bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticoagulation during Cardiopulmonary Bypass in Patients with Heparin-induced Thrombocytopenia Type II and Renal Impairment Using Heparin and the Platelet Glycoprotein IIb–IIIa Antagonist Tirofiban
Authors: Koster Andreas , Kukucka Marian , Bach Friedhelm , Meyer Oliver , Fischer Thomas , Mertzlufft Fritz , Loebe Matthias , Hetzer Roland , Kuppe Hermann
Published: November 2003

Background

Patients with heparin-induced thrombocytopenia type II require an alternative to standard heparin anticoagulation. However, in patients with renal impairment, anticoagulation during cardiopulmonary bypass with agents such as danaparoid sodium or r-hirudin are associated with hemorrhage. Anticoagulation with unfractionated heparins combined with prostacyclin, a potent platelet aggregation inhibitor, is associated with severe hypotension. The authors investigated a new concept using unfractionated heparins after platelet inhibition with the short-acting platelet glycoprotein IIb-IIIa antagonist tirofiban.

Methods

Ten patients with heparin-induced thrombocytopenia type II and renal impairment were enrolled in the investigation. All had heparin-induced thrombocytopenia type II antibodies present as proved by the heparin-induced platelet aggregation assay, the heparin-platelet factor 4 enzyme-linked immunosorbent assay, or both. In all patients, preoperative anticoagulation to an activated partial thromboplastin time of 40-60 s was performed with r-hirudin. Anticoagulation during cardiopulmonary bypass was achieved with a bolus of 400 IU/kg unfractionated heparins after a bolus of tirofiban 10 microg/kg followed by an infusion of tirofiban at a rate of 0.15 microg x kg(-1) x min(-1) until 1 h before conclusion of cardiopulmonary bypass. Additional unfractionated heparins were only administered if activated clotting time decreased below 480 s. Coagulation was monitored by a abciximab-modified TEG and the adenosine diphosphate-stimulated (20 microm) platelet aggregometry. D-dimer concentrations, as a marker of venous thromboembolism, were measured before and 12, 24, and 48 h after surgery. Postoperative antithrombotic therapy was started immediately with r-hirudin to anticoagulation to an activated partial thromboplastin time of 40-60 s.

Results

The postoperative blood loss ranged from 110 to 520 ml. No patient needed reexploration. In no patient was there clinical evidence of thrombosis or embolism in the postoperative period or of a critical increase of the D-dimer concentrations, suggesting venous thromboembolism. Transfusion of platelets was necessary in only two patients.

Conclusions

The protocol is easy to perform and no increased postoperative bleeding and no thromboembolic complications occurred. The combination of unfractionated heparins and tirofiban may be an alternative to other anticoagulation strategies in patients with heparin-induced thrombocytopenia.
Epidural Anesthesia Retards Intestinal Acidosis and Reduces Portal Vein Endotoxin Concentrations during Progressive Hypoxia in Rabbits
Authors: Ai Kimiaki , Kotake Yoshifumi , Satoh Tomoyuki , Serita Ryohei , Takeda Junzo , Morisaki Hiroshi
Published: November 2003

Background

Because it is postulated that gut is important via bacterial translocation in the development of the systemic inflammatory response and multiple organ dysfunction, the preservation of gut integrity is a therapeutic goal for physicians who care for critically ill patients. The aim of the current study was to evaluate whether epidural anesthesia prevented gut injury and subsequent translocation of endotoxin during acute progressive hypoxia in rabbits.

Methods

After the placement of an epidural catheter, 18 male rabbits, anesthetized with buprenorphine-midazolam, were allocated randomly to two groups: 0.5% lidocaine (group E) and saline (group C) groups. The solutions (0.4 ml/kg) were injected epidurally, followed by continuous infusion (0.1 ml x kg(-1) x h(-1)) during the study period. Portal blood flow, portal endotoxin concentrations, and intramucosal pH (pHi) of the ileum were measured at baseline and during two stages of progressive hypoxia (fraction of inspired oxygen [Fio2] = 0.15 and 0.10).

Results

In both study groups, the portal blood flow was preserved to a similar extent during acute hypoxia. However, pHi was reduced to a lesser extent in group E (7.33 +/- 0.12 versus 7.22 +/- 0.12 at an Fio2 of 0.15 and 7.13 +/- 0.15 versus 7.03 +/- 0.12 at an Fio2 of 0.10; mean +/- SD, P < 0.01), concurrently with lower portal endotoxin concentrations (P < 0.05) compared with group C.

Conclusions

The current study showed that epidural anesthesia slowed the progression of intestinal ischemia during acute hypoxia, subsequently preventing translocation of endotoxin through the gut mucosa.
Suppression of Potassium Conductance by Droperidol Has Influence on Excitability of Spinal Sensory Neurons
Authors: Olschewski Andrea , Hempelmann Gunter , Vogel Werner , Safronov Boris V.
Published: November 2003

Background

During spinal and epidural anesthesia with opioids, droperidol is added to prevent nausea and vomiting. The mechanisms of its action on spinal sensory neurons are not well understood. It was previously shown that droperidol selectively blocks a fast component of the Na+ current. The authors studied the action of droperidol on voltage-gated K+ channels and its effect on membrane excitability in spinal dorsal horn neurons of the rat.

Methods

Using a combination of the patch-clamp technique and the "entire soma isolation" method, the action of droperidol on fast-inactivating A-type and delayed-rectifier K+ channels was investigated. Current-clamp recordings from intact sensory neurons in spinal cord slices were performed to study the functional meaning of K+ channel block for neuronal excitability.

