Postoperative course of plasma protein binding of lignocaine, ropivacaine and bupivacaine in sheep.

The plasma protein binding of the 2,6-xylidide local anaesthetic agents lignocaine, ropivacaine and bupivacaine enantiomers was determined by equilibrium dialysis in plasma obtained from chronically catheterized sheep before and up to 21 days after surgery. Three concentrations (1, 5 and 10 mg L-1), were used for each agent. Concentration-dependent binding was evident for each agent throughout the study period. R(+)-Bupivacaine was more extensively bound than S(-)-bupivacaine at the higher concentrations. Compared with pre-surgery, binding of each agent was less on the first postoperative day but did not differ significantly from days 8 to 21.

Adverse haemodynamic effects of the rapid intravenous injection of hypotonic solutions in sheep.

The rapid intravenous administration of 10 ml of sterile water or hypotonic saline to five conscious sheep induced substantial adverse haemodynamic effects lasting 10 to 20 seconds. They included reductions in cardiac output (to 44 per cent of the baseline value measured in the 30 seconds before the injection), arterial blood pressure (67 per cent of baseline), left ventricular systolic pressure (60 per cent of baseline), myocardial contractility (60 per cent of baseline), and left coronary arterial blood flow (39 per cent of baseline), and increases in heart rate to 137 per cent of the baseline. The intensities of these effects were related directly to the rates of injection and inversely to the osmolalities of the solutions injected. Intravascular haemolysis was associated with the effects. These data are of potential importance to anyone administering drugs intravenously to sheep.

Renovascular interaction of epinephrine, dopamine, and intraperitoneal sepsis.

OBJECTIVE: To determine the effect of intraperitoneal sepsis on the systemic and renal actions of the continous infusion of epinephrine or dopamine, and during the concurrent administration of both drugs. DESIGN: Prospective, randomized study. SETTING: Laboratory at a university hospital. SUBJECTS: Seven conscious, chronically catheterized, adult merino sheep. INTERVENTIONS: Epinephrine at 40 micrograms/min or dopamine at 2 micrograms/kg/min, or both drugs concurrently were infused for 4 hrs on separate study days in healthy sheep. This protocol was then repeated following the induction of sepsis after the intraperitoneal injection of 10(11) Escherichia coli, 10(12) Bacteroides fragilis, and bran. MEASUREMENTS AND MAIN RESULTS: Systemic oxygen delivery (DO2) and consumption were measured using thermodilution cardiac output and measured oxygen content. Renal blood flow was measured using an electromagnetic flow transducer, and creatinine clearance was calculated as the quotient of renal blood flow and the renal extraction ratio of creatinine. Infusion of epinephrine augmented systemic DO2 and mean arterial pressure (MAP) during both healthy and septic studies. Systemic oxygen consumption was only increased during epinephrine infusion in the septic study. During the healthy animal study, renal blood flow was initially decreased during epinephrine infusion, but increased to 36% above baseline (p = .003). However, creatinine clearance remained unchanged. During the experimental sepsis study, the infusion of epinephrine had less marked effects on renal blood flow (unchanged from baseline), while an initial reduction (15 mins) in creatinine clearance (p = .04) was not sustained and had returned to baseline by 3 hrs. Dopamine alone produced no change in systemic oxygen variables or MAP during the studies on healthy or septic animals. Although dopamine produced renal vasodilation and an increase in renal blood flow in the healthy state, these results were not found during the septic state. In addition, concurrent infusion of dopamine with epinephrine did not alter the systemic or renal effects of epinephrine during the healthy or septic states. CONCLUSIONS: These results do not support the routine use of low-dose dopamine, and demonstrate a change in renovascular responses to catecholamines during intraperitoneal sepsis. The infusion of epinephrine at 40 micrograms/min had few deleterious effects on the kidney, and augmented both MAP and systemic DO2. Its role as a catecholamine in the management of sepsis may need to be reconsidered.

Experimental analysis of catheter-manometer systems in vitro and in vivo.

