Portal blood flow in man during graded positive end-expiratory pressure ventilation

The cardiovascular response to graded PEEP ventilation (5–10 cm H₂O) was studied peroperatively in patients undergoing chllecystectomy (n=8) or hepatic tumour surgery (n=3). Portal blood flow was measured by the continuous thermodilution technique and cardiac output, in a sub-group of the patients, by impedance cardiography. A parallel reduction in cardiac output and portal blood flow was demonstrated in patients undergoing cholecystectomy as the result of the application of PEEP. Thus, ventilation with 5 cm H₂O of PEEP elicited a 17% decrease in cardiac output and a 26% decrease in portal blood flow. During 10 cm H₂O of PEEP cardiac output decreased by 22% and portal blood flow by 32%. However, there were no significant changes in preportal tissue perfusion pressure by the application of PEEP and preportal vascular resistance increased by 22% and 30%, respectively. This indicates that a vasoconstrictor response, elicited by PEEP, in the preportal tissue is the predominating mechanism for the observed decrease in portal blood flow. Systemic oxygen transport decreased by 214 ml/min during PEEP ventilation, but preportal tissue oxygen utilization was not significantly changed due to a concurrent increase (2.9%; p<0.05) in oxygen extraction.     

Alterations in regional myocardial blood flows during different levels of positive end-expiratory pressure

A decrease in myocardial blood flow (MBF) has been suggested recently as a contributing factor to the depression of cardiac function during application of PEEP. To test this hypothesis, 7 dogs were anesthetized and their chest wall and pericardium were removed. Hemodynamics, myocardial oxygenation status, and left and right ventricular MBF were measured during controlled ventilation without PEEP (IPPV), with 8 cm H2O of PEEP (CPPV8), 15 cm H2O of PEEP (CPPV15), and 25 cm H2O of PEEP (CPPV25). Compared to IPPV, CPPV8 significantly decreased left ventricular endocardial, epicardial, and septal blood flows. Right ventricular MBF and other measured variables were not affected. Compared to control, CPPV15 decreased left ventricular and septal MBFs in all regions, and right ventricular MBF in the endocardial region. CPPV15 also decreased cardiac index (CI) from 3.94 +/- 0.57 L/min X m2 during control to 2.78 +/- 0.34 L/min X m2 (p less than .05). Compared to IPPV, CPPV25 further decreased MBF in all layers of both ventricles and septum. Compared to CPPV8, there were decreases in left ventricular midwall and septal (left ventricular side and midwall) blood flows during CPPV25. During application of CPPV25, compared to IPPV, mean arterial pressure (MAP) was reduced from 99 +/- 5 to 85 +/- 5 mm Hg, left ventricular stroke work index (LVSWI) decreased from 31.8 +/- 5.4 to 13.8 +/- 2.6 g X m/m2, and CI decreased to 2.13 +/- 0.38 L/min X m2 (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Incidence and regional distribution of lung overinflation during mechanical ventilation with positive end-expiratory pressure

OBJECTIVE: In patients with acute lung injury, alveolar recruitment resulting from positive end-expiratory pressure (PEEP) may be associated with overinflation of previously aerated lung regions. The aim of this study was to assess the incidence and regional distribution of lung overinflation resulting from mechanical ventilation with PEEP. DESIGN: Reanalysis with a specific software including a color-coding system of quantitative lung computed tomography data obtained in four previous prospective studies. SETTING: A 20-bed surgical intensive care unit of a Parisian university hospital. PATIENTS: Thirty-two patients with acute lung injury in whom computed tomography of the whole lung was obtained at zero end-expiratory pressure (ZEEP) and PEEP 15 cm H2O. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total lung recruitment was measured as the reaeration of poorly aerated (computed tomography attenuations ranging between -500 and -100 Hounsfield units) and nonaerated (computed tomography attenuations > or = -100 Hounsfield units) lung areas, and overinflation was measured as the lung volume characterized by computed tomography attenuations < or = -900 Hounsfield units. PEEP was associated with a significant alveolar recruitment (423 +/- 178 mL). Concomitantly, a lung overinflation of 123 +/- 138 mL was found in 14 patients (44%). In eight patients without chronic obstructive pulmonary disease, lung overinflation was predominantly found in nondependent lung regions located beneath the dome of diaphragm. In six patients with a past history of chronic obstructive pulmonary disease, PEEP increased the volume of emphysematous areas present in apical lung regions and produced an overinflation of nondependent lung regions located beneath the dome of diaphragm. CONCLUSION: Lung overinflation resulting from mechanical ventilation with PEEP is observed in more than one third of patients with acute lung injury lying supine and predominates in caudal and nondependent lung regions. Furthermore, in patients with a history of chronic obstructive pulmonary disease, PEEP markedly increases the volume of emphysematous lung regions.     

