bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beneficial Effects of Short-term Vasopressin Infusion during Severe Septic Shock
Authors: Patel Bhavesh M. , Chittock Dean R. , Russell James A. , Walley Keith R. 
Published: August 2004

Background
Septic shock is associated with vasopressin deficiency and a hypersensitivity to its exogenous administration. The goal of the current study was to determine whether short-term vasopressin infusion in patients experiencing severe septic shock has a vasopressor sparing effect while maintaining hemodynamic stability and adequate end-organ perfusion.

Methods
Patients experiencing septic shock that required high-dose vasopressor support were randomized to a double-blinded 4-h infusion of either norepinephrine (n = 11) or vasopressin (n = 13), and open-label vasopressors were titrated to maintain blood pressure. To assess end-organ perfusion, urine output and creatinine clearance, gastric mucosal carbon dioxide tension, and electrocardiogram ST segment position were measured.

Results
Patients randomized to norepinephrine went from a median prestudy norepinephrine infusion of 20.0 microg/min to a blinded infusion of 17.0 mug/min at 4 h, whereas those randomized to vasopressin went from a median prestudy norepinephrine infusion of 25.0 microg/min to 5.3 microg/min at 4 h (P < 0.001). Mean arterial pressure and cardiac index were maintained in both groups. Urine output did not change in the norepinephrine group (median, 25 to 15 ml/h) but increased substantially in the vasopressin group (median, 32.5 to 65 ml/h; P < 0.05). Similarly, creatinine clearance did not change in the norepinephrine group but increased by 75% in the vasopressin group (P < 0.05). Gastric mucosal carbon dioxide tension and electrocardiogram ST segments did not change significantly in either group.

Conclusions
The authors conclude that short-term vasopressin infusion spared conventional vasopressor use and improved some measures of renal function in patients with severe septic shock.
The Relationship between Acceleromyographic Train-of-four Fade and Single Twitch Depression
Authors: Kopman Aaron F. , Klewicka Monika M. , Neuman George G. 
Published: August 2004

Background
During offset of nondepolarizing neuromuscular block, a train-of-four (TOF) fade ratio of 0.70 or greater is considered to reliably indicate the return of single twitch height (T1) to its control value. Studies using mechanomyography or electromyography confirm this observation. The authors' impressions when using the acceleromyograph as a neuromuscular monitor did not support these results. Therefore, the authors studied the relation between T1 and the TOF ratio (when measured by acceleromyography) during recovery from neuromuscular block.

Methods
Sixteen adult patients were studied. Anesthesia was induced with intravenous opioid plus 2.0-2.5 mg/kg propofol. Laryngeal mask placement or tracheal intubation was accomplished without the use of muscle relaxants. Anesthesia was maintained with nitrous oxide, desflurane (2.0-3.0%, end-tidal), and fentanyl. The response of the thumb to ulnar nerve stimulation was recorded with the TOF-Guard acceleromyograph (Organon Teknika BV, Boxtel, The Netherlands). TOFs were administered every 15 s. After final calibration, 0.15 mg/kg mivacurium was administered. No further relaxants were administered. T1 and the TOF ratio were then recorded until the TOF ratio had returned to its initial value (+/- 5%).

Results
At a TOF ratio of 0.70 (during recovery of neuromuscular function), T1 averaged only 69 +/- 8% of control. At a TOF ratio of 0.90, T1 averaged 86 +/- 5% of control. To achieve 90% recovery of T1, a TOF ratio of 0.93 +/- 0.08 was required.

Conclusion
Assumptions regarding the relation between T1 and the TOF ratio derived from studies using mechanomyography and electromyography do not necessarily apply to observations obtained using acceleromyography.
Relationship between Intracranial Pressure and Critical Closing Pressure in Patients with Neurotrauma
Authors: Thees Christof , Scholz Martin , Schaller Carlo , Gass Annette , Pavlidis Christos , Weyland Andreas , Hoeft Andreas 
Published: August 2004

Background
The driving pressure gradient for cerebral perfusion is the difference between mean arterial pressure (MAP) and critical closing pressure (CCP = zero flow pressure). Therefore, determination of the difference between MAP and CCP should provide an appropriate monitoring of the effective cerebral perfusion pressure (CPP(eff)). Based on this concept, the authors compared conventional measurements of cerebral perfusion pressure by MAP and intracranial pressure (CPP(ICP)) with CPP(eff).

