8.5 ± 0.5 g/dl or greater in all patients until discharge. Efficacy endpoints included the number of allogeneic and preoperative autologous donation units transfused and the percentage of subjects avoiding transfusion.ResultsBoth groups had similar hemoglobin concentrations at screening (13.5 ± 1.0 g/dl) and at discharge: 10.8 ± 1.2 g/dl (PFC) and 11.1 ± 1.3 g/dl (control). At 24 h, more patients in the PFC group avoided allogeneic and preoperative autologous donation erythrocyte transfusions (53%vs.43%,P< 0.05), and fewer erythrocytes were transfused (1.5 ± 4.8vs.2.1 ± 3.9 units; median, 0vs.1 unit;P= 0.013). By day of discharge, these differences were not significant in the intent-to-treat population, but overall there were less allogeneic and preoperative autologous donation erythrocyte transfusions in the PFC group (696vs.846 units). In the protocol-defined target population (n = 330 subjects with blood loss ≥ 20 ml/kg), significantly greater avoidance of any erythrocyte transfusion was maintained through day of hospital discharge (26%vs.16% in the PFC and control groups, respectively;P< 0.05), and there was also a significant reduction in the number of erythrocyte units transfused (3.4 ± 2.9vs.4.9 ± 2.4 units; median 2vs.4 units;P< 0.001). Adverse events rates were similar in the PFC (86%) and control (81%) groups; however, more serious adverse events were reported in the PFC group (32%) than in controls (21%;P< 0.05). Overall mortality was 3%, and the difference between groups (PFC, 4%vs.controls, 2%) was not statistically significant.ConclusionsAugmented acute normovolemic hemodilution with PFC reduces transfusion needs in patients undergoing noncardiac surgical procedures with blood loss 20 ml/kg or greater.

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundThe pharmacokinetics of both propofol and remifentanil have been described extensively. Although they are commonly administered together for clinical anesthesia, their pharmacokinetic interaction has not been investigated so far. The purpose of the current investigation was to elucidate the nature and extent of pharmacokinetic interactions between propofol and remifentanil.MethodsTwenty healthy volunteers aged 20–43 yr initially received either propofol or remifentanil alone in a stepwise incremental and decremental fashionviaa target controlled infusion. Thereafter, the respective second drug was infused to a fixed target concentration in the clinical range (0–4 &mgr;g/ml and 0–4 ng/ml for propofol and remifentanil, respectively) and the stepwise incremental pattern repeated. Frequent blood samples were drawn for up to 6 h for propofol and 40 min for remifentanil after the end of administration and assayed for the respective drug concentrations with gas chromatography–mass spectrometry. The time courses of the measured concentrations were fitted to standard compartmental models. Calculations were performed with NONMEM. After having established the individual population models for both drugs and an exploratory analysis for hypothesis generation, pharmacokinetic interaction was identified by including an interaction term into the population model and comparing the value of the objective function in the presence and absence of the respective term.ResultsThe concentration–time courses of propofol and remifentanil were described best by a three- and two-compartment model, respectively. In the concentration range examined, remifentanil does not alter propofol pharmacokinetics. Coadministration of propofol decreases the central volume of distribution and distributional clearance of remifentanil by 41% and elimination clearance by 15%. This effect was not concentration-dependent in the examined concentration range of propofol.ConclusionsCoadministration of propofol decreases the bolus dose of remifentanil needed to achieve a certain plasma–effect compartment concentration but does not alter the respective maintenance infusion rates and recovery times to a clinically significant degree.

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundThe potential benefit of propofol dose regimens that use physiologic pharmacokinetic modeling to target the brain has been demonstrated in animals, but no data are available on the rate of propofol distribution to the brain in humans. This study measured the brain uptake of propofol in humans and the simultaneous effects on electroencephalography, cerebral blood flow velocity (Vmca), and cerebral oxygen extraction.MethodsSeven subjects had arterial and jugular bulb catheters placed before induction. Electroencephalography and Vmcawere recorded during induction with propofol while blood samples were taken from both catheters for later propofol analysis. Brain uptake of propofol was calculated using mass balance principles, with effect compartment modeling used to quantitate the rate of uptake.ResultsBispectral index (electroencephalogram) values decreased to a minimum value of approximately 4 at around 7 min from the onset of propofol administration and then slowly recovered. This was accompanied by decreases in Vmca, reaching a minimum value of approximately 40% of baseline. Cerebral oxygen extraction did not change, suggesting parallel changes in cerebral metabolism. There was slow equilibrium of propofol between the blood and the brain (t1/2keoof 6.5 min), with a close relation between brain concentrations and bispectral index, although with considerable interpatient variability. The majority of the decreases in Vmca, and presumably cerebral metabolism, corresponded with bispectral index values reaching 40–50 and the onset of burst suppression.ConclusionDescription of brain distribution of propofol will allow development of physiologic pharmacokinetic models for propofol and evaluation of dose regimens that target the brain.

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundAcoustic reflectometry allows the construction of a one-dimensional image of a cavity, such as the airway or the esophagus. The reflectometric area–distance profile consists of a constant cross-sectional area segment (length of endotracheal tube), followed either by a rapid increase in the area beyond the carina (tracheal intubation) or by an immediate decrease in the area (esophageal intubation).MethodsTwo hundred adult patients were induced and intubated, without restrictions on anesthetic agents or airway adjunct devices. A two-microphone acoustic reflectometer was used to determine whether the breathing tube was placed in the trachea or esophagus. A blinded reflectometer operator, seated a distance away from the patient, interpreted the acoustic area–distance profile alone to decide where the tube was placed. Capnography was used as the gold standard.ResultsOf 200 tracheal intubations confirmed by capnography, the reflectometer operator correctly identified 198 (99% correct tracheal intubation identification rate). In two patients there were false-negative results,i.e., patients with a tracheal intubation were interpreted as having an esophageal intubation. A total of 14 esophageal intubations resulted, all correctly identified by reflectometry, for a 100% esophageal intubation identification rate.ConclusionsAcoustic reflectometry is a rapid, noninvasive method by which to determine whether breathing tube placement is correct (tracheal) or incorrect (esophageal). Reflectometry determination of tube placement may be useful in airway emergencies, particularly in cases where visualization of the glottic area is not possible and capnography may fail, as in patients with cardiac arrest.

