bluuebunny/crossref_metadata_2025 huggingface dataset:
Pressure–Time Curve Predicts Minimally Injurious Ventilatory Strategy in an Isolated Rat Lung Model
Authors: Ranieri V. Marco , Zhang Haibo , Mascia Luciana , Aubin Michael , Lin Chang-Yi , Mullen J. Brendan , Grasso Salvatore , Binnie Matthew , Volgyesi George A. , Eng P. , Slutsky Arthur S.
Published: November 2003

Background

We tested the hypothesis that the pressure-time (P-t) curve during constant flow ventilation can be used to set a noninjurious ventilatory strategy.

Methods

In an isolated, nonperfused, lavaged model of acute lung injury, tidal volume and positive end-expiratory pressure were set to obtain: (1) a straight P-t curve (constant compliance, minimal stress); (2) a downward concavity in the P-t curve (increasing compliance, low volume stress); and (3) an upward concavity in the P-t curve (decreasing compliance, high volume stress). The P-t curve was fitted to: P = a. tb +c, where b describes the shape of the curve, b = 1 describes a straight P-t curve, b < 1 describes a downward concavity, and b > 1 describes an upward concavity. After 3 h, lungs were analyzed for histologic evidence of pulmonary damage and lavage concentration of inflammatory mediators. Ventilator-induced lung injury occurred when injury score and cytokine concentrations in the ventilated lungs were higher than those in 10 isolated lavaged rats kept statically inflated for 3 h with an airway pressure of 4 cm H2O.

Results

The threshold value for coefficient b that discriminated best between lungs with and without histologic and inflammatory evidence of ventilator-induced lung injury (receiver-operating characteristic curve) ranged between 0.90-1.10. For such threshold values, the sensitivity of coefficient b to identify noninjurious ventilatory strategy was 1.00. A significant relation (P < 0.001) between values of coefficient b and injury score, interleukin-6, and macrophage inflammatory protein-2 was found.

Conclusions

The predictive power of coefficient b to predict noninjurious ventilatory strategy in a model of acute lung injury is high.
Use of Intranasal Fentanyl in Children Undergoing Myringotomy and Tube Placement during Halothane and Sevoflurane Anesthesia
Authors: Galinkin Jeffrey L. , Fazi Lisa M. , Cuy Romulo M. , Chiavacci Rosetta M. , Kurth C. Dean , Shah Udayan K. , Jacobs Ian N. , Watcha Mehernoor F.
Published: November 2003

Background

Many children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia.

Methods

In phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 microg/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 microg/kg) or saline. Postoperative agitation, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated.

Results

In phase 1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34 +/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and 0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl.

Conclusions

Serum fentanyl concentrations after intranasal administration exceed the minimum effective steady state concentration for analgesia in adults. The use of intranasal fentanyl during halothane or sevoflurane anesthesia for BMT is associated with diminished postoperative agitation without an increase in vomiting, hypoxemia, or discharge times.
Effect of Renal Failure and Cirrhosis on the Pharmacokinetics and Neuromuscular Effects of Rapacuronium Administered by Bolus Followed by Infusion
Authors: Fisher Dennis M. , Dempsey Gerald A. , Atherton D. Paul L. , Brown Ronald , Abengochea Antonio , Hunter Jennifer M.
Published: November 2003

Background

Recent trials indicate that rapacuronium's pharmacokinetic characteristics are influenced by both renal failure and cirrhosis but the time course of a single bolus dose of 1.5 mg/kg is affected minimally. The authors reassessed these pharmacokinetic findings and examined the time course of the same bolus dose followed by a 30-min infusion.

Methods

During nitrous oxide-isoflurane anesthesia, patients with normal renal and hepatic function (n = 25), those with renal failure (n = 28), and those with cirrhosis (n = 6) received a bolus dose of rapacuronium (1.5 mg/kg) followed by a 30-min infusion adjusted to maintain 90-95% twitch depression. At 25% recovery, neostigmine was administered. Blood was sampled until 8 h after the infusion to determine concentrations of rapacuronium and its active metabolite ORG9488. Rapacuronium's pharmacokinetic parameters were determined using mixed-effects modeling.

Results

Onset and facilitated recovery of twitch depression were similar in the three groups. Patients with renal failure required 22% less rapacuronium to maintain target twitch depression during the infusion. Rapacuronium's plasma clearance was 24% smaller in renal failure and decreased 0.5%/yr of age; rapid distribution clearance was 51% smaller in men than in women. After the infusion, ORG9488 concentrations decreased markedly more slowly in patients with renal failure. Cirrhosis did not alter the pharmacokinetics of rapacuronium.

Conclusion

Rapacuronium's plasma clearance and infusion requirement were decreased by renal failure. By dosing to maintain target twitch depression, recovery was not prolonged. Cirrhosis does not affect the pharmacokinetics or neuromuscular effects of rapacuronium. Persistence of ORG9488 in patients with renal failure might prolong recovery after rapacuronium if target twitch depression is not maintained or with administration of rapacuronium for more than 30 min.
Dopamine and Intraocular Pressure in Critically Ill Patients
Authors: Brath Peter C. , MacGregor Drew A. , Ford Jerry G. , Prielipp Richard C.
Published: November 2003

Background

A recently released dopamine-1 receptor agonist, fenoldopam, increases intraocular pressure (IOP) in both healthy volunteers and patients with chronic ocular hypertension. Dopamine, a potent agonist at both dopamine-1 and -2 receptors, is frequently infused in critically ill patients for its inotropic, renal vasodilatory, and natriuretic effects. The authors hypothesized that low doses of dopamine would significantly increase IOP.

