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* From the Department of Anesthesiology, Critical Care Medicine, and Emergency, Nîmes University Hospital;
the Laboratory of Cardio-Vascular Physiology and Anesthesiology, Montpellier-Nîmes Faculty of Medicine; and
the Department of Medical Information, Biostatistics, and Epidemiology, Nîmes University Hospital, Nîmes, France.
Dr. Michel Dauzat, Montpellier-Nîmes Faculty of Medicine, Avenue Kennedy, 30907 Nîmes cedex, France. Phone: +33 (0)4 66 23 49 73; Fax: +33 (0)4 66 23 55 38; E-mail: dauzat{at}sc.univ-montp1.fr
| Abstract |
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Material and methods: In the anesthetized rabbit, we used implantable Doppler micro-probes to measure blood flow simultaneously in the ascending aorta, inferior vena cava, portal vein, hepatic artery, common carotid artery, and renal artery. We studied spontaneously breathing animals (Group A), and open (Group B) and closed abdomen (Group C) animals mechanically ventilated at 0 (ZEEP) and 12 cm H2O PEEP.
Results: In Group A, all biological and hemodynamic variables remained unchanged for three hours at the end of the surgical procedure. In Groups B and C, ZEEP produced no significant hemodynamic change. PEEP induced a decrease in carotid, hepatic, and renal artery blood flow in Groups B and C, a decrease in heart rate and mean arterial blood pressure in Group B, and a decrease in aorta blood flow in Group C.
Conclusions: These experimental results demonstrate the usefulness of the comprehensive approach of circulatory changes, and confirm that PEEP may have deleterious effects on regional blood flow, even without significant change in cardiac output, especially when the abdomen is open.
| Introduction |
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Therefore, the understanding of PEEP induced circulatory changes requires the simultaneous assessment of multiple regional circulations, in correlation with blood pressure, heart rate, and arterial blood gases. We used this approach to assess the hemodynamic changes induced by MV and PEEP, in open vs closed abdomen anesthetized rabbits.
| Material and methods |
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Premedication consisted of the im injection of ketamine 50 mgkg-1. A fluid filled catheter was introduced in an ear vein, and the animal was anesthetized in the supine position with iv ketamine (bolus 10 mgkg-1 followed by constant infusion at 0.1 mgkg-1min-1), and intubated with a cuffed endotracheal tube. Transperitoneal fluid loss was compensated by the continuous infusion of saline at a rate of 10 mLkg-1hr-1.
The electrocardiogram (CP110 ECG monitor, Philips, Eindhoven, the Netherlands) was monitored continuously from electrodes inserted in the limbs, and the output signal was digitized and displayed on a polygraph. A fluid filled catheter was introduced into the right femoral artery to monitor blood pressure and to sample arterial blood. Arterial pressure was measured with a Gould P23 ID pressure probe and DA 100 transducer amplifier (Biopac Systems, Santa Barbara, CA, USA), then digitized and displayed on the polygraph. Zero reference level for arterial pressure was defined as the mid-thoracic level.
Esophageal pressure was monitored through a fluid filled catheter connected to a P23 ID pressure transducer (Gould Statham, USA), and a DA 100 transducer amplifier. This catheter was positioned while the rabbit was breathing spontaneously in order to obtain a maximal decrease of the esophageal pressure with inspiration. Zero reference level for esophageal pressure was defined as the mid thoracic level. All pressure transducers were calibrated against a mercury column.
Rectal temperature was measured continuously, and a temperature controlled heating pad prevented hypothermia (Harvard Homeothermic Blanket Unit, Harvard, Edenbridge, UK).
Surgical procedures
DBF and HDP 20 MHz implantable Doppler probes (Crystal Biotech, Hopkinton, MA, USA) of adapted diameter were used for blood flow measurement. The chest was opened by transecting the clavicle and the first three ribs on the left side of the sternum, without pleural opening, and Doppler probes were placed around the ascending aorta and the left common carotid artery. The right renal artery was dissected through a right subcostal incision, and a Doppler probe was placed around the vessel. The hepatic artery was then dissected away from the portal vein, downstream from the bifurcation of the common hepatic artery. A Doppler probe was placed around the proper hepatic artery. After incision of the periportal fat tissue, a Doppler probe was placed on the main portal vein 10 mm upstream from its bifurcation. The inferior vena cava blood flow was measured with a Doppler probe placed just downstream from the renal veins. Doppler transducers were connected to a CBI 8000 (Crystal Biotech, Hopkinton, MA, USA) eight channel sonometry system operating in pulsed Doppler mode at 20 MHz emitting frequency and 125 kHz pulse repetition frequency. Crystal Biotech PD-20 Pulsed Doppler modules were used for venous blood flow measurement, and Crystal Biotech HVPD-20 Pulsed Doppler modules (high PRF, anti-aliasing modules for high velocity measurement) were used for arterial blood flow measurement. Each Doppler channel was calibrated for the probe diameter.
At the end of the surgical procedure, the thorax was closed. The abdomen was left open in Groups A and B, and was closed in Group C.
