bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intramuscular Rapacuronium in Infants and Children
Authors: Denman William T. , Kaplan Richard F. , Goudsouzian Nishan G. , Uejima Tetsu , Barcelona Sandra L. , Cote Charles J. , Ginsberg Brian , Hannallah Raafat S. 
Published: November 2003

Background
This multicenter, assessor, blinded, randomized study was conducted to confirm and extend a pilot study in which intramuscular rapacuronium was given to infants and children to confirm efficacy and to evaluate tracheal intubating conditions.

Methods
Ninety-six pediatric patients were studied in two groups: infants aged 1 to 12 months (n = 46) and children aged 1 to 3 yr (n = 50). Infants received 2.8 mg/kg and children 4.8 mg/kg of intramuscular rapacuronium during 1 minimum alveolar concentration halothane anesthesia. These two groups were studied in three subgroups, depending on the time (1.5, 3, or 4 min) at which tracheal intubation was attempted after the administration of intramuscular rapacuronium into the deltoid muscle. Neuromuscular data collected included onset time, duration of action, and recovery data during train-of-four stimulation at 0.1 Hz. Data were analyzed by the Cochran-Mantel-Haenszel procedure.

Results
The tracheal intubating conditions were deemed acceptable in 17, 36, and 64% of infants and 20, 47, and 71% of children at 1.5, 3, or 4 min, respectively. The mean values for % of control twitch height (T1) 2 min after rapacuronium in both groups were similar. The mean (SD) time required to achieve more than or equal to 95% twitch depression in infants was 6.0 (3.7) versus 5.5 (3.8) min in children.

Conclusions
Only 27% of patients achieved clinically acceptable tracheal intubating conditions at 1.5 or 3 min after administration of 2.8 mg/kg and 4.8 mg/kg rapacuronium during 1 minimum alveolar concentration halothane anesthesia. Tracheal intubation conditions at 4 min were acceptable in 69% of subjects. The duration of action of 4.8 mg/kg of rapacuronium in children was longer than 2.8 mg/kg of rapacuronium in infants.
Recirculatory Pharmacokinetics and Pharmacodynamics of Rocuronium in Patients
Authors: Kuipers Jette A. , Boer Fred , Olofsen Erik , Bovill James G. , Burm Anton G. L. 
Published: November 2003

Background
Recirculatory models are capable of accurately describing first-pass pharmacokinetics and the influence of cardiac output (CO), which is important for drugs with a fast onset of effect. The influence of CO on pharmacokinetic and pharmacodynamic parameters of rocuronium in patients was evaluated using a recirculatory pharmacokinetic model.

Methods
Fifteen patients were included to study rocuronium pharmacokinetics and pharmacodynamics. Bolus doses of rocuronium (0.35 mg/kg) and indocyanine green (25 mg) were injected simultaneously via a peripheral intravenous catheter. Blood samples were taken for 240 min from the radial artery. The force of contraction of the adductor pollicis after a train-of-four at 2 Hz every 12 s was measured. Arterial concentration-time curves of rocuronium and indocyanine green were analyzed using a recirculatory model. Pharmacodynamics were described using a sigmoid maximum effect (Emax) model.

Results
The CO of the patients varied from 2.43 to 5.59 l/min. Total distribution volume of rocuronium was 17.3 +/- 4.8 l (mean +/- SD). The CO showed a correlation with the fast tissue clearance (Cl(T_f); r2 = 0.51), with the slow tissue clearance (Cl(T_s); r2 = 0.31) and with the mean transit times of rocuronium except for the mean transit time of the slow tissue compartment. The blood-effect site equilibration constant (k(e0)) was strongly correlated with CO (r2 = 0.70).

Conclusions
Cardiac output influences the pharmacokinetics, including k(e0), for rocuronium in patients. For drugs with a fast onset of effect, a recirculatory model, which includes CO, can give a good description of the relation between concentration and effect, in contrast to a conventional compartmental pharmacokinetic model.
Evidence for Susceptibility to Malignant Hyperthermia in Patients with Exercise-induced Rhabdomyolysis
Authors: Wappler Frank , Fiege Marko , Steinfath Markus , Agarwal Kamayni , Scholz Jens , Singh Surjit , Matschke Jakob , Schulte am Esch Jochen 
Published: November 2003

Background
Malignant hyperthermia (MH), heat stroke, and exercise-induced rhabdomyolysis (ER) were suspected to be related syndromes. However, it is not known whether individuals with history of ER have an increased incidence of susceptibility to MH. To establish an association between ER and susceptibility to MH, the authors determined the MH status in patients with a history of MH-like episodes induced by physical stress.

