bluuebunny/crossref_metadata_2025 huggingface dataset:
Permissive Hypercapnia with and without Expiratory Washout in Patients with Severe Acute Respiratory Distress Syndrome
Authors: Kalfon Pierre , Rao G. S. Umamaheswara , Gallart Lluis , Puybasset Louis , Coriat Pierre , Rouby Jean-Jacques
Published: November 2003

Background

Permissive hypercapnia is a ventilatory strategy aimed at avoiding lung volutrauma in patients with severe acute respiratory distress syndrome (ARDS). Expiratory washout (EWO) is a modality of tracheal gas insufflation that enhances carbon dioxide removal during mechanical ventilation by reducing dead space. The goal of this prospective study was to determine the efficacy of EWO in reducing the partial pressure of carbon dioxide (PaCO2) in patients with severe ARDS treated using permissive hypercapnia.

Methods

Seven critically ill patients with severe ARDS (lung injury severity score, 3.1 +/- 0.3) and no contraindications for permissive hypercapnia were studied. On the first day, hemodynamic and respiratory parameters were measured and the extent of lung hyperdensities was assessed using computed tomography. A positive end-expiratory pressure equal to the opening pressure identified on the pressure-volume curve was applied. Tidal volume was reduced until a plateau airway pressure of 25 cm H2O was reached. On the second day, after implementation of permissive hypercapnia, EWO was instituted at a flow of 15 l/min administered during the entire expiratory phase into the trachea through the proximal channel of an endotracheal tube using a ventilator equipped with a special flow generator. Cardiorespiratory parameters were studied under three conditions: permissive hypercapnia, permissive hypercapnia with EWO, and permissive hypercapnia.

Results

During permissive hypercapnia, EWO decreased PaCO2 from 76 +/- 4 mmHg to 53 +/- 3 mmHg (-30%; P < 0.0001), increased pH from 7.20 +/- 0.03 to 7.34 +/- 0.04 (P < 0.0001), and increased PaO2 from 205 +/- 28 to 296 +/- 38 mmHg (P < 0.05). The reduction in PaCO2 was accompanied by an increase in end-inspiratory plateau pressure from 26 +/- 1 to 32 +/- 2 cm H2O (P = 0.001). Expiratory washout also decreased cardiac index from 4.6 +/- 0.4 to 3.7 +/- 0.3 l.min-1.m-2 (P < 0.01), mean pulmonary arterial pressure from 28 +/- 2 to 25 +/- 2 mmHg (P < 0.01), and true pulmonary shunt from 47 +/- 2 to 36 +/- 3% (P < 0.01).

Conclusions

Expiratory washout is an effective and easy-to-use ventilatory modality to reduce PaCO2 and increase pH during permissive hypercapnia. However, it significantly increases airway pressures and lung volume through expiratory flow limitation, reexposing some patients to a risk of lung volutrauma if the extrinsic positive end-expiratory pressure is not substantially reduced.
Improvement in Oxygenation by Phenylephrine and Nitric Oxide in Patients with Adult Respiratory Distress Syndrome
Authors: Doering Elana B. , Hanson C. William , Reily Daniel J. , Marshall Carol , Marshall Bryan E.
Published: November 2003

Background

Inhaled nitric oxide (NO), a selective vasodilator, improves oxygenation in many patients with adult respiratory distress syndrome (ARDS). Vasoconstrictors may also improve oxygenation, possibly by enhancing hypoxic pulmonary vasoconstriction. This study compared the effects of phenylephrine, NO, and their combination in patients with ARDS.

Methods

Twelve patients with ARDS (PaO2/FIO2  180; Murray score  2) were studied. Each patient received three treatments in random order: intravenous phenylephrine, 50-200 micrograms/min, titrated to a 20% increase in mean arterial blood pressure; inhaled NO, 40 ppm; and the combination (phenylephrine+NO). Hemodynamics and blood gas measurements were made during each treatment and at pre- and posttreatment baselines.

Results

All three treatments improved PaO2 overall. Six patients were "phenylephrine-responders" (delta PaO2 > 10 mmHg), and six were "phenylephrine-nonresponders." In phenylephrine-responders, the effect of phenylephrine was comparable with that of NO (PaO2 from 105 +/- 14 to 132 +/- 14 mmHg with phenylephrine, and from 110 +/- 14 to 143 +/- 19 mmHg with NO), and the effect of phenylephrine+NO was greater than that of either treatment alone (PaO2 from 123 +/- 13 to 178 +/- 23 mmHg). In phenylephrine-nonresponders, phenylephrine did not affect PaO2, and the effect of phenylephrine+NO was not statistically different from that of NO alone (PaO2 from 82 +/- 12 to 138 +/- 28 mmHg with NO; from 84 +/- 12 to 127 +/- 23 mmHg with phenylephrine+NO). Data are mean +/- SEM.