Polygraph recording
ECG, arterial and esophageal pressure, as well as Doppler signals from the aorta, inferior vena cava, carotid, renal, and hepatic arteries, and portal vein were digitized (MP100 system, Biopac Systems, Santa Barbara, CA, USA) and displayed as a polygraph. Calculation, display, and storage were achieved with the Acqknowledge V3.2 software (Biopac Systems, Santa Barbara, CA, USA), on a personal computer.
Blood flow velocity curves were monitored continuously since their systolic modulation ensured the correct positioning of the probe on arteries. The time averaged mean arterial or venous blood flow, as well as mean arterial pressure, were calculated by the Acqknowledge software on eight-second samples selected by two independent investigators.
Protocol
At the end of the surgical procedure, a 45-min stabilization period was allowed, after which stability was assumed if all variables remained unchanged over a 15-min period. Arterial blood gases and hematocrit were measured, and the rectal temperature was recorded (T0).
Seven rabbits breathing spontaneously oxygen-enriched air through a facial mask served as controls (Group A). The systemic (heart rate, mean arterial pressure, aortic and caval blood flow, rectal temperature) and regional (carotid, renal, hepatic artery, and portal vein blood flow) variables were monitored continuously and recorded every 60 min for 180 min. Arterial blood gases and hematocrit level were measured every hour during the session.
In Group B, ten rabbits received vecuronium bromide (0.5 mgkg-1) to ensure neuromuscular blockade, immediately after T0, and were ventilated mechanically (Servo 900 C, Siemens-Elema, Sweden) with 100% FIO2, frequency 40 breathsmin-1, controlled pressure 20 cm H2O, and zero end expiratory pressure (ZEEP). These variables were chosen to ensure zero end inspiratory and expiratory flows. After 20 min, all variables were measured (T1). Thereafter, 4-cm H2O increments of PEEP levels were introduced every 20 min until 12-cm H2O PEEP was reached (T2). Then, the PEEP level was returned to ZEEP and the last measurements were performed after a 20-min stability period (T3).
Air flow and pressure curves were obtained from the ventilator, digitized and displayed on the polygraph to ascertain that preset pressures were transmitted to the rabbit's lungs. Arterial pressure, aortic, carotid, renal, hepatic, portal, and caval blood flow, as well as esophageal pressure, were recorded. Arterial blood gases and hematocrit were measured 20 min after each change in the level of PEEP.
In Group C, six rabbits were managed as in Group B, but the abdominal wound was closed immediately after the surgical procedure.
Statistical analysis
Blood gases and respiratory variables are presented as median values with 25th and 75th percentiles. In all groups, blood flow data are presented as relative changes of the median from T0. In Groups B and C, changes in respiratory variables were expressed relatively to T1.. Intragroup differences were tested by a global Friedmann test. When this test yielded significant results, a two-by-two Dunn's post-test was applied. Differences between Groups B and C regarding changes from T0 were evaluated by unpaired t tests. Correlation between arterial pressure, aortic blood flow, PaCo2 and mean hepatic, carotid, and renal blood flow changes were tested by Spearman analysis. Results were considered significant when P < 0.05.
Statistical calculations were performed using GraphPad Prism V3.0 for Windows (GraphPad Software, San Diego, California, USA).
| Results |
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At T2 , PEEP induced an increase in ventilatory pressure associated with a decrease in ventilatory volumes. There was a slight decrease in heart rate (P < 0.05), and a more marked decrease in mean arterial pressure (P < 0.001). There was no significant change in aorta, inferior vena cava, and portal vein time averaged blood flow with PEEP. Carotid and renal artery blood flow (P < 0.001), as well as hepatic artery blood flow (P < 0.01) decreased at T2. All but the hepatic artery (P < 0.001) blood flows returned to their T1 values when PEEP was reduced to ZEEP (T3); (Figure 1
).
The changes in hepatic, renal, and carotid artery blood flow were not correlated to the changes in aortic blood flow, arterial pressure, or PaCO2.
Effects of mechanical ventilation and PEEP in closed abdomen rabbits (Group C)
In closed abdomen rabbits, PaCO2 decreased and pH increased slightly at T1 (P < 0.001).
PEEP induced an increase in ventilatory pressure associated with a decrease in ventilatory volumes. There was no significant change in heart rate, and the decrease in mean arterial pressure was significant only between T2 and T3. Aorta (P < 0.01), carotid artery (P < 0.05), hepatic artery (P < 0.001), and renal artery (P < 0.01) blood flow decreased. All variables but PaCO2 (P < 0.01) were not significantly different from their T0 values when PEEP was reduced to ZEEP (T3) (Table II
, Figure 2
).