Methods

Patients in the intensive care unit who were currently receiving dopamine infusions of less than 5 microg x kg(-1) x min(-1) were studied After local ocular anesthesia was obtained, baseline IOP was measured in each eye with a hand-held tonometer. IOP was then determined after dopamine was discontinued.

Results

Twenty-three patients received a mean dopamine infusion of 2.6 +/- 0.2 microg x kg(-1) x min(-1). Twelve of the 23 patients were receiving mechanical ventilation during the study. Mean IOPs in nonventilated patients (n = 11) off dopamine were 13.1 +/- 0.9 mmHg (left eye) and 12.6 +/- 0.9 mmHg (right eye). Mean IOPs for the same patients receiving dopamine were significantly higher at 16.1 +/- 0.9 mmHg (left eye) and 15.9 +/- 1.1 mmHg (right eye). Mean IOPs in intubated patients (n = 12) off dopamine were 12.3 +/- 0.7 mmHg (left eye) and 12.5 +/- 1.2 mmHg (right eye). Mean IOPs for the same patients while receiving dopamine were significantly higher in intubated patients at 17.8 +/- 1.3 mmHg (left eye) and 17.3 +/- 1.3 mmHg (right eye). The average mean elevation in IOP in patients while receiving dopamine was significantly higher in intubated patients as compared with nonintubated patients (5.2 +/- 0.9 mmHg vs. 3.1 +/- 0.6 mmHg).

Conclusions

Commonly used doses of dopamine are associated with increased IOP in critically ill patients. Although normal patients should be able to tolerate this elevation safely for several weeks, there may be a potential risk in patients with preexisting glaucomatous nerve damage or ocular hypertension, especially if they are sedated and mechanically ventilated.
Renal Responses to Low-flow Desflurane, Sevoflurane, and Propofol in Patients
Authors: Ebert Thomas J. , Arain Shahbaz R.
Published: November 2003

Background

The contributing factors that result in significant, postoperative proteinuria and glucosuria after low-flow isoflurane and sevoflurane anesthesia are unknown. The present study compared renal responses after anesthesia with desflurane (negligible metabolism), sevoflurane, or intravenous propofol.

Methods

Informed consent was obtained from 52 patients with American Society of Anesthesiologists physical status I-III (aged 36-81 yr). Patients with diabetes or renal insufficiency were excluded. Desflurane (n = 20) or sevoflurane (n = 22), without nitrous oxide, was given at 1 l/min fresh gas flow for elective surgical procedures lasting more than 2 h; 10 patients received propofol without nitrous oxide as the primary anesthetic. Blood and urine chemistries were obtained before surgery. Blood and 24-h urine collections were obtained for 3 days after surgery and were analyzed for liver and renal indices.

Results

Length of surgery averaged approximately 300 min (range, 136-750 min), minimum alveolar concentration-hour averaged 4.3 (range, 1.2-11.0), and infusion rates of propofol were 99-168 microg x kg(-1) x min(-1). Plasma creatinine concentration did not change, plasma blood urea nitrogen decreased significantly, and significant increases in urine glucose, protein, and albumin occurred similarly in all groups. Mean (+/- SD) postoperative urine glucose values for day 1 after desflurane, sevoflurane, and propofol were 1.4 +/- 3.0, 1.1 +/- 2.1, and 1.9 +/- 2.6 g/d (normal, < 0.5 g/d). The average daily protein/creatinine ratios for postoperative days 2-3 after desflurane, sevoflurane, and propofol were 240 +/- 187, 272 +/- 234, and 344 +/- 243 (normal, < 150 mg/g). Regardless of anesthetic, there were significantly greater urine protein concentrations after surgical procedures in central versus peripheral regions.

Conclusions

Alterations in postoperative renal function were common and unrelated to the choice of anesthetic. These findings implicate nonanesthetic factors in producing changes in biochemical indices of renal excretory function.
Tourniquet-induced Changes of Energy Metabolism in Human Skeletal Muscle Monitored by Microdialysis
Authors: Korth Ulrike , Merkel Günter , Fernandez Francisco F. , Jandewerth Oliver , Dogan Günes , Koch Thea , van Ackern Klaus , Weichel Oksana , Klein Jochen
Published: November 2003

Background

Tourniquets are often used as part of orthopedic surgery but may cause local and remote organ injury. The authors hypothesized that the procedures used to induce ischemia (circulatory occlusion or exsanguination) may have differential effects on the metabolic state of the muscle that should be reflected in the interstitial levels of metabolites.

Methods

Microdialysis probes were implanted in both quadriceps femoris muscles of 18 patients. Interstitial fluid was obtained during tourniquet-induced ischemia and reperfusion and was analyzed for glucose, lactate, choline, and purines by high-performance liquid chromatography.

