Clinical validation of electromyography and acceleromyography as sensors for muscle relaxation.

BACKGROUND AND OBJECTIVE: The aim of this study was to determine which of two clinically applied methods, electromyography or acceleromyography, was less affected by external disturbances, had a higher sensitivity and which would provide the better input signal for closed loop control of muscle relaxation. METHODS: In 14 adult patients, anaesthesia was induced with intravenous opioids and propofol. The response of the thumb to ulnar nerve stimulation was recorded on the same arm. Mivacurium was used for neuromuscular blockade. Under stable conditions of relaxation, the infusion-rate was decreased and the effects of turning the hand were investigated. RESULTS: Electromyography and acceleromyography both reflected the change of the infusion rate (P = 0.015 and P < 0.001, respectively). Electromyography was significantly less affected by the hand-turn (P = 0.008) than acceleromyography. While zero counts were detected with acceleromyography, electromyography could still detect at least one count in 51.1%. CONCLUSIONS: Electromyography is more reliable for use in daily practice as it is less influenced by external disturbances than acceleromyography.

Ondansetron does not reduce the shivering threshold in healthy volunteers.

BACKGROUND: Ondansetron, a serotonin-3 receptor antagonist, reduces postoperative shivering. Drugs that reduce shivering usually impair central thermoregulatory control, and may thus be useful for preventing shivering during induction of therapeutic hypothermia. We determined, therefore, whether ondansetron reduces the major autonomic thermoregulatory response thresholds (triggering core temperatures) in humans. METHODS: Control (placebo) and ondansetron infusions at the target plasma concentration of 250 ng ml(-1) were studied in healthy volunteers on two different days. Each day, skin and core temperatures were increased to provoke sweating; then reduced to elicit peripheral vasoconstriction and shivering. We determined the core-temperature sweating, vasoconstriction and shivering thresholds after compensating for changes in mean-skin temperature. Data were analysed using t-tests and presented as means (sds); P<0.05 was taken as significant. RESULTS: Ondensetron plasma concentrations were 278 (57), 234 (55) and 243 (58) ng ml(-1) at the sweating, vasoconstriction and shivering thresholds, respectively; these corresponded to approximately 50 mg of ondansetron which is approximately 10 times the dose used for postoperative nausea and vomiting. Ondansetron did not change the sweating (control 37.4 (0.4) degrees C, ondansetron 37.6 (0.3) degrees C, P=0.16), vasoconstriction (37.0 (0.5) degrees C vs 37.1 (0.3) degrees C; P=0.70), or shivering threshold (36.3 (0.5) degrees C vs 36.3 (0.6) degrees C; P=0.76). No sedation was observed on either study day. CONCLUSIONS: /b>. Ondansetron appears to have little potential for facilitating induction of therapeutic hypothermia.

Blood/gas partition coefficients of halothane, isoflurane and sevoflurane in horse blood.

BACKGROUND: Blood/gas partition coefficients (lambda(b/g)) for volatile agents in horse blood are reported for halothane but not for isoflurane and sevoflurane. We measured the lambda(b/g) of halothane, isoflurane and sevoflurane in the blood of fasted horses. The correlation with age, weight and some haematological and biochemical variables was studied. The temperature correction factor for isoflurane solubility was calculated. METHODS: Twenty-four horses were randomly allocated to halothane (n=8), isoflurane (n=8) or sevoflurane (n=8). Blood samples were taken after 10 h' fasting. Calculation of lambda(b/g) was based on the measurement of anaesthetic partial pressures in blood at 37 degrees C, which was achieved with tonometer equilibration and headspace gas chromatography. RESULTS: Mean lambda(b/g) was 1.66 (SD 0.06) for halothane, 0.92 (0.04) for isoflurane, and 0.47 (0.03) for sevoflurane. The lambda(b/g) values were all significantly lower than in humans (P<0.001). No correlation was found between lambda(b/g) and weight, age, haematocrit, plasma triglycerides, cholesterol or total bilirubin. The change in isoflurane solubility per 1 degrees C temperature increase was -2.63 (0.13)%. CONCLUSION: The lambda(b/g) values of halothane, isoflurane and sevoflurane in fasted horses are significantly lower than those reported in humans. The lambda(b/g) for halothane in this study agrees with values reported in the literature but a positive correlation with plasma triglycerides could not be confirmed. Knowledge of lambda(b/g) can refine models of anaesthetic uptake.