The static and dynamic responses of two combinations of transducer amplifiers, pressure transducers, resonance elimination devices, extension tubing, and transcutaneous cannulae were tested in vitro using a sine-wave pressure generator, and in vivo by square-wave pressures generated by a "fast-flush" device. In addition, carotid arterial blood pressure waveforms recorded by these systems in sheep, at two different heart rates, were compared with those simultaneously recorded with a catheter-tip pressure transducer. A new term, "Working Heart Rate" is defined and allows for the prediction of the maximum heart rate up to which a system of given frequency response and damping coefficient should be accurate. When tested in vitro, all the monitoring systems were underdamped and resonated. The performance of all systems was improved by inclusion of an adjustable resonance elimination device but impaired by a nonadjustable resonance eliminator or by recording with an electronically filtered amplifier. When tested in vivo, the accuracy of mean and diastolic blood pressure measurement was not affected by any combination of heart rate, amplifier, length of extension tubing, or use of resonance eliminators. Both resonance elimination devices improved the performance of all systems. In contrast to predictions based on frequency response and damping, the smallest errors in systolic blood pressure were recorded using the electronic filter or the nonadjustable resonance eliminator. There were considerable and misleading differences between the frequency responses and damping coefficients calculated in vitro and those, for the same systems, derived from the in vivo fast-flush tests. It is concluded that the most accurate and consistent readings of systolic blood pressure will be achieved with the use of either an electronic filter or a nonadjustable resonance eliminator.

Endotoxin alters the systemic disposition of nitric oxide synthase inhibitors in the awake sheep.

1. We evaluated the haemodynamic effects and systemic disposition of the nitric oxide synthase (NOS) inhibitor NL-nitro-L-arginine (NOLA) after intravenous (i.v.) administration of two different doses (5 and 20 mg/kg) in awake healthy sheep and awake sheep given a continuous i.v. infusion of endotoxin (lipopolysaccharide, 12 ng/kg per h, i.v., for 18 h). In addition, we determined the systemic disposition of another NOS inhibitor, NL-nitro-L-arginine methylester (L-NAME; 20 mg/kg, i.v.) in awake healthy sheep only. 2. NL-Nitro-L-arginine produced a dose-dependent decrease in heart rate (HR) and cardiac output (CO) together with a dose-dependent increase in mean arterial pressure (MAP) and peripheral vascular resistance (PVR) when compared to baseline. In endotoxic sheep NOLA produced a greater increase in MAP and mean pulmonary arterial pressure (MPAP). 3. In healthy sheep there was a dose-related increase in total body clearance (Cl) of NOLA. The Cl increased from 0.028 L/min after the lower dose to 0.032 L/min after the higher dose. The infusion of endotoxin caused an increase in Cl of NOLA to 0.040 and 0.047 L/min, respectively, and a decrease in plasma slow half-life (t1/2) from 825 to 546 min and from 780 to 453 min, respectively. 4. NL-Nitro-L-arginine methylester was rapidly cleared from the plasma with a slow half-life of approximately 7.5 min and there was a simultaneous appearance of NOLA in the plasma. 5. These results support the view that nitric oxide has a significant role in regulating vascular tone in healthy and endotoxic sheep and indicate that the increases in Cl of NOLA with an increase in its dose and the presence of endotoxin will be important in influencing appropriate dosage regimens in clinical studies.

An evaluation of blood pressure measurement.

The accuracy of routine measurements by nursing staff of systemic arterial, central venous, pulmonary artery and pulmonary capillary wedge pressures was determined. There was a significant difference between direct mean arterial blood pressure measurements and routine indirect measurements by the nursing staff in the pressure range of 50--100 mmHg, whereas there was no significant difference between direct and indirect measurements when indirect measurements were made by specially trained hypertension clinic personnel. However, there was a good correlation between direct and indirect measurements in each instance, indicating that changes in blood pressure could be adequately followed by both groups. Systems commonly used to measure blood pressure directly were tested. Limits in frequency response preclude the routine direct measurement of systolic or diastolic blood pressures. If direct systolic and diastolic pressure measurements are required, it is necessary to check the performance of the amplifier and recording system, attach the transducer to the patient, and determine and adjust, if necessary, the natural frequency and damping coefficient of each system before each measurement. However, it is suggested that a knowledge of systolic and diastolic pressure measurements seldom improves patient management, and if mean pressures are accepted, reliable routine measurements may be obtained by the nursing staff. The digital display of the systems tested may be accepted for mean arterial pressure, but for accurate mean central venous and pulmonary capillary wedge pressure measurements, it is necessary to interpret the trace on a chart recorder; pulmonary artery pressure can often only be estimated.

Optimizing fresh gas flow and circuit design for the delivery of continuous positive airway pressure.

OBJECTIVE: To examine the effect of varying circuit design and the fresh gas flow rate on the circuit work imposed by a continuous positive airway pressure (CPAP) circuit. DESIGN: Circuit work was measured during simulated inspiration (500 mL) with a lung model at inspiratory flow rates (V) of 40, 60, and 80 L/min during the administration of 10 cm H2O CPAP through either a modified Mapleson-A or modified Mapleson-D circuit, both alone and when connected to a face mask (i.e., simulating an intubated and nonintubated patient). Fresh gas flow was varied from 10 to 250 L/min. RESULTS: The minimum circuit work occurred at a fresh gas flow rate approximating V; however, circuit work was consistently lower for the modified Mapleson-A circuit compared with the modified Mapleson-D circuit. As the fresh gas flow rate was increased sequentially to 250 L/min, circuit work remained close to the minimum value for the modified Mapleson-A, but increased gradually with the modified Mapleson-D, e.g., from 0.017 kg.m/L at a fresh gas flow rate and V of 80 L/min to 0.035 kg.m/L at a fresh gas flow rate of 250 L/min and a V of 80 L/min. Rotation of the fresh gas flow inlet did not change the circuit work vs. fresh gas flow rate relationship. Addition of a face mask resulted in a smaller increase in circuit work for the modified Mapleson-D with increasing fresh gas flow rate. However, unlike the modified Mapleson-A circuit alone, the addition of a mask caused circuit work to increase with increasing fresh gas flow rate. CONCLUSIONS: The modified Mapleson-A circuit at a fresh gas flow rate equal to V minimizes circuit work, and hence represents an optimal CPAP circuit. The increases in circuit work at fresh gas flow rates above V that were found with the modified Mapleson-D circuit are not due to inertial differences, and are likely due to turbulent gas flow.

Cardiovascular effects and regional clearances of i.v. bupivacaine in sheep: enantiomeric analysis.

All currently available aminoacylaniline local anaesthetics, except lignocaine, contain a chiral centre but are used as racemates, a fact usually ignored in pharmacokinetic studies. This study reports the cardiovascular effects, and the regional and total body clearances of the enantiomers of bupivacaine determined at two steady state periods (3-4 h and 23-24 h) during continuous i.v. infusion to subtoxic concentrations in conscious sheep. Racemic (RS)-bupivacaine hydrochloride 1 mg min-1, was infused in five sheep that had been prepared at least 1 week previously with appropriate intravascular cannulae. The infusion of RS-bupivacaine produced constant arterial R(+)- and s(-)-bupivacaine concentrations of 0.20-0.68 mg litre-1 and 0.22-0.94 mg litre-1, respectively. This caused no appreciable cardiovascular effects. The hepatic clearance of R(+)- was greater than that of S(-)-bupivacaine (P less than 0.05) with mean (SD) clearance at the two respective time periods being 1.37 (0.78) and 1.47 (0.57) litre min-1 and 1.01 (0.72) and 1.29 (0.47) litre min-1. There was no significant clearance of either enantiomer by the lungs, brain, heart, gut, kidneys or hindquarters. It was concluded that, although the clearances of the enantiomers differed, the total body clearance of both enantiomers was accounted for by hepatic clearance exclusively. There was no evidence of time dependent kinetics.

An evaluation of body temperature measurement.

The accuracy of routine body temperature measurements, the suitability of various sites for such measurements, and the performance and practicality of various temperature measuring devices were studied. Oral and axillary temperature measurements made by the nursing staff were within 1 degree C of a reference value (within 0.5 degree C in 67%). Both sites were suitable for routine ward temperature measurement. Mercury-in-glass thermometers are recommended for routine ward use. Electronic and disposable chemical thermometers cost more but the latter are suitable in uncooperative patients and children. Forehead skin temperature measurements using liquid crystal plastic discs were unreliable. Pulmonary artery and rectal temperature measurements were satisfactory in operating theatre and intensive care unit; however, electronic thermometers should be subjected to routine checks. The bladder temperature measuring device proved unsuitable for clinical use. When oesophagus, nasopharynx and tympanum sites are used careful placement is necessary to minimise trauma and obtain reliable measurements.

Efficacy of pressure support in compensating for apparatus work.

Breathing through an endotracheal tube, connector, and ventilator demand valve imposes an added load on the respiratory muscles. As respiratory muscle fatigue is thought to be a frequent cause of ventilator dependence, we sought to examine the efficacy of five different ventilators in reducing this imposed work through the application of pressure support ventilation. Using a model of spontaneous breathing, we examined the apparatus work imposed by the Servo 900-C, Puritan Bennett 7200a, Engstrom Erica, Drager EV-A or Hamilton Veolar ventilators, a size 7.0 and 8.0 mm endotracheal tube, and inspiratory flow rates of 40 and 60 l/min. Pressure support of 0, 5, 10, 15, 20 and 30 cm H2O was tested at each experimental condition. Apparatus work was greater with increased inspiratory flow rate and decreased endotracheal tube size, and was lowest for the Servo 900-C and Puritan Bennett 7200a ventilators. Apparatus work fell in a curvilinear fashion when pressure support was applied, with no major difference noted between the five ventilators tested. At an inspiratory flow rate of 40 l/min, a pressure support of 5 and 8 cm H2O compensated for apparatus work through size 8.0 and 7.0 endotracheal tubes and the Servo 900-C and Puritan Bennett 7200a ventilators. However, the maximum negative pressure was greater for the Servo 900-C. The added work of breathing through endotracheal tubes and ventilator demand valves may be compensated for by the application of pressure support. The level of pressure support required depends on inspiratory flow rate, endotracheal tube size, and type of ventilator.

Pharmacokinetics of bupivacaine enantiomers in sheep: influence of dosage regimen and study design.

Bupivacaine is used as a racemate. In previous studies the mean total body clearance of R(+)-bupivacaine was found to be greater than S(-)-bupivacaine by 65% after iv bolus dose of separate enantiomers and by 20% after iv infusion to steady state of racemate. The present studies were performed to determine whether different study designs using different iv dosage regimens could influence the pharmacokinetic parameters determined for either bupivacaine enantiomer. rac-Bupivacaine.HCl was administered iv to 6 adult Merino ewes by bolus, brief infusion, and prolonged infusion. Arterial blood concentrations of R(+)- and S(-)-bupivacaine were measured by enantioselective HPLC. These regimens consistently produced lower arterial blood concentrations of R(+)-bupivacaine than S(-)-bupivacaine due to R(+)-bupivacaine having a greater initial dilution volume by 16 (95% CI = 3-29)%, volume of distribution at steady state equilibrium by 32 (95% CI = 17-32)% and mean total body clearance by 28 (95% CI = 21-35)%. The slow half-life of R(+)-bupivacaine, however, was found to be 15 (95% CI = 0-31)% longer than that of S(-)-bupivacaine. The difference between enantiomers in mean total body clearance thus was similar to the previous study based upon infusion to steady state of rac-bupivacaine. Differences in pharmacokinetics attributable to the dosage regimen consisted of a greater mean total body clearance for R(+)-bupivacaine along with a smaller terminal half life with the bolus regimen and a longer half-life of S(-)-bupivacaine after prolonged infusion. Differences in pharmacokinetics between the bupivacaine enantiomers occurred consistently in both distribution and clearance but the magnitude of the effect was less than 50% in each case. Systematic differences in pharmacokinetics associated with the dosage regimen were found mainly in terminal half-life. Dosage regimen, thus, was found to influence the pharmacokinetic results found experimentally and is therefore a significant variable in its own right.

An assessment of six different pulmonary artery catheters.

The performance of three samples each of six brands of flow-directed pulmonary artery (PA) catheters was evaluated. In vivo studies determined the reproducibility of PA waveforms over a range of controlled heart rates when compared to those obtained from a transducer-tipped catheter. In vitro studies determined their frequency response, thermistor accuracy, balloon characteristics, and the maximum infusion rates possible through their proximal lumens. All catheters performed similarly in vivo, with mean errors in systolic and diastolic pressures ranging, respectively, from +9% to -12%, at a HR of 80 beat/min, to +23% and -30% at a HR of 160 beat/min. The resonant frequencies of all catheters in vitro were similar at 12 Hz or less; we were unable to obtain the frequency responses (17 to 32 Hz) claimed by the manufacturers. All thermistors were accurate for clinical use when tested over the temperature range 32 degrees to 42 degrees C. Balloon characteristics and infusion rates varied with some catheter brands. Maximum infusion rates varied from 164 to 383 ml/h when infusing 20% dextrose, and from 95 to 213 ml/h when infusing 35% dextrose.

An evaluation of intravenous infusion pumps and controllers.

The accuracy, safety, reliability and cost of use of 35 intravenous infusion pumps and 3 flow controllers were assessed. When infusing saline 11 out of 17 syringe pumps, 3 out of 5 peristaltic pumps, 1 out of 2 roller pumps and all 14 cassette pumps tested were accurate to within 5% over their full ranges of operation. There was no significant change in the performance of any of the pumps tested when saline was infused through a standard resistance, except in the cases of the 3 flow controllers which were unable to infuse at all against the resistance. When 50% dextrose was infused, delivery by two peristaltic pumps was reduced by 23 and 38%. No pump cut out or alarmed at pressures of up to 200 mmHg and 21 pumps continued to infuse against pressures of 750 mmHg or greater. Surges of up to 0.5 ml occurred after release of an outlet obstruction. One device was fitted with a variable high pressure alarm. This device could also measure pressure in the infused vessel and was found to be accurate for measurements of central venous pressure. The cost of consumables for a single use for syringe pumps ranges from A$2 to $5, for peristaltic and roller pumps from A$1 to $10, and for cassette pumps from A$7 to $12, with an additional A$2 for a burette. Accurate delivery of intravenous fluids and drugs is available but is expensive and requires the operator to be specially trained. No simple, cheap, accurate device is yet available.

IV bolus administration of subconvulsive doses of lignocaine to conscious sheep: effects on circulatory function.

We have studied the effects of subconvulsive doses of lignocaine on circulatory function in five conscious, chronically instrumented sheep. In the absence of overt signs of central nervous system toxicity, 50-, 75- or 100-mg i.v. bolus doses of lignocaine induced reductions in myocardial contractility, as assessed by the maximum rate of increase in left ventricular pressure (LV dP/dtmax), of 17 (SD 4)%, 25 (4)% and 33 (4)%, respectively. The durations of these reductions in myocardial contractility were 2-3.5 min. There were no significant changes in cardiac output, coronary artery blood flow, mean arterial pressure, heart rate or left ventricular systolic and diastolic pressures. It is concluded that the initial toxic effects of lignocaine are on the heart rather than the central nervous system, as is generally believed. This negative inotropic effect of lignocaine in vivo may be more deleterious to myocardial function when the heart is compromised by pre-existing disease, or the co-administration of other myocardial depressive drugs.

An evaluation of six disposable heat and moisture exchangers.

Six disposable heat and moisture exchangers were tested on patients undergoing anaesthesia requiring mechanical ventilation. Inspiratory humidity and temperature were monitored to find the steady-state values reached with each device together with the times taken for these to be achieved. The exchangers were tested in a non-rebreathing T-piece circuit and in a conventional circle system with a fresh gas flow of 6 l/min: the Siemens 150 provided 28 and 32 mg of water/litre of inspired gas (at about 30 degrees C) in 10 and 5 min respectively, but is rather heavy and bulky. The Portex Humidvent provided 25 and 30 mg/l, and although taking longer to reach steady state (27 and 15 min respectively) is small, light and cheap. The Siemens 151 provided 25 and 27 mg/l in 18 and 10 min respectively, but is heavier than the Portex exchanger. The performances of these three devices were not significantly different from each other in either study (P less than 0.05). For the T-piece system the Pall and Engstrom exchangers were the next most efficient. The Pall device provided 18 and 23 mg/l (in 18 and 8 min respectively) and the Engstrom provided 20 and 23 mg/l (in 19 and 10 min respectively). In the circle system, there were no significant differences between the performances of the Portex, Siemens 151, Pall and Engstrom exchangers. The Pall is also a very effective bacterial filter and has been found to be satisfactory in the intensive care setting. The Terumo appeared to perform no better than a circle system with catheter mount (13 mg/l at 27 degrees C). It would seem that more complex humidification equipment is not necessary during anaesthesia if an efficient heat and moisture exchanger is used.

Tissue distribution of bupivacaine enantiomers in sheep.

rac-Bupivacaine HCl was infused intravenously to constant arterial blood drug concentrations in sheep using a regimen of 4 mg/min for 15 min followed by 1 mg/min to 24 h. At 24 h, arterial blood was sampled, the animal was killed with a bolus of KCl solution, then rapidly dissected and samples were obtained from heart, brain, lung, kidney, liver, muscle, fat, gut, and rumen. Tissue:blood distribution coefficients for (+)-(R)-bupivacaine exceeded those of (-)-(S)-bupivacaine (P < 0.05) for heart, brain, lung, fat, gut, and rumen by an overall mean of 43%. Blood:plasma distribution coefficients of (-)-(S)-bupivacaine exceeded those of (+)-(R)-bupivacaine by a mean of 29% and this offset the tissue:blood distribution coefficients so that the previously significant enantioselective differences disappeared. It is concluded that although enantioselectivity of bupivacaine distribution is shown by the measured tissue:blood distribution coefficients, it is not shown when tissue:plasma water distribution coefficients are calculated, suggesting that there is no intrinsic difference between the bupivacaine enantiomers in tissue affinity. Sheep given fatal intravenous bolus doses of rac-bupivacaine had significantly greater concentrations of (+)-(R)-bupivacaine than (-)-(S)-bupivacaine in brain (P = 0.028) and ventricle (P = 0.036); these could augment the greater myocardial toxicity of this enantiomer found in vitro.

The hemodynamic effects of intravenous bolus doses of meperidine in conscious sheep.

The hemodynamic effects of 100, 200, and 300 mg of meperidine injected intravenously were studied in five chronically instrumented adult ewes. The maximum rate of increase of left ventricular pressure was decreased, respectively, by 27.4% +/- 3.9%, 37.5% +/- 5.6%, and 31.9% +/- 13.0%, and recovery occurred by 5, 8, and 0.5 min, respectively. Mild central nervous system stimulatory effects (agitation) were observed in three of five sheep at 200 mg and moderate effects (rigor and jumping movements) were observed in four of five sheep at 300 mg. These doses also produced increases in heart rate (43%-64%) and mean arterial blood pressure (17%-27%). At these doses, cardiac output was increased for 0.5 min by approximately 25% without changes in stroke volume and left ventricular stroke work. Coronary blood flow was increased by 44%-81% for 0.5 min. We conclude that, in unpremedicated sheep, meperidine has a brief direct negative inotropic effect on the myocardium, but that at larger doses this is overridden by stimulatory central nervous system (CNS) and indirect hemodynamic effects.

Epinephrine infusion in sheep: systemic and renal hemodynamic effects.

