bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Evaluation of a Graphical Anesthesia Drug Display
Authors: Syroid Noah D. , Agutter James , Drews Frank A. , Westenskow Dwayne R. , Albert Robert W. , Bermudez Julio C. , Strayer David L. , Prenzel Hauke , Loeb Robert G. , Weinger Matthew B.
Published: August 2004

Background

Usable real-time displays of intravenous anesthetic concentrations and effects could significantly enhance intraoperative clinical decision-making. Pharmacokinetic models are available to estimate past, present, and future drug effect-site concentrations, and pharmacodynamic models are available to predict the drug's associated physiologic effects.

Methods

An interdisciplinary research team (bioengineering, architecture, anesthesiology, computer engineering, and cognitive psychology) developed a graphic display that presents the real-time effect-site concentrations, normalized to the drugs' EC(95), of intravenous drugs. Graphical metaphors were created to show the drugs' pharmacodynamics. To evaluate the effect of the display on the management of total intravenous anesthesia, 15 anesthesiologists participated in a computer-based simulation study. The participants cared for patients during two experimental conditions: with and without the drug display.

Results

With the drug display, clinicians administered more bolus doses of remifentanil during anesthesia maintenance. There was a significantly lower variation in the predicted effect-site concentrations for remifentanil and propofol, and effect-site concentrations were maintained closer to the drugs' EC(95). There was no significant difference in the simulated patient heart rate and blood pressure with respect to experimental condition. The perceived performance for the participants was increased with the drug display, whereas mental demand, effort, and frustration level were reduced. In a post-simulation questionnaire, participants rated the display to be a useful addition to anesthesia monitoring.

Conclusions

The drug display altered simulated clinical practice. These results, which will inform the next iteration of designs and evaluations, suggest promise for this approach to drug data visualization.
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.
Performance of the ARX-derived Auditory Evoked Potential Index as an Indicator of Anesthetic Depth
Authors: Struys Michel M. R. F. , Jensen Erik Weber , Smith Warren , Smith N. Ty , Rampil Ira , Dumortier Frank J. E. , Mestach Christel , Mortier Eric P.
Published: August 2004

Background

Autoregressive modeling with exogenous input of middle-latency auditory evoked potential (A-Line autoregressive index [AAI]) has been proposed for monitoring anesthetic depth. The aim of the current study was to compare the accuracy of this new index with the Bispectral Index (BIS), predicted effect-site concentration of propofol, and hemodynamic measures.

Methods

Twenty female patients scheduled for ambulatory gynecologic surgery received effect compartment controlled infusion of propofol. Target effect-site concentration was started at 1.5 microg/ml and increased every 4 min by 0.5 microg/ml. At every step, sedation level was compared with monitoring values using different clinical scoring systems and reaction to noxious stimulus.

Results

Bispectral Index, AAI, and predicted propofol effect-site concentration were accurate indicators for the level of sedation and loss of consciousness. Hemodynamic variables were poor indicators of the hypnotic-anesthetic status of the patient. BIS correlated best with propofol effect-site concentration, followed by AAI. Hemodynamic measurements did not correlate well. No indicators predicted reaction to noxious stimulus. Poststimulus, BIS and AAI showed an increase as a result of arousal. This reaction occurred more rapidly with the AAI than with BIS.

Conclusion

Bispectral Index, AAI, and predicted propofol effect-site concentration revealed information on the level of sedation and loss of consciousness but did not predict response to noxious stimulus.
Automatic CPAP Compared with Conventional Treatment for Episodic Hypoxemia and Sleep Disturbance after Major Abdominal Surgery
Authors: Drummond Gordon B. , Stedul Kristina , Kingshott Ruth , Rees Karen , Nimmo Alastair F. , Wraith Peter , Douglas Neil J.
Published: August 2004

Background

After major surgery, analgesia with opioids can cause obstructive apnea and intermittent hypoxemia, probably from loss of upper airway control. Since this resembles the obstructive sleep apnea syndrome, we tested the possibility that nasal continuous positive airway pressure (nCPAP) would reduce episodes of reduced oxygen saturation and sleep disruption. Because oxygen therapy is frequent after surgery, we also assessed the effect of oxygen on sleep disruption.