Methods
Simultaneous synchronized recordings of pressure waveforms of the radial artery and blood flow velocities of the middle cerebral artery were performed in 70 head trauma patients. CCP was calculated from pressure-flow velocity plots by linear extrapolation to zero flow.

Results
Intracranial pressure measured by intraventricular probes and CCP ranged from 3 to 71 and 4 to 70 mmHg, respectively. Linear correlation between ICP and CCP was r = 0.91. CPP(ICP) was 77 +/- 20 mmHg and did not differ from CPP(eff); linear correlation was r = 0.92. However, limits of agreement were only +/- 16.2 mmHg. Therefore, in 51.4% of the patients, CPP(ICP) overestimated CPP(eff) by 19.8 mmHg at most.

Conclusion
Assuming that CPP(eff) (MAP - CCP) takes into account more determinants of cerebral downstream pressure, in individual cases, the actual gold standard of CPP determination (MAP - ICP) might overestimate the CPP(eff) of therapeutic significance.
Morphologic Changes in the Upper Airway of Children during Awakening from Propofol Administration
Authors: Litman Ronald S. , Weissend Eric E. , Shrier David A. , Ward Denham S. 
Published: August 2004

Background
The purpose of this study was to determine the morphologic changes that occur in the upper airway of children during awakening from propofol sedation.

Methods
Children undergoing magnetic resonance imaging of the head underwent additional scans of the upper airway during deep sedation with propofol; this was repeated on awakening. Axial views were obtained at the most posterior sites of the pharynx at the levels of the soft palate and tongue. Measurements were then obtained of the anterior-posterior (A-P) diameter, transverse diameter, and cross-sectional areas at these levels.

Results
Data were obtained on 16 children, aged 10 months to 7 yr. In both sedated and awakening states, most children had the smallest cross-sectional area of the pharynx at the level of the soft palate. During the sedated state, at the soft palate level, the transverse diameter was most narrow in 11 children, the A-P diameter was most narrow in 1 child, and they were equal in 2 children. During the sedated state, at the level of the tongue, the transverse diameter was most narrow in 9 children, the A-P diameter was most narrow in 5 children, and they were equal in 2 children. During awakening, at the soft palate level, the transverse diameter was most narrow in none of the children, the A-P diameter was most narrow in 13 children, and they were equal in 1 child. At the level of the tongue, the transverse diameter was most narrow in 4 children, and the A-P diameter was most narrow in 12 children. During awakening, the A-P diameter of the pharynx at the level of the soft palate decreased in 12 children, increased in 1 child, and remained the same in 1 child. (P < 0.001). The transverse diameter increased in 11 children, decreased in 1 child, and remained the same in 2 children (P = 0.001). The cross-sectional area at the level of the soft palate increased in 4 children, decreased in 8 children, and stayed the same in 2 children (P = 0.5). During awakening, the A-P diameter of the pharynx at the level of the tongue decreased in 11 children, increased in 4 children, and remained the same in 1 child. (P = 0.01). The transverse diameter increased in 11 children and decreased in 5 children (P = 0.07). The cross-sectional area at the level of the tongue increased in 7 children, decreased in 7 children, and stayed the same in 2 children (P = 0.9).

Conclusions
The dimensions of the upper airways of children change shape significantly on awakening from propofol sedation. When sedated, the upper airway is oblong shaped, with the A-P diameter larger than the transverse diameter. On awakening, the shape of the upper airway in most children changed such that the transverse diameter was larger. Cross-sectional areas between sedated and awakening states were unchanged. These changes may reflect the differential effects of propofol on upper airway musculature during awakening.
Pharmacology of Spinal Glutamatergic Receptors in Post–Thermal Injury–evoked Tactile Allodynia and Thermal Hyperalgesia
Authors: Nozaki-Taguchi Natsuko , Yaksh Tony L. 
Published: August 2004

Background
After a focal thermal injury to the heel of a rat, thermal hyperalgesia appears at the injury site (primary thermal hyperalgesia), and tactile allodynia appears at the off-injury site (secondary tactile allodynia). The pharmacology of spinal glutamatergic receptors in the initiation and maintenance of secondary tactile allodynia was examined.