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| Discussion |
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Effects of PEEP on systemic hemodynamics
In our study, the net effect of PEEP was a decrease in mean arterial blood pressure, especially in open abdomen animals. In the rabbit, the decrease in mean arterial blood pressure during PEEP11 is explained by a decrease in cardiac output,12 a reflex decrease in autonomic tone and, at high lung volume, an increase in pulmonary vascular resistance and a direct mechanical interaction with the heart in a way that limits absolute cardiac volume.13 In our study, the fall in cardiac output, reflected by aortic blood flow, was significant only in closed abdomen animals. Although we didnt measure abdominal pressure, we can assume that it was higher in closed than in open abdomen animals, whereas lung inflation was higher in open abdomen animals. Conversely, the fall in mean arterial blood pressure was associated with a decrease in heart rate only in open abdomen animals. As lung inflation was limited in closed abdomen animals, the inflation-vasodilatation reflex13 may have contributed to the greater fall in mean arterial blood pressure and heart rate in the open abdomen animal.
Effects of PEEP on carotid blood flow
PEEP, but not mechanical ventilation in itself, produced a decrease in common carotid blood flow. In patients with severe head trauma, mechanical ventilation alters the venous return from the brain, inducing an increase in intracranial pressure and a decrease in cerebral blood flow.14 In physiological conditions, autoregulation of cerebral blood flow should limit the decrease in cerebral blood flow. Conversely, the decrease in PaCO2 at ZEEP, and its increase during PEEP, could have induced, respectively, cerebral vasoconstriction and relaxation, but PaCO2 remained low after the onset of mechanical ventilation. Therefore, the decrease in carotid blood flow may have been the combined result of decreased arterial blood pressure, increased venous pressure, and hypocapnia. For technical reasons, we measured only common carotid blood flow but neither internal carotid artery blood flow nor intracranial pressure. Therefore, our results do not allow a definitive conclusion in this regard.
Effects of PEEP on hepatic artery and portal vein blood flow
Bonnet et al.,7 reported a decrease in hepatic blood flow with PEEP correlated to the decrease in CO, but these authors did not measure the mean arterial blood pressure. Hugues et al.9 suggested a correlation with the fall in arterial PaCO2 whereas others attributed the reduction to an increase in hepatic vascular resistance.15 We observed a decrease in hepatic artery blood flow without significant change in portal vein blood flow during PEEP, in open and in closed abdomen animals, and without correlation with CO or PaCO2 changes. The hepatic arterial buffer response by which an increase in portal vein blood flow elicits hepatic artery constriction16 can probably not explain the marked decrease in hepatic artery blood flow we observed since portal vein blood flow rose non significantly and only in open abdomen animals. For Fujita,17 high levels of PEEP are associated with a decrease in hepatic blood flow and oxygen supply along with hepatic congestion. This was possible, although not measured, in open abdomen animals, but probably limited by the rise in abdominal pressure in closed abdomen animals.
Effects of PEEP on renal artery blood flow
Renal blood flow was altered significantly by high PEEP levels, as reported by others.1821 These authors suggested that some reflex vasoconstriction mechanism involving sympathetic activation, and high plasma renin activity, was induced by PEEP and may explain the decrease in renal function.18,19
Limitations of this study
The measurement of cardiac output by the means of an ultrasonic Doppler probe positioned on the ascending aorta has been demonstrated to be as accurate as the thermodilution technique.2224 We used high pulse repetition frequency pulsed Doppler modules for blood flow measurement in small arteries, in order to avoid the aliasing phenomenon that could have resulted in unreadable graphs or false values. Nevertheless, although implanted Doppler probes are widely used for volume blood flow measurement in physiological studies, there are some causes of error. Firstly, not unlike electromagnetic blood flow measurement, pulsed Doppler ultrasound requires the use of fixed diameter probes. Therefore, vasodilatation is not allowed at the exact site of measurement, and the velocity profile may be altered when flow volume increases. This is not a problem with small diameter vessels, since the sample volume covers a large part of the vessel diameter. Conversely, changes in flow velocity profile, from parabolic to flat, may result in underestimation of the flow volume in large vessels, where the Doppler sample volume encompasses only a small portion of the vessel lumen. This effect is minimized when the chosen probe diameter is slightly lower than the vessel diameter in basal conditions.
A thorough evaluation of the venous return to the heart requires the measurement of superior as well as inferior vena cava blood flow. This was not feasible in our study, since this would have implied a large chest opening, with major consequences on ventilation and thoracic pressure.
| Conclusion |
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Revision received December 17, 2001. Accepted for publication August 20, 2001.
| References |
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Schuster S, Erbel R, Weilemann LS, et al. Hemodynamics during PEEP ventilation in patients with severe left ventricular failure studied by transesophageal echocardiography. Chest 1990; 97: 11819.
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Johnson EE, Hedley-Whyte J. Continuous positive-pressure ventilation and portal flow in dogs with pulmonary edema. J Appl Physiol 1972; 33: 3859.
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Priebe H-J, Heimann JC, Hedley-Whyte J. Mechanisms of renal dysfunction during positive end-expiratory pressure ventilation. J Appl Physiol 1981; 50: 6439.
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Haywood JR, Shaffer RA, Fastenow C, Fink GD, Brody MJ. Regional blood flow measurement with pulsed Doppler flowmeter in conscious rat. Am J Physiol 1981; 241: H2738.
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