The American Heart Association Dietary Guidelines for 2000: a summary report.

Recently, the American Heart Association published a revision of its dietary guidelines. The recommendations are based on new scientific findings, and address the contribution of growing rates of obesity, hypertension, and diabetes to heart disease in the United States. The guidelines for the general public are similar to dietary recommendations made by other health-related groups and government agencies and, therefore, place a greater emphasis on the adoption of healthy eating patterns and behaviors rather than a singular focus on dietary fat intake.

Effect of various levels of supplementation with sodium pivalate on tissue carnitine concentrations and urinary excretion of carnitine in the rat.

In previous studies, sodium pivalate has been administered to rats in their drinking water (20 mmoles/L; equivalent to 0.3% of the diet) as a way to lower the concentration of carnitine in tissues and to produce a model of secondary carnitine deficiency. Although this level of supplementation results in a marked decrease in carnitine concentration in a variety of tissues, it does not produce the classical signs of carnitine deficiency (i.e., decreased fatty acid oxidation and ketogenesis). The present study was designed (1) to determine if increasing the level of pivalate supplementation (0.6, 1.0% of the diet) would further reduce the concentrations of total and free carnitine in rat tissues without altering growth or food intake, and (2) to examine the effect of length of feeding (4 vs. 8 weeks) on these variables. Male, Sprague-Dawley rats were randomly assigned to either a control (0.2% sodium bicarbonate) or experimental diet (0.3, 0.6, 1.0% sodium pivalate) for either four or eight weeks. Animals (n = 6/group) were housed in metabolic cages; food and water were provided ad libitum throughout the study. Supplementation with sodium pivalate did not alter water intake or urine output. Ingestion of a diet containing 1.0% pivalic acid decreased food intake (g/day; P < 0.05), final body weight (P < 0.007), and growth rate (P < 0.001) after four weeks. The concentration of total carnitine in plasma, heart, liver, muscle, and kidney was reduced in all experimental groups (P < 0.001), regardless of level of supplementation or length of feeding. The concentration of free carnitine in heart, muscle, and kidney was also reduced (P < 0.001) in rats treated with pivalate for either four or eight weeks. The concentration of free carnitine in liver was reduced in animals supplemented with pivalate for eight weeks (P < 0.05), but no effect was observed in livers from rats treated for four weeks. Excretion of total carnitine and short chain acylcarnitine in urine was increased in pivalate supplemented rats throughout the entire feeding period (P < 0.001). Free carnitine excretion was increased during Weeks 1 and 2 (P < 0.01), but began to decline during Week 3 in experimental groups. During Weeks 6 and 8, free carnitine excretion in pivalate supplemented rats was less than that of control animals (P < 0.01). In summary, no further reduction in tissue carnitine concentration was observed when rats were supplemented with sodium pivalate at levels greater than 0.3% of the diet. Food intake (g/day) and growth were decreased in rats fed a diet containing 1.0% sodium pivalate. These data indicate that maximal lowering of tissue carnitine concentrations is achieved by feeding diets containing 0.3% sodium pivalate or less.

Adding sodium bicarbonate to lidocaine enhances the depth of epidural blockade.

UNLABELLED: It is controversial whether adding CO2 or sodium bicarbonate to local anesthetics enhances the depth of epidural blockade. Repeated electrical stimulation is a reliable test for assessing epidural analgesia and evokes temporal summation. We used this test to investigate the analgesic effect of lidocaine, with or without CO2 or bicarbonate. Twenty-four patients undergoing epidural blockade with 20 mL lidocaine 2% at L2-3 were randomly divided into three groups: lidocaine hydrochloride, lidocaine CO2, and lidocaine plus 2 mL sodium bicarbonate 8.4%. Pain threshold after repeated electrical stimulation (five impulses at 2 Hz), pinprick, and cold test were performed at S1 and L4. Motor block was assessed. The addition of bicarbonate resulted in higher pain thresholds (P < 0.0001), faster onset of action (P = 0.009), and higher degree of motor block (P = 0.004) compared with lidocaine hydrochloride. We found no significant differences between lidocaine CO2 and hydrochloride. Most of these results were not confirmed by pinprick and cold tests. We conclude that the addition of sodium bicarbonate to lidocaine enhances the depth of epidural blockade, increases inhibition of temporal summation, and hastens the onset of block. Pinprick and cold are inadequate tests for comparing drugs for epidural anesthesia. IMPLICATIONS: We measured pain perception during epidural anesthesia by delivering electrical stimuli to the knee and foot. We found that the addition of sodium bicarbonate to the local anesthetic lidocaine enhances analgesia. We observed no effect of adding carbon dioxide to lidocaine.