Methods

We recruited 48 patients about to have major abdominal surgery. We present data for 34 patients: 27 who received patient-controlled intravenous morphine and 7 who received epidural opioid. Treatment was randomized to either nCPAP or conventional therapy with an oxygen mask. Alternate periods of administration of air and 35% oxygen were used in both groups. If the oxygen saturation as measured by pulse oximetry was consistently <90% on air, the patient was withdrawn from the study. We measured sleep, arousals, oxygenation, episodes of desaturation, and disturbances of respiration. Values are given as median and quartiles.

Results

The median proportion of time awake was 65% (45-79%) among control patients and 74% (55-87%) among those undergoing nCPAP. Oxygen administration did not affect the sleep pattern. The median frequency of arousals per hour of sleep was very similar in each group: during air breathing from nCPAP, 125 (76-187), and during air breathing by mask, 116 (84-187). Oxygen therapy had no effect. Oxygenation and hypoxemic events were not improved by nCPAP. Oxygen therapy improved oxygenation and reduced but did not eliminate episodes of desaturation.

Conclusions

Nasal CPAP does not improve sleep and oxygenation or reduce hypoxemic events in the first night after major abdominal surgery.
Usefulness of Nitric Oxide Treatment for Pulmonary Hypertensive Infants during Cardiac Anesthesia
Authors: Kadosaki Mamoru , Kawamura Takae , Oyama Kotaro , Nara Noriko , Wei Jicheng , Mori Naohisa
Published: August 2004

Background

The beneficial effect of inhaled nitric oxide (NO) on pulmonary hypertension is well known. However, the indications for NO inhalation therapy for pulmonary hypertension associated with congenital heart lesions are still unclear. The aim of the current study was to seek a measure that would predict the effectiveness of inhaled NO in infants undergoing cardiac surgery.

Methods

Forty-six infants with pulmonary hypertension were studied. Pulmonary vascular resistance (PVR) measured at the time of cardiac catheterization was used as an indicator and compared with pulmonary arterial pressure/systemic blood pressure ratio (Pp/Ps) at the time of weaning from cardiopulmonary bypass. The effect of 40 ppm of inhaled NO for 15 min was evaluated in patients whose Pp exceeded systemic values.

Results

Preoperative PVR correlated positively with Pp/Ps at the time of weaning from cardiopulmonary bypass (r2 = 0.86; P < 0.05; n = 46). A Pp/Ps greater than or equal to 1 was not observed in any cases in which the preoperative PVR values were less than 7 Wood units m2; Pp/Ps ratio greater than or equal to 1 occurred in four patients. Each of these had PVR values greater than 7 Wood units m2. Three of these patients who had PVR values in the 7-12 Wood units m2 range were responsive to inhaled NO. The fourth patient, whose PVR value was greater than 15 Wood units m2, was unresponsive. Lung biopsy specimens were obtained in two patients whose preoperative PVR values were greater than 10 Wood units m2.

Conclusion

Preoperative PVR correlates reasonably well with postbypass Pp/Ps.
Analgesic Effects of Intravenous Lidocaine and Morphine on Postamputation Pain
Authors: Wu Christopher L. , Tella Prabhav , Staats Peter S. , Vaslav Rachel , Kazim Debra A. , Wesselmann Ursula , Raja Srinivasa N.
Published: August 2004

Background

Phantom and stump pains, common sequelae of limb amputations, are significant impediments to rehabilitation of amputees. The pathophysiology and optimal treatment of postamputation pain states are unclear. While stump pain may result from neuromas in the stump, phantom pain is thought to be related to cortical reorganization. The authors hypothesized that morphine and lidocaine may have differential effectiveness on stump and phantom pains.