Results

Droperidol blocked delayed-rectifier K+ currents in isolated somata of dorsal horn neurons with a half-maximum inhibiting concentration of 20.6 microm. The A-type K+ current was insensitive to up to 100 microm droperidol. At droperidol concentrations insufficient for suppression of an action potential, the block of delayed-rectifier K+ channels led to an increase in action potential duration and, as a consequence, to lowering of the discharge frequency in the neuron.

Conclusions

Droperidol blocks delayed-rectifier K+ channels in a concentration range close to that for suppression of Na+ channels. The block of delayed-rectifier K+ channels by droperidol enhances the suppression of activity in spinal sensory neurons at drug concentrations insufficient for complete conduction block.
Effects of Xenon on Cerebral Blood Flow and Cerebral Glucose Utilization in Rats
Authors: Frietsch Thomas , Bogdanski Ralph , Blobner Manfred , Werner Christian , Kuschinsky Wolfgang , Waschke Klaus F.
Published: November 2003

Background

The effects of xenon inhalation on mean and local cerebral blood flow (CBF) and mean and local cerebral glucose utilization (CGU) were investigated using iodo-[14C]antipyrine and [14C]deoxyglucose autoradiography.

Methods

Rats were randomly assigned to the following groups: conscious controls (n = 12); 30% (n = 12) or 70% xenon (n = 12) for 45 min for the measurement of local CBF and CGU; or 70% xenon for 2 min (n = 6) or 5 min (n = 6) for the measurement of local CBF only.

Results

Compared with conscious controls, steady state inhalation of 30 or 70% xenon did not result in changes of either local or mean CBF. However, mean CBF increased by 48 and 37% after 2 and 5 min of 70% xenon short inhalation, which was entirely caused by an increased local CBF in cortical brain regions. Mean CGU determined during steady state 30 or 70% xenon inhalation remained unchanged, although local CGU decreased in 7 (30% xenon) and 18 (70% xenon) of the 40 examined brain regions. The correlation between CBF and CGU in 40 local brain structures was maintained during steady state inhalation of both 30 and 70% xenon inhalation, although at an increased slope at 70% xenon.

Conclusion

Effects of 70% xenon inhalation on CBF in rats are time-dependent. During steady state xenon inhalation (45 min), mean values of CBF and CGU do not differ from control values, and the relation of regional CBF to CGU is maintained, although reset at a higher level.
Absence of Direct Antioxidant Effects from Volatile Anesthetics in Primary Mixed Neuronal–Glial Cultures
Authors: Kudo Masaya , Aono Mitsuo , Lee Yoonki , Massey Gary , Pearlstein Robert D. , Warner David S.
Published: November 2003

Background

Volatile anesthetics decrease ischemic brain injury. Mechanisms for this protection remain under investigation. The authors hypothesized that volatile anesthetics serve as antioxidants in a neuronal-glial cell culture system.

Methods

Primary cortical neuronal-glial cultures were prepared from fetal rat brain. Cultures were exposed to iron, H2O2, or xanthine-xanthine oxidase for 30 min in serum-free media containing dissolved isoflurane (0-3.2 mm), sevoflurane (0-3.6 mm), halothane (0-4.1 mm), n-hexanol, or known antioxidants. Cell damage was assessed by release of lactate dehydrogenase (LDH) and trypan blue exclusion 24 h later. Lipid peroxidation was measured by the production of thiobarbituric acid-reactive substances in a cell-free lipid system. Iron and calcium uptake and mitochondrial depolarization were measured after exposure to iron in the presence or absence of isoflurane.

Results

Deferoxamine reduced LDH release caused by H2O2 or xanthine-xanthine oxidase, but the volatile anesthetics had no effect. Iron-induced LDH release was prevented by the volatile anesthetics (maximum effect for halothane = 1.2 mm, isoflurane = 1.2 mm, and sevoflurane = 2.1 mm aqueous phase). When corrected for lipid solubility, the three volatile anesthetics were equipotent against iron-induced LDH release. In the cell-free system, there was no effect of the anesthetics on thiobarbituric acid-reactive substance formation in contrast to Trolox, which provided complete inhibition. Isoflurane (1.2 mm) reduced mean iron uptake by 46% and inhibited mitochondrial depolarization but had no effect on calcium uptake.

Conclusions

Volatile anesthetics reduced cell death induced by oxidative stress only in the context of iron challenge. The likely reason for protection against iron toxicity is inhibition of iron uptake and therefore indirect reduction of subsequent intracellular oxidative stress caused by this challenge. These data argue against a primary antioxidant effect of volatile anesthetics.
Influence of Hemorrhagic Shock on Remifentanil
Authors: Johnson Ken B. , Kern Steven E. , Hamber Elizabeth A. , McJames Scott W. , Kohnstamm Katelijne M. , Egan Talmage D.
Published: November 2003

Background

Hemorrhagic shock is known to alter significantly the pharmacokinetics of fentanyl, an opioid that requires delivery to the liver for metabolism. The authors hypothesized that the pharmacokinetics and pharmacodynamics of remifentanil, an esterase metabolized opioid that does not require delivery to a metabolic organ, would be altered less by hemorrhagic shock that those of fentanyl.

Methods

Sixteen pigs were assigned randomly to control and shock groups. The shock group was bled using an isobaric hemorrhage model. Remifentanil 10 microg x kg(-1) x min(-1) was infused for 10 min to both groups. Arterial samples were collected for remifentanil concentration assay. Pharmacokinetic parameters were estimated using a three-compartment model. The electroencephalogram spectral edge was used as a measure of drug effect. The pharmacodynamics were characterized using a sigmoid inhibitory maximal effect model.