Hemodynamic effects of positive end-expiratory pressure during high-frequency ventilation

We studied the intrapleural and hemodynamic effects of positive end-expiratory pressure (PEEP) during high-frequency ventilation (HFV) with a Venturi high-frequency ventilator (Bird). Ten healthy mongrel dogs were anesthetized with sodium pentobarbital, catheterized with intrapleural and thermodilution pulmonary artery lines, and subjected to oleic acid-induced pulmonary edema. A mean PEEP of 16 +/- 6 (SD) cm H2O restored venous admixture to baseline in nine animals. Both mean airway pressure (Paw) and mean intrapleural pressure (Ppl) increased significantly with each increment of PEEP during HFV. Approximately 50% of Paw was transmitted to the intrapleural space. Cardiac index (CI) decreased with increments of PEEP in spite of constant transmural central venous and pulmonary capillary wedge pressures, so that oxygen delivery decreased despite increased PaO2. Possible mechanisms of PEEP-induced depression of CI during HFV are discussed. We conclude that both hemodynamic and intrapleural effects of PEEP during HFV are similar to those during conventional mechanical ventilation.     

Mean airway pressure vs. positive end-expiratory pressure during mechanical ventilation

To investigate the effects of both positive end-expiratory pressure (PEEP) and mean airway pressure (Paw) on gas exchange, we used lung lavage to induce severe respiratory insufficiency in six lambs. The animals were then mechanically ventilated at constant tidal volume, respiratory rate, and inspired O2 fraction. PEEP levels were varied -5, +5 and +10 cm H2O around the pressure (Pflex) corresponding to a major change in slope of the inspiratory limb of the respiratory volume-pressure curve. In each animal the effects of the three PEEP levels were studied at two Paw levels, differing by 5 cm H2O. Increasing Paw significantly improved PaO2 and reduced venous admixture. A 5-cm H2O PEEP increase from +5 to +10 did not affect oxygenation; however, oxygenation was significantly better when PEEP was greater than Pflex. Both PaCO2 and anatomic dead space were higher at higher PEEP, and decreased with increasing Paw. Hence, Paw was a major determinant of oxygenation, although a PEEP greater than Pflex appeared necessary to optimize oxygenation at a constant Paw.     

Hemodynamic relationship between renal venous pressure and blood flow regulation during positive end-expiratory pressure

The hemodynamic relationship between renal venous pressure (RVP) and renal blood flow (RBF) during PEEP was investigated using adult mongrel dogs. When continuous mechanical ventilation (CMV) with 10 cm H2O of PEEP was applied to dogs previously on CMV with zero PEEP, RVP increased from 6.6 to 8.7 mm Hg (p less than .01), and left RBF decreased from 66 to 57 ml/min (p less than .05). RBF recovered by 49% of the difference as soon as PEEP was discontinued when the RVP elevation was maintained at the level observed during 10 cm H2O of PEEP. With 20 cm H2O of PEEP, RVP increased further to 10 mm Hg (p less than .01) and left RBF decreased to 48 ml/min (p less than .05). When the left renal vein was occluded and the RVP was maintained at the level seen during 20 cm H2O of PEEP, left RBF recovered only 50% of the difference from the flow during zero PEEP. We conclude that the reduction in RBF with PEEP application is caused by several factors; however, RVP elevation during CMV with PEEP is influential in decreasing RBF.     