Methods

The authors conducted a randomized double-blind, active-placebo-controlled, crossover trial to compare the analgesic effects of intravenous morphine and lidocaine on postamputation stump and phantom pains. An intravenous bolus followed by an intravenous infusion of morphine (0.05 mg/kg bolus + 0.2 mg/kg infusion over 40 min), lidocaine (1 mg/kg bolus + 4 mg/kg infusion) and the active placebo, diphenhydramine (10 mg bolus + 40 mg infusion), were performed on three consecutive days. Phantom and stump pain ratings and sedation scores were recorded at 5-min intervals using a 0-100 visual analog scale. Pain measures were initiated 30 min before drug infusion and continued until 30 min after the end of infusion. Subjects' self-reported pain relief and satisfaction were assessed at the end of each infusion.

Results

Thirty-one of 32 subjects enrolled completed the study. Eleven subjects had both stump and phantom pains, 11 and 9 subjects had stump and phantom pain alone, respectively. Baseline pain scores were similar in the three drug groups. Compared with placebo, morphine reduced both stump and phantom pains significantly (P < 0.01). In contrast, lidocaine decreased stump (P < 0.01), but not phantom pain. The changes in sedation scores for morphine and lidocaine were not significantly different from placebo. Compared with placebo, self-reported stump pain relief was significantly greater for lidocaine (P < 0.05) and morphine (P < 0.01), while phantom pain relief was greater only for morphine (P < 0.01). Satisfaction scores were significantly higher for lidocaine (mean +/- SD: 39.3 +/- 37.8, P < 0.01) and morphine (45.9 +/- 35.5, P < 0.01) when compared with placebo (9.6 +/- 21.0).

Conclusions

Stump pain was diminished both by morphine and lidocaine, while phantom pain was diminished only by morphine, suggesting that the mechanisms and pharmacological sensitivity of stump and phantom pains are different.
Performance of Infusion Pumps during Hyperbaric Conditions
Authors: Lavon Haim , Shupak Avi , Tal Dror , Ziser Avishai , Abramovich Amir , Yanir Yoav , Shoshani Oren , Gil Amnon , Leiba Ronit , Nachum Zohar
Published: August 2004

Background

Many hyperbaric facilities use infusion pumps inside the chamber. It is therefore important to ensure that this equipment will perform accurately during hyperbaric conditions. The authors tested the function and accuracy of the Imed 965 and Infutec 520 volumetric infusion pumps, the Easy-pump MZ-257 peristaltic infusion pump, and the Graseby 3100 syringe pump.

Methods

The authors calculated the deviations of infused volumes at low and high rates (12-18 and 60-100 ml/h) on three different hyperbaric protocols (up to 2.5, 2.8, and 6 atmospheres absolute [ATA]), resembling a standard hyperbaric oxygen treatment and US Navy treatment tables used for decompression illness and for arterial gas embolism. Two examples of each pump model were examined in every experiment.

Results

The Easy-pump MZ-257 failed to function completely beyond a chamber pressure of 1.4 ATA, making it unsuitable for use inside the hyperbaric chamber. The Graseby 3100 failed to respond to all keyboard functions at 2.5-2.8 ATA, making it unsuitable for use in most hyperbaric treatments. The Imed 965 performed within an acceptable volume deviation (< or =10%) during most hyperbaric conditions. During the compression phase of the profiles used, and for the low infusion rates only, exceptional volume deviations of 20-40% were monitored. The Infutec 520 demonstrated an acceptable deviation (within 10%) throughout all the hyperbaric profiles used, unaffected by changes in ambient pressure or infusion rate.