Conclusions

Phenylephrine alone can improve PaO2 in patients with ARDS. In phenylephrine-responsive patients, phenylephrine augments the improvement in PaO2 seen with inhaled NO. These results may reflect selective enhancement of hypoxic pulmonary vasoconstriction by phenylephrine, which complements selective vasodilation by NO.
Assessment of Cytochrome P450 3A4 Activity during the Menstrual Cycle Using Alfentanil as a Noninvasive Probe
Authors: Kharasch Evan D. , Russell Michael , Garton Kyle , Lentz Gretchen , Bowdle T. Andrew , Cox Kathy
Published: November 2003

Background

Gender-dependent differences in cytochrome P450 activity, drug metabolism, drug elimination, and their clinical consequences are increasingly apparent. P450 3A4 is the most abundant P450 isoform in the human liver and is responsible for metabolizing a vast and diverse assortment of therapeutic agents, including opioids, benzodiazepines, and local anesthetics. P450, 3A4 activity is higher in women, influenced by steroid hormone levels, and is speculated to vary during the menstrual cycle. This investigation tested the hypothesis that P450 3A4 activity varies during the menstrual cycle. Alfentanil clearance was used as a metabolic probe for P450 3A4 activity.

Methods

Alfentanil (20 micrograms/kg bolus) was administered to nine nonsmoking, nonpregnant female volunteers (age, 26 +/- 5 yr) with normal menstrual cycles on three separate occasions during the same menstrual cycle: days 2 (menstrual phase), 13 (estrogen peak), and 21 (progesterone peak). Venous plasma alfentanil concentrations were determined by gas chromatography-mass spectrometry. Alfentanil clearance was determined by noncompartmental methods and by a three-compartment model with both pooled population and two-stage analysis.

Results

There was no significant difference in any measure of alfentanil clearance. Noncompartmental clearances (mean +/- SD) were 3.62 +/- 0.76, 3.81 +/- 0.96, and 3.60 +/- 0.84 ml/kg/ min, respectively, on days 2, 13, and 21 of the menstrual cycle.

Conclusions

Alfentanil clearances were not different on menstrual cycle days 2, 13, and 21, strongly suggesting no change in P450 3A4 activity. Menstrual cycle differences in alfentanil clearances do not contribute to interindividual variability in alfentanil disposition in women. If other P450 3A4 substrates are comparable, then menstrual cycle variability in their metabolism may not be a consideration in dosing or in the design of pharmacokinetic investigations.
Remifentanil versus Remifentanil/midazolam for Ambulatory Surgery during Monitored Anesthesia Care
Authors: Gold Martin I. , Watkins W. David , Sung Yung-Fong , Yarmush Joel , Chung Frances , Uy Nonita T. , Maurer Walter , Clarke Marcia Y. , Jamerson Brenda D.
Published: November 2003

Background

This study was designed to define the appropriate dose of remifentanil hydrochloride alone or combined with midazolam to provide satisfactory comfort and maintain adequate respiration for a monitored anesthesia care setting.

Methods

One hundred fifty-nine patients scheduled for outpatient surgery participated in this multicenter, double-blind study. Patients were randomly assigned to one of two groups: remifentanil, 1 microgram/kg, given over 30 s followed by a continuous infusion of 0.1 microgram.kg-1.min-1 (remifentanil), remifentanil, 0.5 microgram/kg, given over 30 s followed by a continuous infusion of 0.05 microgram.kg-1.min-1 (remifentanil+midazolam). Five minutes after the start of the infusion, patients received a loading dose of saline placebo (remifentanil) or midazolam, 1 mg, (remifentanil+midazolam). If patients were not oversedated, a second dose of placebo or midazolam, 1 mg, was given. Remifentanil was titrated (in increments of 50% from the initial rate) to limit patient discomfort or pain intraoperatively, and the infusion was terminated at the completion of skin closure.

Results

At the time of the local anesthetic, most patients in the remifentanil and remifentanil+midazolam groups experienced no pain (66% and 60%, respectively) and no discomfort (66% and 65%, respectively). The final mean (+/-SD) remifentanil infusion rates were 0.12 +/- 0.05 microgram.kg-1.min-1 (remifentanil) and 0.07 +/- 0.03 microgram.kg-1.min-1 (remifentanil+midazolam). Fewer patients in the remifentanil+midazolam group experienced nauses compared with the remifentanil group (16% vs. 36%, respectively; P < 0.05). Four patients (5%) in the remifentanil group and two patients (2%) in the remifentanil+midazolam group experienced brief periods of oxygen desaturation (SpO2 < 90%) and hypoventilation (< 8 breaths/ min).

Conclusions

Remifentanil alone or combined with midazolam provided adequate analgesia and maintained adequate respiration at the doses reported. The low dose of remifentanil combined with 2 mg midazolam, compared with remifentanil alone, resulted in fewer side effects, slightly greater sedation, and less anxiety.
Intracuff Pressures Do Not Predict Laryngopharyngeal Discomfort after Use of the Laryngeal Mask Airway
Authors: Rieger Armin , Brunne Bergit , Striebel Hans Walter
Published: November 2003

Background

The laryngeal mask airway (LMA) is a large foreign body that exerts pressure on the pharyngeal mucosa, which may lead to throat discomfort. To determine whether intracuff pressures are associated with such discomfort, a randomized, double-blind study was performed to determine the effect of high versus low intracuff pressures.

Methods

Seventy healthy women were randomly allocated to two groups with different LMA intracuff pressures: 30 mmHg (low pressure) or 180 mmHg (high pressure). Pressures were controlled with a microprocessor-controlled monitor. Insertion of the LMA was performed by one investigator and facilitated with propofol and verified fiberoptically. Anesthesia was maintained with enflurane and nitrous oxide. The LMAs were removed while the patients were still asleep. Patients assessed their laryngopharyngeal complaints (sore throat, dysphagia, hoarseness) at 8, 24, and 48 h after operation on a 101-point numerical rating scale.