Results

Remifentanil blood levels were higher in the shocked group. The central clearance was slower and the central compartment was smaller in shocked animals. No difference between groups was observed in the magnitude or time course of the remifentanil-induced decrease in spectral edge.

Conclusions

Hemorrhagic shock altered the pharmacokinetics of remifentanil, suggesting that less remifentanil would be required to maintain a target plasma concentration. However, because of its rapid metabolism, the impact of hemorrhagic shock on the concentration decline of remifentanil after termination of the infusion was minimal. Hemorrhagic shock did not alter the pharmacodynamics of remifentanil.
The Effect of Hypothermia on Isoflurane MAC in Children
Authors: Liu Mingzheng , Hu Xiaoqin , Liu Jin
Published: November 2003

Background

Hypothermia has been shown to decrease the requirement for inhaled anesthetics in animals, but information in humans is limited.

Methods

Thirty-three unpremedicated children with congenital left-to-right shunt heart diseases undergoing open heart surgeries were assigned to one of three groups, with nasopharyngeal temperatures at the time of skin incision of 37, 34, or 31 degrees C. Anesthesia was induced and maintained with isoflurane in oxygen. End-tidal isoflurane concentration and nasopharyngeal temperature were kept at stable levels for at least 15 min before the skin incision. Isoflurane minimum alveolar concentration was determined by using the Dixon up-and-down approach.

Results

Isoflurane minimum alveolar concentration values were 1.69 +/- 0.14%, 1.47 +/- 0.10%, and 1.22 +/- 0.15% (mean +/- SD) at 37, 34, and 31 degrees C, respectively.

Conclusions

Hypothermia decreases the isoflurane requirement in children by 5.1 degrees C.
Reduced Need for Vasopressors in Patients Receiving Aprotinin during Orthotopic Liver Transplantation
Authors: Quintus Molenaar I. , Begliomini Bruno , Martinelli Gerardo , Putter Hein , Terpstra Onno T. , Porte Robert J.
Published: November 2003

Background

Graft reperfusion in orthotopic liver transplantation is often associated with significant hemodynamic changes, including decreased systemic vascular resistance and arterial blood pressure. Vasopressive drugs are often required to maintain adequate perfusion pressure during the early postreperfusion period. The exact mechanism of this postreperfusion syndrome is unknown, but release of bradykinin, a potent vasodilatator, via the kallikrein system may play a role. Aprotinin is a broad-spectrum inhibitor of serine proteases such as kallikrein and therefore may ameliorate the postreperfusion syndrome and reduce the need for vasopressors.

Methods

In a randomized, double-blind study, the authors compared hemodynamic variables (systemic vascular resistance, cardiac index, arterial blood pressure, mean pulmonary artery pressure, central venous pressure) and the requirement of epinephrine during transplantation in 67 patients who received either high-dose aprotinin (2 x 10(6) kallikrein inhibitor units [KIU] at induction, continuous infusion of 1 x 10(6) KIU/h, 1 x 10(6) KIU before reperfusion; n = 24), regular-dose aprotinin (2 x 10(6) KIU at induction, continuous infusion of 0.5 x 10(6) KIU/h; n = 21), or placebo (n = 22).

Results

Baseline characteristics were similar for all three groups. Erythrocyte transfusion requirement was significantly higher in the placebo group compared with both aprotinin-treated groups. No major differences in hemodynamic variables were found between the three groups. The total amount of epinephrine (median, range) used during transplantation, however, was significantly lower in patients who received aprotinin (high dose, 20, 0-170 microg; regular dose, 30, 0-140 microg), compared with patients who received placebo (70, 0-2,970 microg; P = 0.0017). This difference was largely attributable to differences in the early postreperfusion period.

Conclusions

Prophylactic use of aprotinin ameliorates the postreperfusion syndrome in orthotopic liver transplantation, as reflected by a significant reduction in vasopressor requirements.
Analgesic Effect of Low-dose Intrathecal Morphine after Spinal Fusion in Children
Authors: Gall Olivier , Aubineau Jean-Vincent , Bernière Josée , Desjeux Luc , Murat Isabelle
Published: November 2003

Background

This study was designed to assess the postoperative analgesic effect of low-dose intrathecal morphine after scoliosis surgery in children.

Methods

Thirty children, 9-19 yr of age, scheduled for spinal fusion, were randomly allocated into three groups to receive a single dose of 0 (saline injection), 2, or 5 microg/kg intrathecal morphine. After surgery, a patient-controlled analgesia device (PCA) provided free access to additional intravenous morphine. Children were monitored for 24 h in the postanesthesia care unit.

Results

The three groups were similar for age, weight, duration of surgery, and time to extubation. The time to first PCA demand was dose-dependently delayed by intrathecal morphine. The first 24 h of PCA morphine consumption was 49 +/- 17, 19 +/- 10, and 12 +/- 12 mg (mean +/- SD) in the saline, 2 microg/kg morphine, and 5 microg/kg morphine groups, respectively. Pain scores at rest were significantly lower over the whole study period after 2 and 5 microg/kg intrathecal morphine than after saline, but there was no difference between intrathecal doses. Pain scores while coughing and the incidence of side effects were similar in the three groups.