Methods
In rats prepared with chronic intrathecal catheters, the heel of one hind paw was exposed to a 52 degrees C surface for 45 s, resulting in a local erythema without blistering. Intrathecal N-methyl-d-aspartate (NMDA) receptor antagonists (MK-801, AP5) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-kainate (AMPA-KA) receptor antagonists (CNQX, NBQX, NS257, etc.) were administered either before (pretreatment) or after (posttreatment) the induction of the injury. Tactile withdrawal thresholds and thermal paw withdrawal latencies were assessed.

Results
Pretreatment and posttreatment with AMPA-KA antagonists produced a dose-dependent blockade of secondary tactile allodynia. However, NMDA antagonists, in doses that effectively block other models of facilitated states, showed little or no effect. Primary thermal hyperalgesia was blocked only by high-dose AMPA-KA antagonists.

Conclusion
Spinal AMPA-KA receptors play a major role in the initiation of secondary tactile allodynia induced by focal thermal injury. In contrast, spinal NMDA receptors play only a minimal role.
Mechanisms Involved in the Antiplatelet Activity of Midazolam in Human Platelets
Authors: Sheu Joen R. , Hsiao George , Luk Hsiung N. , Chen Yi W. , Chen Ta L. , Lee Lin W. , Lin Chien H. , Chou Duen S. 
Published: August 2004

Background
Midazolam is widely used as a sedative and anesthetic induction agent. The aim of this study was to systematically examine the inhibitory mechanisms of midazolam in platelet aggregation.

Methods
The inhibitory mechanisms of midazolam in platelet aggregation were explored by means of analysis of the platelet glycoprotein IIb-IIIa complex, phosphoinositide breakdown, intracellular Ca+2 mobilization, measurement of membrane fluidity, thromboxane B2 formation, and protein kinase C activity.

Results
In this study, midazolam dose-dependently (6-26 microm) inhibited platelet aggregation in human platelets stimulated by agonists. Midazolam also dose-dependently inhibited phosphoinositide breakdown and intracellular Ca+2 mobilization in human platelets stimulated by collagen. Midazolam (6-26 mum) significantly inhibited thromboxane A2 formation stimulated by collagen in human platelets. Moreover, midazolam (15 and 26 mum) dose-dependently decreased the fluorescence of platelet membranes tagged with diphenylhexatriene. Rapid phosphorylation of a platelet protein of Mr 47,000 (P47), a marker of protein kinase C activation, was triggered by collagen (2 microg/ml). This phosphorylation was markedly inhibited by midazolam (26 microm).

Conclusions
These results indicate that the antiplatelet activity of midazolam may be involved in the following pathways: the effects of midazolam may initially be caused by induction of conformational changes in platelet membrane, leading to a change in the activity of phospholipase C, and subsequent inhibition of phosphoinositide breakdown and thromboxane A2 formation, thereby leading to inhibition of both intracellular Ca+2 mobilization and phosphorylation of P47 protein.
Ketamine Inhibits Presynaptic and Postsynaptic Nicotinic Excitation of Identified Cardiac Parasympathetic Neurons in Nucleus Ambiguus
Authors: Irnaten Mustapha , Wang Jijiang , Venkatesan Priya , Evans Cory , K. Chang Kyoung S. , Andresen Michael C. , Mendelowitz David 
Published: August 2004

Background
Ketamine increases both blood pressure and heart rate, effects commonly thought of as sympathoexcitatory. The authors investigated possible central nervous system actions of ketamine to inhibit cardiac parasympathetic neurons in the brainstem by inhibiting multiple nicotinic excitatory mechanisms.

Methods
The authors used a novel in vitro approach to study the effect of ketamine on identified cardiac parasympathetic preganglionic neurons in rat brainstem slices. The cardiac parasympathetic neurons in the nucleus ambiguus were retrogradely prelabeled with the fluorescent tracer by placing rhodamine into the pericardial sac. Dye-labeled neurons were visually identified for patch clamp recording. The effects of ketamine were tested on nicotine-evoked ligand-gated currents and spontaneous glutamatergic miniature synaptic currents (mini) in cardiac parasympathetic preganglionic neurons.