Conclusions

Commercially available infusion pumps operating during hyperbaric conditions demonstrate substantial variations in performance and accuracy. It is therefore important that the hyperbaric facility staff make a careful examination of such instruments to anticipate possible deviations in the accuracy of the equipment during use.
Oxygen Reverses Deficits of Cognitive Function and Memory and Increased Heart Rate Induced by Acute Severe Isovolemic Anemia
Authors: Weiskopf Richard B. , Feiner John , Hopf Harriet W. , Viele Maurene K. , Watson Jessica J. , Kramer Joel H. , Ho Rachel , Toy Pearl
Published: August 2004

Background

Erythrocytes are transfused to improve oxygen delivery and prevent or treat inadequate oxygenation of tissues. Acute isovolemic anemia subtly slows human data processing and degrades memory, increases heart rate, and decreases self-assessed energy level. Erythrocyte transfusion is efficacious in reversing these effects of acute anemia. We tested the hypothesis that increasing arterial oxygen pressure (Pao2) to 350 mmHg or greater would supply sufficient oxygen to be equivalent to augmenting hemoglobin concentration by 2-3 g/dl and thus reverse the effects of acute anemia.

Methods

Thirty-one healthy volunteers, aged 28 +/- 4 yr (mean +/- SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and twice after acute isovolemic reduction of their hemoglobin concentration to 5.7 +/- 0.3 g/dl. Two sets of tests were performed in randomized order at the lower hemoglobin concentration: with the volunteer breathing room air or oxygen. The subject and those administering the tests and recording the results were unaware which gas was administered. As an additional control for duration of the experiment, 10 of these volunteers also completed the same tests on a separate day, without alteration of hemoglobin concentration, at times of the day similar to those on the experimental day. Heart rate, mean arterial blood pressure, and self-assessed sense of energy were recorded at the time of each test.

Results

Reaction time for digit-symbol substitution test increased, delayed memory was degraded, mean arterial pressure and energy level decreased, and heart rate increased at a hemoglobin concentration of 5.7 g/dl (all P < 0.05). Increasing Pao2 to 406 +/- 47 mmHg reversed the digit-symbol substitution test result and the delayed memory changes to values not different from those at the baseline hemoglobin concentration of 12.7 +/- 1.0 g/dl, and decreased heart rate (P < 0.05). However, mean arterial pressure and energy level changes were not altered with increased Pao2 during acute anemia.

Conclusion

The authors confirmed that acute isovolemic anemia subtly slows human reaction time, degrades memory, increases heart rate, and decreases energy level. The findings of this study support the hypothesis that increasing Pao2 to 350 mmHg or greater by breathing oxygen reverses all of these effects of acute anemia except for decreased energy.
Sleep Tendency as a Measure of Recovery after Drugs Used for Ambulatory Surgery
Authors: Lichtor J. Lance , Alessi Richard , Lane Bradford S.
Published: August 2004

Background

Although tests of psychomotor function indicate that drug effects after ambulatory anesthesia are short-lived, patients often feel washed out for long periods of time. Among the psychomotor tests that measure different motor and cognitive functions, none directly measures sleepiness or alertness. The authors hypothesized that sleepiness, measured by a sleep latency test, would be a more sensitive indicator of drug effect after an anesthetic than psychomotor tests. The second objective was to determine a sedation regimen that produced the least residual effect.

Methods

On four separate occasions, volunteers (N = 12) received an injection of propofol 2.5 mg/kg; propofol 2.0 mg/kg and fentanyl 2 microg/kg; propofol 2.0 mg/kg and midazolam 2 mg/70 kg; or midazolam 0.07 mg/kg and fentanyl 2 microg/kg. Dependent measures included the multiple sleep latency test (MSLT), Maddox Wing and digit symbol substitution tests, auditory and visual reaction times, and a divided attention task.

Results

The multiple sleep latency test demonstrated sleepiness up to 4 h after injection, and in some patients, sleepiness continued up to 8 h afterward. Psychomotor function was impaired only at 2 h after injection of the drug combination.