Conclusions

These data demonstrate that low-dose intrathecal morphine supplemented by PCA morphine provides better analgesia than PCA morphine alone after spinal fusion in children. The doses of 2 and 5 microg/kg seem to have similar effectiveness and side-effect profiles, whereas a reduction of intraoperative bleeding was observed in patients who received 5 microg/kg but not 2 microg/kg intrathecal morphine.
Mathematical Modeling of Carbon Monoxide Exposures from Anesthetic Breakdown
Authors: Woehlck Harvey J. , Mei David , Dunning Marshall B. , Ruiz Franklin
Published: November 2003

Background

Carbon monoxide (CO) is produced by reaction of isoflurane, enflurane, and desflurane in desiccated carbon dioxide absorbents. The inspiratory CO concentration depends on the dryness and identity of the absorbent and anesthetic. The adaptation of existing mathematical models to a rebreathing circuit allows identification of patient factors that predispose to more severe exposures, as identified by carboxyhemoglobin concentration.

Methods

From our companion study, the authors used quantitative in vitro CO production data for 60 min at 7.5% desflurane or 1.5% isoflurane at 1 l/min fresh gas flow. The carboxyhemoglobin concentration was calculated by iteratively solving the Coburn Forster Kane equation modified for a rebreathing system that incorporates the removal of CO by patient absorption. Demonstrating good fit of predicted carboxyhemoglobin concentrations to published data from animal and human exposures validated the model. Carboxyhemoglobin concentrations were predicted for exposures of various severity, patients of different sizes, hematocrit, and fraction of inspired oxygen.

Results

The calculated carboxyhemoglobin concentrations closely predicted the experimental results of other investigators, thereby validating the model. These equations indicate the severity of CO poisoning is inversely related to the hemoglobin quantity of a subject. Fraction of inspired oxygen had the greatest effect in patients of small size with low hematocrit values, where equilibrium and not the rate of uptake determined carboxyhemoglobin concentrations.

Conclusion

This model predicts that patients with low hemoglobin quantities will have more severe CO exposures based on the attainment of a higher carboxyhemoglobin concentration. This includes patients of small size (pediatric population) and patients with anemia.
Effects of Dantrolene on Rat Diaphragm Muscle during Postnatal Maturation
Authors: Orliaguet Gilles , Langeron Olivier , Coirault Catherine , Fratea Sylvia , Coriat Pierre , Riou Bruno
Published: November 2003

Background

Dantrolene is the only known effective treatment for malignant hyperthermia. However, its effects on diaphragm muscle during postnatal maturation remain unknown.

Methods

The effects of dantrolene (10(-8) to 10(-4) M) were investigated in vitro on diaphragm muscle strips in adult rats and in postnatal rats aged 3, 10, and 17 days, and compared with those of ryanodine (10(-8) to 10(-6) M). The authors studied contraction and relaxation under isotonic and isometric conditions (29 degrees C, Krebs-Henseleit solution, tetanic stimulation at 50 Hz). Data are mean +/- SD.

Results

During postnatal maturation, the authors observed a progressive increase in active force developed per cross-sectional area (from 34 +/- 25 to 69 +/- 32 mN/mm2; P < 0.05) and maximum shortening velocity (from 2.9 +/- 0.5 to 4.9 +/- 1.4 Lmax/s; P < 0.05). Dantrolene induced a negative inotropic effect in diaphragm muscles in isotonic and isometric conditions in all groups, but this effect was significantly less marked in the 3-day-old rats compared with older rats. Dantrolene did not induce significant lusitropic effects during postnatal maturation. Developmental changes in the pharmacologic response to dantrolene were more rapid than those of ryanodine.

Conclusion

Dantrolene induced less pronounced negative inotropic effects on the diaphragm in neonatal rats as compared with adult rats. Our study suggests that developmental changes in the pharmacologic response to dantrolene are more rapid than those of ryanodine.
Blockade of AMPA Receptors and Volatile Anesthetics
Authors: Joo Daisy T. , Gong Diane , Sonner James M. , Jia Zhengping , MacDonald John F. , Eger Edmond I. , Orser Beverley A.
Published: November 2003

Background

The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of glutamate receptor mediates fast excitatory neurotransmission in the central nervous system. Many general anesthetics inhibit AMPA receptors in vitro; however, it is not certain if this inhibition contributes to the behavioral properties of these drugs. AMPA receptors lacking the GluR2 subunit are resistant to blockade by barbiturates in vitro. Paradoxically, GluR2 null mutant (-/-) mice are more sensitive to barbiturate-induced loss of the righting reflex (LORR) compared with wild-type (+/+) littermates. To determine if interactions between anesthetics and AMPA receptors account for the increased sensitivity of (-/-) mice, the effects of volatile anesthetics that do not directly inhibit AMPA receptors were examined.

Methods

Isoflurane, halothane, desflurane, or sevoflurane were administered to (-/-) and (+/+) littermate controls. Anesthetic requirements for LORR, movement to tail clamp (minimum alveolar concentration [MAC]), and hind-paw withdrawal latency (HPWL) were determined. Electrophysiologic methods examined the inhibition of AMPA receptors by isoflurane and halothane.

Results

Anesthetic requirements for LORR and HPWL were decreased, whereas MAC values were unchanged in (-/-) mice. Isoflurane and halothane caused minimal inhibition of AMPA receptors at clinically relevant concentrations.

Conclusions

Direct blockade of AMPA receptors did not account for the increased sensitivity to volatile anesthetics in GluR2 null mutant mice for HPWL or LORR. Thus, the deficiency of GluR2-containing AMPA receptors increases the sensitivity of neuronal circuitry mediating these end points, but not MAC. GluR2-containing receptors do not contribute appreciably to MAC in this mouse model. These results illustrate the difficulties in attributing behavioral responses to drug-receptor interactions in genetically engineered animals.
Mechanisms of Isoflurane-mediated Hyperpolarization of Vascular Smooth Muscle in Chronically Hypertensive and Normotensive Conditions
Authors: Stekiel Thomas A. , Contney Stephen J. , Kokita Naohiro , Bosnjak Zeljko J. , Kampine John P. , Stekiel William J.
Published: November 2003

Background

The purpose of this study was to compare the effects of isoflurane on membrane and intracellular mechanisms that regulate vascular smooth muscle (VSM) transmembrane potential (Em; which is related to VSM tone) in the spontaneously hypertensive rat (SHR) model of essential hypertension and its normotensive Wistar-Kyoto (WKY) control.