Results

At a flow rate of 2 microl/min, the average baseline concentrations in the dialysate were 2.5 mM for glucose, 1.7 mM for lactate, 5.2 microM for choline, and 14.3 microM for hypoxanthine. Circulatory occlusion by tourniquet caused a 40% decrease of the extracellular glucose concentration within 30 min. Concomitantly, the interstitial levels of lactate and hypoxanthine increased in a linear fashion to 206% (lactate) and 241% (hypoxanthine) of basal values. The extracellular concentration of choline was also significantly elevated. After exsanguination, the glucose levels were significantly more reduced (by 65%), and the levels of lactate (to 268%) and hypoxanthine (to 286%) were more increased than after circulatory occlusion alone.

Conclusion

Our microdialysis results demonstrate that the interstitial concentrations of glucose, lactate, and hypoxanthine, which are indicators of tissue ischemia, change more prominently after exsanguination than after circulatory occlusion alone.
Changes in Pulmonary Blood Flow during Gaseous and Partial Liquid Ventilation in Experimental Acute Lung Injury
Authors: Max Martin , Nowak Bernd , Dembinski Rolf , Schulz Gernot , Kuhlen Ralf , Buell Udalrich , Rossaint Rolf
Published: November 2003

Background

It has been proposed that partial liquid ventilation (PLV) causes a compression of the pulmonary vasculature by the dense perfluorocarbons and a subsequent redistribution of pulmonary blood flow from dorsal to better-ventilated middle and ventral lung regions, thereby improving arterial oxygenation in situations of acute lung injury.

Methods

After induction of acute lung injury by repeated lung lavage with saline, 20 pigs were randomly assigned to partial liquid ventilation with two sequential doses of 15 ml/kg perfluorocarbon (PLV group, n = 10) or to continued gaseous ventilation (GV group, n = 10). Single-photon emission computed tomography was used to study regional pulmonary blood flow. Gas exchange, hemodynamics, and pulmonary blood flow were determined in both groups before and after the induction of acute lung injury and at corresponding time points 1 and 2 h after each instillation of perfluorocarbon in the PLV group.

Results

During partial liquid ventilation, there were no changes in pulmonary blood flow distribution when compared with values obtained after induction of acute lung injury in the PLV group or to the animals submitted to gaseous ventilation. Arterial oxygenation improved significantly in the PLV group after instillation of the second dose of perfluorocarbon.

Conclusions

In the surfactant washout animal model of acute lung injury, redistribution of pulmonary blood flow does not seem to be a major factor for the observed increase of arterial oxygen tension during partial liquid ventilation.
Evaluation of Low-dose Endotoxin Administration during Pregnancy as a Model of Preeclampsia
Authors: Sakawi Yasser , Tarpey Margaret , Chen Yiu Fai , Calhoun David A. , Connor Michael G. , Chestnut David H. , Parks Dale A.
Published: November 2003

Background

Recent evidence implicates nitric oxide (*NO) in the pathogenesis of preeclampsia. The authors tested the hypothesis that administration of low-dose endotoxin to pregnant rats mimics the signs of preeclampsia in humans and that *NO and *NO-derived species play a role in that animal model.

Methods

Endotoxin was infused at doses of 1, 2 and 10 microg/kg over 1 h to rats on day 14 of pregnancy. Mean arterial pressure, urinary protein, urinary and plasma nitrite plus nitrate (NO2- + NO3-) concentrations, and platelet count were measured before and after the endotoxin infusion. In another group of pregnant rats, the nitric oxide synthase inhibitor L-nitroarginine methyl ester (L-NAME) was administered in drinking water at a dose of 3 mg x kg(-1) x d(-1) starting on day 7 of pregnancy. Endotoxin was then infused at 10 microg/kg on day 14 of pregnancy. Kidneys and uteroplacental units were examined histologically and analyzed immunohistochemically for 3-nitrotyrosine.

Results

Endotoxin administration at doses of 2 and 10 microg/kg caused proteinuria and thrombocytopenia in pregnant rats, but did not result in hypertension. Urinary NO2- + NO3- concentration, reflective of tissue *NO production rates, was significantly elevated in pregnant rats that received endotoxin at 10 microg/kg. Ingestion of L-NAME caused hypertension. Tissues from pregnant rats treated with L-NAME, endotoxin at 10 microg/kg, and a combination of L-NAME and endotoxin had increased 3-nitrotyrosine immunoreactivity.

Conclusion

Nitric oxide either directly or through secondary species plays a significant role in the biochemical and physiologic changes that occur in a rodent model of endotoxin-induced injury.
Flow Modulation of Pressure-sensitive Tone in Rat Pial Arterioles
Authors: Ward Michael E. , Yan Lu , Kelly Suzanne , Angle Mark R.
Published: November 2003

Background

Cerebral arteriolar tone is modulated in response to changes in transmural pressure and luminal flow. The effect of flow on the relation between pressure and diameter has not been fully evaluated in these vessels. This study was conducted to investigate this interaction and to determine the role of the endothelium in mediating it.

Methods

Rat pial arterioles from the territory of the posterior cerebral artery were mounted in a perfusion myograph. In some arterioles, the endothelium was removed by air perfusion. Diameters were recorded at pressures from 20 to 200 mmHg in the presence and absence of flow (10 microl/min). The response to flow (0-30 microl/min) was recorded at 60 and 120 mmHg.