Conclusion

The multiple sleep latency test may be a more sensitive measure of a drug's effect than other tests of psychomotor function. For up to 8 h after an injection of midazolam and fentanyl, patients must consider driving or operating heavy machinery unsafe activities.
Mechanisms Underlying Greater Sensitivity of Neonatal Cardiac Muscle to Volatile Anesthetics
Authors: Prakash Y.S. , Seckin Inanc , Hunter Larry W. , Sieck Gary C.
Published: August 2004

Background

In neonatal heart, plasma membrane Na+-Ca2+ exchange (NCX) and Ca2+ influx channels play greater roles in intracellular Ca2+ concentration [Ca2+]i regulation compared with the sarcoplasmic reticulum (SR). In neonatal (aged 0-3 days) and adult (aged 84 days) rat cardiac myocytes, we determined the mechanisms underlying greater sensitivity of the neonatal myocardium to inhibition by volatile anesthetics.

Methods

The effects of 1 and 2 minimum alveolar concentration halothane and sevoflurane on Ca2+ influx during electrical stimulation in the presence or blockade of NCX and the Ca2+ channel agonist BayK8644 were examined. [Ca2+]i responses to caffeine were used to examine anesthetic effects on SR Ca2+ release (via ryanodine receptor channels) and reuptake (via SR Ca2+ adenosine triphosphatase). Ca2+ influx via NCX was examined during rapid activation in the presence of the reversible SR Ca2+ adenosine triphosphatase inhibitor cyclopiazonic acid and ryanodine to inhibit the SR. Efflux mode NCX was examined during activation by extracellular Na+ in the absence of SR reuptake.

Results

Intracellular Ca2+ concentration transients during electrical stimulation were inhibited to a greater extent in neonates by halothane (80%) and sevoflurane (50%). Potentiation of [Ca2+]i responses by BayK8644 (160 and 120% control in neonates and adults, respectively) was also blunted by anesthetics to a greater extent in neonates. [Ca2+]i responses to caffeine in neonates ( approximately 30% adult responses) were inhibited to a lesser extent compared with adults (35 vs. 60% by halothane). Both anesthetics inhibited Ca2+ reuptake at 2 minimum alveolar concentration, again to a greater extent in adults. Reduction in NCX-mediated influx was more pronounced in neonates (90%) compared with adults (65%) but was comparable between anesthetics. Both anesthetics also reduced NCX-mediated efflux to a greater extent in neonates. Potentiation of NCX-mediated Ca2+ efflux by extracellular Na+ and NCX-mediated Ca2+ influx by intracellular Na+ were both prevented by halothane, especially in neonates.

Conclusions

These data indicate that greater myocardial depression in neonates induced by volatile anesthetics may be mediated by inhibition of NCX and Ca2+ influx channels rather than inhibition of SR Ca2+ release.
Interaction of Morphine, Fentanyl, Sufentanil, Alfentanil, and Loperamide with the Efflux Drug Transporter P-glycoprotein
Authors: Wandel Christoph , Kim Richard , Wood Margaret , Wood Alastair
Published: August 2004

Background

The efflux transporter P-glycoprotein, a member of the adenosine triphosphate-binding cassette superfamily, is a major determinant of the pharmacokinetics and pharmacodynamics of the opioid loperamide, a well-recognized antidiarrheal agent. Animal studies indicate that P-glycoprotein limits morphine entry into the brain. In this study, the authors examined whether other opioids of importance to anesthesiologists such as fentanyl, sufentanil, and alfentanil, and also morphine-6-glucuronide and morphine-3-glucuronide, are P-glycoprotein substrates and whether, in turn, these opioids act also as P-glycoprotein inhibitors.

Methods

The transcellular movement of the various opioids, including loperamide and morphine, was assessed in L-MDR1 (expressing P-glycoprotein) and LLC-PK1 cell monolayers (P-glycoprotein expression absent). A preferential basal-to-apical versus apical-to-basal transport in the L-MDR cells but not the LLC-PK1 cells is seen for P-glycoprotein substrates. In addition, the effect of the various opioids on the transcellular movement of the prototypical P-glycoprotein substrate digoxin was examined in Caco-2 cell monolayers. IC50 values were calculated according to the Hill equation.