Results

No significant difference was found in the overall incidence of complaints between both groups (low pressure: 50%; high pressure: 42%). On the day of surgery, dysphagia (38%) was more frequent than sore throat (16%) or hoarseness (6%) (P < 0.05) within the high-pressure group. In the low-pressure group, the incidence of these complaints was not significantly different (33%, 20%, and 23%, respectively). On the following day, dysphagia was still present in 20% of the women in both groups, and other symptoms comprised 10% or less of the reported complaints.

Conclusions

Differences in LMA intracuff pressures did not influence either the incidence or severity of laryngopharyngeal complaints.
Blockade of Myocardial ATP-sensitive Potassium Channels by Ketamine
Authors: Ko Seong-Hoon , Lee Sang-Kyi , Han Young-Jin , Choe Huhn , Kwak Yong-Geun , Chae Soo-Wan , Cho Kyu-Park , Song He-Sun
Published: November 2003

Background

The adenosine triphosphate (ATP)-sensitive potassium (KATP) channel underlies the increase in potassium permeability during hypoxia and ischemia. The increased outward potassium current during ischemia may be an endogenous cardioprotective mechanism. This study was designed to determine the effects of ketamine on KATP channel in rat hearts.

Methods

Inside-out and cell-attached configurations of patch-clamp techniques and 3 M potassium chloride-filled conventional microelectrodes were used to investigate the effect of ketamine on KATP channel currents in single rat ventricular myocytes and on the action potential duration of rat papillary muscles, respectively.

Results

Ketamine inhibited KATP channel activity in rat ventricular myocytes in a concentration-dependent manner. In the inside-out patches, the concentration of ketamine for half-maximal inhibition and the Hill coefficient were 62.9 microM and 0.54, respectively. In a concentration-dependent manner, ketamine inhibited pinacidil- and 2,4-dinitrophenol-activated KATP channels in cell-attached patches. The application of ketamine to the intracellular side of membrane patches did not affect the conduction of single-channel currents of KATP channels. Ketamine increased the action potential duration, which was then shortened by pinacidil in a concentration-dependent manner.

Conclusions

Ketamine inhibited KATP channel activity in a concentration-dependent manner. These results suggest that ketamine may attenuate the cardioprotective effects of the KATP channel during ischemia and reperfusion in the rat myocardium.
Direct Effects of Ropivacaine and Bupivacaine on Spinal Pial Vessels in Canine
Authors: Iida Hiroki , Watanabe Yukinaga , Dohi Shuji , Ishiyama Tadahiko
Published: November 2003

Background

Ropivacaine produces a vasoconstriction of cutaneous vessels in contrast to vasodilation produced by bupivacaine. To evaluate direct spinal microvascular actions of these local anesthetics, the authors investigated the concentration-related effects of ropivacaine and bupivacaine on spinal pial vascular diameters using the spinal window technique.

Methods

Anesthetized dogs (n = 14) divided into two groups (ropivacaine, n = 7; bupivacaine, n = 7) were prepared for measurement of spinal pial vessel diameters by intravital microscopy in a spinal window preparation. The authors administered six concentrations of each drug (10(-8)-10(-3) M) under the window and directly measured the spinal pial arteriolar and venular diameters at sequential times. Physiologic data including mean arterial blood pressure (MAP) and heart rate (HR) were determined before and after topical application of each concentration of the drugs. In additional experiments (n = 18), the action of topical ropivacaine and bupivacaine solution on spinal vessels was evaluated in the presence of yohimbine, prazosin, and propranolol.

Results

Ropivacaine significantly constricted whereas bupivacaine dilated pial arterioles and venules, both in a concentration-dependent manner. Microvascular alteration was not blocked with any of the adrenoceptor antagonists tested (yohimbine, prazosin, propranolol), each of which per se did not affect pial vessel diameters. Topical application of ropivacaine or bupivacaine did not induce any change in MAP or HR.

Conclusions

The present results indicate that ropivacaine constricts and bupivacaine dilates the pial vessels of the spinal cord in a concentration-dependent fashion, and the mechanisms involved in such actions do not seem to be mediated via alpha- or beta-adrenoceptor of spinal vasculature.
Halothane Attenuation of Calcium Sensitivity in Airway Smooth Muscle
Authors: Bremerich Dorothee H. , Hirasaki Akihito , Jones Keith A. , Warner David O.
Published: November 2003

Background

In airway smooth muscle, muscarinic receptor stimulation is thought to increase calcium (Ca2+) sensitivity via a guanosine 5'-triphosphate (GTP)-binding protein/protein kinase C (PKC)-mediated mechanism. This study treated the hypothesis that halothane reduces Ca2+ sensitivity during muscarinic receptor stimulation by inhibiting these second messenger pathways.

Methods

A beta-escin permeabilized canine tracheal smooth muscle preparation was used in which the cytosolic Ca2+ concentration ([Ca2+]i) is controlled and the GTP-binding protein/ PKC pathways remain intact and can be activated. The muscarinic receptor was activated with acetylcholine plus GTP; the GTP-binding proteins were directly activated with a nonhydrolyzable form of GTP, guanosine 5'-O-(3-thiotriphosphate; GTP gamma S); and PKC was directly activated with the PKC agonist phorbol 12,13-dibutyrate (PDBu).