OBJECTIVE: To evaluate the dose-response effects of graded epinephrine infusions on systemic and renal hemodynamics. DESIGN: Prospective, dose-response study. SETTING: Laboratory at a university hospital. SUBJECTS: Thirteen conscious, chronically catheterized, adult merino sheep. INTERVENTIONS: Ten sheep received five infusions of epinephrine (5, 10, 20, and 40 micrograms/min; the 40-micrograms/min dose was repeated) and a placebo (saline) on separate days (at least 1 day apart). Each drug infusion was administered for 4 hrs on separate days after a 90-min baseline was established. Plasma catecholamine values and renin activity were measured in an additional three sheep infused with 40 micrograms/min epinephrine. MEASUREMENTS AND MAIN RESULTS: Renal blood flow was measured, using an electromagnetic flow transducer; these data, along with aortic and pulmonary arterial pressure, were continuously recorded after analog-to-digital conversion. Cardiac output was intermittently measured by thermodilution. Epinephrine resulted in a dose-dependent increase in mean arterial pressure (p < .001), and in cardiac output at 30, 60, and 120 mins after the start of the infusion. Concurrently, systemic vascular resistance was initially depressed below baseline, but then gradually increased during the 4-hr infusion period. Although a dose-dependent increase in renal vascular resistance was found, 5- and 10-micrograms/min of epinephrine failed to alter renal vascular resistance. However, 20- and 40-micrograms/min of epinephrine increased renal vascular resistance by 77% and 94% respectively, at 10 mins, but these values decreased to 17% and 16% of baseline by 120 mins. Consequently, an early dose-dependent decrease in renal blood flow was also time dependent, with renal blood flow increasing back to or above baseline at all studied infusion rates of epinephrine. CONCLUSIONS: Using a clinically relevant dose regimen, epinephrine increased mean arterial pressure and cardiac output. Renal blood flow decreased transiently, but returned to baseline within 30 to 60 mins.

Cardiovascular effects and regional clearances of intravenous ropivacaine in sheep.

The purpose of this study was to determine the cardiovascular effects and the total body and regional clearances of ropivacaine during its continuous intravenous infusion to subtoxic levels in five conscious unrestrained sheep that had been previously prepared with appropriate intravascular cannulas. Ropivacaine HCl.H2O, 1 mg/min, produced constant arterial blood concentrations which ranged from 0.70 to 1.84 mg/L. This caused no appreciable cardiovascular effects. The mean total body clearance (+/- SD) of ropivacaine was 1.00 +/- 0.27 L/min. There was significant clearance of ropivacaine by the liver (0.85 +/- 0.32 L/min), gut (0.09 +/- 0.07 L/min), and kidneys (0.04 +/- 0.03 L/min). There was no significant clearance of ropivacaine by the lungs, brain, heart, or hindquarters. It was concluded that the liver accounts for the majority of ropivacaine clearance.

A comparative study of the measurement of mean arterial blood pressure using automatic oscillometers, arterial cannulation and auscultation.

Mean brachial artery pressures determined by five different non-invasive automatic oscillometric and one auscultatory preferred (oscillometric back-up) blood pressure (BP) monitors were compared with mean arterial pressures (MAP) obtained by cannulation of the radial artery of the same arm. The devices tested all performed similarly, showing a wide range of variation (+40% to -29%) compared with the directly measured MAP, and all tended to over-read at low values and under-read at high values. Trend information was generally acceptable, but occasionally was misleading. In addition, using one of the devices, systolic and diastolic blood pressure measurements were compared with those obtained by auscultation. This gives a range of differences from +22 to -25 mmHg for systolic and +20 to -12 mmHg for diastolic BP measurements. (The average fell within 1.0 mmHg of the auscultatory measurement, with a standard deviation of 10 mmHg.) Thus, the automatic oscillometric BP monitors tested were comparable in accuracy to auscultatory BP measurement, and are satisfactory for routine use in the appropriate clinical context. However, in settings where significance is to be attached to individual BP readings rather than to trends, or where a high degree of accuracy is required, automatic oscillometric machines cannot be regarded as satisfactory alternatives to arterial cannulation.