Results

In the absence of flow, endothelium-intact arterioles demonstrated tone at distending pressures between 40 and 140 mmHg. In the presence of flow, tone did not develop until pressure exceeded 100 mmHg, and the vessels remained active at pressures up to 200 mmHg. Endothelium-denuded arterioles developed tone at the same pressure when perfused as when unperfused, but perfused vessels were able to maintain active tone at higher pressures. At 60 mmHg, flow caused dilation if the endothelium was intact and constriction if it had been removed. At 120 mmHg, flow caused constriction. Endothelium-dependent flow-relaxation was inhibited by N(G)-nitro-L-arginine methyl ester (10(-5) M) and abolished by indomethacin (10(-5) M).

Conclusion

Flow inhibits the development of pial arteriolar tone at low intraluminal pressures through endothelium-dependent mechanisms. Conversely, perfusion extends the upper limit of the myogenically regulated pressure range through endothelium-independent activation of arteriolar smooth muscle contraction.
Impairment of Cardiac β-Adrenoceptor Cellular Signaling by Decreased Expression of Gsαin Septic Rabbits
Authors: Matsuda Naoyuki , Hattori Yuichi , Akaishi Yasuhiro , Suzuki Yukari , Kemmotsu Osamu , Gando Satoshi
Published: November 2003

Background

Abnormalities in the beta-adrenergic control of cardiac function play a role in the pathogenesis of several disease states. Because circulatory failure in patients with septic shock is known to be less responsive to catecholamines, we investigated whether the beta-adrenoceptor-linked signal transduction mechanisms are altered in the heart of a septic animal model

Methods

Rabbits were rendered endotoxemic by an intravenous injection of 100 microg/kg Escherichia coli lipopolysaccharide. Three and 6 h later, the myocardial tissues were used for the experiments.

Results

The positive inotropic response to isoproterenol was significantly impaired in papillary muscles isolated from septic rabbits compared with those from controls. The impaired inotropic responsiveness to isoproterenol was not prevented by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine, indicating no involvement of nitric oxide overproduction. Adenylate cyclase activity stimulated with isoproterenol and 5'-guanylyl imidodiphosphate was markedly reduced in septic myocardium. The contractile and adenylate cyclase responses to colforsin daropate, a direct adenylate cyclase activator, were unaffected by sepsis. Radioligand binding experiments with (-)[125I]iodocyanopindolol revealed no significant alteration in myocardial beta-adrenoceptor density or affinity in sepsis. Determination of cardiac G(s alpha) level by Western blotting showed a reduction of approximately 50% in sepsis. The relative content of G(s alpha) messenger RNA in septic myocardium also was reduced from the control level by about 50%, as determined by Northern blot analysis. Little change was found in protein and messenger RNA levels of G(s alpha) in septic myocardium.

Conclusions

Impairment of myocardial functional responsiveness to beta-adrenoceptor stimulation appears in the early stage of sepsis. The impaired response to beta-adrenoceptor stimulation in the heart in this pathologic state may result in part from a decreased level of G(s alpha) protein which occurs at the level of gene expression.
Effects of Sevoflurane on the Intracellular Ca2+Transient in Ferret Cardiac Muscle
Authors: Bartunek Anna E. , Housmans Philippe R.
Published: November 2003

Background

Sevoflurane depresses myocardial contractility by decreasing transsarcolemmal Ca2+ influx. In skinned muscle fibers, sevoflurane affects actin-myosin cross-bridge cycling, which might contribute to the negative inotropic effect. It is uncertain to what extent decreases in Ca2+ sensitivity of the contractile proteins play a role in the negative inotropic effect of sevoflurane in intact cardiac muscle tissue. The aim of this study was to assess whether sevoflurane decreases myofibrillar Ca2+ sensitivity in intact living cardiac fibers and to quantify the relative importance of changes in myofibrillar Ca2+ sensitivity versus changes in myoplasmic Ca2+ availability by sevoflurane.

Methods

The effects of sevoflurane 0-4.05% vol/vol (0-1.5 minimum alveolar concentration [MAC]) on isometric and isotonic variables of contractility and on the intracellular calcium transient were assessed in isolated ferret right ventricular papillary muscles microinjected with the Ca2+-regulated photoprotein aequorin. The intracellular calcium transient was analyzed in the context of a multicompartment model of intracellular Ca2+ buffers in mammalian ventricular myocardium.

Results

Sevoflurane decreased contractility, time to peak force, time to half isometric relaxation, and the [Ca2+]i transient in a reversible, concentration-dependent manner. Increasing [Ca2+]o in the presence of sevoflurane to produce peak force equal to control increased intracellular Ca2+ transient higher than control.

Conclusions

Sevoflurane decreases myoplasmic Ca2+ availability and myofibrillar Ca2+ sensitivity in equal proportions except at 4.05% vol/vol (1.5 MAC), where Ca2+ availability is decreased more. These changes are at the basis of the negative inotropic effect of sevoflurane in mammalian ventricular myocardium.
Tranexamic Acid Administration after Cardiac Surgery
Authors: Casati Valter , Bellotti Ferdinando , Gerli Chiara , Franco Annalisa , Oppizzi Michele , Cossolini Mariangelo , Calori Giliola , Benussi Stefano , Alfieri Ottavio , Torri Giorgio
Published: November 2003

Background

Many different doses and administration schemes have been proposed for the use of the antifibrinolytic drug tranexamic acid during cardiac surgery. This study evaluated the effects of the treatment using tranexamic acid during the intraoperative period only and compared the results with the effects of the treatment continued into the postoperative period.