Results

Free Ca2+ caused a concentration-dependent increase in force. Acetylcholine plus GTP significantly decreased the median effective concentration for free Ca2+ from 0.52 +/- 0.06 microM to 0.21 +/- 0.02 microM, demonstrating an increase in Ca2+ sensitivity. Halothane (0.99 +/- 0.04 mM, equivalent to approximately 4 minimum alveolar concentration in dogs) significantly attenuated this increase in Ca2+ sensitivity induced by acetylcholine plus GTP, increasing the median effective concentration for free Ca2+ from 0.21 +/- 0.02 microM to 0.31 +/- 0.03 microM. However, halothane did not affect the increases in Ca2+ sensitivity induced by GTP gamma S or PDBu.

Conclusions

Halothane had no effect on increased Ca2+ sensitivity caused by direct activation of GTP-binding proteins with GTP gamma S or PKC with PDBu, suggesting that halothane attenuates acetylcholine-induced Ca2+ sensitization via a mechanism independent of these pathways in beta-escin-permeabilized canine tracheal smooth muscle.
Positive Inotropic and Lusitropic Effects of Triiodothyronine in Conscious Dogs with Pacing-induced Cardiomyopathy
Authors: Jamali Iyad N. , Pagel Paul S. , Hettrick Douglas A. , Lowe Dermot , Kersten Judy R. , Tessmer John P. , Warltier David C.
Published: November 2003

Background

The effects of triiodothyronine (T3) on systemic hemodynamics, myocardial contractility (preload recruitable stroke work slope; Mw), and left ventricular (LV) isovolumic relaxation (time constant; tau) were examined before and after the development of pacing-induced cardiomyopathy in conscious dogs.

Methods

Dogs (n = 8) were chronically instrumented for measurement of aortic and LV pressure, dP/dtmax, subendocardial segment length, and cardiac output. Dogs received escalating doses (0.2, 2.0, and 20.0 mg/kg, intravenous) of T3 over 5 min at 1-h intervals, and peak hemodynamic effects were recorded 10 min after each dose and 24 h after the final dose. Dogs were then continuously paced at 220-240 beats/min for 21 +/- 2 days. Pacing was temporarily discontinued after the development of severe LV dysfunction, and administration of T3 was repeated.

Results

T3 produced immediate and sustained (24 h) increases (P < 0.05) in Mw and dP/dtmax in dogs before the initiation of pacing, consistent with a positive inotropic effect. No changes in tau occurred. Rapid ventricular pacing over 3 weeks increased baseline heart rate (sinus rhythm) and LV end-diastolic pressure, decreased mean arterial and LV systolic pressures, and caused LV systolic (decreases in Mw and dP/dtmax) and diastolic (increases in tau) dysfunction. T3 caused immediate and sustained increases in Mw (63 +/- 7 during control to 82 +/- 7 mmHg after the 2 mg/kg dose) and decreases in tau (65 +/- 8 during control to 57 +/- 6 ms after the 20 mg/kg dose), indicating that this hormone enhanced myocardial contractility and shortened LV relaxation, respectively, in the presence of chronic LV dysfunction. In contrast to the findings in dogs with normal LV function, T3 did not affect heart rate and calculated indices of myocardial oxygen consumption and reduced LV end-diastolic pressure (27 +/- 3 during control to 20 +/- 2 mmHg after the 2 mg/kg dose) in cardiomyopathic dogs.

Conclusions

The findings indicate that T3 produces favorable alterations in hemodynamics and modest positive inotropic and lusitropic effects in conscious dogs with LV dysfunction produced by rapid LV pacing.
The Effect of Electronic Record Keeping and Transesophageal Echocardiography on Task Distribution, Workload, and Vigilance During Cardiac Anesthesia
Authors: Weinger Matthew B. , Herndon Oliver W. , Gaba David M.
Published: November 2003

Background

Electronic anesthesia record keeping (EARK) systems increasingly are used in the operating room, but studies have only recently begun to investigate their effect on anesthesia task performance. Teak analysis, workload assessment, and vigilance assessment techniques were used to study senior residents providing anesthesia for coronary artery bypass graft (CABG) procedures. The impact on anesthesia residents' workload of the routine use of transesophageal echocardiography (TEE) also was examined.

Methods

Before each case, the record keeping system was randomly selected as either electronic (Distek ARKIVE; EARK) or traditional manual recording (MAN). Twenty CABG procedures (10 EARK and 10 MAN) were examined, with observation commencing with anesthetic induction and terminating on initiation of cardiopulmonary bypass. The activities of each resident, divided into 32 task categories (e.g., "laryngoscopy," "observe monitors," etc.), were recorded by a trained observer using a computer. The response latency to a randomly activated alarm light was used as a measure of vigilance ("vigilance latency"). Workload was rated by subject and observer at random 10- to 15-min intervals throughout the case. Data analysis included calculation of workload density (number of tasks/min multiplied by task-specific workload values) and task-links (relationship between sequential tasks).

Results

The two groups had a similar distribution of tasks before intubation. In only 4 of the 20 cases studied did any manual record keeping occur before intubation. After intubation, the EARK group spent less time record keeping and using the TEE but more time observing the monitors and conversing with the attending physician than the MAN group did. All subjects reported significantly higher workload scores before intubation compared with after intubation. Similarly, vigilance latency was greater before intubation compared with after intubation (57 vs. 31 s; P < 0.001). There were no significant differences between the two record keeping groups in subjective workload scores, workload density, or vigilance latency. During TEE use, vigilance latency was significantly longer, and workload density was greater than during other monitoring or recording tasks.