Results
Ketamine (10 microm) inhibited (1) the nicotine (1 microm)-evoked presynaptic facilitation of glutamate release (mini frequency, 18 +/- 7% of control; n = 9), and (2) the direct postsynaptic ligand-gated current (27 +/- 8% of control; n = 9), but ketamine did not alter the amplitude of postsynaptic miniature non-N-methyl-D-aspartate currents. alpha Bungarotoxin, an antagonist of alpha 7 containing nicotinic presynaptic receptors, blocked ketamine actions on mini frequency (n = 10) but not mini amplitude.

Conclusions
Ketamine inhibits the presynaptic nicotinic receptors responsible for facilitating neurotransmitter release, as well as the direct ligand-gated inward current, but does not alter the nicotinic augmentation of non-N-methyl-D-aspartate currents in brainstem parasympathetic cardiac neurons. Such actions may mediate the decrease in parasympathetic cardiac activity and increase in heart rate that occurs with ketamine.
Is Isoflurane-induced Preconditioning Dose Related?
Authors: Kehl Franz , Krolikowski John G. , Mraovic Boris , Pagel Paul S. , Warltier David C. , Kersten Judy R. 
Published: August 2004

Background
Volatile anesthetics precondition against myocardial infarction, but it is unknown whether this beneficial action is threshold- or dose-dependent. The authors tested the hypothesis that isoflurane decreases myocardial infarct size in a dose-dependent fashion in vivo.

Methods
Barbiturate-anesthetized dogs (n = 40) were instrumented for measurement of systemic hemodynamics including aortic and left ventricular pressures and rate of increase of left ventricular pressure. Dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion and were randomly assigned to receive either 0.0, 0.25, 0.5, 1.0, or 1.25 minimum alveolar concentration (MAC) isoflurane in separate groups. Isoflurane was administered for 30 min and discontinued 30 min before left anterior descending coronary artery occlusion.

Results
Infarct size (triphenyltetrazolium staining) was 29 +/- 2% of the area at risk in control experiments (0.0 MAC). Isoflurane produced significant (P < 0.05) reductions of infarct size (17 +/- 3, 13 +/- 1, 14 +/- 2, and 11 +/- 1% of the area at risk during 0.25, 0.5, 1.0, and 1.25 MAC, respectively). Infarct size was inversely related to coronary collateral blood flow (radioactive microspheres) in control experiments and during low (0.25 or 0.5 MAC) but not higher concentrations of isoflurane. Isoflurane shifted the linear regression relation between infarct size and collateral perfusion downward (indicating cardioprotection) in a dose-dependent fashion.

Conclusions
Concentrations of isoflurane as low as 0.25 MAC are sufficient to precondition myocardium against infarction. High concentrations of isoflurane may have greater efficacy to protect myocardium during conditions of low coronary collateral blood flow.
Propofol Attenuates β-Adrenoreceptor–mediated Signal Transduction via a Protein Kinase C–dependent Pathway in Cardiomyocytes
Authors: Kurokawa Hiromi , Murray Paul A. , Damron Derek S. 
Published: August 2004

Background
Activation of beta adrenoreceptors by catecholamines is an important mechanism for increasing the inotropic state of the heart. The objectives of the current study were to investigate the effects of propofol on beta-adrenoreceptor-mediated increases in cardiomyocyte intracellular Ca2+ concentration ([Ca2+]i), cell shortening, L-type Ca2+ current (ICa) and cyclic adenosine monophosphate (cAMP) accumulation. The authors also investigated the site of action of propofol in the beta-adrenoreceptor signaling pathway, as well as the role of protein kinase C (PKC), and tested the hypothesis that propofol would inhibit the beta-adrenoreceptor signaling pathway via a PKC-dependent mechanism.

Methods
Freshly isolated ventricular myocytes were obtained from adult rat and guinea pig hearts. Myocyte shortening (video edge detection) and [Ca2+]i (fura-2, 340/380 ratio) were monitored simultaneously in individual cells. Conventional whole cell patch clamp analysis was used to measure the ICa in individual myocytes. cAMP production was assessed in suspensions of myocytes using an enzyme immunoassay kit.