Methods
Twelve unrelated patients with ER, 18 patients with anesthesia-induced MH, and 28 controls were investigated with the in vitro contracture test (IVCT) according to the European MH Group protocol and the ryanodine contracture test. In addition, all patients were screened for genetic mutations, and histology was performed on muscle specimens.

Results
Ten ER patients had positive IVCT results, one patient had a negative test result, and one patient showed equivocal responses. Samples from patients with positive IVCT results showed pronounced contractures after exposition to ryanodine, as opposed to specimens from patients with negative IVCT results, which developed contractures slowly. Three ER patients had mutations at the ryanodine receptor gene. All anesthesia-induced MH patients had positive IVCT results, two of them presented the C1840T mutation. The control patients had normal contracture test results and no typical MH mutations. Histologic examination determined no specific myopathies in any patient.

Conclusions
Regarding these results, the authors recommend performing muscle biopsies for histologic examination and IVCT in patients with ER. In addition, the patient should be seen by a neurologist and screened for genetic abnormalities to shed light on the genetics of MH.
Effect of Drugs Used for Neuropathic Pain Management on Tetrodotoxin-resistant Na+Currents in Rat Sensory Neurons
Authors: Bräu Michael E. , Dreimann Marc , Olschewski Andrea , Vogel Werner , Hempelmann Gunter 
Published: November 2003

Background
Tetrodotoxin-resistant Na(+) channels play an important role in generation and conduction of nociceptive discharges in peripheral endings of small-diameter axons of the peripheral nervous system. Pathophysiologically, these channels may produce ectopic discharges in damaged nociceptive fibers, leading to neuropathic pain syndromes. Systemically applied Na(+) channel--blocking drugs can alleviate pain, the mechanism of which is rather unresolved. The authors investigated the effects of some commonly used drugs, i.e., lidocaine, mexiletine, carbamazepine, amitriptyline, memantine, and gabapentin, on tetrodotoxin-resistant Na+ channels in rat dorsal root ganglia.

Methods
Tetrodotoxin-resistant Na(+) currents were recorded in the whole-cell configuration of the patch-clamp method in enzymatically dissociated dorsal root ganglion neurons of adult rats. Half-maximal blocking concentrations were derived from concentration-inhibition curves at different holding potentials (-90, -70, and -60 mV).

Results
Lidocaine, mexiletine, and amitriptyline reversibly blocked tetrodotoxin-resistant Na(+) currents in a concentration- and use-dependent manner. Block by carbamazepine and memantine was not use-dependent at 2 Hz. Gabapentin had no effect at concentrations of up to 3 mm. Depolarizing the membrane potential from -90 mV to -60 mV reduced the available Na(+) current only by 23% but increased the sensitivity of the channels to the use-dependent blockers approximately fivefold. The availability curve of the current was shifted by 5.3 mV to the left in 300 microm lidocaine.

Conclusions
Less negative membrane potential and repetitive firing have little effect on tetrodotoxin-resistant Na(+) current amplitude but increase their sensitivity to lidocaine, mexiletine, and amitriptyline so that concentrations after intravenous administration of these drugs can impair channel function. This may explain alleviation from pain by reducing firing frequency in ectopic sites without depressing central nervous or cardiac excitability.
Critical Hematocrit in Intestinal Tissue Oxygenation during Severe Normovolemic Hemodilution
Authors: van Bommel Jasper , Siegemund Martin , Pieter Henny C. , Trouwborst Adrianus , Ince Can 
Published: November 2003

Background
A critical point in oxygen supply for microvascular oxygenation during normovolemic hemodilution has not been identified. The relation between organ microvascular oxygen partial pressure (microPO2) and organ oxygen consumption (VO2) during a decreasing oxygen delivery (DO2) is not well understood. The present study was designed to determine the systemic hematocrit and organ DO2 values below which organ microPO2 and VO2 cannot be preserved by regulatory mechanisms during normovolemic hemodilution.

Methods
Eighteen male Wistar rats were randomized between an experimental group (n = 12), in which normovolemic hemodilution was performed with pasteurized protein solution (PPS), and a control group (n = 6). Systemic hemodynamic and intestinal oxygenation parameters were monitored. Intestinal microPO2 was measured using the oxygen-dependent quenching of palladium-porphyrin phosphorescence.