Conclusions

This study provides an objective description of the task distribution and workload during the administration of anesthesia for cardiac surgery. Under the conditions of this study. EARK use modestly decreased the time spent record keeping during the postintubation prebypass period. However, there was no effect of EARK either on vigilance or several measures of workload. TEE use was associated with increased workload and possibly decreased vigilance.
An Algorithm for Assessing Intraoperative Mean Arterial Pressure Lability
Authors: Reich David L. , Osinski Todd K. , Bodian Carol , Krol Marina , Sarier Kaya , Roth Ram , Konstadt Steven N.
Published: November 2003

Background

Intraoperative blood pressure lability may be related to risk factors, hypovolemia, light anesthesia, and morbid outcomes, but the measurements of lability in previous studies have been limited by imprecise and infrequent data collection methods. Computerized intraoperative data acquisition systems have provided an opportunity to readdress the issue of intraoperative blood pressure lability with more abundant and precise data. This study sought to derive and validate an algorithm (expert system) to measure mean arterial pressure (MAP) lability.

Methods

Two hundred thirty-nine computerized anesthesis records were reviewed retrospectively. Three anesthesiologists separately rated MAP as very stable, average, or very labile. The parameters of a computer algorithm that measured the change of median MAP between consecutive 2-min epochs were optimized to achieve the best possible agreement among the anesthesiologists. The algorithm was then validated on 229 additional anesthesia records.

Results

The proportion of consecutive 2-min epochs in which the absolute value of the fractional change of median MAP exceeded 0.06 (i.e., 6%) correlated strongly with the anesthesiologists' ratings (r = 0.78; P < 0.0001). The optimal sensitivity and specificity of the algorithm for detecting MAP lability were 98% and 59%, respectively.

Conclusions

One potential application of expert systems to anesthesia practice is a "smart alarm" to detect blood pressure lability. It may also provide a better tool to assess the relation between lability and outcome than has been available previously.
Reduction in the Incidence of Carbon Monoxide Exposures in Humans Undergoing General Anesthesia
Authors: Woehlck Harvey J. , Dunning Marshall , Connolly Lois A.
Published: November 2003

Background

Carbon monoxide forms via reaction of isoflurane, enflurane, and desflurane with dried CO2 absorbents. The authors hypothesize that interventions by nonphysician support personnel to decrease absorbent drying will decrease the exposure rate of patients to carbon monoxide from anesthetic breakdown.

Methods

In the control group, all anesthetizing personnel were made aware of the factors enabling CO generation from anesthetic breakdown, and prevention techniques were left to the anesthetizing personnel. After data collection was complete, the following interventions were initiated to reduce absorbent drying: Anesthesia technicians and housekeeping personnel were instructed to turn off all anesthesia machines after the last case of the day in each room, and the CO2 absorbent was changed each morning if fresh gas was found flowing. Baralyme was used in all phases of this study.

Results

Five cases of intraoperative carbon monoxide exposure occurred among 1,085 (0.46%) first cases in the control group. Postintervention, patient carbon monoxide exposures decreased (P < 0.05), with one exposure among 1,961 (0.051%) first cases in the main operating room. Two exposures among 68 (2.9%) first cases occurred in remote locations (P < 0.001) versus main operating room. Predisposing factors for absorbent drying include the prolonged use of anesthesia machines for monitored anesthesia care, inappropriate drying techniques for expiratory flowmeters, understaffing of support personnel, and anesthesia in remote locations.

Conclusions

These interventions reduced patient exposure to carbon monoxide. Monitoring for carbon monoxide exposures during general anesthesia may be necessary to recognize and end patient exposures that occur despite preventative measures.
Twenty-four-Hour Pharmacokinetics of Rectal Acetaminophen in Children
Authors: Birmingham Patrick K. , Tobin Michael J. , Henthorn Thomas K. , Fisher Dennis M. , Berkelhamer Maura C. , Smith Frederick A. , Fanta Kaaren B. , Cote Charles J.
Published: November 2003

Background

Rectal acetaminophen is often administered during operation to provide supplemental analgesia or antipyresis in children. Recent studies examining current dose guidelines are limited by short sampling times. The authors extended the drug sampling period to more clearly define acetaminophen pharmacokinetics in children having surgery.

Methods

Children (n = 28) were randomized to receive a single dose of 10, 20, or 30 mg/kg rectal acetaminophen after induction of anesthesia. Venous blood samples were taken every 30 min for 4 h, every 60 min for 4 h, and every 4 h for 16 h. Data were analyzed using a mixed-effects modeling technique (using NONMEM software) to determine the volume of distribution and clearance normalized for bioavailability. Additional models accounted for suppository dissolution followed by acetaminophen absorption.

Results

Age, weight, estimated blood loss, volume of intravenous fluid administered, and anesthesia time were similar in the three groups. Most patients did not achieve peak or sustained serum values in the 10-20 microg/ml serum concentration range associated with antipyresis. The volume of distribution was 385 ml/kg, and clearance normalized for bioavailability, F, was 5.46 ml x kg(-1) x min(-1). Pharmacokinetic models suggest that absorption of acetaminophen is a function of zero-order dissolution of suppositories and first-order absorption from the rectum. Suppository dose size also may affect absorption characteristics.

