bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pharmacodynamic Effect of a Remifentanil Bolus on Ventilatory Control
Authors: Babenco H. Daniel , Conard Pattilyn F. , Gross Jeffrey B.
Published: November 2003

Background

In doses typically administered during conscious sedation, remifentanil may be associated with ventilatory depression. However, the time course of ventilatory depression after an initial dose of remifentanil has not been determined previously.

Methods

In eight healthy volunteers, the authors determined the time course of the ventilatory response to carbon dioxide using the dual isohypercapnic technique. Subjects breathed via mask from a to-and-fro circuit with variable carbon dioxide absorption, allowing the authors to maintain end-tidal pressure of carbon dioxide (PET(CO2)) at approximately 46 or 56 mm Hg (alternate subjects). After 6 min of equilibration, subjects received 0.5 microg/kg remifentanil over 5 s, and minute ventilation (V(E)) was recorded during the next 20 min. Two hours later, the study was repeated using the other carbon dioxide tension (56 or 46 mm Hg). The V(E) data were used to construct two-point carbon dioxide response curves at 30-s intervals after remifentanil administration. Using published pharmacokinetic values for remifentanil and the method of collapsing hysteresis loops, the authors estimated the effect-site equilibration rate constant (k(eo)), the effect-site concentration producing 50% respiratory depression (EC50), and the shape parameter of the concentration-response curve (gamma).

Results

The slope of the carbon dioxide response decreased from 0.99 [95% confidence limits 0.72 to 1.26] to a nadir of 0.27 l x min(-1) x mm Hg(-1) [-0.12 to 0.66] 2 min after remifentanil (P<0.001); within 5 min, it recovered to approximately 0.6 l x min(-1) x mm Hg(-1), and within 15 min of injection, slope returned to baseline. The computed ventilation at PET = 50 mm Hg (VE50) decreased from 12.9 [9.8 to 15.9] to 6.1 l/min [4.8 to 7.4] 2.5 min after remifentanil injection (P<0.001). This was caused primarily by a decrease in tidal volume rather than in respiratory rate. Estimated pharmacodynamic parameters based on computed mean values of VE50 included k(eo) = 0.24 min(-1) (T1/2 = 2.9 min), EC50 = 1.12 ng/ml, and gamma = 1.74.

Conclusions

After administration of 0.5 microg/kg remifentanil, there was a decrease in slope and downward shift of the carbon dioxide ventilatory response curve. This reached its nadir approximately 2.5 min after injection, consistent with the computed onset half-time of 2.9 min. The onset of respiratory depression appears to be somewhat slower than previously reported for the onset of remifentanil-induced electroencephalographic slowing. Recovery of ventilatory drive after a small dose essentially was complete within 15 min.
Comparison of Plasma Compartment versus Two Methods for Effect Compartment–controlled Target-controlled Infusion for Propofol
Authors: Struys Michel M. R. F. , De Smet Tom , Depoorter Birgit , Versichelen Linda F. M. , Mortier Eric P. , Dumortier Frank J. E. , Shafer Steven L. , Rolly Georges
Published: November 2003

Background

Target-controlled infusion (TCI) systems can control the concentration in the plasma or at the site of drug effect. A TCI system that targets the effect site should be able to accurately predict the time course of drug effect. The authors tested this by comparing the performance of three control algorithms: plasmacontrol TCI versus two algorithms for effect-site control TCI.

Methods

One-hundred twenty healthy women patients received propofol via TCI for 12-min at a target concentration of 5.4 microg/ml. In all three groups, the plasma concentrations were computed using pharmacokinetics previously reported. In group I, the TCI device controlled the plasma concentration. In groups II and III, the TCI device controlled the effect-site concentration. In group II, the effect site was computed using a half-life for plasma effect-site equilibration (t1/2k(eo)) of 3.5 min. In group III, plasma effect-site equilibration rate constant (k(eo)) was computed to yield a time to peak effect of 1.6 min after bolus injection, yielding a t1/2keo of 34 s. the time course of propofol was measured using the bispectral index. Blood pressure, ventilation, and time of loss of consciousness were measured.

Results

The time course of propofol drug effect, as measured by the bispectral index, was best predicted in group III. Targeting the effect-site concentration shortened the time to loss of consciousness compared with the targeting plasma concentration without causing hypotension. The incidence of apnea was less in group III than in group II.

Conclusion

Effect compartment-controlled TCI can be safely applied in clinical practice. A biophase model combining the Marsh kinetics and a time to peak effect of 1.6 min accurately predicted the time course of propofol drug effect.
Critical Oxygen Delivery in Conscious Humans Is Less Than 7.3 ml O2· kg−1· min−1
Authors: Lieberman Jeremy A. , Weiskopf Richard B. , Kelley Scott D. , Feiner John , Noorani Mariam , Leung Jacqueline , Toy Pearl , Viele Maurene
Published: November 2003

Background

The "critical" level of oxygen delivery (DO2) is the value below which DO2 fails to satisfy the metabolic need for oxygen. No prospective data in healthy, conscious humans define this value. The authors reduced DO2 in healthy volunteers in an attempt to determine the critical DO2.

Methods

With Institutional Review Board approval and informed consent, the authors studied eight healthy, conscious volunteers, aged 19-25 yr. Hemodynamic measurements were obtained at steady state before and after profound acute isovolemic hemodilution with 5% albumin and autologous plasma, and again at the reduced hemoglobin concentration after additional reduction of DO2 by an infusion of a beta-adrenergic antagonist, esmolol.