Results
Baseline values in hemodilution and control group were similar. Hemodilution decreased hematocrit to 6.2 +/- 0.8% (mean +/- SD). Constant central venous pressure measurements suggested maintenance of isovolemia. Despite an increasing mesenteric blood flow, intestinal DO2 decreased immediately. Initially, microPO2 was preserved, whereas mesenteric venous PO2 (P(mv)O2) decreased; below a hematocrit of 15%, microPO2 decreased significantly below P(mv)O2. Critical DO2 was 1.5 +/- 0.5 ml x kg(-1) x min(-1) for VO2, and 1.6 +/- 0.5 ml x kg(-1) x min(-1) for microPO2. Critical hematocrit values for VO2 and microPO2 were 15.8 +/- 4.6% and 16.0 +/- 3.5%, respectively.

Conclusions
Intestinal microPO2 and VO2 were limited by a critical decrease in DO2 and hematocrit at the same time. Beyond these critical points not only shunting of oxygen from the microcirculation could be demonstrated, but also a significant correlation between intestinal microPO2 and VO2.
Assessment of Depth of Anesthesia and Postoperative Respiratory Recovery after Remifentanil-versus Alfentanil-based Total Intravenous Anesthesia in Patients Undergoing Ear–Nose–Throat Surgery
Authors: Wuesten Rainer , Van Aken Hugo , Glass Peter S. A. , Buerkle Hartmut 
Published: November 2003

Background
The authors investigated whether total intravenous anesthesia (TIVA) with precalculated equipotent infusion schemes for remifentanil and alfentanil would ensure appropriate analgesia and that remifentanil would result in better recovery characteristics.

Methods
Forty consenting patients (classified as American Society of Anesthesiologists physical status I-III) scheduled for microlaryngoscopy were randomized to receive, in a double-blind manner, either remifentanil (loading dose 1 microg/kg; maintenance infusion, 0.25 microg x kg(-1) x min-1) or alfentanil (loading dose, 50 microg/kg; maintenance infusion, 1 microg x kg(-1) x min-1) as the analgesic component of TIVA. They were combined with propofol (loading dose, 2 mg/kg; maintenance infusion, 100 microg x kg(-1) min(-1)). To insure an equal state of anesthesia, the opioids were titrated to maintain heart rate and mean arterial pressure within 20% of baseline, and propofol was titrated to keep the bispectral index (BIS) less than 60. Neuromuscular blockade was achieved with succinylcholine. Drug dosages and the times from cessation of anesthesia to extubation, verbal response, recovery of ventilation, and neuropsychological testing, orientation, and discharge readiness were recorded.

Results
Demographics, duration of surgery, and anesthesia were similar between the two groups. Both groups received similar propofol doses. There were no difference in BIS values preoperatively (mean, 96), intraoperatively (mean, 55), and postoperatively (mean, 96). Recovery of BIS and times for verbal response did not differ. At 20, 30, and 40 min after terminating the opioid infusion, the peripheral oxygen saturation and respiratory rate were significantly higher in the remifentanil group compared with the alfentanil group.

Conclusions
When both the hypnotic and analgesic components of a TIVA-based anesthetic are administered in equipotent doses, remifentanil provides a more rapid respiratory recovery, even after brief surgical procedures, compared with alfentanil.
Nosocomial Infections and Outcome of Critically Ill Elderly Patients after Surgery
Authors: Stéphan François , Cheffi Ali , Bonnet Francis 
Published: November 2003

Background
The relation between older age and nosocomial infection and mortality in the intensive care unit (ICU) is still a controversial issue.

Methods
The authors prospectively studied 406 patients admitted to a surgical ICU, 106 of whom were more than 75 yr old. Information concerning ICU-acquired nosocomial infections, severity of illness, therapeutic activity, and hospital outcome was collected. A Cox proportional hazard analysis was used to evaluate potential risk factors for ICU-acquired nosocomial infections, ICU, and hospital death.

Results
During their ICU stay, 23 elderly patients experienced 40 nosocomial infections, 28 "young" patients (< 60 yr) experienced 54 nosocomial infections, and 52 "intermediate age" patients (60-75 yr) experienced 98 nosocomial infections. Incidence density of nosocomial infections was 4.9% patient days for elderly patients, 4.7% for young patients, and 6.0% for intermediate age patients (no significance). The frequency distribution of the various microorganisms isolated was similar between the three groups. Compared with younger patients, elderly patients had a higher Acute Physiology and Chronic Health Evaluation II score and a higher ICU and hospital mortality rate. Despite a higher level of severity of illness, elderly patients had a reduction of therapeutic activity. However, Cox proportional hazard analysis showed that age more than 75 yr was not a risk factor for ICU-acquired nosocomial infection, ICU, or hospital death.