Conclusions

The current recommended rectal acetaminophen dose of 10-15 mg/kg yields peak serum concentrations less than the antipyretic serum concentration of 10-20 microg/ml. Based on the observed kinetics, the authors recommend that the initial dose should be approximately 40 mg/kg.
Diagnosis of Ventilator-associated Pneumonia
Authors: Papazian Laurent , Autillo-Touati Amapola , Thomas Pascal , Bregeon Fabienne , Garbe Louise , Saux Pierre , Seite Raymond , Gouin Francois
Published: November 2003

Background

Ventilator-associated pneumonia (VAP) requires early diagnosis and adequate antibiotic therapy. The aim of this prospective postmortem study was to assess the accuracy of direct examination and quantification of intracellular organisms (ICO) for the diagnosis of VAP.

Methods

Total and differential cell counts were performed on fluids recovered using nonbronchoscopic sampling techniques (blind bronchial sampling [BBS], mini-bronchoalveolar lavage [mini-BAL]) and from bronchoalveolar lavage (BAL) performed during fiberscopy. These 3 sampling techniques were done within 15 min of death without discontinuing mechanical ventilation. Quantification of ICO was performed on each sample recovered from the various sampling procedures. Gram reaction and morphology of bacteria were evaluated on Gram smears.

Results

The results of each technique were compared with histology and culture of lung tissue specimens obtained by surgical pneumonectomies in 28 patients who died after at least 72 h of mechanical ventilation. Histology was positive in 13 patients and negative in 15 patients. When only VAP with positive lung culture was considered (histologic signs of bronchopneumonia plus positive lung tissue culture), the sensitivity of Gram staining on BAL, mini-BAL, and BBS was 56%, 44%, and 56%, respectively. If all samples were considered, the sensitivity and the specificity of the determination of the percentage of ICO were low (less than 70%) whatever the sampling technique.

Conclusions

For initial therapeutic guidance, direct examination and presence of ICO do not contribute for establishing the diagnosis of VAP, essentially because of a lack of sensitivity. However, when positive, Gram staining can obviously guide initial antibiotherapy.
Neuroprotective Effects of Dexmedetomidine in the Gerbil Hippocampus after Transient Global Ischemia
Authors: Kuhmonen Johanna , Pokorny Jaroslav , Miettinen Riitta , Haapalinna Antti , Jolkkonen Jukka , Riekkinen Paavo Sr. , Sivenius Juhani
Published: November 2003

Background

Cerebral ischemia induces a massive release of norepinephrine associated with neuronal death in the brain. It has been demonstrated that alpha2-adrenoceptor agonists decrease the release and turnover of noradrenaline, and this might prove advantageous in counteracting the neurodegeneration in ischemic brain. Therefore, in the present study, the authors tested whether dexmedetomidine, a selective alpha2-receptor agonist, has neuroprotective effects in a gerbil transient global ischemia model.

Methods

Ischemia was induced by bilateral carotid occlusion for 5 min in diethylether-anesthetized normothermic gerbils. Dexmedetomidine was administered subcutaneously in four different treatment paradigms (6-8 animals/group): 3 or 30 microg/kg 30 min before and thereafter at 3, 12, 24, and 48 h after the occlusion, or 3 or 30 microg/kg at 3, 12, 24, and 48 h after the occlusion. Control animals were subjected to forebrain ischemia but received only saline injections. One week after occlusion, animals were transcardially perfused for histochemistry. Neuronal death in the CA1 and CA3 regions of the hippocampus and in the hilus of the dentate gyrus was evaluated in silver-stained 60-microm coronal sections.

Results

Compared with saline-treated ischemic animals, dexmedetomidine at a dose of 3 microg/kg given before and continued after the induction of ischemia reduced the number of damaged neurons in the CA3 area (2 +/- 3 vs. 17 +/- 20 degenerated neurons/mm2; P < 0.05). Also in the dentate hilus, the number of damaged neurons was reduced by dexmedetomidine (3 microg/kg) given before and continued after ischemia (5 +/- 7 vs. 56 +/- 42 degenerated neurons/mm2; P < 0.01).

Conclusions

The present data demonstrate that dexmedetomidine effectively prevents delayed neuronal death in CA3 area and in the dentate hilus in gerbil hippocampus when the management is started before the onset of ischemia and continued for 48 h after reperfusion. Inhibition of ischemia-induced norepinephrine release may be associated with neuroprotection by dexmedetomidine.
In Vitro Negative Inotropic Effect of Plasma Collected at the Time of Reperfusion in Humans undergoing Liver Transplantation
Authors: Chemla Denis , Jayais Pascal , Ecoffey Claude , Declere Adrien Descorps , Lecarpentier Yves
Published: November 2003

Background

During orthotopic liver transplantation (OLT), acute depression of myocardial contractility has been suspected at the time of the graft reperfusion.

Methods

The authors tested the hypothesis that plasma collected at the time of reperfusion in OLT patients exerted a negative inotropic effect on isolated rat myocardium. Plasma from 13 OLT patients was collected either before surgical incision (group 1, n = 8) or 3-5 min after vena cava and portal vein unclamping (group 2, n = 9). Six patients had their pre- and postincision plasma analyzed. A postreperfusion syndrome was observed in 3 of 13 patients. Left ventricular rat papillary muscles were studied at baseline (T0), 30 min after the addition of plasma (T30), and 60 min after the addition of plasma (T60). The authors recorded contraction parameters (maximum unloaded shortening velocity [Vmax], peak extent of systolic shortening at preload [deltaL], maximum active isometric tension [AFi], positive peak tension derivative [+dFi/dt], time-to-peak shortening [TPS], and time-to-peak force [TPF]) and relaxation parameters (maximum lengthening velocity at preload [VI], negative peak tension derivative [-dFi/dt], index of load sensitivity of relaxation [tRi]).