Methods

Vascular smooth muscle Em values were measured in situ in locally denervated, superfused, intact, small (200-300-microm OD) mesenteric arteries and veins in anesthetized 9-12-week-old SHR and WKY. Effects of 1.0 minimum alveolar concentration (0.60 mM) superfused isoflurane on VSM Em were measured before and during superfusion with specific inhibitors of VSM calcium-activated (KCa) and adenosine triphosphate-regulated (KATP) potassium channels, and with endogenous mediators of vasodilatation (nitric oxide, cyclic guanosine monophosphate, protein kinase G, cyclic adenosine monophosphate, and protein kinase A).

Results

Isoflurane significantly hyperpolarized small arteries (5 +/- 3.4 mV) and veins (6 +/- 4.7 mV) (pooled SHR and WKY, mean +/- SD). Inhibition of KCa and KATP channels, cyclic adenosine monophosphate, and protein kinase A, but not nitric oxide, cyclic guanosine monophosphate, and protein kinase G, abolished such hyperpolarization equally in SHR and WKY vessels.

Conclusions

Isoflurane-induced in situ VSM hyperpolarization in denervated, small mesenteric vessels involves a similar activation of KCa and KATP channels and cyclic adenosine monophosphate, but not nitric oxide or cyclic guanosine monophosphate, second messenger pathways in both SHR and WKY. A greater isoflurane-induced VSM hyperpolarization (observed previously in neurally intact SHR vessels) suggests enhanced inhibition of elevated sympathetic neural input as a major mechanism underlying such hyperpolarization (and coupled relaxation) in this neurogenic model of hypertension.
The Concentration of Isoflurane Required to Suppress Learning Depends on the Type of Learning
Authors: Dutton Robert C. , Maurer Anya J. , Sonner James M. , Fanselow Michael S. , Laster Michael J. , Eger Edmond I.
Published: November 2003

Background

Recent reports suggest that one type of learning, fear conditioning to context, requires more neural processing than a related type, fear conditioning to tone. To determine whether these types of learning were differentially affected by anesthesia, the authors applied isoflurane during the training phases of fear conditioning paradigms for freezing to context and freezing to tone.

Methods

The authors trained seven groups of eight rats to fear tone by administering a tone (conditioned stimulus) while breathing various concentrations of isoflurane from 0.00 to 0.75 minimum alveolar concentration (MAC; one concentration per group) separated by 0.12-MAC steps. On the succeeding day, and in the absence of isoflurane, the authors presented the tone (without shock) in a different context (different cage shape and odor) and measured the time each rat froze (became immobile). Six other groups of eight rats were trained to fear context by applying the shock in the absence of a tone but in the presence of environmental cues such as cage shape, texture, and odor. Fear to context was determined the succeeding day by returning the rat to the training cage (without shock) and measuring duration of freezing. Control groups (16 per group) received 0.75 MAC isoflurane but no foot shocks. Group scores were compared using analysis of variance, and the ED50 values for quantal responses of individual rats were calculated using logistic regression.

Results

Conditioning to context occurred at 0.00 and 0.13 MAC (P < 0.05 compared with unshocked control) but not 0.25 MAC; the ED50 was 0.25 +/- 0.03 MAC (mean +/- SEM). In contrast, conditioning to tone occurred at 0.48 MAC (P < 0.05) but not 0.62 MAC; the ED50 was 0.47 +/- 0.02 MAC (P < 0.01 for the difference between ED50 values).

Conclusions

Suppression of fear conditioning to tone required approximately twice the isoflurane concentration that suppressed fear conditioning to context. Thus, the concentration of anesthetic required to suppress learning may depend on the neural substrates of learning. Our results suggest that isoflurane concentrations greater than 0.5 MAC may be needed to suppress both forms of fear conditioning.
BIS Monitoring to Prevent Awareness during General Anesthesia
Authors: O’Connor Michael F. , Daves Suanne M. , Tung Avery , Cook Richard I. , Thisted Ronald , Apfelbaum Jeffery
Published: November 2003

Background

Unexpected awareness is a rare but well-described complication of general anesthesia that has received increased scientific and media attention in the past few years. Transformed electroencephalogram monitors, such as the Bispectral Index monitor, have been advocated as tools to prevent unexpected recall.

Methods

The authors conducted a power analysis to estimate how many patients would be needed in an appropriately powered study to demonstrate the Bispectral Index monitor reduces awareness, as well as a cost analysis to assess the cost of using the monitor for this purpose alone.

Results

If unexpected recall is rare (1 in 20,000), it will require a large study to demonstrate that the monitor reduces awareness (200,000-800,000 patients), and the cost of using it for this purpose alone would be high ($400,000 per case prevented). If awareness is common (1 in 100), then the number of patients needed in a study to demonstrate that the monitor works becomes tractable (1,000-4,000 patients), and the cost of using the monitor for this purpose alone becomes lower ($2,000 per case prevented). Because there are reported cases of awareness despite Bispectral Index monitoring, the authors are certain that the effectiveness of the monitor is less than 100%. As the performance of the monitor decreases from 100%, the size of the study needed to demonstrate that it works increases, as does the cost of using it to prevent awareness.