Conclusions
In patients referred to a surgical ICU after a surgical procedure, age more than 75 yr by itself does not appear to be a significant predictor of ICU-acquired nosocomial infection or mortality rate during the ICU stay. However, it appears that patients more than 60 yr have a higher incidence of nosocomial infection in ICU.
Efficacy of Acute Normovolemic Hemodilution Assessed as a Function of Fraction of Blood Volume Lost
Authors: Weiskopf Richard B. 
Published: November 2003

Background
It has been recommended that intraoperative acute normovolemic hemodilution (ANH) be considered for patients expected to experience surgical blood loss of 20% or more of their blood volume. Previous mathematical analyses have not evaluated the potential efficacy of ANH in terms of fraction of blood volume lost. Since decrease of oxygen-carrying capacity is a function of erythrocyte loss relative to blood volume, the purpose of this analysis was to provide an assessment of ANH applicable to all blood volumes and to determine whether this recommendation is appropriate.

Methods
Equations were developed to describe the fractional blood volume loss (blood volume loss/blood volume; VReM/VBld) required to reduce hematocrit below a "trigger" hematocrit with maintenance of isovolemia. This is also the minimum fractional blood volume loss required for initial erythrocyte savings by any conservation technique. Equations were also developed to describe the fractional surgical blood volume loss for which ANH will obviate the need for transfusion of erythrocytes from any source other than those removed by ANH, and the fractional surgical blood volume loss required for ANH to save a defined volume of erythrocytes.

Results
Acute normovolemic hemodilution can extend the allowable fractional surgical blood loss before erythrocyte transfusion is required. The VRem/VBld required to initiate erythrocyte savings is approximately 0.5-0.9. The efficacy of ANH in terms of erythrocytes saved cannot be expressed as a function of the fractional blood volume lost alone. To save 1 unit of erythrocytes requires a fractional surgical blood loss of approximately 0.7-1.2 for the usual surgical patient when the transfusion trigger hematocrit is 0.18-0.21.

Conclusions
This analysis suggests that surgical blood loss should be 0.50 or more for ANH to begin to "save" erythrocytes and 0.70 or more of the patient's blood volume for ANH to save 1 unit erythrocytes, for the usual surgical patient with an initial hematocrit of 0.32-0.36 and a transfusion "trigger" hematocrit (the value at which transfusion is initiated) of 0.18-0.21.
Effect of Inhaled Prostacyclin in Combination with Almitrine on Ventilation–Perfusion Distributions in Experimental Lung Injury
Authors: Dembinski Rolf , Max Martin , López Frank , Kuhlen Ralf , Kurth Roland , Rossaint Rolf 
Published: November 2003

Background
Inhaled prostacyclin and intravenous almitrine have both been shown to improve pulmonary gas exchange in acute lung injury (ALI). This study was performed to investigate a possible additive effect of prostacyclin and almitrine on pulmonary ventilation-perfusion (VA/Q) ratio in ALI compared with inhaled prostacyclin or intravenous almitrine alone.

Methods
Experimental ALI was established in 24 pigs by repeated lung lavage. Animals were randomly assigned to receive either 25 ng.kg(-1).min(-1) inhaled prostacyclin alone, 1 microg.kg(-1).min(-1) almitrine alone, 25 ng.kg(-1).min(-1) inhaled prostacyclin in combination with 1 microg.kg(-1).min(-1) almitrine, or no specific treatment (controls) for 30 min. For each intervention, pulmonary gas exchange and hemodynamics were analyzed and VA/Q distributions were calculated using the multiple inert gas elimination technique. The data was analyzed within and between the groups by analysis of variance for repeated measurements, followed by the Student-Newman-Keuls test for multiple comparison when analysis of variance revealed significant differences.

Results
All values are expressed as mean +/- SD. In controls, pulmonary gas exchange, hemodynamics, and VA/Q distribution remained unchanged. With prostacyclin alone and almitrine alone, arterial oxygen partial pressure (PaO2) increased, whereas intrapulmonary shunt (QS/QT) decreased (P < 0.05). Combined prostacyclin and almitrine also increased PaO2 and decreased QS/QT (P < 0.05). When compared with either prostacyclin or almitrine alone, the combined application of both drugs revealed no additional effect in gas exchange or VA/Q distribution.