Results

Reduction of hemoglobin from 12.5+/-0.8 g/dl to 4.8+/-0.2 g/dl (mean +/- SD) increased heart rate, stroke volume index, and cardiac index, and reduced DO2 (14.0+/-2.9 to 9.9+/-20 ml O2 x kg(-1) x min(-1); all P<0.001). Oxygen consumption (VO2; 3.0+/-0.5 to 3.4+/-0.6 ml O2 x kg(-1) x min(-1); P<0.05) and plasma lactate concentration (0.50+/-0.10 to 0.62+/-0.16 mM; P<0.05; n = 7) increased slightly. Esmolol decreased heart rate, stroke volume index, and cardiac index, and further decreased DO2 (to 7.3+/-1.4 ml O2 x kg(-1) x min(-1); all P<0.01 vs. before esmolol). VO2 (3.2+/-0.6 ml O2 x kg(-1) x min(-1); P>0.05) and plasma lactate (0.66+/-0.14 mM; P>0.05) did not change further. No value of plasma lactate exceeded the normal range.

Conclusions

A decrease in DO2 to 7.3+/-1.4 ml O2 x kg(-1) min(-1) in resting, healthy, conscious humans does not produce evidence of inadequate systemic oxygenation. The critical DO2 in healthy, resting, conscious humans appears to be less than this value.
Comparison of Intravenous or Epidural Patient-controlled Analgesia in the Elderly after Major Abdominal Surgery
Authors: Mann Claude , Pouzeratte Yvan , Boccara Gilles , Peccoux Christophe , Vergne Christine , Brunat Georges , Domergue Jacques , Millat Bertrand , Colson Pascal
Published: November 2003

Background

Patient-controlled analgesia (PCA) with intravenous morphine and patient-controlled epidural analgesia (PCEA), using an opioid either alone or in combination with a local anesthetic, are two major advances in the management of pain after major surgery. However, these techniques have been evaluated poorly in elderly people. This prospective, randomized study compared the effectiveness on postoperative pain and safety of PCEA and PCA after major abdominal surgery in the elderly patient.

Methods

Seventy patients older than 70 yr of age and undergoing major abdominal surgery were assigned randomly to receive either combined epidural analgesia and general anesthesia followed by postoperative PCEA, using a mixture of 0.125% bupivacaine and sufentanil (PCEA group), or general anesthesia followed by PCA with intravenous morphine (PCA group). Pain intensity was tested three times daily using a visual analog scale. Postoperative evaluation included mental status, cardiorespiratory and gastrointestinal functions, and patient satisfaction scores.

Results

Pain relief was better at rest (P = 0.001) and after coughing (P = 0.002) in the PCEA group during the 5 postoperative days. Satisfaction scores were better in the PCEA group. Although incidence of delirium was comparable in the PCA and PCEA groups (24% vs. 26%, respectively), mental status was improved on the fourth and fifth postoperative days in the PCEA group. The PCEA group recovered bowel function more quickly than did the PCA group. Cardiopulmonary complications were similar in the two groups.

Conclusion

After major abdominal surgery in the elderly patient, patient-controlled analgesia, regardless of the route (epidural or parenteral), is effective. The epidural route using local anesthetics and an opioid provides better pain relief and improves mental status and bowel activity.
Bupivacaine Inhibits Acylcarnitine Exchange in Cardiac Mitochondria
Authors: Weinberg Guy L. , Palmer June W. , VadeBoncouer Timothy R. , Zuechner Mikko B. , Edelman Guy , Hoppel Charles L.
Published: November 2003

Background

The authors previously reported that secondary carnitine deficiency may sensitize the heart to bupivacaine-induced arrhythmias. In this study, the authors tested whether bupivacaine inhibits carnitine metabolism in cardiac mitochondria.

Methods

Rat cardiac interfibrillar mitochondria were prepared using a differential centrifugation technique. Rates of adenosine diphosphate-stimulated (state III) and adenosine diphosphate-limited (state IV) oxygen consumption were measured using a Clark electrode, using lipid or nonlipid substrates with varying concentrations of a local anesthetic.

Results

State III respiration supported by the nonlipid substrate pyruvate (plus malate) is minimally affected by bupivacaine concentrations up to 2 mM. Lower concentrations of bupivacaine inhibited respiration when the available substrates were palmitoylcarnitine or acetylcarnitine; bupivacaine concentration causing 50% reduction in respiration (IC50 +/- SD) was 0.78+/-0.17 mM and 0.37+/-0.03 mM for palmitoylcarnitine and acetylcarnitine, respectively. Respiration was equally inhibited by bupivacaine when the substrates were palmitoylcarnitine alone, or palmitoyl-CoA plus carnitine. Bupivacaine (IC50 = 0.26+/-0.06 mM) and etidocaine (IC50 = 0.30+/-0.12 mM) inhibit carnitine-stimulated pyruvate oxidation similarly, whereas the lidocaine IC50 is greater by a factor of roughly 5, (IC50 = 1.4+/-0.26 mM), and ropivacaine is intermediate, IC50 = 0.5+/-0.28 mM.

Conclusions

Bupivacaine inhibits mitochondrial state III respiration when acylcarnitines are the available substrate. The substrate specificity of this effect rules out bupivacaine inhibition of carnitine palmitoyl transferases I and II, carnitine acetyltransferase, and fatty acid beta-oxidation. The authors hypothesize that differential inhibition of carnitine-stimulated pyruvate oxidation by various local anesthetics supports the clinical relevance of inhibition of carnitine-acylcarnitine translocase by local anesthetics with a cardiotoxic profile.
Changes in Intravascular Volume during Acute Normovolemic Hemodilution and Intraoperative Retransfusion in Patients with Radical Hysterectomy
Authors: Rehm Markus , Orth Victoria , Kreimeier Uwe , Thiel Manfred , Haller Mathias , Brechtelsbauer Heinz , Finsterer Udilo
Published: November 2003

Background

Changes in blood volume during acute normovolemic hemodilution (ANH) and their consequences for the perioperative period have not been investigated sufficiently.