Conclusion

The contention that Bispectral Index monitoring reduces the risk of awareness is unproven, and the cost of using it for this indication is currently unknown.
Celiac Plexus Block
Authors: De Cicco Marcello , Matovic Mira , Bortolussi Roberto , Coran Franco , Fantin Dario , Fabiani Fabio , Caserta Maria , Santantonio Cristina , Fracasso Augusto
Published: November 2003

Background

The success of the neurolytic celiac plexus block, despite different approaches and methods used, depends on adequate spread of the injectate in the celiac area. This retrospective study was conducted to evaluate the patterns of alcohol spread and pain relief in patients with cancer or therapy-related anatomic distortion of the celiac area.

Methods

From 177 cancer patients who underwent computed tomography (CT)-guided single-needle neurolytic celiac plexus block via an anterior approach, a radiologist, blind to the aim of the study, retrospectively selected 105 patients with abnormal anatomy of the celiac area as judged by CT images obtained before the block. To evaluate CT patterns of neurolytic (mixed with contrast) spread, the celiac area was divided on the frontal plane into four quadrants: upper right and left and lower right and left, as related to the celiac artery. Results were expressed as the number of quadrants into which contrast spread, ie., four, three, two, or one quadrants with contrast. The patterns of contrast spread according to the number of quadrants with anatomic distortion were analyzed. Patient assessment by visual analog scale was reviewed to evaluate the degree of pain relief. Pain relief 30 days after block was considered long-lasting. Pain relief at 30 days after block was analyzed according to the number of quadrants with contrast.

Results

Overall, four, three, two, and one quadrants with contrast were observed in 9 (8%), 21 (20%), 49 (47%), and 26 (25%) patients, respectively. An inverse correlation was observed between the number of quadrants with anatomic distortion and the number of quadrants with contrast (P < 0.001). Long-lasting pain relief was noticed in nine of nine patients (100%; 95% confidence interval, 66-100) with contrast in four-quadrants, and in 10 of 21 patients (48%; 95% confidence interval, 26-70) with contrast in 3 quadrants (P < 0.01). None of the 75 patients with contrast in two quadrants or one quadrant experienced long-lasting pain relief.

Conclusions

These findings suggest that, using the single-needle anterior approach, the neurolytic spread in the celiac area is highly hampered by the regional anatomic alterations. It also appears that only a complete (four quadrants) neurolytic spread in the celiac area can guarantee long-lasting analgesia, and that this picture may be obtained in a very limited fraction of patients with regional anatomic alterations.
Caudal Ropivacaine in Infants
Authors: Hansen Tom G. , Ilett Kenneth F. , Reid Chris , Im Lim Soo , Peter Hackett L. , Bergesio Riccardo
Published: November 2003

Background

Ropivacaine is a new long-acting amino-amide local anesthetic. However, there are no data on its use in infants. In the current study, the authors investigated the pharmacokinetics of caudal ropivacaine in 30 infants younger than 12 months.

Methods

Two groups of infants (group 1 [n = 15], aged 0-3 months; group 2 [n = 15], aged 3-12 months) were given a caudal bolus dose of 0.2% ropivacaine (2 mg/kg) and a standardized general anesthetic technique. Serial blood samples taken for up to 12 h were analyzed for total and free ropivacaine using high-performance liquid chromatography. Population pharmacokinetic modeling was performed to yield estimates of clearance, volume of distribution, and absorption rate constant. An analysis of covariates on the kinetic parameters also was made.

Results

Median maximum free ropivacaine concentration was significantly higher in group 1 (99 micog/l) than in group 2 (38 microg/l) (P = 0.0002), as was the median free fraction of ropivacaine (10% vs. 5%; P = 0.01). Pharmacokinetic variables of the total population were best described by a one-compartment model with first-order absorption. Mean clearance was 0.31 l.h(-1).kg(-1) (coefficient of variation [CV], 51%), volume of distribution was 2.12 l/kg (CV, 34%), and absorption rate constant was 1.61 h(-1) (CV, 46%). Mean absorption and elimination half-lives were 0.43 and 5.1 h, respectively. Age and percentage of free ropivacaine were significant covariates for clearance. Posterior Bayesian estimates of clearance were significantly higher (38%) in older children.

Conclusion

Total and free plasma ropivacaine concentrations after caudal ropivacaine (0.2%, 2 mg/kg) in infants were within the range of concentrations previously reported in adults and older children. Age and percentage of free ropivacaine were significant covariates of clearance.
Comparison of Multiplane Transesophageal Echocardiography and Contrast-enhanced Helical CT in the Diagnosis of Blunt Traumatic Cardiovascular Injuries
Authors: Vignon Philippe , Boncoeur Marie-Paule , François Bruno , Rambaud Geoffray , Maubon Antoine , Gastinne Hervé
Published: November 2003

Background

Multiplane transesophageal echocardiography (TEE) and helical computed tomography (CT) of the chest have been validated separately against aortography for the diagnosis of acute traumatic aortic injuries (ATAI). However, their respective diagnostic accuracy in identifying blunt traumatic cardiovascular lesions has not been compared.

Methods

During a 3-yr period, 110 consecutive patients with severe blunt chest trauma (age: 41 +/- 17 yr; injury severity score: 34 +/- 14) prospectively underwent TEE and chest CT as part of their initial evaluation. Results of both imaging methods were interpreted independently by experienced investigators and subsequently compared. All cases of subadventitial acute traumatic aortic injury were surgically confirmed.