Results

Loperamide was a substrate showing high dependence on P-glycoprotein in that basal-apical transport was nearly 10-fold greater than in the apical-basal direction in L-MDRI cells. Morphine also showed a basal-to-apical gradient in the L-MDR1 cell monolayer, indicating that it too is a P-glycoprotein substrate, but with less dependence than loperamide in that only 1.5-fold greater basal-apical directional transport was observed. Fentanyl, sufentanil, and alfentanil did not behave as P-glycoprotein substrates, whereas the morphine glucuronides did not cross the cell monolayers at all, whether P-glycoprotein was present or not. Loperamide, sufentanil, fentanyl, and alfentanil inhibited P-glycoprotein-mediated digoxin transport in Caco-2 cells with IC50 values of 2.5, 4.5, 6.5, and 112 microm, respectively. Morphine and its glucuronides (20 microm) did not inhibit digoxin (5 microm) transport in Caco-2 cells, and therefore IC50 values were not determined.

Conclusions

Opioids have a wide spectrum of P-glycoprotein activity, acting as both substrates and inhibitors, which might contribute to their varying central nervous system-related effects.
Isoflurane Preconditions Myocardium against Infarction via Release of Free Radicals
Authors: Müllenheim Jost , Ebel Dirk , Fräβdorf Jan , Preckel Benedikt , Thämer Volker , Schlack Wolfgang
Published: August 2004

Background

Isoflurane exerts cardioprotective effects that mimic the ischemic preconditioning phenomenon. Generation of free radicals is implicated in ischemic preconditioning. The authors investigated whether isoflurane-induced preconditioning may involve release of free radicals.

Methods

Sixty-one alpha-chloralose-anesthetized rabbits were instrumented for measurement of left ventricular (LV) pressure (tip-manometer), cardiac output (ultrasonic flowprobe), and myocardial infarct size (triphenyltetrazolium staining). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits of all six groups underwent a treatment period consisting of either no intervention for 35 min (control group, n = 11) or 15 min of isoflurane inhalation (1 minimum alveolar concentration end-tidal concentration) followed by a 10-min washout period (isoflurane group, n = 12). Four additional groups received the radical scavenger N-(2-mercaptoproprionyl)glycine (MPG; 1 mg. kg-1.min-1) or Mn(III)tetrakis(4-benzoic acid)porphyrine chloride (MnTBAP; 100 microg.kg-1.min-1) during the treatment period with (isoflurane + MPG; n = 11; isoflurane + MnTBAP, n = 9) or without isoflurane inhalation (MPG, n = 11; MnTBAP, n = 7).

Results

Hemodynamic baseline values were not significantly different between groups (LV pressure, 97 +/- 17 mmHg [mean +/- SD]; cardiac output, 228 +/- 61 ml/min). During coronary artery occlusion, LV pressure was reduced to 91 +/- 17% of baseline and cardiac output to 94 +/- 21%. After 2 h of reperfusion, recovery of LV pressure and cardiac output was not significantly different between groups (LV pressure, 83 +/- 20%; cardiac output, 86 +/- 23% of baseline). Infarct size was reduced from 49 +/- 17% of the area at risk in controls to 29 +/- 19% in the isoflurane group (P = 0.04). MPG and MnTBAP themselves had no effect on infarct size (MPG, 50 +/- 14%; MnTBAP, 56 +/- 15%), but both abolished the preconditioning effect of isoflurane (isoflurane + MPG, 50 +/- 24%, P = 0.02; isoflurane + MnTBAP, 55 +/- 10%, P = 0.001).

Conclusion

Isoflurane-induced preconditioning depends on the release of free radicals.