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundFunctional stereotactic surgery requires careful titration of sedation since patients with Parkinson disease need to be rapidly awakened for testing. This study reports a population pharmacodynamic model of propofol sedation and airway obstruction in the Parkinson disease population.MethodsTwenty-one patients with advanced Parkinson disease undergoing functional stereotactic surgery were included in the study and received propofolviatarget-controlled infusion to achieve an initial steady state concentration of 1 &mgr;g/ml. Sedation was measured using the Ramsay Sedation Scale. Airway obstruction was measured using a four-category score. Blood samples were drawn for propofol measurement. Individual pharmacokinetic profiles were constructed nonparametrically using linear interpolation. Time course of sedation and respiratory effects were described with population pharmacodynamic models using NONMEM. The probability (P) of a given level of sedation or airway obstruction was related to the estimated effect-site concentration of propofol (Ce) using a logistic regression model.ResultsThe concentrations predicted by the target-controlled infusion system generally exceeded the measured concentrations. The estimates of C50for Ramsay scores 3, 4, and 5 were 0.1, 1.02, and 2.28 &mgr;g/ml, respectively. For airway obstruction scores 2 and 3, the estimates of C50were 0.32 and 2.98 &mgr;g/ml, respectively. Estimates of ke0were 0.24 and 0.5 1/min for the sedation and respiratory effects, respectively.ConclusionsThe pharmacokinetic behavior of propofol in patients with Parkinson disease differs with respect to the population from which the model used by the target-controlled infusion device was developed. Based on the results from the final models, a typical steady state plasma propofol concentration of 0.35 &mgr;g/ml eliciting a sedation score of 3 with only minimal, if any, airway obstruction has been defined as the therapeutic target.

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundThis study was designed to evaluate transcutaneous electrical acupoint stimulation (acustimulation) using the ReliefBand® compared with ondansetron for the treatment of established postoperative nausea and vomiting (PONV) after outpatient laparoscopic surgery.MethodsAfter the authors obtained institutional review board approval and written informed consent, 268 outpatients were enrolled in this randomized, double-blind, placebo- and sham-controlled study. All patients received antiemetic prophylaxis with metoclopramide, 10 mg intravenously, or droperidol, 0.625 mg intravenously, after induction of anesthesia. A total of 90 patients developed PONV in the recovery units and were randomized to one of three treatment groups: (1) the ondansetron group received 4 mg intravenous ondansetron and a sham ReliefBand®; (2) the acustimulation group received 2 ml intravenous saline and a ReliefBand®; and (3) the combination group received 4 mg intravenous ondansetron and a ReliefBand®. A rescue antiemetic (10 mg intravenous metoclopramide) was administered only if the PONV symptoms persisted for 15 min or longer after initiating the treatment. A blinded observer recorded the recovery times, emetic symptoms, rescue antiemetics, maximum nausea scores, complete response to study treatment, and time to achieve discharge criteria. Postdischarge side effects, as well as patient satisfaction and quality of recovery scores, were assessed at 24 and 72 h after surgery.ResultsThe combination group had a significantly higher complete response rate than the acustimulation group (73%vs.40%,P< 0.01). In addition, fewer patients (8vs.18) in the combination (vs.acustimulation) group experienced subsequent emetic events (P< 0.03). However, there were no significant differences between the three groups with respect to patient satisfaction and quality of recovery scores.ConclusionsAcustimulation with the ReliefBand® can be used as an alternative to ondansetron for the treatment of established PONV. However, the use of ondansetron (4 mg intravenously) in combination with the ReliefBand® device improved the complete response rate to the acustimulation therapy.

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundPropofol is a commonly used anesthetic induction agent in pediatric anesthesia that, until recently, was used with caution as an intravenous infusion agent for sedation in pediatric intensive care. Few data have described propofol kinetics in critically ill children.MethodsTwenty-one critically ill ventilated children aged 1 week to 12 yr were sedated with 4–6 mg · kg−1· h−1of 2% propofol for up to 28 h, combined with a constant morphine infusion. Whole blood concentration of propofol was measured at steady state and for 24 h after infusion using high-performance liquid chromatography.ResultsA propofol infusion rate of 4 mg · kg−1· h−1achieved adequate sedation scores in 17 of 20 patients. In 2 patients the dose was reduced because of hypotension, and 1 patient was withdrawn from the study because of a increasing metabolic acidosis. Mixed-effects population models were fitted to the blood propofol concentration data. The pharmacokinetics were best described by a three-compartment model. Weight was a significant covariate for all structural model parameters; Cl, Q2, Q3, V1, and V2were proportional to weight. Estimates for these parameters were 30.2, 16.0, and 13.3 ml · kg−1· min−1and 0.584 and 1.36 l/kg, respectively. The volume of the remaining peripheral compartment, V3, had a constant component (103 l) plus an additional weight-related component (5.67 l/kg). Values for Cl were reduced (typically by 26%) in children who had undergone cardiac surgery.ConclusionsPropofol kinetics are altered in very small babies and in children recovering from cardiac surgery. Increased peripheral distribution volume and reduced metabolic clearance following surgery causes prolonged elimination.

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID