bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of Spinal Cord Motoneuron Excitability Correlates with Surgical Immobility during Isoflurane Anesthesia
Authors: Zhou Henry H. , Jin Tsen-Tsen , Qin Binsheng , Turndorf Herman
Published: November 2003

Background

Recent evidence suggests that the spinal cord is an important site of anesthetic action that produces surgical immobility. Inhalation anesthetics depress the Hoffmann's reflex (H reflex) and F wave, indicating spinal motoneuron suppression. The aim of this study was to assess the correlation between isoflurane-induced immobility and H- and F-wave suppression.

Methods

The baseline H reflex and F wave were measured before anesthesia in 15 adult patients. After induction, 1% end-tidal isoflurane was maintained for 20 min before the H and F waves were reelicited. Using an electric stimulus applied to the forearm and grading the response as movement or no movement, the authors increased or decreased the isoflurane concentration in 0.1% steps, depending on the movement responses. The H and F waves were recorded 20 min after each change of isoflurane concentration. The correlation between H- and F-wave suppression and surgical immobility was analyzed using a paired t test with Bonferroni correction.

Results

H-reflex amplitude (2.74 +/- 1.63 mV) and F-wave persistence (70.69 +/- 26.19%) at the highest isoflurane concentration that allowed movement response to a stimulus are different (P < 0.01) from these (1.97 +/- 1.46 mV; 43.16 +/- 22.91%) at the lowest isoflurane concentration that suppressed response. At 0.8% isoflurane, the H-reflex amplitude was 3.69 +/- 1.83 mV with movement and 1.01 +/- 1.14 mV without movement (P < 0.01); F-wave amplitude was 0.29 +/- 0.15 mV with movement and 0.11 +/- 0.06 mV without movement (P < 0.01); F-wave persistence was 80 +/- 22.36% with movement and 34.9 +/- 25.75% without movement (P < 0.01).

Conclusions

The degree of H- and F-wave amplitude and F-wave persistence suppression correlates with movement response, suggesting that isoflurane-suppressive action in the spinal cord plays a significant role in producing surgical immobility.
The Relation between the Platelet-activated Clotting Test (HemoSTATUS) and Blood Loss after Cardiopulmonary Bypass
Authors: Ereth Mark H. , Nuttall Gregory A. , Santrach Paula J. , Klindworth Jacinta T. , Oliver William C. , Schaff Hartzell V.
Published: November 2003

Background

Platelet dysfunction is one of several major causes of bleeding after cardiopulmonary bypass. A timely, simple, point-of-care determinant of platelet function recently became available for clinical use. Adding platelet-activating factor to conventional activated clotting time methods (platelet-activated clotting test [PACT]) produces rapid results (<15 min) and may yield a measure of platelet responsiveness and whole-blood procoagulant activity.

Methods

Blood samples were drawn from 100 patients after cardiac surgery on their arrival in the intensive care unit for PACT, platelet count, prothrombin time (PT), and activated partial thromboplastin time (aPTT). Cumulative blood loss at 4, 8, and 12 h after arrival in the intensive care unit and perioperative transfusion requirements were quantitated. Coagulation tests and mediastinal blood loss were compared using the Spearman rank test and Pearson correlation. The sensitivity and specificity of the laboratory tests for predicting blood loss were analyzed using the receiver operating characteristic method.

Results

The PT was the only test that correlated with blood loss at 4, 8, and 12 h. The PACT did not correlate with blood loss at 4, 8, or 12 h, nor did the PACT correlate with the PT or the aPTT. The sensitivity and specificity of the PACT were less than those of the PT in predicting blood loss. Only the PT correlated with platelet and fresh frozen plasma transfusion.

Conclusions

The PT correlated with blood loss and transfusion requirements and was superior to PACT, aPTT, and platelet count for predicting excessive blood loss after cardiopulmonary bypass.
A Randomized Controlled Trial Comparing the Cuffed Oropharyngeal Airway and the Laryngeal Mask Airway in Spontaneously Breathing Anesthetized Adults
Authors: Greenberg Robert S. , Brimacombe Joseph MB , Berry Alison , Gouze Victoria , Piantadosi Steven , Dake Elizabeth M.
Published: November 2003

Background

The cuffed oropharyngeal airway (COPA), a modified Guedel airway, was compared with the laryngeal mask airway (LMA) during spontaneous breathing anesthesia. Specifically examined were ease of use, physiologic tolerance, and the frequency of problems.

Methods

Adult patients consented to random (2:1) assignment to either COPA (n = 302) or LMA (n = 151) for airway management during anesthesia with propofol, nitrous oxide, and oxygen.

Results

Ease of insertion was similar, but the first-time successful insertion rate was higher with the LMA (COPA, 81% compared with LMA, 89%; P = 0.05). More brief manipulations (head tilt, chin lift, jaw thrust) were reported in the COPA group (average total number of manipulations: COPA, 1.1 +/- 1.6 compared with LMA, 0.1 +/- 0.2; P < 0.001). Continuous airway support was used more frequently in the COPA group (COPA, 30% compared with LMA, 0%; P < 0.0005). The incidences of aspiration, regurgitation, laryngospasm, wheezing, succinylcholine administration, oxygen saturation (SpO2) < 92%, failed use, and minor intraoperative problems were similar. When the airways were removed, blood was detected on the COPA less frequently than on the LMA (COPA, 5.8% compared with LMA, 15.3%; P = 0.001). The incidence of early and late sore throat was greater with the LMA (early: COPA, 4.7% compared with LMA, 21.9% [P = 0.001]; late: COPA, 8.4% compared with LMA, 16.1%; P = 0.01). The LMA did better than the COPA when anesthetists analyzed the technical aspects of the two devices.

Conclusions

Although the COPA and LMA are equivalent devices in terms of physiologic alterations and overall clinical problems associated with their use, the LMA was associated with a higher first-time insertion rate and fewer manipulations, suggesting that it is easier to use. The COPA was associated with less blood on the device and fewer sore throats, suggesting it may cause less pharyngeal trauma. Ultimately, both devices were similar in establishing a safe and effective airway for spontaneously breathing anesthetized adults.
The Pharmacokinetics and Steady State Pharmacodynamics of Mivacurium in Children
Authors: Markakis Dorothea A. , Lau Marie , Brown Ronald , Luks Andrew M. , Sharma Manohar L. , Fisher Dennis M.
Published: November 2003

Background

The authors previously showed that children require larger infusion rates of mivacurium than adults to maintain target twitch depression. Here, they determined whether there are differences between children and adults in mivacurium's pharmacokinetic and pharmacodynamic properties.

Methods

Twenty-seven patients aged 1-58 yr were anesthetized with nitrous oxide and isoflurane. Cholinesterase activity and adductor pollicis twitch tension in response to train-of-four stimuli were measured. Mivacurium was infused, targeting 90% twitch depression. When twitch was stably depressed 85%-95% for 10 min with no change in infusion rate for 15 min, plasma was sampled to determine concentrations of mivacurium's stereoisomers. Clearance of the trans-trans (Cl(trans-trans)) and cis-trans (Cl(cis-trans)) isomers was determined as the mivacurium infusion rate (adjusted for isomer composition) divided by the concentration of that isomer. Using the Hill equation, assuming equipotency of the trans-trans and cis-trans isomers, and ignoring the contribution of the nonpotent cis-cis isomer, the authors estimated the steady state plasma concentration yielding 90% twitch depression, C90. The effect of age on cholinesterase activity, the infusion rate depressing twitch tension by 90% (IR90), C90, Cl(trans-trans), and Cl(cis-trans) was determined using linear regression.

Results

Cholinesterase activity, IR90, and C90 did not vary with age. Both Cl(trans-trans) (r2 = 0.19, P = 0.01) and Cl(cis-trans) (r2 = 0.19, P = 0.02) decreased with age.

Conclusion

Clearance of mivacurium's potent isomers is larger in younger patients, consistent with the larger mivacurium infusion requirement in children than in adults reported previously.
Effects of Neuromuscular Blocking Agents on Excitatory Transmission and γ-Aminobutyric Acid-A-mediated Inhibition in the Rat Hippocampal Slice
Authors: Chiodini Florence C. , Tassonyi Edomer , Fuchs-Buder Thomas , Fathi Marc , Bertrand Daniel , Muller Dominique
Published: November 2003

Background

Although neuromuscular blocking agents do not cross the blood-brain barrier, they may penetrate the central nervous system under particular circumstances and eventually cause neurotoxic consequences.

Methods

The effects of neuromuscular blocking agents on excitatory and inhibitory transmission in area CA1 of rat hippocampal slices were investigated using extracellular and intracellular recording techniques.

Results

Application of atracurium in the perfusion medium resulted in a dose-dependent enhancement of excitatory synaptic responses averaging 48.7 +/- 4.3% at a concentration of 10 nM. This effect was correlated with an increase in the size of the presynaptic fiber volley. Laudanosine, but not pancuronium bromide or vecuronium bromide, produced similar changes. In addition, atracurium and laudanosine blocked inhibitory transmission and reduced intracellularly recorded gamma-aminobutyric acidA receptor-mediated potentials. These effects were observed only at concentrations >1 microM and were not reproduced by pancuronium bromide and vecuronium bromide.

Conclusions

Atracurium and its metabolite, laudanosine, contrary to pancuronium bromide and vecuronium bromide, produce two distinct effects on hippocampal slices. They enhance excitatory transmission and neuronal excitability and they block inhibitory gamma-aminobutyric acidA-mediated synaptic responses.
Induction of Cyclooxygenase-2 in Alveolar Macrophages after Acid Aspiration
Authors: Ohara Maria , Sawa Teiji , Kurahashi Kiyoyasu , Wiener-Kronish Jeanine P. , Doshi Vatsal , Kudoh Ichidai , Gropper Michael A.
Published: November 2003

Background

Gastric acid aspiration can result in acute lung injury. In this study, the authors determined whether alveolar macrophages express cyclooxygenase-2 as a source of inflammatory mediators after acid aspiration.

Methods

Seventy-five microliters of hydrochloric acid solution, pH 1.15, was instilled into one lung in mice. After exposure, alveolar macrophages were harvested, and competitive polymerase chain reaction and enzyme-linked immunosorbent assay were performed to measure expression of cyclooxygenase-1 and -2, interleukin-1beta and -6, tumor necrosis factor-alpha, and inducible nitric oxide synthase (iNOS). The authors used immunocytochemistry to demonstrate expression of cyclooxygenase-2 in alveolar macrophages. Selective cyclooxygenase-2 blockade using N-2(-cyclohexyloxy-4-nitrophenyl) methane-sulphonamide was done to characterize prostaglandin-cytokine interaction.

Results

Acid aspiration induced upregulation of cyclooxygenase-2 and interleukin-6. Tumor necrosis factor-alpha and iNOS were not upregulated. Interleukin-1beta was upregulated even with saline instillation but could not be detected in the supernatant of the cell culture. Alveolar macrophages harvested from mice instilled with acid showed a trend toward more production of prostaglandin E2 and produced higher concentrations of interleukin-6 compared with alveolar macrophages from mice instilled with saline. Selective cyclooxygenase-2 blockade significantly decreased release of interleukin-6 from alveolar macrophages harvested from mice instilled with acid.

Conclusions

Acid aspiration induces strong expression of cyclooxygenase-2 and production of interleukin-6 in alveolar macrophages. Selective cyclooxygenase-2 blockade reduced production of interleukin-6 by acid-stimulated alveolar macrophages. These studies suggest that the induction of cyclooxygenase-2 plays an important role in the systemic inflammatory response induced by acid aspiration.
Effect of Differential Delivery of Isoflurane to Head and Torso on Lumbar Dorsal Horn Activity
Authors: Antognini Joseph F. , Carstens Earl , Tabo Etsuo , Buzin Viktor
Published: November 2003

Background

The spinal cord appears to be the site where anesthetic agents prevent movement in response to noxious stimuli. When isoflurane is differentially delivered to the head and torso (with low torso concentrations), cranial anesthetic requirements increase compared with systemic administration. The aim of the current study was to test the hypothesis that isoflurane action in the brain has descending influences on spinal cord dorsal horn neurons. A secondary aim was to determine the association, if any, of high cranial concentrations of isoflurane (>6%) with dorsal horn activity.

Methods

Ten goats were anesthetized with isoflurane and the carotid arteries and jugular veins isolated and cannulated for cerebral bypass. A laminectomy was performed for recording from single lumbar dorsal horn neurons with hind limb mechanical receptive fields (one cell per goat). A standard noxious mechanical stimulus was applied to the dew claw or hoof bulb during a control period with end-tidal isoflurane at 1.3% and during bypass with the following head/torso isoflurane concentrations: 1.3%/1.3%, 3.2%/1.3%, 9.4%/1.3%, 1.3%/0.2%, 3.0%/0.2% and 8.8%/0.3%.

Results

When torso isoflurane concentration was 1.3%, increasing cranial isoflurane concentration to 3% or 9% had no significant effect on the activity of dorsal horn units. When torso isoflurane was 0.2-0.3%, spontaneous activity increased; however, at these torso concentrations, evoked responses were significantly decreased (-60%) only when cranial isoflurane concentration was increased to 9%.

Conclusions

Isoflurane action in the brain had an inhibitory effect on dorsal horn activity with the combination of supraclinical cranial and low torso concentrations.
Pretreatment or Resuscitation with a Lipid Infusion Shifts the Dose-Response to Bupivacaine-induced Asystole in Rats
Authors: Weinberg Guy L. , VadeBoncouer Timothy , Ramaraju Gopal A. , Garcia-Amaro Marcelo F. , Cwik Michael J.
Published: November 2003

Background

The authors sought to confirm a chance observation that intravenous lipid treatment increases the dose of bupivacaine required to produce asystole in rats. The authors also measured the partitioning of bupivacaine between the lipid and aqueous phases of a plasma-lipid emulsion mixture.

Methods

Anesthetized Sprague-Dawley rats were used in pretreatment (protocol 1) and resuscitation (protocol 2) experiments. In protocol 1, animals were pretreated with saline or 10%, 20%, or 30% Intralipid (n = 6 for all groups), then received 0.75% bupivacaine hydrochloride at a rate of 10 ml x kg x min(-1) to asystole. In protocol 2, mortality was compared over a range of bolus doses of bupivacaine after resuscitation with either saline or 30% Intralipid (n = 6 for all groups). The lipid:aqueous partitioning of bupivacaine in a mixture of plasma and Intralipid was measured using radiolabeled bupivacaine.

Results

Median doses of bupivacaine (in milligrams per kilogram) producing asystole in protocol 1 were for 17.7 for saline, 27.6 for 10% Intralipid, 49.7 for 20% Intralipid, and 82.0 for 30% Intralipid (P < 0.001 for differences between all groups). Differences in mean +/- SE concentrations of bupivacaine in plasma (in micrograms per milliliter) were significant (P < 0.05) for the difference between saline (93.3 +/- 7.6) and 30% Intralipid (212 +/- 45). In protocol 2, lipid infusion increased the dose of bupivacaine required to cause death in 50% of animals by 48%, from 12.5 to 18.5 mg/kg. The mean lipid:aqueous ratio of concentrations of bupivacaine in a plasma-Intralipid mixture was 11.9 +/- 1.77 (n = 3).

Conclusions

Lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Partitioning of bupivacaine into the newly created lipid phase may partially explain this effect. These results suggest a potential application for lipid infusion in treating cardiotoxicity resulting from bupivacaine.
Effects of Halothane on the Sarcoplasmic Reticulum Ca2+Stores and Contractile Proteins in Rabbit Pulmonary Arteries
Authors: Su Judy Y. , Tang Luo-Jia
Published: November 2003

Background

The authors' purpose of this study was to elucidate the mechanisms of direct effects of halothane on the contractile proteins and Ca2+ release from the sarcoplasmic reticulum Ca2+ stores using isolated skinned strips (sarcolemma permealized with saponin) from rabbit pulmonary arteries.

Methods

The sarcoplasmic reticular Ca2+ stores were examined by immersing the skinned strips sequentially in solutions to load Ca2+ into and release Ca2+ from the sarcoplasmic reticulum using caffeine, inositol 1,4,5-trisphosphate, or halothane. The contractile proteins were assessed by activating the strips with Ca2+ followed by administration of halothane (with or without protein kinase C inhibitors). Tension, fura-2 fluorescence activated by Ca2+ release, and phosphorylation of myosin light chains were measured.

Results

Halothane (0.07-3.00%) increased Ca2+, tension, and phosphorylation of myosin light chains in a dose-dependent manner. Halothane decreased accumulation of Ca2+ in the sarcoplasmic reticulum and enhanced the caffeine-induced tension transients. In strips pretreated with caffeine or inositol 1,4,5-trisphosphate, halothane-induced tension transients were reduced but Ca2+ was not. In strips activated by 1 microM Ca2+, halothane (0.5-3.0%) decreased 20-45% of the activated force at 15 min. Halothane (3%) transiently increased the force (20%) associated with increases in Ca2+ and phosphorylation of myosin light chains. The increased force was abolished and the subsequent relaxation was enhanced by the protein kinase C inhibitor bisindolylmaleimide but not by indolocarbazole Gö-6976.

Conclusions

In skinned pulmonary arterial strips, halothane, at clinical concentrations, inhibits uptake of Ca2+ by and induces release of Ca2+ from intracellular stores possibly shared by caffeine and inositol 1,4,5-trisphosphate, which are regulated by phosphorylation of myosin light chains. The time-dependent inhibition of the contractile proteins by halothane may be mediated by Ca2+-independent protein kinase C.
Profound Increase in Epinephrine Concentration in Plasma and Cardiovascular Stimulation after [micro sign]-Opioid Receptor Blockade in Opioid-addicted Patients during Barbiturate-induced Anesthesia for Acute Detoxification
Authors: Kienbaum Peter , Thurauf Norbert , Michel Martin C. , Scherbaum Norbert , Gastpar Markus , Peters Jurgen
Published: November 2003

Background

Acute displacement of opioids from their receptors by administration of large doses of opioid antagonists during general anesthesia is a new approach for detoxification of patients addicted to opioids. The authors tested the hypothesis that mu-opioid receptor blockade by naloxone induces cardiovascular stimulation mediated by the sympathoadrenal system.

Methods

Heart rate, cardiac index, and intravascular pressures were measured in 10 patients addicted to opioids (drug history; mean +/- SD, 71 +/- 51 months) during a program of methadone substitution (96 +/- 57 mg/day). Cardiovascular variables and concentrations of catecholamine in plasma were measured in the awake state, during methohexital-induced anesthesia (dose, 74 +/- 44 microg x kg(-1) x min(-1)) before administration of naloxone, and repeatedly during the first 3 h of mu-opioid receptor blockade. Naloxone was administered initially in an intravenous dose of 0.4 mg, followed by incremental bolus doses (0.8, 1.6, 3.2, and 6.4 mg) at 15-min intervals until a total dose of 12.4 mg had been administered within 60 min; administration was then continued by infusion (0.8 mg/h).

Results

Concentration of epinephrine in plasma increased 30-fold (15 +/- 9 to 458 +/- 304 pg/ml), whereas concentration of norepinephrine in plasma only increased to a minor extent (76 +/- 44 to 226 +/- 58 pg/ml, P < 0.05). Cardiac index increased by 74% (2.7 +/- 0.41 to 4.7 +/- 1.7 min(-1) x m(-2)), because of increases in heart rate (89 +/- 16 to 108 +/- 17 beats/min) and stroke volume (+44%), reaching maximum 45 min after the initial injection of naloxone. In parallel, systemic vascular resistance index decreased (-40%). Systolic arterial pressure significantly increased (113 +/- 16 to 138 +/- 16 mmHg), whereas diastolic arterial pressure did not change.

Conclusions

Despite barbiturate-induced anesthesia, acute mu-opioid receptor blockade in patients addicted to opioids induces profound epinephrine release and cardiovascular stimulation. These data suggest that long-term opioid receptor stimulation changes sympathoadrenal and cardiovascular function, which is acutely unmasked by mu-opioid receptor blockade. Because of the attendant cardiovascular stimulation, acute detoxification using naloxone should be performed by trained anesthesiologists or intensivists.
Comparison of the Effect of Etomidate and Desflurane on Brain Tissue Gases and pH during Prolonged Middle Cerebral Artery Occlusion
Authors: Hoffman William E. , Charbel Fady T. , Edelman Guy , Misra Mukesh , Ausman James I.
Published: November 2003

Background

The authors compared the effects of etomidate and desflurane on brain tissue oxygen pressure (PO2), carbon dioxide pressure (PCO2), and pH in patients who had middle cerebral artery occlusion for > 15 min.

Methods

After a craniotomy, a probe that measures PO2, PCO2, and pH was inserted into cortical tissue at risk for ischemia during middle cerebral artery occlusion. A burst suppression pattern of the electroencephalogram was induced with etomidate (n = 6) or 9% end-tidal desflurane (n = 6) started before middle cerebral artery occlusion. Mean blood pressure was supported with phenylephrine to 90-95 mmHg.

Results

During baseline conditions, tissue PO2, PCO2, and pH were similar between the two groups (PO2 = 15 mmHg, PCO2 = 60 mmHg, pH = 7.1). During administration of etomidate before middle cerebral artery occlusion, tissue PO2 decreased in five of six patients without a change in PCO2 or pH. During administration of 9% desflurane, tissue PO2 and pH increased before middle cerebral artery clipping. Middle cerebral artery occlusion for an average of 33 min with etomidate and 37 min with desflurane produced a decrease in pH with etomidate (7.09 to 6.63, P < 0.05) but not with desflurane (7.12 to 7.15).

Conclusion

These results suggest that tissue hypoxia and acidosis are often observed during etomidate treatment and middle cerebral artery occlusion. Treatment with desflurane significantly increases tissue PO2 alone and attenuates acidotic changes to prolonged middle cerebral artery occlusion.
The Glottic Aperture Seal Airway
Authors: Benumof Jonathan L.
Published: November 2003

Background

None of the presently used airway devices are ideal regarding ease of insertion, alignment with the laryngeal inlet, and provision of a high-pressure seal from the environment. The purpose of this study was to determine, in awake volunteers, the performance of a new ventilatory device, the glottic aperture seal airway, regarding ease of insertion, alignment with the laryngeal inlet, and forced exhalation seal pressure (PFES).

Methods

The glottic aperture seal airway consists of a curved tubular component that ends in the middle of an elliptical foam cushion glottic component. The posterior surface of the foam has a curved flexible plastic backing, which imparts a 60 degree angle between the proximal half and the distal half of the foam cushion. When the glottic aperture seal airway is properly in situ in a supine patient, the proximal half of the foam cushion is opposite the laryngeal inlet. The posterior surface of the plastic backing has a balloon attached to it. Inflation of the balloon presses the ventilation hole and foam cushion up against the laryngeal inlet, thereby creating a seal from the environment. Using the laryngeal mask airway as a control device, the glottic aperture seal airway was tested for time and ease of insertion, fiberoptic alignment with the laryngeal inlet, and PFES in 18 lightly sedated and locally anesthetized volunteers.

Results

The glottic aperture seal and laryngeal mask airways were inserted with equal ease and speed. The fiberoptic alignment with the larynx was excellent for both the glottic aperture seal and laryngeal mask airways. In all volunteers, the mean +/- SD PFES values at 0-, 10-, 20-, 30-, and 40-ml balloon inflation volumes of the glottic aperture seal airway were 23.4 +/- 11.8, 29.6 +/- 12.4, 42.7 +/- 12.5, 56.9 +/- 5.6, and 60 +/- 0 cm H2O, respectively; the PFES at > or = 20 ml balloon inflation volume of the glottic aperture seal airway was significantly greater than with the laryngeal mask airway (19.4 +/- 6.7 cm H2O, P < 0.01). A PFES of > or =60 cm H2O was achieved with the glottic aperture seal airway in all volunteers (n = 2 at 10 ml, n = 3 at 20 ml, n = 9 at 30 ml, and n = 4 at 40 ml). The glottic aperture seal airway did not cause any trauma.

Conclusion

In awake volunteers, the glottic aperture seal and laryngeal mask airways were equally easy to insert and position. The glottic aperture seal airway was capable of achieving a higher PFES than the laryngeal mask airway.
Nitric Oxide Synthase Inhibitors Alter Ventilation in Isoflurane Anesthetized Rats
Authors: Patel Gaurav M. , Horstman Damian J. , Adams Milton J. , Rich George F.
Published: November 2003

Background

Nitric oxide (NO) is present in medullary structures and can modulate respiratory rhythm. The authors determined if spontaneous ventilation at rest and in response to increased carbon dioxide is altered by selective neuronal NO synthase (NOS; 7-nitro-indazole, 7-NI) or nonselective (neuronal plus endothelial) NOS (NG-L-arginine methyl ester [L-NAME] and NG-monomethyl L-arginine [L-NMMA]) inhibitors in rats anesthetized with isoflurane.

Methods

Fifty-four rats received either L-NAME or L-NMMA (1, 10, and 30 mg/kg) or 7-NI (20, 80, and 400 mg/kg) and were compared with time controls (isoflurane = 1.4%), with isoflurane concentrations (1.6%, 1.8%, and 2%) increased consistent with the increased anesthetic depth caused by NOS inhibitors, or with L-arginine (300 mg/kg). Tidal volume (VT), respiratory frequency (f), minute ventilation (VE), and ventilatory responses to increasing carbon dioxide were determined.

Results

L-NAME and L-NMMA decreased resting VT and VE, whereas 7-NI had no effect. Increasing concentrations of isoflurane decreased resting f, VT, and VE. L-NAME and L-NMMA decreased VT and VE, whereas 7-NI had no effect at 8%, 9%, and 10% end-tidal carbon dioxide (ETCO2). Increasing concentrations of isoflurane decreased f, VT, and VE at 8%, 9%, and 10% ETCO2. The slope of VE versus ETCO2 was decreased by isoflurane but was unaffected by L-NAME, L-NMMA, or 7-NI. L-arginine alone had no effect on ventilation.

Conclusions

Nonselective NOS inhibitors decreased VT and VE at rest and at increased carbon dioxide levels but did not alter the slope of the carbon dioxide response. Selective neuronal NOS inhibition had no effect, suggesting that endothelial NOS may be the isoform responsible for altering ventilation. Finally, the cause of the decreased ventilation is not a result of the enhanced anesthetic depth caused by NOS inhibitors.
Acetylcholinesterase and Butyrylcholinesterase Are Expressed in the Spinal Meninges of Monkeys and Pigs
Authors: Ummenhofer Wolfgang C. , Brown Sean M. , Bernards Christopher M.
Published: November 2003

Background

Acetylcholinesterase inhibition at the spinal level has been shown to produce a potent antinociceptive effect. However, the site of cholinesterase inhibition is unknown. To determine whether the spinal meninges participate in acetylcholine metabolism, the spinal meninges of monkeys and pigs were assayed for cholinesterase activity.

Methods

Spinal cord, dura mater, and arachnoid mater specimens from anesthetized pigs and monkeys were mechanically homogenized and cholinesterase activity was determined quantitatively using a commercially available colorimetric assay. The ability of neostigmine to inhibit cholinesterase activity in vitro was also measured. Finally, the reverse transcriptase polymerase chain reaction (RT-PCR) was used to identify the cholinesterase metabolizing enzymes expressed by the spinal meninges.

Results

All spinal cord and meningeal specimens showed cholinesterase activity. In pigs, the dura mater showed less enzyme activity (36 +/- 17.7 U/mg protein) than the arachnoid mater (73.4 +/- 30.3 U/mg protein; P < 0.05), and the arachnoid mater showed less activity than the spinal cord (131.3 +/- 55.2 U/mg protein; P < 0.05). In monkeys, the dura mater again showed less cholinesterase activity (45.8 +/- 20.1 U/mg protein; P < 0.05), whereas cholinesterase activity in the arachnoid mater (90.3 +/- 45.9 U/mg protein) and spinal cord specimens (101.9 +/- 37.5 U/mg protein) were not significantly different. There were no significant species-related differences in cholinesterase activity. Neostigmine inhibited cholinesterase activity in a log-dose-dependent manner. The RT-PCR identified mRNA for acetylcholinesterase and butyrylcholinesterase in monkey pia-arachnoid mater.

Conclusions

These data show that the spinal meninges express acetylcholinesterase and butyrylcholinesterase; for monkeys, although not pigs, the level of cholinesterase activity is comparable with that found in the spinal cord. This finding suggests that the meninges may be an important site for acetylcholine metabolism and may play a role in the analgesic effect produced by intrathecally administered cholinesterase inhibitors.
Intravenous Lidocaine Attenuates Acute Lung Injury Induced by Hydrochloric Acid Aspiration in Rabbits
Authors: Nishina Kahoru , Mikawa Katsuya , Takao Yumiko , Shiga Makoto , Maekawa Nobuhiro , Obara Hidefumi
Published: November 2003

Background

Neutrophils play a crucial role in the pathogenesis of acid-induced acute lung injury. Lidocaine inhibits the function of neutrophils. This study aimed to determine whether lidocaine attenuates acute lung injury induced by hydrochloric acid (HCl) instillation.

Methods

In study 1, rabbits were divided into four groups (n = 7 each). Lung injury was induced by intratracheal HCl (0.1 N, 3 ml/kg) in two groups. The other two groups received saline intratracheally. Lidocaine given intravenously (2 mg/ g bolus + 2 mg x kg(-1) x h(-1) infusion) was started 10 min before intratracheal instillation in one HCl and one saline group, and saline was given intravenously in the other two groups. In study 2, rabbits (four groups of seven animals each) received HCl (0.1 N, 3 ml/kg) intratracheally. Treatment with intravenous lidocaine was started 10 min before, 10 min after, or 30 min after acid instillation, or saline was given intravenously 10 min before instillation.

Results

In study 1, HCl caused deterioration of the partial pressure of oxygen (PaO2), lung leukosequestration, decreased lung compliance, and increased the lung wet-to-dry weight ratio and albumin, interleukin-6 (IL-6), and IL-8 levels in bronchoalveolar lavage fluid. Lidocaine pretreatment attenuated these changes. Hydrochloric acid increased superoxide anion production by neutrophils and caused morphologic lung damage, both of which were lessened by lidocaine. In study 2, lidocaine given 10 min after acid instillation was as effective as pretreatment in PaO2, lung mechanics, and histologic examination. However, PaO2 changes in lidocaine 30 min after injury were similar to those in saline given intravenously.

Conclusions

Intravenous lidocaine started before and immediately after acid instillation attenuated the acute lung injury, in part by inhibiting the sequestration and activation of neutrophils.
Ketorolac and Enoxaparin Affect Arterial Thrombosis and Bleeding in the Rabbit
Authors: Delaporte-Cerceau Sonia , Samama Charles-Marc , Riou Bruno , Bonnin Philippe , Guillosson Jean-Jacques , Coriat Pierre
Published: November 2003

Background

Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with hemostasis during the perioperative period, and the combination of NSAID and enoxaparin could increase this effect. The aim of this prospective, blinded experimental study was to assess these effects using a model of arterial thrombosis and bleeding in the rabbit.

Methods

After anesthesia was induced and monitors placed, the common carotid arteries were exposed, and 60% stenosis of the right common carotid artery was produced. Twenty minutes later, a compression injury of the artery was produced that triggered a series of cyclic episodes of thrombosis and clot lysis. This was manifested as cyclic flow reductions (CFR; measured with an electromagnetic flow meter). After the first flow reduction was noted, the rabbits were immediately and randomly assigned to one of four groups (n = 10 each) that received intravenous infusions: control, ketorolac (2 mg/kg), enoxaparin (0.5 mg/kg), and ketorolac plus enoxaparin (2 mg/kg and 0.5 mg/kg, respectively). The number of CFRs that occurred in the subsequent 20-min period was used as a measure of treatment effect. The contralateral common carotid artery was exposed, and both stenosis and injury were produced. The ability of the administered drug to prevent thrombosis was assessed as the number of CFRs that occurred during the first 20-min period after vessel injury. In addition, both before and after group assignment and drug injection, bleeding times were noted and a platelet aggregation test was performed. Laparotomy was followed by a spleen section, and the extent of the wound and the amount of splenic bleeding were measured.

Results

The treatment effect was indicated by the median number of CFRs, which was 5.5 in the control group, 1 in the ketorolac group, 2 in the enoxaparin group, and 0 in the ketorolac + enoxaparin group. The prevention effect was indicated by the median number of CFRs, which was 4 in the control group, 0 in the ketorolac group, 2 in the enoxaparin group, and 0.5 in the ketorolac + enoxaparin group. Bleeding time was significantly lengthened in the enoxaparin and in the ketorolac + enoxaparin groups. Splenic and wound bleeding was greater in the ketorolac group. Platelet aggregation was completely inhibited in the ketorolac and the ketorolac + enoxaparin groups.

Conclusions

Ketorolac had an important antithrombotic activity. The association of enoxaparin with ketorolac seemed to lengthen the bleeding time observed with ketorolac.
A Method to Compare Costs of Drugs and Supplies among Anesthesia Providers
Authors: Dexter Franklin , Lubarsky David A. , Gilbert Bill C. , Thompson Christine
Published: November 2003

Background

Comparison of costs among anesthesia providers using "cost per case" does not adjust for variations in casemix (such as the type of procedure and patient condition). The authors propose an alternative method for comparing costs using the American Society of Anesthesiologists' Relative Value Scale (ASARVS) system, which incorporates basic units (for the procedure), modifier units (for the patient's physical condition), "other" units (such as for the placement of invasive monitors), and time units (proportional to the case duration).

Methods

Data were obtained from a series of 3,340 anesthetics performed at a tertiary hospital. Administered and discarded drug, supply, and fluid costs were used.

Results

Costs expressed as dollars per ASARVS unit had 54% less variability than costs expressed as dollars per case (P < 0.0001). Pearson correlations between demographic variables and cost per ASARVS unit ranged from -0.10 to 0.13. Total (e.g., quarterly) costs for simulated sets of cases were predicted within 0.0 +/- 2.3% by multiplying (1) their sum of units and (2) a like set of case's sum of costs divided by sum of units.

Conclusions

Costs of anesthetic supplies and drugs of a case were more accurately reported as "cost per unit" than as "cost per case." This method of calculating the cost of anesthetic drugs and supplies has several applications, including (1) comparison of costs among anesthesia providers and (2) benchmarking costs among hospitals and anesthesia groups. By design, anesthesia providers' time is quantified by their ASARVS units. Together anesthesia costs (personnel, supplies, and drugs) are better reported as "cost per unit" than as "cost per case."
Perioperative Cost-finding Analysis of the Routine Use of Intraoperative Forced-air Warming during General Anesthesia
Authors: Fleisher Lee A. , Metzger Scott E. , Lam Janet , Harris Andrew
Published: November 2003

Background

Despite the well-documented ability of forced-air warming (FAW) to maintain normothermia, it is unclear whether this technique results in a net increase or decrease in costs. The authors did a prospective cost-finding study comparing FAW with routine thermal care in patients at low risk for perioperative complications who were undergoing general anesthesia.

Methods

After institutional review board approval was received, 100 patients were studied who were having elective surgery scheduled for more than 2 h during general endotracheal anesthesia. Patients were randomly assigned to one of two groups: FAW or routine thermal care. All patients received a standardized anesthetic. Anesthesia providers were blinded to core temperatures and the use of FAW. Primary outcomes were those associated with perioperative costs.

Results

The time from completion of surgical dressing until tracheal extubation was significantly reduced in the FAW group (10 +/- 1 min compared with 14 +/- 1 min; mean +/- SEM; P < 0.01). There was no demonstrable difference in attainment of postanesthesia care unit discharge criteria between the two groups, although the FAW group used one less cotton blanket there. The net savings related to the use of the FAW depends on the percentage of the intraoperative costs that are fixed rather than variable ($15 additional for FAW if all costs are fixed compared with $29 savings if all costs were variable).

Conclusions

Routine intraoperative FAW significantly reduced time until extubation and use of cotton blankets in the postanesthesia care unit. These results suggest that the influence of FAW on net total perioperative costs depends on patient and surgical characteristics and institutional factors related to cost accounting.
Do Shorter-acting Neuromuscular Blocking Drugs or Opioids Associate with Reduced Intensive Care Unit or Hospital Lengths of Stay after Coronary Artery Bypass Grafting?
Authors: Butterworth John , James Robert , Prielipp Richard C. , Cerese Julie , Livingston Jean , Burnett David A.
Published: November 2003

Background

The authors hypothesized that shorter-acting opioid and neuromuscular blocking drugs would be associated with reductions in duration of intubation, length of stay (LOS) in the intensive care unit (ICU) after tracheal extubation, or postoperative (exclusive of ICU) LOS, and that shorter durations of intubation would be associated with reduced ICU LOS after extubation and postoperative (exclusive of ICU) LOS.

Methods

One-thousand ninety-four patients undergoing primary coronary artery bypass graft surgery at 40 academic health centers were studied. Multiple patient-related factors were included in multivariate models for hypothesis testing.

Results

The duration of tracheal intubation, ICU LOS after extubation, and postoperative (exclusive of ICU) LOS all varied significantly by site. There was no difference between vecuronium and pancuronium in duration of intubation, ICU LOS after extubation, or postoperative (exclusive of ICU) LOS. Use of sufentanil rather than fentanyl was associated with a significant (P=0.045) reduction of 1.9 h (95% CI, 0.04 to 4.1 h) in duration of tracheal intubation but had no significant effect on ICU LOS after extubation, total ICU LOS, postoperative (exclusive of ICU) LOS, or total postoperative LOS. The authors' best model predicts a complex association between increasing duration of intubation and both ICU LOS after tracheal extubation and postoperative (exclusive of ICU) LOS, which was associated with an increase in those measures when duration of intubation exceeded 7.3 or 3 h, respectively.

Conclusions

The LOS measures varied considerably among the institutions. Use of shorter-acting opioid and neuromuscular blocking drugs had no association with ICU LOS after tracheal extubation or with postoperative (exclusive of ICU) LOS. Only when the duration of intubation exceeded threshold values was it associated with increased LOS measures.
Early Extubation following Cardiac Surgery in a Veterans Population
Authors: London Martin J. , Shroyer Laurie A. , Coll Joseph R. , MaWhinney Samantha , Fullerton David A. , Hammermeister Karl E. , Grover Frederick L.
Published: November 2003

Background

Early tracheal extubation is an important component of the "fast track" cardiac surgery pathway. Factors associated with time to extubation in the Department of Veterans Affairs (DVA) population are unknown. The authors determined associations of preoperative risk and intraoperative clinical process variables with time to extubation in this population.

Methods

Three hundred four consecutive patients undergoing coronary artery bypass graft, valve surgery, or both on a fast track clinical pathway between October 1, 1993 and September 30, 1995 at a university-affiliated DVA medical center were studied retrospectively. After univariate screening of a battery of preoperative risk and intraoperative clinical process variables, stepwise logistic regression was used to determine associations with tracheal extubation < or = 10 h (early) or > 10 h (late) after surgery. Postoperative lengths of stay, complications, and 30-day and 6-month mortality rates were compared between the two groups.

Results

One hundred forty-six patients (48.3%) were extubated early; one patient required emergent reintubation (0.7%). Of the preoperative risk variables considered, only age (odds ratio, 1.80 per 10-yr increment) and preoperative intraaortic balloon pump (odds ratio, 7.88) were multivariately associated with time to extubation (model R) ("late" association is indicated by an odds ratio >1.00; "early" association is indicated by an odds ratio <1.00). Entry of these risk variables into a second regression model, followed by univariately significant intraoperative clinical process variables, yielded the following associations (model R-P): age (odds ratio, 1.86 per 10-yr increment), sufentanil dose (odds ratio, 1.54 per 1-microg/kg increment), major inotrope use (odds ratio, 5.73), platelet transfusion (odds ratio, 10.03), use of an arterial graft (odds ratio, 0.32), and fentanyl dose (odds ratio, 1.45 per 10-microg/kg increment). Time of arrival in the intensive care unit after surgery was also significant (odds ratio, 1.42 per 1-h increment). Intraoperative clinical process variables added significantly to model performance (P < 0.001 by the likelihood ratio test).

Conclusions

In this population, early tracheal extubation was accomplished in 48% of patients. Intraoperative clinical process variables are important factors to be considered in the timing of postoperative extubation after fast track cardiac surgery.
Prophylactic Angiotensin II Infusion during Spinal Anesthesia for Elective Cesarean Delivery
Authors: Vincent Robert D. , Werhan Carol F. , Norman Patricia F. , Shih Grace H. , Chestnut David H. , Ray Tapati , Ross Elaine L. , Bofill James A. , Shaw Douglas B.
Published: November 2003

Background

Angiotensin II may prove useful in treating regional anesthesia-induced hypotension in obstetric patients, because it causes less uterine vasoconstriction than do other vasoconstrictor drugs (such as phenylephrine). This study compared (1) maternal blood pressure and heart rate and (2) fetal status at delivery in parturients given either prophylactic angiotensin II or ephedrine infusion during spinal anesthesia for elective cesarean delivery.

Methods

Fifty-four women were randomized to receive either angiotensin II or ephedrine infusion intravenously during spinal anesthesia for elective cesarean section delivery. Simultaneous with subarachnoid injection, infusion of angiotensin II (2.5 microg/ml) or ephedrine (5 mg/ml) was initiated at 10 ng x kg(-1) x min(-1) and 50 microg x kg(-1) x min(-1), respectively. The rate of each infusion was adjusted to maintain maternal systolic blood pressure at 90-100% of baseline.

Results

Cumulative vasopressor doses (mean+/-SD) through 10, 20, and 30 min were 150+/-100, 310+/-180, and 500+/-320 ng/kg in the angiotensin group and 480+/-210, 660+/-390, and 790+/-640 microg/kg in the ephedrine group. Maternal heart rate was significantly higher (P < 0.001) during vasopressor infusion in the ephedrine group than in the angiotensin group. Umbilical arterial and venous blood pH and base excess were all significantly higher (P < 0.05) in the angiotensin group than in the ephedrine group.

Conclusions

Angiotensin II infusion maintained maternal systolic blood pressure during spinal anesthesia without increasing maternal heart rate or causing fetal acidosis.
Causes and Prediction of Maldistribution during Continuous Spinal Anesthesia with Isobaric or Hyperbaric Bupivacaine
Authors: Biboulet Philippe , Capdevila Xavier , Aubas Pierre , Rubenovitch Josh , Deschodt Jacques , d'Athis Francoise
Published: November 2003

Background

Many cases of cauda equina syndrome after maldistribution of local anesthetics during continuous spinal anesthesia have been reported. In experiments, a caudad route of catheter travel and the use of hyperbaric agents have been shown to induce these limited blocks. The aim of this clinical study was to verify this hypothesis and seek a predictive factor for the maldistribution of bupivacaine.

Method

Continuous spinal anesthesia via a 19-gauge end port spinal catheter was performed in 80 elderly patients randomly assigned to receive either isobaric or hyperbaric solutions. Successive injections of 2.5 mg bupivacaine were performed at 5-min intervals until a sensory level at or cranial to T8 was obtained. Maldistribution was defined by a sensory level caudal to T12 despite a total dose of 17.5 mg of either isobaric or hyperbaric bupivacaine. After surgery, all catheters were injected with contrast media and examined radiographically.

Results

The frequency of maldistribution was not significantly different in the isobaric and hyperbaric groups. A caudally oriented catheter tip was found to be a major cause of maldistribution (P < 10(-5)). A thoracic sensory level could be reached in all patients presenting a limited block by simply changing the baricity of the bupivacaine, the position of the patient, or both. The sensory level obtained 10 min after the first injection of 2.5 mg isobaric or hyperbaric bupivacaine was found to be a predictive factor of maldistribution.

Conclusions

Hyperbaric solutions do not appear to be a clinical factor in the development of limited block. The principle factor causing the maldistribution of bupivacaine is the caudal orientation of the tip of the end-hole catheter rather than its level or the route of catheter travel.