Effect of partial pressure on solubility of isoflurane in blood.

The effect of partial pressure of isoflurane on its solubility in blood of different haematocrit was determined at different isoflurane partial pressures, using a syringe--flask method and gas chromatography with blood from one donor. The solubility of isoflurane decreased with increasing blood haematocrit (39.5%, 51.9% and 61.9%) and isoflurane partial pressure from 1 MAC to 4 MAC. The solubility in 50% and 60% haematocrit blood at 2, 3 and 4 MAC was significantly different from the solubility in normal blood at 1 MAC (P < 0.05). We conclude that the solution of isoflurane in blood (especially in high haematocrit blood) does not obey Henry's law.

Carbon dioxide analysers: accuracy, alarm limits and effects of interfering gases.

Six mainstream and twelve sidestream infrared carbon dioxide (CO2) analysers were tested for accuracy of the CO2 display value, alarm activation and the effects of nitrous oxide (N2O), oxygen (O2) and water vapour according to the ISO Draft International Standard (DIS)#9918. Mainstream analysers (M-type): Novametrix Capnogard 1265; Hewlett Packard HP M1166A (CO2-module HP M1016A); Datascope Passport; Marquette Tramscope 12; Nellcor Ultra Cap N-6000; Hellige Vicom-sm SMU 611/612 ETC. Sidestream analysers: Brüel & Kjaer Type 1304; Datex Capnomac II; Marquette MGA-AS; Datascope Multinex; Ohmeda 4700 OxiCap (all type S1: respiratory cycles not demanded); Biochem BCI 9000; Bruker BCI 9100; Dräger Capnodig and PM 8020; Criticare Poet II; Hellige Vicom-sm SMU 611/612 A-GAS (all type S2: respiratory cycles demanded). The investigations were performed with premixed test gases (2.5, 5, 10 vol%, error < or = 1% rel.). Humidification (37 degrees C) of gases were generated by a Dräger Aquapor. Respiratory cycles were simulated by manually activated valves. All monitors complied with the tolerated accuracy bias in CO2 reading (< or = 12% or 4 mmHg of actual test gas value) for wet and dry test gases at all concentrations, except that the Marquette MGA-AS exceeded this accuracy limit with wet gases at 5 and 10 vol% CO2. Water condensed in the metal airway adapter of the HP M1166A at 37 degrees C gas temperature but not at 30 degrees C. The Servomex 2500 (nonclinical reference monitor), Passport (M-type), Multinex (S1-type) and Poet II (S2-type) showed the least bias for dry and wet gases. Nitrous oxide and O2 had practically no effect on the Capnodig and the errors in the others were max. 3.4 mmHg, still within the tolerated bias in the DIS (same as above). The difference between the display reading at alarm activation and the set point was in all monitors (except in the Capnodig: bias 1.75 mmHg at 5 vol% CO2) below the tolerated limit of the DIS (difference < or = 0.2 vol%). The authors conclude that the tested monitors are safe for clinical used (except those failing the DIS limits). The accuracy of the CO2-reading (average of mean absolute bias) is better in the M-type than in the S1- or S2-type analysers although no statistical (nor clinical) significant differences could be detected. Most manufacturers work with stricter limits than those proposed by the DIS.

Accuracy, alarm limits and rise times of 12 oxygen analysers.

The Comité Européen de Normalisation recently proposed a new standard for 'the particular requirements of oxygen monitors for medical use'. The feasibility of this proposed standard was tested in respect of (1) accuracy of alarm activation (2) accuracy of oxygen display value during both continuous and cyclical gas flows (3) rise time during rapid changes in oxygen concentration in the following 12 analysers: Datex Capnomac II and Servomex 570A (paramagnetic); Brüel & Kjaer 1304 (magnetoacoustic); Criticare Poet II, Multinex, Dräger Oxydig, Dräger PM 8030, Megamed 046A (part of the Megamed 700 ventilator), Ohmeda 5120, Spacelabs Multigas, Teledyne TED 200 (galvanic); Kontron OM 810 (polarographic). All the analysers tested displayed an oxygen reading which was within +/- 3 vol% of the actual oxygen concentrations of the test gases (15, 21, 40, 60 and 100 vol%). A cyclical pressure of between -1.5 to +8 kPa did not affect the measured oxygen concentration as displayed by the Brüel & Kjaer 1304, Datex Capnomac II and Servomex 570A analysers. The remainder, however, showed, depending on their measuring principle, a display error of between -1 and +6 vol%. After exposure to high pressure all the oximeters functioned normally. Some of the tested devices showed more than 2% of deviation between their alarm activation and the preset alarm limits. Only the Kontron OM 810, the Megamed 046A and the Spacelabs Multigas monitors satisfied the requirements at all the tested oxygen concentrations. The time required by the oxygen analyser to display the rise from 29 to 92 vol % after a sudden change of concentration from 21 to 100 vol % O2 is defined as "rise time" and must not, according to the Comité Européen de Normalisation standard proposal, exceed the manufacturers' specification by more than a factor of 1.15.(ABSTRACT TRUNCATED AT 250 WORDS)

Dexmedetomidine decreases thiopental dose requirement and alters distribution pharmacokinetics.

BACKGROUND: alpha 2-Adrenergic agonists such as dexmedetomidine can be used to reduce the dose requirement of intravenous and volatile anesthetics. Whereas dexmedetomidine and volatile anesthetics interact pharmacodynamically (reduction of MAC), the mechanism of interaction between dexmedetomidine and intravenous anesthetics is not known. METHODS: Fourteen male ASA physical status 1 patients were randomly assigned to serve as control subjects (n = 7) or to be treated with dexmedetomidine (n = 7; 100, 30, and 6 ng.kg-1.min-1 for 10 min, 15 min, and thereafter, respectively). After 35 min, in all patients, thiopental (100 mg/min) was infused until burst suppression appeared in the raw tracing of the electroencephalogram. By using concentrations of thiopental in plasma and the electroencephalogram as a continuous pharmacologic effect measure, the apparent effect site concentrations for thiopental were estimated in both groups. Three-compartment pharmacokinetics were calculated for thiopental. RESULTS: Dexmedetomidine reduced the thiopental dose requirement for electroencephalographic burst suppression by 30%. There was no difference in estimated thiopental effect site concentrations between dexmedetomidine and control patients, suggesting the absence of a major pharmacodynamic interaction. Dexmedetomidine significantly decreased distribution volumes (V2, V3, and Vdss) and distribution clearances (Cl12 and Cl13) of thiopental. CONCLUSIONS: The thiopental dose-sparing effect of dexmedetomidine on the electroencephalogram is not the result of a pharmacodynamic interaction but rather can be explained by a dexmedetomidine-induced decrease in thiopental distribution volume and distribution clearances. Dexmedetomidine reduces thiopental distribution, most probably by decreasing cardiac output and regional blood flow.

Automated determination of midazolam in human plasma by high-performance liquid chromatography using column switching.

An automated gradient high-performance liquid chromatographic method using a column-switching technique was developed in order to determine and quantify midazolam (separated from the metabolite alpha-hydroximidazolam) in human plasma. After dilution with an internal standard (flurazepam) solution, containing 20% acetonitrile, 400 microliters of the plasma samples were injected onto a precolumn (17 x 4.6 mm I.D., C18 Corasil 37-53 microns) and retained. Proteins and polar plasma components were washed out using a 0.1 M sodium hydroxide solution, followed by an equilibration with a phosphate buffer of pH 8.0. After column-switching midazolam and flurazepam were eluted and transferred to the analytical column (RP-select B) in the backflush mode, separated by gradient elution and detected at 230 nm by ultraviolet detection. Precision of replicate analyses on the same day was 1.5% for midazolam and 0.7% for flurazepam. Recovery of midazolam was in the range 80-89% and the detection limit was 2 ng/ml plasma.

Anesthetic depth defined using multiple noxious stimuli during isoflurane/oxygen anesthesia. I. Motor reactions.

BACKGROUND: Potency of inhaled anesthetics usually is defined by determining the minimal alveolar concentration (MAC) that prevents movement in 50% of patients in response to skin incision. Skin incision, however, is usually only a single event and, thus, determination of potency cannot be repeated in one patient. Traditional MACskin incision cannot be used to predict response to other noxious stimuli. The aim of this study was to investigate the effects of other noxious stimulation patterns and then compare these to MACskin incision measuring the end-tidal isoflurane concentrations with the corresponding arterial concentrations. METHODS: In 26 patients, the end-tidal and corresponding arterial isoflurane concentrations needed to suppress eye opening to verbal command and motor response after trapezius squeeze, 50 Hz electric tetanic stimulation, laryngoscopy, skin incision, and tracheal intubation in 50% of all patients were determined. RESULTS: The end-tidal (equivalent arterial) isoflurane concentrations (mean +/- SE, adjusted to sea level) expressed in vol% (to allow comparison) increased in the following order (mean +/- SE): vocal command 0.37 +/- 0.09 (0.36 +/- 0.09); trapezius squeeze 0.84 +/- 0.07 (0.65 +/- 0.07); laryngoscopy 1.00 +/- 0.12 (0.78 +/- 0.09); tetanic stimulation 1.03 +/- 0.09 (0.80 +/- 0.06); skin incision 1.16 +/- 0.10 (0.97 +/- 0.17); and intubation 1.76 +/- 0.13 (1.32 +/- 0.11). CONCLUSIONS: Different stimuli require different isoflurane concentrations to suppress motor responses. Tetanic stimulation and, to some extent, trapezius squeeze are reproducible and noninvasive stimulation patterns that can be used as an alternative to skin incision when evaluating potency of an anesthetic agent. In contrast to skin incision, they can be repeated.

Accuracy and cross-sensitivity of 10 different anesthetic gas monitors.

OBJECTIVE: The objective of this study was to test the accuracy and cross-sensitivity of commercially available anesthetic gas monitors. METHODS: Using gas chromatography (GC) as a reference method, the accuracy, cross-sensitivity, and ability to recognize an erroneously selected agent were determined in the following 10 monitors for volatile anesthetics: Datex Capnomac Ultima-S, Datex Capnomac, Ohmeda 5330 agent monitor, Iris Dräger, Andros Dräger PM 8020 (all monochromatic, infrared analyzers), Nellcor N-2500E, Criticare POET II, Irina Dräger (all polychromatic, infrared analyzers), Siemens Servo Gas Monitor 120 (a piezoelectric analyzer), and Brüel & Kajer Type 1304 (a photoacoustic analyzer). Accuracy was determined at 0.5, 1, 2, and 4 times the minimal alveolar concentration (MAC) of either halothane or isoflurane in oxygen (O2). The cross-sensitivity tests were performed with 70 vol% nitrous oxide in O2, 5 vol% carbon dioxide in O2, 0.032 vol% alcohol in O2, and 70% water vapor in O2. The photoacoustic analyzer showed a higher accuracy for isoflurane than the polychromatic infrared monitors. The greatest inaccuracy with isoflurane was found in the Iris Dräger monitor, which had a maximal bias percentage by volume (vol%) of 0.09 at 0.5 MAC. (This bias was within the manufacturer's specified tolerance of +/- 0.1 vol% or 10% relative difference of reading, whichever is greater.) Irina Dräger was the most accurate analyzer with halothane (mean % bias [relative %] +/- SD, 0.9 +/- 2.0%). The greatest bias with halothane was found in the monochromatic infrared analyzers, with a maximal % bias at 0.5 MAC of 50.3% of the GC reading (12.4% with a new inner Nafion tube) found in the Datex Ultima monitor. The Siemens gas monitor showed a cross-sensitivity for water vapor (-0.248 vol%). The monochromatic infrared analyzers showed a small sensitivity to alcohol (additional deviation of 0.011 to 0.147 vol% at 2 MAC isoflurane) but no sensitivity to nitrous oxide. No cross-sensitivity was found in the polychromatic infrared and photoacoustic analyzers. An incorrect selection of anesthetic agent when using a monochromatic infrared analyzer can be fatal; for example, when using halothane and selecting isoflurane the values measured by the Datex Capnomac monitor were nearly 6 times: below the actual value (i.e., 1 vol% "isoflurane" on the display = 6 vol% halothane in reality). CONCLUSIONS: The photoacoustic measurement principle is more accurate than the other methods, although the polychromatic infrared analyzers are safer because they detect erroneously selected agents.

Nitrous oxide decreases solubility of isoflurane and halothane in blood.

This study investigated the effects of carrier gases on the solubility of isoflurane or halothane in blood. The blood/gas partition coefficients (lambda blood/gas) of 1 minimum alveolar anesthetic concentration of isoflurane or halothane in 100% oxygen, 30% oxygen with 70% nitrous oxide, 100% nitrous oxide or air were measured at 37 degrees C, with blood from four donors. The values of isoflurane or halothane in 100% nitrous oxide (1.42 +/- 0.03; 2.59 +/- 0.05) were lower (P < 0.05) than those obtained when using 100% oxygen (1.53 +/- 0.02; 2.71 +/- 0.05) or air (1.54 +/- 0.03; 2.74 +/- 0.05). To determine the effect of absence of oxygen in the blood containing nitrous oxide on solubility, lambda blood/gas of 1 minimum alveolar anesthetic concentration of isoflurane or halothane in 100% oxygen, a gas mixture (30% oxygen and 70% nitrous oxide) or 100% nitrous oxide were measured under the same conditions. The values of isoflurane or halothane in 100% nitrous oxide (1.29 +/- 0.03; 2.25 +/- 0.08) and in a gas mixture of 30% oxygen and 70% nitrous oxide (1.33 +/- 0.04; 2.29 +/- 0.05) were lower (P < 0.05) than those obtained with 100% oxygen (1.40 +/- 0.03; 2.37 +/- 0.04). We conclude that nitrous oxide decreases the lambda blood/gas of isoflurane or halothane, and that this change of solubility, although small, increases the uptake rate of halothane or isoflurane.

An evaluation of the Rapid Infusion System.

The performance of the Rapid Infusion System was evaluated in the laboratory. Using a conventional mixture of two units of packed red cells, two units of fresh frozen plasma and 500 ml crystalloid, a single line and a driving pressure of 300 mmHg, the highest flow in our study was 970 ml.min-1 (2.8 mm catheter, no stopcock). With a 1.6 mm venous cannula the measured flow was 640 ml.min-1. Additional diluting of the standard 'blood cocktail' did not add much to the performance of the system. When primed with tap water 21 degrees C (12 degrees C respectively), the fluid at the outlet of the system reached a maximum temperature of 37.8 degrees C (37.4 degrees C) after 6 min at a flow of 400 ml.min-1. At flows higher than 1150 ml.min-1 (priming with 12 degrees C tap water: 800 ml.min-1), the system slowed down to flows of 700 to 1000 ml.min-1 in order to maintain an adequate temperature. We conclude, that the Rapid Infusion System is a valuable tool for situations where a rapid but controlled replacement with warmed blood at rates up to at least 1100 ml.min-1 is needed. The use of large bore intravenous catheters and avoiding additional resistors such as standard 3-way stopcocks is highly recommended.

Comparison of amino acid sequence analysis by electron ionization and negative-ion chemical ionization mass spectrometry.

The positive electron ionization and negative chemical ionization mass spectra of 15 different derivatives of the tripeptide Phe-Ala-Leu have been compared. Total ion currents and ion currents of sequence-characterizing ions have been measured and compared. The negative-ion spectra, using 10% carbon dioxide in argon as moderator gas, proved to be simpler and contained more abundant sequence ions than the positive electron ionization spectra.