Results
Propofol (0.1-10 mum) had no effect on steady state [Ca2+]i, cell shortening, ICa, or cAMP production. In contrast, propofol caused dose-dependent decreases in isoproterenol-stimulated increases in [Ca2+]i, shortening, ICa, and cAMP. Forskolin-induced increases in [Ca2+]i, shortening, and cAMP production were not altered by propofol. PKC activation with phorbol myristate acetate attenuated isoproterenol-stimulated cAMP production. Inhibition of PKC with bisindolylmaleimide (broad range inhibitor) or Gö 6976 (inhibitor of Ca2+-dependent PKC isoforms) abolished propofol-induced inhibition of isoproterenol-stimulated increases in [Ca2+]i, shortening, and cAMP production.

Conclusions
Clinically relevant concentrations of propofol attenuate beta-adrenergic signal transduction in cardiac myocytes via inhibition of cAMP production. The inhibitory site of action of propofol is upstream of adenylyl cyclase and involves activation of PKC alpha.
Pharmacodynamic Modeling of Muscle Relaxants
Authors: Paul Matthias , Fisher Dennis M. 
Published: August 2004

Background
Pharmacodynamic studies of muscle relaxants use different dosing regimens (such as administration by bolus vs. infusion and doses that produce complete vs. incomplete paralysis). The authors used published data to evaluate the effect of modeling assumptions on pharmacodynamic estimates.

Methods
The authors used a pharmacokinetic-pharmacodynamic dataset in which patients received cisatracurium, 75 or 300 microg/kg (1.5 or 6 x ED95), to generate plasma concentration (Cp) and twitch depression (effect) curves. They then evaluated the impact of the following: assuming that Cp decreased monotonically versus increasing initially before decreasing monotonically; misrecording effect data by 6 s or less; and doses targeting incomplete versus complete paralysis. Parameters evaluated were the steady state Cp depressing twitch tension 50% (C50) and the rate constant for equilibration between plasma and effect site concentrations (k(e0)).

Results
With the large dose, increasing the time at which Cp peaked from 0.0 to 1.5 min decreased C50 and increased k(e0) markedly; with the small dose, changes in both were small. Misrecording the timing of effect had a larger impact with the large dose compared with the small dose. Doses smaller than ED50 or those producing prolonged, complete twitch depression yielded biased and variable estimates.

Conclusion
The erroneous assumption that Cp decreases monotonically after bolus administration affects accuracy of pharmacodynamic estimates with doses producing rapid, complete twitch depression. Other errors (e.g., misrecording the time of drug administration) impact on pharmacodynamic estimates, particularly with large doses. The authors' findings suggest that investigators performing neuromuscular (and other) pharmacodynamic studies should carefully consider the impact of study design on their parameter estimates.
Use of Linear Programming to Estimate Impact of Changes in a Hospital's Operating Room Time Allocation on Perioperative Variable Costs
Authors: Dexter Franklin , Blake John T. , Penning Donald H. , Sloan Brian , Chung Patricia , Lubarsky David A. 
Published: August 2004

Background
Administrators at hospitals with a fixed annual budget may want to focus surgical services on priority areas to ensure its community receives the best health services possible. However, many hospitals lack the detailed managerial accounting data needed to ensure that such a change does not increase operating costs. The authors used a detailed hospital cost database to investigate by how much a change in allocations of operating room (OR) time among surgeons can increase perioperative variable costs.

Methods
The authors obtained financial data for all patients who underwent outpatient or same-day admit surgery during a year. Linear programming was used to determine by how much changing the mix of surgeons can increase total variable costs while maintaining the same total hours of OR time for elective cases.

Results
Changing OR allocations among surgeons without changing total OR hours allocated will likely increase perioperative variable costs by less than 34%. If, in addition, intensive care unit hours for elective surgical cases are not increased, hospital ward occupancy is capped, and implant use is tracked and capped, perioperative costs will likely increase by less than 10%. These four variables predict 97% of the variance in total variable costs.

Conclusions
The authors showed that changing OR allocations among surgeons without changing total OR hours allocated can increase hospital perioperative variable costs by up to approximately one third. Thus, at hospitals with fixed or nearly fixed annual budgets, allocating OR time based on an OR-based statistic such as utilization can adversely affect the hospital financially. The OR manager can reduce the potential increase in costs by considering not just OR time, but also the resulting use of hospital beds and implants.