Methods

Patients undergoing elective cardiac surgery with use of cardiopulmonary bypass (N = 510) were treated intraoperatively with tranexamic acid and then were randomized in a double-blind fashion to one of three postoperative treatment groups: group A: 169 patients, infusion of saline for 12 h; group B: 171 patients, infusion of tranexamic acid, 1 mg x kg(-1) x h(-1) for 12 h; group C: 170 patients, infusion of tranexamic acid, 2 mg x kg(-1) x h(-1) for 12 h. Bleeding was considered to be a primary outcome variable. Hematologic data, allogeneic transfusions, thrombotic complications, intubation time, and intensive care unit and hospital stay duration also were evaluated.

Results

No differences were found among groups regarding postoperative bleeding and outcomes; however, the group treated with 1 mg x kg(-1) x h(-1) tranexamic acid required more units of packed red blood cells because of a significantly lower basal value of hematocrit, as shown by multivariate analysis.

Conclusions

Prolongation of treatment with tranexamic acid after cardiac surgery is not advantageous with respect to intraoperative administration alone in reducing bleeding and number of allogeneic transfusions. Although the prevalence of postoperative complications was similar among groups, there is an increased risk of procoagulant response because of antifibrinolytic treatment. Therefore, the use of tranexamic acid during the postoperative period should be limited to patients with excessive bleeding as a result of primary fibrinolysis.
Effect of Remifentanil on Pain and Secondary Hyperalgesia Associated with the Heat–Capsaicin Sensitization Model in Healthy Volunteers
Authors: Petersen Karin L. , Jones Bruce , Segredo Veronica , Dahl Jørgen B. , Rowbotham Michael C.
Published: November 2003

Background

The heat--capsaicin sensitization model was developed as a noninvasive and noninjurious human experimental pain model. The sequential application of moderate intensity thermal and topical chemical stimuli produces stable and long-lasting areas of cutaneous secondary hyperalgesia. The aim of the present study was to validate the heat--capsaicin sensitization model as a tool for testing analgesic drug efficacy. Responsivity of model-associated measures was tested with remifentanil, a potent and ultrashort acting mu-opioid agonist.

Methods

Sensitization was induced by heating forearm skin with a thermode at 45 degrees C for 5 min, immediately followed by application of 0.075% capsaicin cream for 30 min. Sensitization was rekindled four times at 40-min intervals with the thermode at 40 degrees C for 5 min. After each rekindling, areas of secondary hyperalgesia were measured, and the painfulness of thermal stimulation in normal skin with 45 degrees C for 1 min (long thermal stimulation [LTS]) was rated. Before and during the second rekindling, remifentanil 0.10 microg x kg(-1) x min(-1) or saline-placebo was infused for 35 min.

Results

Infusion of remifentanil reduced the areas of secondary hyperalgesia to 29--30% of baseline size compared with 75--83% during placebo. Similarly, remifentanil reduced the painfulness of LTS to 29% of baseline severity compared with 84% during placebo. Areas of secondary hyperalgesia and LTS painfulness returned to baseline levels by the time of the third rekindling, demonstrating rapid disappearance of remifentanil analgesia and possibly transient spontaneous opioid withdrawal hyperalgesia.

Conclusion

Using the heat-capsaicin sensitization model, opioid analgesia and suppression of secondary hyperalgesia was reliably demonstrated without skin injury.
Effects of Probenecid on Renal Function in Surgical Patients Anesthetized with Low-flow Sevoflurane
Authors: Higuchi Hideyuki , Wada Hiroki , Usui Yumi , Goto Kohichiro , Kanno Masuyuki , Satoh Tetsuo
Published: November 2003

Background

Dehydrofluorination of sevoflurane by carbon dioxide absorbents in anesthesia machines produces compound A, which is nephrotoxic in rats. Several clinical studies indicate that prolonged low-flow sevoflurane anesthesia is associated with an increased urinary excretion of biochemical markers, such as protein. Probenecid, a competitive inhibitor of organic anion transport, diminishes compound A nephrotoxicity in rats. The purpose of the present study was to examine the effects of low- and high-flow sevoflurane anesthesia on urinary excretion of biochemical markers in humans and to examine the effects of probenecid on urinary excretion of these markers.

Methods

Elective surgical patients (n = 64) were assigned to four groups (n = 16 each): low-flow sevoflurane plus probenecid (LSP), low-flow sevoflurane (LS), high-flow sevoflurane plus probenecid (HSP), and high-flow sevoflurane (HS). Probenecid (2.0 g) was administered orally 2 h before the induction of anesthesia in both the LSP and HSP groups. Nothing was administered orally 2 h before the induction of anesthesia in either the LS or HS groups. All patients underwent prolonged low-flow (1 l/min) or high-flow (6 l/min) sevoflurane anesthesia. Urinary excretion of protein, albumin, beta(2)-microglobulin, glucose, and N-acetyl-beta-d-glucosaminidase was measured for up to 7 days postoperatively.

Results

Sevoflurane doses were similar in all four groups. There were no differences in blood urea nitrogen, creatinine, or creatinine clearance among the four groups after anesthesia. Average values for urinary excretion of protein, beta(2)-microglobulin, and N-acetyl-beta-d-glucosaminidase in the LS group were significantly higher than those in the other groups (LSP, HSP, HS; P < 0.05). There was no significant difference between the LS and LSP groups in average values for urinary excretion of albumin and glucose, although there were significant differences between the LS and both high-flow sevoflurane groups (HSP, HS).