Results

In group 1, contraction parameters remained unchanged, with the exception of a decreased Vmax at T30 and AFi at T60 (each P < 0.05). In group 2, all contraction parameters were significantly decreased at T30 and at T60, with the exception of AFi at T60. Both types of plasma decreased V1 and altered tRi at T30 and T60, whereas only reperfusion plasma decreased -dFi/dt at T30 and T60. At T30, deltaL, -dFi/dt, and tRi were significantly more impaired in group 2 than in group 1. There was no relationship between inotropic changes and mean arterial pressure decrease at the time of reperfusion.

Conclusion

Plasma collected at the time of graft reperfusion in OLT patients exerted negative effects on contraction and relaxation performance in isolated rat left ventricular papillary muscle.
Postoperative Inflammatory Response after Autologous and Allogeneic Blood Transfusion
Authors: Avall Anders , Hyllner Monica , Bengtson Jan Peter , Carlsson Lars , Bengtsson Anders
Published: November 2003

Background

Allogeneic blood transfusions cause immunosuppression. The aim of this study was to determine whether complement anaphylatoxins, cytokines, or both are released in the recipient, after blood transfusions in general, and after autologous blood transfusions in particular.

Methods

Thirty-one patients having total hip joint replacement surgery were randomized to receive either allogeneic red blood cells (n = 15) or predeposited autologous whole blood transfusion (n = 16). Plasma concentrations of the anaphylatoxins C3a and C5a, the terminal C5b-9 complement complex, and cytokines IL-6 and IL-8 in the recipients were repeatedly analyzed before, during, and after surgery.

Results

Significantly increased concentrations of IL-6 and IL-8 appeared in both groups, with a significantly greater increase in the autologous blood group. Patients in both groups developed a moderate but significant increase of C3a without a significant difference between them. C5a and terminal C5b-9 complement complex were not greatly changed.

Conclusions

The study showed a greater increase in cytokine concentration after autologous blood transfusion than after allogeneic blood transfusion. The lower response in the latter may result from transfusion-induced suppression of cellular immunity.
Reducing Pain after Inguinal Hernia Repair in Children
Authors: Splinter William M. , Reid Craig W. , Roberts David J. , Bass Juan
Published: November 2003

Background

The optimal method to achieve analgesia after inguinal hernia repair in children is unknown. This study compared the analgesic efficacy, adverse events, and the costs associated with supplementation of local anesthesia (infiltration of the wound) with either intravenous ketorolac or caudal analgesia in children having inguinal hernia repair.

Methods

With parental consent and institutional review board approval, children aged 2-6 yr having elective, outpatient inguinal hernia repair were studied in this randomized, single-blinded investigation. Anesthesia was induced by inhalation with nitrous oxide and halothane or intravenously with propofol. Anesthesia was maintained with nitrous oxide and halothane. Patients were randomly assigned to receive caudal analgesia (1 ml/kg 0.20% bupivacaine with 1/200,000 epinephrine) or intravenous ketorolac (1 mg/kg) immediately after induction of anesthesia. Both groups received field blocks with 0.25% bupivacaine administered by the surgeon under direct vision during operation. Patients were assessed for 24 h. In-hospital pain was assessed using a behavior-based pain score. Parents assessed pain with a visual linear analog pain scale with anchors of 0 (no pain) and 100 (worst pain imaginable).

Results

The authors studied 164 children, with 84 patients in the ketorolac group. The groups had similar demographic data. In-hospital analgesic requirements and pain scores were almost identical in both groups. Pain at home was significantly less in the ketorolac group, with visual linear analog pain scale scores of 10 (0-80) compared with 20 (0-80) (median [range]) for ketorolac versus caudal (P = 0.002 by the Mann-Whitney U test). The ketorolac group also had a lower incidence of vomiting, ambulated more rapidly, and micturated earlier (P < 0.05).

Conclusion

The use of intravenous ketorolac to supplement local anesthesia infiltrated by the surgeon during pediatric inguinal hernia repair is superior to supplementation with caudal analgesia.
Correlation between Evoked Motor Response of the Sciatic Nerve and Sensory Blockade
Authors: Benzon Honorio T. , Kim Charles , Benzon Hazel P. , Silverstein Mark E. , Jericho Barbara , Prillaman Katherine , Buenaventura Ricardo
Published: November 2003

Background

Incomplete sensory blockade of the foot after sciatic nerve block in the popliteal fossa may be related to the motor response that was elicited when the block was performed. We investigated the appropriate motor response when a nerve stimulator is used in sciatic nerve block at the popliteal fossa.

Methods

Six volunteers classified as American Society of Anesthesiologists' physical status I underwent 24 sciatic nerve blocks. Each volunteer had four sciatic nerve blocks. During each block, the needle was placed to evoke one of the following motor responses of the foot: eversion, inversion, plantar flexion, or dorsiflexion. Forty milliliters 1.5% lidocaine was injected after the motor response was elicited at < 1 mA intensity. Sensory blockade of the areas of the foot innervated by the posterior tibial, deep peroneal, superficial peroneal, and sural nerves was checked in a blinded manner. Motor blockade was graded on a three-point scale. The width of the sciatic nerve and the orientation of the tibial and common peroneal nerves were also examined in 10 cadavers.