Methods

In 15 patients undergoing radical hysterectomy, preoperative ANH to a hematocrit of 24% was performed using 5% albumin solution. Intraoperatively, saline 0.9% solution was used for volume substitution, and intraoperative retransfusion was started at a hematocrit of 20%. Plasma volume (indocyanine green dilution technique), hematocrit, and plasma protein concentration were measured before and after ANH, before retransfusion, and postoperatively. Red cell volume (labeling erythrocytes with fluorescein) was determined before and after ANH and postoperatively.

Results

Mean normal plasma volumes (1,514 +/- 143 ml/m2) and reduced red cell volumes (707 +/- 79 ml/m2) were measured preoperatively. Blood (1,150 +/- 196 ml) was removed and replaced with 1,333 +/- 204 ml of colloid. Blood volume before and after ANH was equal and amounted to 3,740 ml. Intraoperatively, plasma volume did not increase until retransfusion despite infusing 3,389 +/- 1,021 ml of crystalloid (corrected for urine output) to compensate for an estimated surgical blood loss of 727 +/- 726 mi. Postoperatively, after retransfusion of all autologous blood, blood volume was 255 +/- 424 ml higher than preoperatively before ANH. Despite mean calculated blood loss of 1,256 +/- 892 ml, only one patient received allogeneic blood.

Conclusions

During ANH, normovolemia was exactly maintained. After surgical blood loss of 1,256 +/- 892 ml, crystalloid and colloid supplies of 5,752 +/- 1,462 ml and 1,667 +/- 548 ml, respectively, and complete intraoperative retransfusions of autologous blood in every patient, mean blood volume was 250 ml higher than preoperatively before ANH.
Effect of Ambient Temperature on Human Pain and Temperature Perception
Authors: Strigo Irina A. , Carli Franco , Bushnell M. Catherine
Published: November 2003

Background

Animal studies show reduced nociceptive responses to noxious heat stimuli and increases in endogenous beta-endorphin levels in cold environments, suggesting that human pain perception may be dependent on ambient temperature. However, studies of changes in local skin temperature on human pain perception have yielded variable results. This study examines the effect of both warm and cool ambient temperature on the perception of noxious and innocuous mechanical and thermal stimuli.

Methods

Ten subjects (7 men and 3 women, aged 20-23 yr) used visual analog scales to rate the stimulus intensity, pain intensity, and unpleasantness of thermal (0-50 degrees C) and mechanical (1.2-28.9 g) stimuli applied on the volar forearm with a 1-cm2 contact thermode and von Frey filaments, respectively. Mean skin temperatures were measured throughout the experiment by infrared pyrometer. Each subject was tested in ambient temperatures of 15 degrees C (cool), 25 degrees C (neutral), and 35 degrees C (warm) on separate days, after a 30-min acclimation to the environment. Studies began in the morning after an 8-h fast.

Results

Mean skin temperature was altered by ambient temperature (cool room: 30.1 degrees C; neutral room: 33.4 degrees C; warm room: 34.5 degrees C; P < 0.0001). Ambient temperature affected both heat (44-50 degrees C) and cold (25-0 degrees C) perception (P < 0.01). Stimulus intensity ratings tended to be lower in the cool than in the neutral environment (P < 0.07) but were not different between the neutral and warm environments. Unpleasantness ratings revealed that cold stimuli were more unpleasant than hot stimuli in the cool room and that noxious heat stimuli were more unpleasant in a warm environment. Environmental temperature did not alter ratings of warm (37 and 40 degrees C) or mechanical stimuli.

Conclusions

These results indicate that, in humans, a decrease in skin temperature following exposure to cool environments reduces thermal pain. Suppression of Adelta primary afferent cold fiber activity has been shown to increase cold pain produced by skin cooling. Our current findings may represent the reverse phenomenon, i.e., a reduction in thermal nociceptive transmission by the activation of Adelta cutaneous cold fibers.
Relationship between Local Cerebral Blood Flow and Metabolism during Mild and Moderate Hypothermia in Rats
Authors: Frietsch Thomas , Krafft Peter , Piepgras Axel , Lenz Christian , Kuschinsky Wolfgang , Waschke Klaus F.
Published: November 2003

Background

Hypothermia may interfere with the relationship between cerebral blood flow (CBF) and metabolism. Because this conclusion was based on the analysis of global values, the question remains whether hypothermic CBF/metabolism uncoupling exists on a local cerebral level. This study investigated the effects of hypothermic anesthesia on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU).

Methods

Thirty-six rats were anesthetized with isoflurane (1 minimum alveolar concentration) and artificially ventilated to maintain normal arterial carbon dioxide partial pressure (pH-stat). Pericranial temperature was maintained as normothermic (37.5 degrees C, n = 12) or was reduced to 35 degrees C (n = 12) or 32 degrees C (n = 12). Pericranial temperature was maintained constant for 60 min until LCBF or LCGU were measured by autoradiography. Twelve conscious rats served as normothermic controls.

Results

Compared with conscious animals, mean CBF remained unchanged during normothermic anesthesia. Mean CBF significantly increased during mild hypothermia but was unchanged during moderate hypothermia. During normothermic anesthesia, mean CGU was 45% lower than in conscious controls (P < 0.05). No further CGU reduction was found during mild hypothermia, whereas CGU further decreased during moderate hypothermia (48%; P < 0.05). Local analysis showed a linear LCBF/LCGU relationship in conscious (r = 0.94) and anesthetized (r = 0.94) normothermic animals, as well as in both hypothermic groups (35 degrees C: r = 0.92; 32 degrees C: r = 0.95; P < 0.05). The LCBF-to-LCGU ratio increased from 1.4 (conscious controls) to 2.4 (normothermic isoflurane) and 3.6 ml/micromol (mild and moderate hypothermia, P < 0.05).

Conclusions

Decrease of mean CGU at unchanged or increased mean CBF during hypothermic anesthesia may not indicate uncoupling. Local analysis shows a maintained linear relationship that is reset to a higher CBF/CGU ratio.
Isoflurane Increases the Apparent Agonist Affinity of the Nicotinic Acetylcholine Receptor by Reducing the Microscopic Agonist Dissociation Constant
Authors: Raines Douglas E. , Zachariah Vinu T.
Published: November 2003

Background

Isoflurane increases the apparent agonist affinity of ligand-gated ion channels. This action reflects a reduction in the receptor's agonist dissociation constant and/or the preopen/open channel state equilibrium. To evaluate the effect of isoflurane on each of these kinetic constants in the nicotinic acetylcholine receptor, the authors analyzed isoflurane's actions on (1) the binding of the fluorescent agonist Dns-C6-Cho to the nicotinic acetylcholine receptor's agonist self-inhibition site and (2) the desensitization kinetics induced by the binding of the weak partial agonist suberyldicholine.

Methods

The dissociation constant for Dns-C6-Cho binding to the self-inhibitory site was determined using stopped-flow fluorescence spectroscopy. The values of the kinetic constants for agonist binding, channel gating, and desensitization were determined by modeling the suberyldicholine concentration-dependence of the apparent rate of desensitization.

Results

Isoflurane did not significantly alter the dissociation constant for Dns-C6-Cho binding to the self-inhibitory site even at a concentration as high as 1.5 mM, the highest concentration studied. At this concentration, isoflurane substantially reduced the dissociation constant for suberyldicholine binding to its channel opening site by 97% from 17 +/- 5 microM to 0.5 +/- 0.2 microM, whereas the preopen/open channel state equilibrium was reduced only from 19.1 to 5 +/- 1.

Conclusions

Isoflurane increases the apparent agonist affinity of the nicotinic acetylcholine receptor primarily by reducing the agonist dissociation constant of the site responsible for channel opening rather than altering channel gating kinetics.
Complete Prevention but Stimulus-dependent Reversion of Morphine Tolerance by the Glycine/NMDA Receptor Antagonist (+)-HA966 in Neuropathic Rats
Authors: Christensen Dennis , Guilbaud Gisèle , Kayser Valérie
Published: November 2003

Background

Tolerance to the analgesic effect of morphine complicates the management of chronic pain states. The authors studied the ability of the glycine/N-methyl-D-aspartate receptor antagonist (+)-HA966 to modify morphine tolerance in a rat model of neuropathic pain.

Methods

Mononeuropathy was induced by placing four ligatures around the common sciatic nerve. The 4-day pretreatment regimens with two daily subcutaneous injections of saline and saline, saline and morphine (10 mg/kg), (+)-HA966 (2.5 mg/kg) and morphine, or (+)-HA966 and saline were begun on post-operative day 12 to test the ability of (+)-HA966 to prevent the development of tolerance. Behavioral experiments were performed on postoperative day 16, when the pain-related behavior reached a stable maximum. The effect of an acute dose of morphine (1 mg/kg intravenously) was tested against both mechanical (vocalization threshold to paw pressure) and thermal (struggle latency to hind paw immersion into a 46 degrees C hot-water bath) stimuli. In addition, to test the ability of a single injection of (+)-HA966 to reverse established morphine tolerance, groups of morphine-pretreated rats received injections of either (+)-HA966 (2.5 mg/kg subcutaneously) and morphine (1 mg/kg intravenously), saline and morphine, or (+)-HA966 and saline.

Results

Baseline vocalization thresholds and struggle latencies did not differ in the various pretreatment groups, indicating that the pretreatments had no effect on pain-related behavior. Coadministration of (+)-HA966 prevented the reduction of the effect observed with morphine alone in both the mechanical test and the thermal test. (+)-HA966 reversed morphine tolerance in the thermal but not in the mechanical test.

Conclusion

(+)-HA966 prevented morphine tolerance in both mechanical and thermal tests but reversed established morphine tolerance in the thermal test only.
Efficacy of Continuous Insufflation of Oxygen Combined with Active Cardiac Compression–Decompression during Out-of-hospital Cardiorespiratory Arrest
Authors: Saïssy Jean-Marie , Boussignac Georges , Cheptel Eric , Rouvin Bruno , Fontaine David , Bargues Laurent , Levecque Jean-Paul , Michel Alain , Brochard Laurent
Published: November 2003

Background

During experimental cardiac arrest, continuous insufflation of air or oxygen (CIO) through microcannulas inserted into the inner wall of a modified intubation tube and generating a permanent positive intrathoracic pressure, combined with external cardiac massage, has previously been shown to be as effective as intermittent positive pressure ventilation (IPPV).

Methods

After basic cardiorespiratory resuscitation, the adult patients who experienced nontraumatic, out-of-hospital cardiac arrest with asystole, were randomized to two groups: an IPPV group tracheally intubated with a standard tube and ventilated with standard IPPV and a CIO group for whom a modified tube was inserted, and in which CIO at a flow rate of 15 l/min replaced IPPV (the tube was left open to atmosphere). Both groups underwent active cardiac compression-decompression with a device. Resuscitation was continued for a maximum of 30 min. Blood gas analysis was performed as soon as stable spontaneous cardiac activity was restored, and a second blood gas analysis was performed at admission to the hospital.

Results

The two groups of patients (47 in the IPPV and 48 in the CIO group) were comparable. The percentages of patients who underwent successful resuscitation (stable cardiac activity; 21.3 in the IPPV group and 27.1% in the CIO group) and the time necessary for successful resuscitation (11.8 +/- 1.8 and 12.8 +/- 1.9 min) were also comparable. The blood gas analysis performed after resuscitation (8 patients in the IPPV and 10 in the CIO group) did not show significant differences. The arterial blood gases performed after admission to the hospital and ventilation using a transport ventilator (seven patients in the IPPV group and six in the CIO group) showed that the partial pressure of arterial carbon dioxide (PaCO2) was significantly lower in the CIO group (35.7 +/- 2.1 compared with 72.7 +/- 7.4 mmHg), whereas the pH and the partial pressure of arterial oxygen (PaO2) were significantly higher (all P < 0.05).

Conclusions

Continuous insufflation of air or oxygen alone through a multichannel open tube was as effective as IPPV during out-of-hospital cardiac arrest. A significantly greater elimination of carbon dioxide and a better level of oxygenation in the group previously treated with CIO probably reflected better lung mechanics.
Malignant Hyperthermia Phenotype
Authors: Sigg Daniel C. , Iaizzo Paul A.
Published: November 2003

Background

Succinylcholine causes immediate and severe arterial hypotension in swine with the malignant hyperthermia phenotype. The underlying mechanisms are unknown.

Methods

Malignant hyperthermia-susceptible (MHS; n = 10) and normal swine (n = 5) were anesthetized with thiopental. The following were monitored: electrocardiogram; arterial blood pressure; pulmonary artery, central venous, and left and right ventricular pressure; cardiac output; end-tidal carbon dioxide; core temperature; peripheral-blood flows; and arterial blood gases. After a control period, 2 mg/kg succinylcholine was given intravenously. Three MHS animals received 1 mg/kg vecuronium and two MHS animals received 2.5 mg/kg dantrolene intravenously. The effects of succinylcholine on left and right ventricular pressure and contractility were analyzed in isolated hearts. The effects of 0.06 mm succinylcholine on isometric tension development were recorded in isolated femoral artery rings.

Results

Succinylcholine caused an early, severe decrease in blood pressure, cardiac output, left ventricular pressure, and left ventricular contractility in MHS swine but not in normal swine; no significant differences were found in heart rate, right ventricular parameters, systemic vascular resistance, and preload (pulmonary diastolic pressure, central venous pressure). The succinylcholine-induced hypotension and associated effects were not prevented by dantrolene. However, pretreatment with high-dose vecuronium prevented not only the cardiovascular depression, but also MH. In addition, no phenotypic differences of succinylcholine on contractility or left ventricular pressure were observed in the isolated working hearts. Similary, succinylcholine did not cause a significantly different relaxation in rings in either phenotype.

Conclusion

Succinylcholine-induced hypotension occurred before muscle hypermetabolism in MHS swine. Succinylcholine had no differential physiologic effects on either the isolated heart or on isolated arteries. This hypotension could not be prevented by dantrolene but was prevented by pretreatment with high-dose vecuronium. Thus, an indirect mechanism such as the release of a cardiac depressant from skeletal muscle may have caused this hypotensive response.
Anesthesia-related Cardiac Arrest in Children
Authors: Morray Jeffrey P. , Geiduschek Jeremy M. , Ramamoorthy Chandra , Haberkern Charles M. , Hackel Alvin , Caplan Robert A. , Domino Karen B. , Posner Karen , Cheney Frederick W.
Published: November 2003

Background

The Pediatric Perioperative Cardiac Arrest (POCA) Registry was formed in 1994 in an attempt to determine the clinical factors and outcomes associated with cardiac arrest in anesthetized children.

Methods

Institutions that provide anesthesia for children are voluntarily enrolled in the POCA Registry. A representative from each institution provides annual institutional demographic information and submits anonymously a standardized data form for each cardiac arrest (defined as the need for chest compressions or as death) in anesthetized children 18 yr of age or younger. Causes and factors associated with cardiac arrest are analyzed.

Results

In the first 4 yr of the POCA Registry, 63 institutions enrolled and submitted 289 cases of cardiac arrest. Of these, 150 arrests were judged to be related to anesthesia. Cardiac arrest related to anesthesia had an incidence of 1.4 +/- 0.45 (mean +/- SD) per 10,000 instances of anesthesia and a mortality rate of 26%. Medication-related (37%) and cardiovascular (32%) causes of cardiac arrest were most common, together accounting for 69% of all arrests. Cardiovascular depression from halothane, alone or in combination with other drugs, was responsible for two thirds of all medication-related arrests. Thirty-three percent of the patients were American Society of Anesthesiologists physical status 1-2; in this group, 64% of arrests were medication-related, compared with 23% in American Society of Anesthesiologists physical status 3-5 patients (P < 0.01). Infants younger than 1 yr of age accounted for 55% of all anesthesia-related arrests. Multivariate analysis demonstrated two predictors of mortality: American Society of Anesthesiologists physical status 3-5 (odds ratio, 12.99; 95% confidence interval, 2.9-57.7), and emergency status (odds ratio, 3. 88; 95% confidence interval, 1.6-9.6).

Conclusions

Anesthesia-related cardiac arrest occurred most often in patients younger than 1 yr of age and in patients with severe underlying disease. Patients in the latter group, as well as patients having emergency surgery, were most likely to have a fatal outcome. The identification of medication-related problems as the most frequent cause of anesthesia-related cardiac arrest has important implications for preventive strategies.
In Vivo Whole-Body Resting Energy Expenditure and Insulin Action in Human Malignant Hyperthermia
Authors: Freymond Daniel , Dériaz Olivier , Frascarolo Philippe , Reiz Sebastian , Jéquier Eric , Urwyler Albert
Published: November 2003

Background

Malignant hyperthermia (MH) is a pharmacogenetic disease triggered by volatile anesthetics or succinylcholine. The disorder is heterogenetic and caused by abnormal calcium regulation within skeletal muscle cells. No clear metabolic differences have been found in MH-susceptible (MHS) persons in vivo while not having MH episodes, but some reported signs suggest that insulin action and energy turnover might be altered in muscle of MHS persons.

Methods

In fasting and insulin-stimulated conditions, using the glucose clamp technique and indirect calorimetry, we assessed in vivo resting energy expenditure (REE) and nutrient utilization rates in 10 MHS, 5 MH-equivocal (MHE) and 10 MH-negative (MHN) persons from 14 families. With a model using the persons' fat-free mass, fat mass, age, and gender, we calculated their predicted REE and compared it with measured REE in 10 MHS and 10 MHN persons (measured - predicted = residual REE).

Results

In vivo measured REE and glucose disposal rates were similar in 10 MHS and 10 MHN persons. Only during insulin stimulation was residual REE greater in MHS persons (6.4%; P = 0. 013).

Conclusions

In vivo insulin action is unimpaired in MHS persons. Although the absolute values of whole-body REE are the same in MHS and MHN persons, the part of REE independent of the determinants fat-free mass, fat mass, age, and gender is moderately greater in MHS than in MHN persons during insulin exposure. This suggests that MH susceptibility might influence insulin-stimulated energy turnover in muscle.
Airway Occlusion Pressure to Titrate Positive End-expiratory Pressure in Patients with Dynamic Hyperinflation
Authors: Mancebo Jordi , Albaladejo Pierre , Touchard Dominique , Bak Ela , Subirana Mireia , Lemaire François , Harf Alain , Brochard Laurent
Published: November 2003

Background

Although the use of external positive end-expiratory pressure (PEEP) is recommended for patients with intrinsic PEEP, no simple method exists for bedside titration. We hypothesized that the occlusion pressure, measured from airway pressure during the phase of ventilator triggering (P0.1t), could help to indicate the effects of PEEP on the work of breathing (WOB).

Methods

Twenty patients under assisted ventilation with chronic obstructive pulmonary disease were studied with 0, 5, and 10 cm H2O of PEEP while ventilated with a fixed level of pressure support.

Results

PEEP 5 significantly reduced intrinsic PEEP (mean +/- SD, 5.2 +/- 2.4 cm H2O at PEEP 0 to 3.6 +/- 1.9 at PEEP 5; P < 0.001), WOB per min (12. 6 +/- 6.7 J/min to 9.1 +/- 5.9 J/min; P = 0.003), WOB per liter (1.2 +/- 0.4 J/l to 0.8 +/- 0.4 J/l; P < 0.001), pressure time product of the diaphragm (216 +/- 86 cm H2O. s-1. min-1 to 155 +/- 179 cm H2O. s-1. min-1; P = 0.001) and P0.1t (3.3 +/- 1.5 cm H2O to 2.3 +/- 1.4 cm H2O; P = 0.002). At PEEP 10, no further significant reduction in muscle effort nor in P0.1t (2.5 +/- 2.1 cm H2O) occurred, and transpulmonary pressure indicated an increase in end-expiratory lung volume. Significant correlations were found between WOB per min and P0.1t at the three levels of PEEP (P < 0.001), and between the changes in P0.1t versus the changes in WOB per min (P < 0.005), indicating that P0.1t and WOB changed in the same direction. A decrease in P0.1 with PEEP indicated a decrease in intrinsic PEEP with a specificity of 71% and a sensitivity of 88% and a decrease in WOB with a specificity of 86% and a sensitivity of 91%.

Conclusion

These results show that P0.1t may help to assess the effects of PEEP in patients with intrinsic PEEP.
Difficult Intubation in Acromegalic Patients
Authors: Schmitt Hubert , Buchfelder Michael , Radespiel-Tröger Martin , Fahlbusch Rudolf
Published: November 2003

Background

Previous studies have suggested that the incidence of difficult intubation in acromegalic patients is higher than in normal patients. However, these studies were retrospective and did not include preoperative assessment of the airways. The aims of this study were to determine the incidence of difficult intubation and to assess the usefulness of preoperative tests in predicting difficult laryngoscopy.

Methods

One hundred twenty-eight consenting acromegalic patients requiring general anesthesia and tracheal intubation were studied. Preoperatively, Mallampati classification, thyromental distance, and head and neck movement were determined in each patient. After induction of anesthesia and muscle paralysis, laryngoscopic grade was assessed during direct laryngoscopy; Cormack and Lehane grade III or IV were classified as difficult. The association of individual airway assessment with laryngeal view was evaluated using the Fisher exact test. Predictors of difficult laryngoscopy were evaluated by calculating their sensitivity and specificity.

Results

Laryngoscopy was difficult (grade III) in 33 of 128 patients (26%). Application of external laryngeal pressure improved laryngeal visualization to grade II in 20 of these 33 patients. In the remaining 13 patients (10%), intubation was difficult (more than two attempts, blade change, use of gum-elastic bougie). Mallampati classes 3 and 4 were significantly related to laryngoscopy grade III (Fisher exact test, P = 0.001).

Conclusions

The incidence of difficult laryngoscopy and intubation in acromegalic patients is higher than in normal patients. Preoperative Mallampati scores of 3 and 4 were of value in predicting difficult laryngoscopy. Nevertheless, even this test will miss a significant number of patients with a difficult airway.
Intestinal Inflammation and Morphine Tolerance Alter the Interaction between Morphine and Clonidine on Gastrointestinal Transit in Mice
Authors: Puig Margarita M. , Warner William , Pol Olga
Published: November 2003

Background

Morphine and clonidine show synergy or antagonism inhibiting gastrointestinal transit depending on their proportion and level of effect. Their interaction during morphine tolerance and intestinal inflammation were assessed.

Methods

Gastrointestinal transit in mice was evaluated with charcoal and antitransit effects expressed as percent mean values +/- SEM. Tolerance was induced with a morphine pellet (75 mg) implanted for 72 h, and inflammation with intragastric croton oil. Dose-response curves for morphine and clonidine alone and combined at a 1:1 potency ratio were obtained, and doses producing a 50% and 60% inhibition were calculated (ED50, ED60). Interaction was established by isobolograms, interaction indexes, and analysis of variance.

Results

In naive and tolerant mice, the combination induced linear dose-response curves up to the ED60 and then reached a plateau. In naive mice, ED50 values were as follows: morphine 1.52 +/- 0.15 mg/kg, clonidine 0.09 +/- 0.008 mg/kg, and combined 0.506 +/- 0.084 mg/kg (0.478 +/- 0.08 mg/kg morphine plus 0.028 +/- 0.004 mg/kg clonidine). During tolerance, ED50 values were as follows: morphine 9.73 +/- 0.8 mg/kg, clonidine 0.09 +/- 0.007 mg/kg, combination 0.131 +/- 0.09 mg/kg (morphine 0. 13 +/- 0.09 mg/kg plus clonidine 0.0013 +/- 0.0005 mg/kg). In both groups, the interaction was synergistic up to the ED60 and antagonistic thereafter; synergy was enhanced during tolerance. During inflammation, ED50 values were as follows: morphine 0.17 +/- 0.04 mg/kg, clonidine 0.015 +/- 0.006 mg/kg, combined 0.62 +/- 0.04 mg/kg (morphine 0.568 +/- 0.04 mg/kg plus clonidine 0.052 +/- 0.004 mg/kg); thus, potencies of morphine and clonidine increased 9.3 and 7.1 times, while the combination remained unaltered. Moreover, inflammation transformed synergy into antagonism.

Conclusions

The interaction between morphine and clonidine was significantly altered during tolerance and inflammation. During tolerance, synergy was present up to 60% effect and then became antagonistic. Inflammation converted synergy to antagonism. A common pathway in signal transduction could partially explain the results.
Competence of the Internal Jugular Vein Valve Is Damaged by Cannulation and Catheterization of the Internal Jugular Vein
Authors: Wu Xianren , Studer Wolfgang , Erb Thomas , Skarvan Karl , Seeberger Manfred D.
Published: November 2003

Background

Experimental results suggest that the competence of the internal jugular vein (IJV) valve may be damaged when the IJV is cannulated for insertion of a central venous catheter. It has further been hypothesized that the risk of causing incompetence of the proximally located valve might be reduced by using a more distal site for venous cannulation. The present study evaluated these hypotheses in surgical patients.

Methods

Ninety-one patients without preexisting incompetence of the IJV valve were randomly assigned to undergo distal or proximal IJV cannulation (> or = 1 cm above or below the cricoid level, respectively). Color Doppler ultrasound was used to study whether new valvular incompetence was present during Valsalva maneuvers after insertion of a central venous catheter, immediately after removal of the catheter, and, in a subset of patients, several months after catheter removal, when compared with baseline findings before cannulation of the IJV.

Results

Incompetence of the IJV valve was frequently induced both by proximal and distal cannulation and catheterization of the IJV. Its incidence was higher after proximal than after distal cannulation (76% vs. 41%; P < 0.01) and tended to be so after removal of the catheter (47% vs. 28%; P = 0.07). Valvular incompetence persisting immediately after removal of the catheter did not recover within 8-27 months in most cases.

Conclusions

Cannulation and catheterization of the IJV may cause persistent incompetence of the IJV valve. Choosing a more distal site for venous cannulation may slightly lower the risk of causing valvular incompetence but does not reliably avoid it.
Use of the Intubating Laryngeal Mask Airway
Authors: van Vlymen Janet M. , Coloma Margarita , Tongier W. Kendall , White Paul F.
Published: November 2003

Background

The intubating laryngeal mask airway (ILMA) is designed to facilitate blind tracheal intubation. The effect of a muscle relaxant on the ability to perform tracheal intubation through the ILMA device has not been previously evaluated. This randomized, double-blind, placebo-controlled study was designed to evaluate rocuronium, 0.2 or 0.4 mg/kg administered intravenously, on the success rate and incidence of complications associated with ILMA-assisted tracheal intubation.

Methods

A total of 75 healthy patients were induced with propofol 2 mg/kg and fentanyl 1 microg/kg intravenously. After insertion of the ILMA device, patients were administered either saline, rocuronium 0.2 mg/kg, or rocuronium 0.4 mg/kg in a total volume of 5 ml. At 90 s after administration of the study drug, tracheal intubation was attempted using a disposable polyvinyl tube. If unsuccessful, a reusable silicone tube was tried. In addition to recording the time and number of attempts required to secure the airway, the incidence of complications during placement of the tracheal tube and removal of the ILMA were noted.

Results

Tracheal intubation was successful in 76-96% of the patients. The overall success rates and times required to secure the airway were similar in all three treatment groups. The high-dose rocuronium group experienced less patient movement (8 vs. 28 and 48%) and coughing (12 vs. 20 and 52%) than the low-dose rocuronium and saline groups, respectively. Use of rocuronium was also associated with a dose-related decrease in the requirement for supplemental bolus doses of propofol during intubation and removal of the ILMA device.

Conclusions

Use of rocuronium did not significantly improve the success rate in performing tracheal intubation through the ILMA. However, it produced dose-related decreases in coughing and movement after tracheal intubation and reduced difficulties associated with removal of the ILMA device.
Effects of Intravenous Zaprinast and Inhaled Nitric Oxide on Pulmonary Hemodynamics and Gas Exchange in an Ovine Model of Acute Respiratory Distress Syndrome
Authors: Adrie Christophe , Holzmann Alexandra , Hirani W. Mona , Zapol Warren M. , Hurford William E.
Published: November 2003

Background

Inhaled nitric oxide (No) selectively dilates the pulmonary vasculature and improves gas exchange in acute respiratory distress syndrome. Because of the very short half-life of NO, inhaled NO is administered continuously. Intravenous Zaprinast (2-o-propoxyphenyl-8-azapurin-6-one), a cyclic guanosine monophosphate phosphodiesterase inhibitor, increases the efficacy and prolongs the duration of action of inhaled NO in models of acute pulmonary hypertension. Its efficacy in lung injury models is uncertain. The authors hypothesized that the use of intravenous Zaprinast would have similar beneficial effects when used in combination with inhaled NO to improve oxygenation and dilate the pulmonary vasculature in a diffuse model of acute lung injury.