Conclusions

Low-flow sevoflurane, which produces a sevenfold higher compound A exposure than high-flow sevoflurane, resulted in significant increases of several biochemical markers in half of the patients. Probenecid appears to provide protection against these renal effects.
Speed of Recovery and Side-effect Profile of Sevoflurane Sedation Compared with Midazolam
Authors: Ibrahim Andra E. , Ghoneim Mohamed M. , Kharasch Evan D. , Epstein Richard H. , Groudine Scott B. , Ebert Thomas J. , Binstock Wendy B. , Philip Beverly K.
Published: November 2003

Background

Sedation for surgical procedures performed with regional or local anesthesia has usually been achieved with intravenous medications, whereas the use of volatile anesthetics has been limited. The use of sevoflurane for sedation has been suggested because of its characteristics of nonpungency, rapid induction, and quick elimination. The purpose of this investigation was to assess the quality, recovery, and side effects of sevoflurane sedation compared with midazolam.

Methods

One hundred seventy-three patients undergoing surgery with local or regional anesthesia were enrolled in a multicenter, open-label, randomized investigation comparing sedation with sevoflurane versus midazolam. Sedation level was titrated to an Observer's Assessment of Alertness--Sedation score of 3 (responds slowly to voice). Recovery was assessed objectively by Observer's Assessment of Alertness--Sedation, Digit Symbol Substitution Test (DSST), and memory scores, and subjectively by visual analog scales.

Results

Significantly more patients in the sevoflurane group had to be converted to general anesthesia because of excessive movement (18 sevoflurane and 2 midazolam; P = 0.043). Of remaining patients, 141 were assessable for efficacy and recovery data (93 sevoflurane and 48 midazolam). Sevoflurane and midazolam produced dose-related sedation. Sevoflurane patients had higher DSST and memory scores during recovery. Seventy-six percent (sevoflurane) compared with 35% (midazolam) returned to baseline DSST at 30 min postoperatively (P < 0.05). More frequent excitement-disinhibition was observed with sevoflurane (15 [16%] vs. midazolam; P = 0.008).

Conclusions

Sevoflurane for sedation produces faster recovery of cognitive function as measured by DSST and memory scores compared with midazolam. However, sevoflurane for sedation is complicated by a high incidence of intraoperative excitement.
S (+)-Ketamine Increases Muscle Sympathetic Activity and Maintains the Neural Response to Hypotensive Challenges in Humans
Authors: Kienbaum Peter , Heuter Thorsten , Pavlakovic Goran , Michel Martin C. , Peters Jürgen
Published: November 2003

Background

S(+)-Ketamine is reported to exert twofold greater analgesic and hypnotic effects but a shorter recovery time in comparison with racemic ketamine, indicating possible differential effects of stereoisomers. However, cardiovascular regulation during S(+)-ketamine anesthesia has not been studied. Muscle sympathetic activity (MSA) may be an indicator of the underlying alterations of sympathetic outflow. Whether S(+)-ketamine decreases MSA in a similar manner as the racemate is not known. Thus, the authors tested the hypothesis that S(+)-ketamine changes MSA and the muscle sympathetic response to a hypotensive challenge.

Methods

Muscle sympathetic activity was recorded by microneurography in the peroneal nerve of six healthy participants before and during anesthesia with S(+)-ketamine (670 microg/kg intravenously followed by 15 microg x kg(-1) x min(-1)). Catecholamine and ketamine plasma concentrations, heart rate, and arterial blood pressure were also determined. MSA responses to a hypotensive challenge were assessed by injection of sodium nitroprusside (2-10 microg/kg) before and during S(+)-ketamine anesthesia. In the final step, increased arterial pressure observed during anesthesia with S(+)-ketamine was adjusted to preanesthetic values by sodium nitroprusside infusion (1-6 microg x kg(-1) x min(-1)).

Results

Anesthesia with S(+)-ketamine (ketamine plasma concentration 713 +/- 295 microg/l) significantly increased MSA burst frequency (mean +/- SD; 18 +/- 6 to 35 +/- 11 bursts/min) and burst incidence (32 +/- 10 to 48 +/- 15 bursts/100 heartbeats) and was associated with a doubling of norepinephrine plasma concentration (from 159 +/- 52 to 373 +/- 136 pg/ml) parallel to the increase in MSA. Heart rate and arterial blood pressure also significantly increased. When increased arterial pressure during S(+)-ketamine was decreased to awake values with sodium nitroprusside, MSA increased further (to 53 +/- 24 bursts/min and 60 +/- 20 bursts/100 heartbeats, respectively). The MSA increase in response to the hypotensive challenge was fully maintained during anesthesia with S(+)-ketamine.

Conclusions

S(+)-Ketamine increases efferent sympathetic outflow to muscle. Despite increased MSA and arterial pressure during S(+)-ketamine anesthesia, the increase in MSA in response to arterial hypotension is maintained.
Effect of Hypothermia on the Hepatic Uptake and Biliary Excretion of Vecuronium in the Isolated Perfused Rat Liver
Authors: Beaufort Ton M. , Proost Johannes H. , Maring Jan-Gerard , Scheffer Emiel R. , Wierda J. Mark K. H. , Meijer Dirk K. F.
Published: November 2003

Background

Hypothermia prolongs the time course of action of nondepolarizing muscle relaxants. It is not known whether this prolongation is caused by a reduced rate of extrahepatic distribution or elimination, liver uptake, metabolic clearance, or biliary excretion. Therefore, the authors studied the effects of hypothermia on the net hepatic uptake, metabolism, and biliary excretion of vecuronium in isolated perfused rat liver.