Conclusions
The authors conclude that, in this experimental model of ALI, the combination of 25 ng.kg(-1).min(-1) prostacyclin and 1 microg.kg(-1).min(-1) almitrine does not result in an additive improvement of pulmonary gas exchange or VA/Q distribution when compared with prostacyclin or almitrine alone.
Technique for Using Video Microscopy and Indicator Dilution for Repeated Measurements of Cardiac Output in Small Animals
Authors: Rivers Richard J. , Beckman Judy B. , Frame Mary D. S. 
Published: November 2003

Background
The authors developed an indicator dilution technique for small animals to repeatedly determine cardiac output and blood volume without cardiac instrumentation or blood sampling.

Methods
Observations were made in the hamster (N = 32, 70 mg/kg pentobarbital) cremaster using in vivo fluorescence videomicroscopy. Fluorescein isothiocyanate-conjugated bovine serum albumin (10 mg/ml) was injected as a bolus dose (right jugular) while video recording the light intensity in a 20-microm arteriole (intensified charge-coupled device [CCD] camera at fixed gain). The intensity signal was analyzed over time (background subtracted) and calibrated to the dye concentration. The ex vivo calibration was performed using a constant optical path length (20 microm) and a range of dye and hematocrit concentrations. In vivo tube hematocrit was determined using standard methods with fluorescently labeled erythrocytes. Thus, quenching of the fluorescence signal by hemoglobin was corrected for the calibration, and the plasma space in the arteriole was determined. The steady state dye concentration measured by the light intensity at 2 min was not different from the dye concentration found by direct spectrophotometric analysis of the plasma.

Results
Cardiac index was calculated as milliliters of blood per minute per kilogram body weight. The calculated cardiac index was 359 +/- 18 ml.min(-1).kg(-1), which is not different from the reported values for hamsters. Cardiac output was increased twofold when enough intravenous nitroprusside or nitroglycerine was injected to decrease mean arterial pressure from 90 to 70 mmHg. Cardiac output was elevated during dobutamine infusion (16 microg.kg(-1).min(-1)) and decreased during esmolol infusion (50, 75.kg(-1).min(-1)). Blood volume determined from the steady state dye concentrations was 6.2 +/- 0.5 ml/100 g body weight, within the normal range for hamsters.

Conclusions
Fluorescent dye dilution and video microscopy can be used to repeatedly determine cardiac output or blood volume in small animals.
Automated Responsiveness Test (ART) Predicts Loss of Consciousness and Adverse Physiologic Responses during Propofol Conscious Sedation
Authors: Doufas Anthony G. , Bakhshandeh Maryam , Bjorksten Andrew R. , Greif Robert , Sessler Daniel I. 
Published: November 2003

Background
The authors evaluated a device designed to provide conscious sedation with propofol (propofol-air), or propofol combined with 50% nitrous oxide (N2O; propofol-N2O). An element of this device is the automated responsiveness test (ART), a method for confirming that patients remain conscious. The authors tested the hypotheses that the ART predicts loss of consciousness and that failure to respond to the ART precedes sedation-induced respiratory or hemodynamic toxicity.

Methods
The protocol consisted of sequential 15-min cycles in 20 volunteers. After a 15-min control period, propofol was infused to an initial target effect-site concentration of 0.0 microg/ml with N2O or 1.5 microg/ml with air. Subsequently, the propofol target effect-site concentration was increased by a designated increment (0.25 and 0.5 microg/ml) and the process repeated. This sequence was continued until loss of consciousness, as defined by an Observer's Assessment of Alertness/Sedation (OAA/S) score of 10/20 or less, or until an adverse physiologic event was detected.

Results
The OAA/S score at which only 50% of the volunteers were able to respond to the ART (P50) during propofol-N2O was 11.1 of 20 (95% confidence interval [CI]: 10.6-11.8); the analogous P50 was 11.8 of 20 (95% CI: 11.4-12.3) with propofol-air. Failure to respond to the ART occurred at a plasma propofol concentration of 0.7 +/- 0.6 microg/ml with propofol-N2O and 1.6 +/- 0.6 microg/ml with propofol-air, whereas loss of consciousness occurred at 1.2 +/- 0.8 microg/ml and 1.9 +/- 0.7 microg/ml, respectively. There were no false-normal ART responses.

Conclusion
The ART can guide individual titration of propofol because failure to respond to responsiveness testing precedes loss of consciousness and is not susceptible to false-normal responses. The use of N2O with propofol for conscious sedation decreases the predictive accuracy of the ART.