Results

A significantly greater number of posterior tibial, deep peroneal, superficial peroneal, and sural nerves were blocked when inversion or dorsiflexion was seen before injection than after eversion or plantar flexion (P < 0.05). Motor blockade of the foot was significantly greater after inversion. Anatomically, the tibial and common peroneal nerves may be separate from each other throughout their course. The sciatic nerve ranged from 0.9-1.5 cm in width and was divided into the tibial and common peroneal nerves at 8 +/- 3 (range, 4-13) cm above the popliteal crease.

Conclusions

Inversion is the motor response that best predicts complete sensory blockade of the foot. Incomplete blockade of the sciatic nerve may be a result of the size of the sciatic nerve, to separate fascial coverings of the tibial and common peroneal nerves, or to blockade of either the tibial or common peroneal nerves after branching from the sciatic nerve.
The Effect of Clonidine on Cerebral Blood Flow Velocity, Carbon Dioxide Cerebral Vasoreactivity, and Response to Increased Arterial Pressure in Human Volunteers
Authors: Lee Hye-Won , Caldwell James E. , Dodson Barbara , Talke Pekka , Howley Joan
Published: November 2003

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.
Doxycycline Reduces Early Neurologic Impairment after Cerebral Arterial Air Embolism in the Rabbit
Authors: Reasoner Daniel K. , Hindman Bradley J. , Dexter Franklin , Subieta Alberto , Cutkomp Johann , Smith Tom
Published: November 2003

Background

Previous studies indicate leukocytes play a role in the pathogenesis of cerebral arterial air embolism. Because doxycycline inhibits numerous leukocyte activities, the authors hypothesized doxycycline would decrease neurologic impairment after cerebral arterial air embolism.

Methods

New Zealand White rabbits anesthetized with methohexital received either intravenous saline (n = 7) or 10 mg/kg doxycycline (n = 7) 1 h before administration of 100 microl/kg of air into the internal carotid artery. Somatosensory-evoked potentials (SSEPs) were recorded at 30-min intervals for the next 2 h. After the final recording, the anesthetic was discontinued, and animals recovered. Animals were neurologically evaluated 4 h after air embolism on a scale of 0 (normal) to 99 (coma) points.

Results

At 4 h, doxycycline animals had lesser neurologic impairment (46 +/- 23; median, 41) than animals that received saline (77 +/- 20; median, 81); P = 0.007. SSEP amplitude was greater in the doxycycline group at 60, 90, and 120 min after air embolism; P = 0.001, 0.006, 0.026, respectively. SSEP amplitudes at 30, 60, 90, and 120 min inversely correlated with 4 h neurologic impairment; tau = -0.43, -0.75, -0.85, -0.79, respectively.

Conclusions

Doxycycline decreased electrophysiologic and neurologic abnormalities after cerebral air embolism. Because groups could be distinguished electrophysiologically as soon as 1 h after air embolism and because SSEP amplitude inversely correlated with neurologic impairment, doxycycline appears to inhibit a key early (approximately 1 h) process in the pathophysiology of cerebral air embolism.
Leukocyte-Endothelium Interaction in the Rat Mesenteric Microcirculation during Halothane or Sevoflurane Anesthesia
Authors: Morisaki Hiroshi , Suematsu Makoto , Wakabayashi Yoshiyuki , Moro-oka Shigeaki , Fukushima Kazuaki , Ishimura Yuzuru , Takeda Junzo
Published: November 2003

Background

The effects of inhalational anesthetics on the microcirculation, including leukocyte dynamics, remain to be clarified. The authors investigated halothane and sevoflurane anesthesia to determine if these agents evoked leukocyte adhesion through endothelial cell-dependent mechanisms involving such adhesion molecules.

Methods

Rats were anesthetized with halothane or sevoflurane in 100% oxygen and the lungs were mechanically ventilated. Leukocyte behavior in mesenteric venules was recorded through intravital video microscopy under monitoring microvascular hemodynamics. To examine the mechanisms for leukocyte rolling and adhesion, these studies were repeated after animals were pretreated with a monoclonal antibody against P-selectin (MAb PB1.3) or against intracellular adhesion molecule-1 (ICAM-1; MAb 1A29): P-selectin required for rolling of circulating leukocytes and ICAM-1 for firm adhesive interactions with leukocyte integrins.

Results

Under baseline anesthetic conditions (1 minimum alveolar concentration [MAC]), venular wall shear rates, an index of the disperse force on marginating leukocytes, in the sevoflurane-treated rats were about two times higher than those with halothane. At 2 MAC, halothane caused a marked arteriolar constriction and decreasing shear rates concurrent with an increasing density of venular leukocyte adhesion. Sevoflurane at 2 MAC induced leukocyte rolling and adhesion, which were attenuated by PB1.3 and 1A29, without alterations in the wall shear rates. Halothane-induced leukocyte adhesion was not prevented by PB1.3 but it was by 1A29.

Conclusions

Halothane or sevoflurane anesthesia induces venular leukocyte rolling and adhesion: P-selectin upregulation plays a crucial role in leukocyte rolling and adhesion during sevoflurane anesthesia, whereas low-flow perfusion is likely to evoke ICAM-1-dependent leukocyte adhesion during halothane anesthesia.