Methods

Livers of Wistar rats were perfused with Krebs Ringer solution (1% albumin, 3.3% carbon dioxide in oxygen, pH 7.36-7.42, 38 degrees C). Each perfusion experiment (recirculatory perfusion system) was divided into three phases. In phase 1, a bolus dose of vecuronium (950 microg) was followed by a continuous infusion of vecuronium (63 microg/min) throughout the perfusion experiment. In phase 2, the temperature was reduced to 28 degrees C. In phase 3, temperature was restored. In controls, the temperature was kept constant throughout the perfusion. Concentrations of vecuronium and its metabolites were measured in perfusion medium, bile, and liver homogenate. Parameters of a multicompartmental liver model were fitted to the concentration patterns in perfusion medium and in bile.

Results

Hypothermia increased vecuronium concentrations in the perfusion medium from 4.0 microg/ml (range, 2.5-6.6) to 15.6 microg/ml (11.5-18.4 microg/ml; P = 0.018). Hypothermia reduced the biliary excretion rate of 3-desacetyl vecuronium from 18% (range, 6-37%) to 16% (range, 4-19%) of that of vecuronium (P = 0.018). Pharmacokinetic analysis confirmed that hypothermia reduced the rate constants of hepatic uptake and metabolism from 0.219 to 0.053 and from 0.059 to 0.030, respectively.

Conclusions

Hypothermia significantly and reversibly reduced the net hepatic uptake of vecuronium. Hypothermia reduced the metabolism of vecuronium and the biliary excretion rate of 3-desacetyl vecuronium.
Low Concentrations of Halothane Increase Response to a Noxious Thermal Stimulus and Attenuate the Antinociceptive Effect of Intraventricular but Not Intrathecal Morphine
Authors: Drasner Kenneth
Published: November 2003

Background

Classically, the first plane of anesthesia is known as the stage of analgesia. Nonetheless, clinical evidence suggests that low doses of inhaled agents might enhance pain perception. The present experiments test the hypothesis that low concentrations of halothane increase response to a noxious thermal stimulus and attenuate the antinociceptive effect of intraventricular morphine via disruption of descending inhibition.

Methods

In the first experiment, the temperature at which rats withdraw their tails from a heat source was measured in animals breathing various concentrations of halothane. In the second experiment, the effect of intraventricular or intrathecal morphine on tail-flick latency was assessed in rats breathing either oxygen or 0.23% halothane.

Results

Low concentrations of halothane decreased the temperature threshold for tail-flick with a maximum effect at 0.06% atmospheres. Halothane attenuated the antinociceptive potency of intraventricular morphine but enhanced the efficacy of intrathecal morphine.

Conclusions

Subanesthetic concentrations of halothane may enhance response to a noxious stimulus. The differential effect on intraventricular and intrathecal morphine suggests that this enhancement results from disruption of descending inhibition.
Agent-selective Effects of Volatile Anesthetics on GABAAReceptor–mediated Synaptic Inhibition in Hippocampal Interneurons
Authors: Nishikawa Koichi , MacIver M. Bruce
Published: November 2003

Background

A relatively small number of inhibitory interneurons can control the excitability and synchronization of large numbers of pyramidal cells in hippocampus and other cortical regions. Thus, anesthetic modulation of interneurons could play an important role for the maintenance of anesthesia. The aim of this study was to compare effects produced by volatile anesthetics on inhibitory postsynaptic currents (IPSCs) of rat hippocampal interneurons.

Methods

Pharmacologically isolated gamma-aminobutyric acid type A (GABAA) receptor-mediated IPSCs were recorded with whole cell patch-clamp techniques in visually identified interneurons of rat hippocampal slices. Neurons located in the stratum radiatum-lacunosum moleculare of the CA1 region were studied. The effects of clinically relevant concentrations (1.0 rat minimum alveolar concentration) of halothane, enflurane, isoflurane, and sevoflurane were compared on kinetics of both stimulus-evoked and spontaneous GABAA receptor-mediated IPSCs in interneurons.

Results

Halothane (1.2 vol% approximately 0.35 mm), enflurane (2.2 vol% approximately 0.60 mm), isoflurane (1.4 vol% approximately 0.50 mm), and sevoflurane (2.7 vol% approximately 0.40 mm) preferentially depressed evoked IPSC amplitudes to 79.8 +/- 9.3% of control (n = 5), 38.2 +/- 8.6% (n = 6), 52.4 +/- 8.4% (n = 5), and 46.1 +/- 16.0% (n = 8), respectively. In addition, all anesthetics differentially prolonged the decay time constant of evoked IPSCs to 290.1 +/- 33.2% of control, 423.6 +/- 47.1, 277.0 +/- 32.2, and 529 +/- 48.5%, respectively. The frequencies of spontaneous IPSCs were increased by all anesthetics (twofold to threefold). Thus, the total negative charge transfer mediated by GABAA receptors between synaptically connected interneurons was enhanced by all anesthetics.