Results

Seventeen patients had vascular injury and 11 had cardiac lesions. TEE and CT identified all subadventitial disruptions involving the aortic isthmus (n = 10) or the ascending aorta (n = 1) that necessitated surgical repair. In contrast, CT only depicted one disruption of the innominate artery. TEE detected injuries involving the intimal or medial layer, or both, of the aortic isthmus in four patients with apparently normal CT results who underwent successful conservative treatment. All cardiac injuries but two were identified only by TEE.

Conclusions

In patients with severe blunt chest trauma, TEE and CT have similar diagnostic accuracy for the identification of surgical acute traumatic aortic injuy. TEE also allows the diagnosis of associated cardiac injuries and is more sensitive than CT for the identification of intimal or medial lesions of the thoracic aorta.
Propofol Attenuates Diaphragmatic Dysfunction Induced by Septic Peritonitis in Hamsters
Authors: Mikawa Katsuya , Nishina Kahoru , Kodama Shun-ichi , Obara Hidefumi
Published: November 2003

Background

Sepsis or peritonitis impairs diaphragmatic contractility and endurance capacity. Peroxynitrite, a powerful oxidant formed by superoxide and nitric oxide, has been implicated in the pathogenesis. Propofol scavenges this reactive molecule. The authors conducted the current study to evaluate whether propofol prevents diaphragmatic dysfunction induced by septic peritonitis.

Methods

Forty male Golden-Syrian hamsters (120-140 g) were randomly classified into five groups. Groups sham and sham-propofol 50 underwent sham laparotomy alone, whereas groups sepsis, sepsis-propofol 25, and sepsis-propofol 50 underwent cecal ligation with puncture. Groups sham and sepsis received infusion of intralipid, whereas groups sham-propofol 50, sepsis-propofol 25, and sepsis-propofol 50 received propofol at rates of 50, 25, and 50 mg.kg(-1).h(-1), respectively. Intralipid or propofol was subcutaneously infused from 3 h before surgery until 24 h after operation, when all hamsters were killed. Diaphragmatic contractility and fatigability were assessed in vitro using diaphragm muscle strips. Peroxynitrite formation in the diaphragm was assessed by nitrotyrosine immunostaining. Plasma nitrite-nitrate concentrations and diaphragmatic concentrations of malondialdehyde were determined. Using another set of animals, diaphragmatic inducible nitric oxide synthase activity was also measured.

Results

Twitch, tetanic tensions, and tensions during fatigue trials were reduced in group sepsis compared with group sham. In group SEPSIS, diaphragm malondialdehyde and inducible nitric oxide synthase activity, and plasma nitrite-nitrate concentrations increased, and positive immunostaining for nitrotyrosine residues was found. Propofol attenuated these changes.

Conclusions

Pretreatment with propofol attenuated diaphragmatic dysfunction induced by septic peritonitis in hamsters assessed by contractile profiles and endurance capacity. This beneficial effect of propofol may be caused, in part, by inhibition of lipid peroxidation in the diaphragm caused by the powerful oxidant.
A Comparison of Tracheal Tube Tip Designs on the Passage of an Endotracheal Tube during Oral Fiberoptic Intubation
Authors: Ruari Greer J. , Smith Sharon P. , Strang Tim
Published: November 2003

Background

The design of an endotracheal tube has been shown to influence the passage of the tube through the glottis during fiberoptic intubation. Difficulty in passing the endotracheal tube can occur if the aryepiglottic folds obstruct the passage of the bevel. The relevant aspects of endotracheal tube design include the shape of the bevel, the material used by the manufacturer, and the ability of the tube to conform to the shape of the fiberscope. The aim of the current study was to compare the ease of passage through the glottis of two different tubes. One tube was a wire reinforced polyvinyl chloride tube with a standard bevel and the other was a newly designed tube with a bevel of different shape and made of silicone rubber. The new design is for use with the a commerical intubating laryngeal mask.

Methods

The authors studied a population of 30 patients who received a standard anesthetic. In all cases, oral fiberoptic intubation was attempted. Anesthetic was administered to each patient using both tubes, and before the study the order of the tubes was randomized. The difficulty in passing the tube was assessed by a blinded observer and graded using a three-point scale (grade 1: no difficulty passing the tube; grade 2: obstruction to passing the tube relieved by withdrawal and a 90 degrees anticlockwise rotation; grade 3: obstruction necessitating more than one manipulation or external laryngeal manipulation).

Results

In 27 patients, no difficulty was shown by use of the silicone-tipped tube. In only three patients was there difficulty that necessitated a 90 degrees anticlockwise twist. With the wire-reinforced tube, no difficulty was experienced on 14 occasions. Grade 1 difficulty was experienced eight times and difficulty necessitating more than one maneuver, head movement, or external laryngeal manipulation was seen on eight occasions. Statistical significance was achieved at P = 0.0002 (Wilcoxon signed rank test).

Conclusions

The authors conclude that the use of the silicone-tipped tube with the new bevel design may provide an advantage in the clinical situation of fiberoptic intubation.
Minimum Analgesic Dose of Epidural Sufentanil for First-stage Labor Analgesia
Authors: Capogna Giorgio , Parpaglioni Raffaella , Lyons Gordon , Columb Malachy , Celleno Danilo
Published: November 2003

Background

The aim of this prospective, double-blind, sequential allocation study was to compare the effects of spontaneous and prostaglandin-induced labor on the minimum analgesic dose of epidural sufentanil in the first stage of labor.

Methods

Seventy healthy, nulliparous women, at more than 37 weeks' gestation with cervical dilatation from 2 to 4 cm, requesting epidural pain relief in labor were enrolled. The subjects were assigned to two different groups according to whether labor was spontaneous or induced with dinoprostone 0.5 mg. Parturients received 10 ml of the study solution through a lumbar epidural catheter. The initial dose was sufentanil 25 microg, and subsequent doses were determined by the response of the previous patient in the same group using up-down sequential allocation. The analgesic effectiveness was assessed using 100-mm visual analog pain scores. The up-down sequences were analyzed using the method of independent paired reversals and probit regression.

Results

The minimum analgesic dose of sufentanil in spontaneous labor was 22.2 microg (95% CI: 19.6, 22.8) and 27.3 microg (95% CI: 23.8, 30.9) in induced labor. The minimum analgesic dose of sufentanil in induced labor was significantly greater (P = 0.0014) than that in spontaneous labor (95% CI difference: 2.9, 9.3) by a factor of 1.3 (95% CI: 1.1, 1.5).

Conclusion

Prostaglandin induction of labor produces a significantly greater analgesic requirement than does spontaneous labor.
Hemoglobin Desaturation after Succinylcholine-induced Apnea
Authors: Heier Tom , Feiner John R. , Lin Jim , Brown Ronald , Caldwell James E.
Published: November 2003

Background

Because of the rapid recovery of neuromuscular function after succinylcholine administration, there is a belief that patients will start breathing sufficiently rapidly to prevent significant oxygen desaturation. The authors tested whether this belief was valid.

Methods

Twelve healthy volunteers aged 18-45 yr participated in the study. After preoxygenation to an end-tidal oxygen concentration greater than 90%, each subject received 5 mg/kg thiopental and 1 mg/kg succinylcholine. Oxygen saturation (SaO2) was measured at both a finger and an ear lobe (beat to beat). During the period of apnea and as they were recovering, the volunteers received continuous verbal reassurance by the investigators. If the SaO2 decreased below 80%, the volunteers received chin lift and, if necessary, assisted ventilation. The length of time the subject was apneic and level of desaturation were related by linear regression analysis. One hour after recovery and again 1 week later, subjects were asked a series of questions regarding their emotional experience.

Results

In six volunteers, SaO2 decreased below 95% during apnea; in four, SaO2 decreased below 80%, necessitating chin lift and assisted ventilation in three. Apnea time was significantly longer in volunteers who reached SaO2 less than 80% than in those who did not (7.0+/-0.4 and 4.1+/-0.3 min, respectively), and there was a significant correlation between the length of time the subject was apneic and the magnitude of desaturation.

Conclusions

Spontaneous recovery from succinylcholine-induced apnea may not occur sufficiently quickly to prevent hemoglobin desaturation in subjects whose ventilation is not assisted.
Efficacy of a Simple Intraoperative Transfusion Algorithm for Nonerythrocyte Component Utilization after Cardiopulmonary Bypass
Authors: Nuttall Gregory A. , Oliver William C. , Santrach Paula J. , Bryant Sandra , Dearani Joseph A. , Schaff Hartzell V. , Ereth Mark H.
Published: November 2003

Background

Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test-based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding.

Methods

The authors performed a randomized prospective trial comparing allogeneic transfusion practices in 92 adult patients with abnormal bleeding after CPB. Patients with abnormal bleeding were randomized to one of two groups: a control group following individual anesthesiologist's transfusion practices and a protocol group using a transfusion algorithm guided by coagulation tests.

Results

Among 836 eligible patients having all types of elective cardiac surgery requiring CPB, 92 patients developed abnormal bleeding after CPB (incidence, 11%). The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB (median, 0 units; range, 0-7 units) than the control group (median, 3 units; range, 0-10 units) (P = 0.0002). The median number of platelet units transfused in the operating room after CPB was 4 (range, 0-12) in the algorithm group compared with 6 (range, 0-18) in the control group (P = 0.0001). Intensive care unit (ICU) mediastinal blood loss was significantly less in the algorithm group. Multivariate analysis demonstrated that transfusion algorithm use resulted in reduced ICU blood loss. The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding (11.8% vs. 0%; P = 0.032).

Conclusions

Use of a coagulation test-based transfusion algorithm in cardiac surgery patients with abnormal bleeding after CPB reduced non-erythrocyte allogeneic transfusions in the operating room and ICU blood loss.
Density Detection in Dependent Left Lung Region Using Transesophageal Echocardiography
Authors: Tsubo Toshihito , Sakai Ichiro , Suzuki Akiko , Okawa Hirobumi , Ishihara Hironori , Matsuki Akitomo
Published: November 2003

Background

Densities in dependent lung regions worsen oxygenation in patients with acute respiratory distress syndrome. Identification of these densities requires examination using computed tomography (CT). In this study, the authors evaluated the use of transesophageal echocardiography (TEE) to estimate densities in the dependent lung.

Methods

Forty consecutive patients with acute lung injury or acute respiratory distress syndrome who underwent CT and TEE examination were included in this study. Densities in the lower left lung area were detected through the descending aorta by TEE. Density areas observed by TEE were compared with those obtained by CT. The effect of positive end-expiratory pressure (PEEP) application on density area was also evaluated.

Results

Density areas in the dependent lung region measured by TEE were 12.0+/-6.1 cm2 (mean +/- SD) at mid esophageal position. Density areas evaluated using TEE in the left lung correlated significantly with those estimated with CT in the left and right lungs (P < 0.01 in both lungs). In addition, the authors observed a significant correlation between PaO2/FIO2 and density areas estimated using TEE (P < 0.05). During positive end-expiratory pressure application, the area of density estimated with TEE decreased and PaO2 improved.

Conclusions

The authors clearly demonstrated that it is possible to estimate the density area of the dependent left lung regions in patients with acute lung injury or acute respiratory distress syndrome using TEE. It is also possible to observe the changes of density areas during application of positive end-expiratory pressure.