Methods

The authors studied two groups of sheep with lung injury produced by saline lavage. In the first group, 0, 5, 10, and 20 ppm of inhaled NO were administered in a random order before and after an intravenous Zaprinast infusion (2 mg/kg bolus followed by 0.1 mg. kg-1. min-1). In the second group, inhaled NO was administered at the same concentrations before and after an intravenous infusion of Zaprinast solvent (0.05 m NaOH).

Results

After lavage, inhaled NO decreased pulmonary arterial pressure and resistance with no systemic hemodynamic effects, increased arterial oxygen partial pressure, and decreased venous admixture (all P < 0.05). The intravenous administration of Zaprinast alone decreased pulmonary artery pressure but worsened gas exchange (P < 0.05). Zaprinast infusion abolished the beneficial ability of inhaled NO to improve pulmonary gas exchange and reduce pulmonary artery pressure (P < 0. 05 vs. control).

Conclusions

This study suggests that nonselective vasodilation induced by intravenously administered Zaprinast at the dose used in our study not only worsens gas exchange, but also abolishes the beneficial effects of inhaled NO.
Anesthetic Effects on Cerebral Metabolic Rate Predict Histologic Outcome from Near-complete Forebrain Ischemia in the Rat
Authors: Nellgård Bengt , Mackensen G. Burkhard , Pineda Jose , Wellons John C. , Pearlstein Robert D. , Warner David S.
Published: November 2003

Background

Although reduction of cerebral metabolic rate is thought to contribute to anesthetic neuroprotection, histologic evidence to support this concept has not been provided. In this study, histologic outcome was evaluated in rats subjected to different durations of severe forebrain ischemia while anesthetized with volatile anesthetics that have substantially different effects on cerebral metabolic rate.

Methods

Normothermic rats that underwent fasting were anesthetized with 0.75 minimum alveolar concentration (MAC) isoflurane-60% nitrous oxide (N2O) or 0.75 MAC halothane-60% N2O. Ischemia was induced with use of a combination of bilateral carotid occlusion and controlled hypotension. Rats in the isoflurane group were subjected to 6.5 min or 8.0 min ischemia, whereas the halothane group received 6.5 min ischemia. Histologic damage was assessed 4 days later.

Results

With 6.5 min ischemia, mean +/- SD, hippocampal CA1 percent of dead (% dead) neurons was reduced with isoflurane-N2O (45 +/- 18) versus halothane-N2O (60 +/- 23, P = 0. 023). Eight minutes of ischemia increased % dead neurons in the isoflurane-N2O group (60 +/- 17, P = 0.017). There was no difference between the isoflurane 8.0-min and halothane 6.5-min groups (P = 0. 935). A similar pattern was observed in hippocampal CA4 and the neocortex. Striatal damage was not affected by anesthetic or ischemic duration.

Conclusions

At 6.5 min ischemia, isoflurane provided improved outcome versus halothane. Previous research has shown that 0.75 MAC isoflurane-N2O increases the time to onset of ischemic depolarization by 1.5 min and reduces cerebral metabolic rate by 42% versus 0.75 MAC halothane-N2O. In the current study, when the duration of ischemia was increased by 1.5 min in the isoflurane-N2O group, histologic outcome became similar to that in halothane-N2O-anesthetized rats. These results provide evidence that cerebral metabolic rate reduction has an advantageous effect on outcome from severe brain ischemia, but also suggest that such benefit is likely to be small.
Effects of Radolmidine, A Novel α2-Adrenergic Agonist Compared with Dexmedetomidine in Different Pain Models in the Rat
Authors: Xu Mei , Kontinen Vesa K. , Kalso Eija
Published: November 2003

Background

Intrathecally administered alpha2-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Radolmidine is a novel alpha2-adrenoceptor agonist with a different pharmacokinetic profile compared with the well-researched dexmedetomidine. This study determined the antinociceptive and sedative effects of radolmidine in different models of acute and chronic pain. Dexmedetomidine and saline served as controls.

Methods

Male Sprague-Dawley rats were studied in acute pain (tail flick), carrageenan inflammation, and the spinal nerve ligation model of neuropathic pain. Mechanical allodynia was assessed with von Frey filaments, cold allodynia with the acetone test, and thermal hyperalgesia with the paw flick test. Locomotor activity-vigilance was assessed in a dark field. Dexmedetomidine and radolmidine were administered intrathecally in doses of 0.25 microg, 2.5 microg, 5 microg, and 10 microg.

Results

In the tail flick test, radolmidine showed a dose-dependent antinociceptive effect, being equipotent compared with dexmedetomidine. In carrageenan inflammation, intrathecal doses of 2.5 microg or 5 microg of dexmedetomidine/radolmidine produced significant antinociception compared with saline (P < 0.01). The two drugs were equianalgesic. In the neuropathic pain model, an intrathecal dose of 5 microg dexmedetomidine-radolmidine had a significant antiallodynic effect compared with saline (P < 0.01). The two drugs were equipotent. Intrathecal administration of both dexmedetomidine and radolmidine dose dependently decreased spontaneous locomotor acitivity-vigilance, but this effect was significantly smaller after intrathecal administration of radolmidine than after intrathecal dexmedetomidine.

Conclusions

Radolmidine and dexmedetomidine had equipotent antinociceptive effects in all tests studied. However, radolmidine caused significantly less sedation than dexmedetomidine, probably because of a different pharmacokinetic profile.