Conclusions

Volatile anesthetics differentially enhanced GABAA receptor-mediated synaptic inhibition in rat hippocampal interneurons, suggesting that hippocampal interneuron circuits are depressed by these anesthetics in an agent-specific manner.
Protective Effects of Volatile Agents against Methacholine-induced Bronchoconstriction in Rats
Authors: Habre Walid , Peták Ferenc , Sly Peter D. , Hantos Zoltán , Morel Denis R.
Published: November 2003

Background

The protective properties of common volatile agents against generalized lung constriction have previously been addressed only via estimations of parameters that combine airway and tissue mechanics. Their effectiveness in preventing airway constriction have not been compared systematically. Therefore, the authors investigated the abilities of halothane, isoflurane, sevoflurane, and desflurane to provide protection against airway constriction induced by methacholine.

Methods

Low-frequency pulmonary impedance data were collected in open-chest rats under baseline conditions and during three consecutive intravenous infusions of methacholine (32 microg x kg(-1) x min(-1)) while the animals were anesthetized with intravenous pentobarbital (control group). Methacholine challenges were performed in four other groups of rats, first during intravenous anesthesia and then repeated during the inhalation of halothane, isoflurane, sevoflurane, or desflurane at concentrations of 1 and 2 minimum alveolar concentration (MAC). Airway resistance and inertance, parenchymal damping, and elastance were estimated from the impedance data by model fitting.

Results

The methacholine-induced increases in airway resistance during intravenous pentobarbital anesthesia (204 +/- 53%) were markedly and significantly (P < 0.005) reduced by 1-MAC doses of halothane (80 +/- 48%), isoflurane (112 +/- 59%), sevoflurane (68 +/- 34%), and desflurane (96 +/- 34%), with no significant difference between the gases applied. Increasing the concentration to 2 MAC did not lead to any significant further protection against the increase in airway resistance.

Conclusions

These data demonstrate that isoflurane, sevoflurane, and desflurane are as effective as the widely accepted halothane in protecting against methacholine-induced airway constriction.
Surgical Stimulation Shifts EEG Concentration–Response Relationship of Desflurane
Authors: Röpcke Heiko , Rehberg Benno , Koenen-Bergmann Michael , Bouillon Thomas , Bruhn Jörgen , Hoeft Andreas
Published: November 2003

Background

Anesthesiologists routinely increase the delivered anesthetic concentration before surgical stimulation in anticipation of increased anesthetic requirement to achieve certain goals (e.g., amnesia, unconsciousness, and immobility). Electroencephalographic monitoring is one method of determining indirectly anesthetic effect on the brain. The present study investigated the effect of surgical stimuli on the concentration-response relation of desflurane-induced electroencephalographic changes.

Methods

The electroencephalographic activity was recorded from 24 female patients who received only desflurane after a single induction dose of propofol. Twelve patients served as a control group before surgical stimulation. The other 12 patients, all undergoing lower abdominal surgery, were investigated between opening and closure of the peritoneum. Desflurane vaporizer settings were randomly increased and decreased between 0.5 and 1.6 minimum alveolar concentration as long as anesthesia was considered adequate. Spectral edge frequency 95, median power frequency, and Bispectral Index were calculated. Desflurane effect-site concentrations and the concentration-effect curves for spectral edge frequency 95, median power frequency, and Bispectral Index were determined by simultaneous pharmacokinetic and pharmacodynamic modeling.

Results

Surgical stimulation shifted the desflurane concentration-electroencephalographic effect curves for spectral edge frequency 95, median power frequency, and Bispectral Index toward higher desflurane concentrations. In the unstimulated group, 2.2 +/- 0.74 vol% desflurane were necessary to achieve a Bispectral Index of 50, whereas during surgery, 6.8 +/- 0.98 vol% (mean +/- SE) were required.

Conclusions

During surgery, higher concentrations of the volatile anesthetic are required to achieve a desired level of cortical electrical activity and, presumably, anesthesia.
Early Preload Adaptation in Septic Shock?
Authors: Vieillard-Baron Antoine , Schmitt Jean-Marie , Beauchet Alain , Augarde Roch , Prin Sebastien , Page Bernard , Jardin François
Published: November 2003

Background

An accepted concept in septic shock is that preload adaptation by acute left ventricular dilatation, when occurring spontaneously or with the aid of volume loading, permits maintenance of an adequate cardiac output, leading to final recovery. From a physiologic point of view, this concept appears debatable because a normal pericardium exerts a restraining action on a normal heart.

Methods

During a 26-month period, the authors investigated, by transesophageal echocardiography, 40 patients hospitalized in their unit for an episode of septic shock. Transesophageal echocardiography was performed in the first hours after admission, proceeded by correction of any hypovolemia, and stabilization of arterial pressure by vasoactive agent infusion if necessary. Left ventricular dimensions were obtained in long- and short-axis views, permitting calculation of left ventricular ejection fraction (long axis) and fractional area contraction (short axis). Stroke index was simultaneously measured by the Doppler technique.

Results

Stroke index was strongly correlated with both echocardiographic left ventricle ejection fraction (r = 0.75; P < 0.0001) and left ventricle fractional area contraction (r = 0.76; P < 0.0001), whereas it was independent of echocardiographic left ventricle diastolic dimensions.

Conclusions

The transesophageal echocardiography study was unable to confirm the reality of the concept of early preload adaptation by left ventricular dilatation in septic shock. Conversely, because left ventricular volume always remained in a normal range after correcting hypovolemia, systolic function was the unique determinant of stroke index in septic shock.