Myocardial blood flow and oxygen consumption during positive end-expiratory pressure ventilation at different levels of cardiac inotropy and frequency

Effects of PEEP on cardiac function, myocardial blood flow (MBF) and myocardial oxygen consumption (mVO2) were studied in eight mongrel dogs anesthetized with pentobarbital. Myocardial oxygen demand was increased by isoproterenol infusion or atrial pacing, or decreased by beta-receptor blockade. PEEP was set to 15 cm H2O in all groups. The greatest reduction in cardiac output due to PEEP was seen during isoproterenol infusion (44%), and the smallest during beta-receptor blockade (18%). This is attributed to increased sensitivity to the reduced left ventricular (LV) preload induced by PEEP, when cardiac inotropy is augmented by isoproterenol, compared to normal and reduced cardiac inotropy. PEEP decreased MBF similarly and significantly in all groups. However, myocardial oxygen extraction did not increase, and reduction in MBF caused by PEEP was closely related to concomitant reduction in mVO2. A significant correlation was also observed between reductions in LV work and reduction in mVO2 when PEEP was applied in all groups. We conclude that the reduced MBF observed with use of PEEP was probably due to reduced myocardial oxygen demand.     

Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation

OBJECTIVE: Acute respiratory dysfunction frequently occurs following severe aneurysmal subarachnoid hemorrhage requiring positive end-expiratory pressure (PEEP) ventilation to maintain adequate oxygenation. High PEEP levels, however, may negatively affect cerebral perfusion. The goal of this study was, to examine the influence of various PEEP levels on intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, and systemic hemodynamic variables. DESIGN: Animal research and clinical intervention study. SETTING: Surgical intensive care unit of a university hospital. SUBJECTS AND PATIENTS: Experiments were carried out in five healthy pigs, followed by a clinical investigation of ten patients suffering subarachnoid hemorrhage. INTERVENTIONS: Under continuous monitoring of intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, mean arterial pressure, and cardiac output, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O in the experimental part and from baseline to 20 cm H2O in the clinical part. MEASUREMENTS AND MAIN RESULTS: In animals, high PEEP levels had no adverse effect on intracranial pressure, brain tissue oxygen tension, or regional cerebral blood flow. In patients with severe subarachnoid hemorrhage, stepwise elevation of PEEP resulted in a significant decrease of mean arterial pressure and regional cerebral blood flow. Analyses of covariance revealed that these changes of regional cerebral blood flow depended on mean arterial pressure changes as a result of a disturbed cerebrovascular autoregulation. Consequently, normalization of mean arterial pressure restored regional cerebral blood flow to baseline values. CONCLUSIONS: Application of high PEEP does not impair intracranial pressure or regional cerebral blood flow per se but may indirectly affect cerebral perfusion via its negative effect on macrohemodynamic variables in case of a disturbed cerebrovascular autoregulation. Therefore, following severe subarachnoid hemorrhage, a PEEP-induced decrease of mean arterial pressure should be reversed to maintain cerebral perfusion.     

Setting positive end-expiratory pressure during jet ventilation to replicate the mean airway pressure of oscillatory ventilation

BACKGROUND: High-frequency ventilation can be delivered with either oscillatory ventilation (HFOV) or jet ventilation (HFJV). Traditional clinician biases may limit the range of function of these important ventilation modes. We hypothesized that (1) the jet ventilator can be an accurate monitor of mean airway pressure (P (aw)) during HFOV, and (2) a mathematical relationship can be used to determine the positive end-expiratory pressure (PEEP) setting required for HFJV to reproduce the P (aw) of HFOV. METHODS: In phase 1 of our experiment, we used a differential pressure pneumotachometer and a jet adapter in-line between an oscillator circuit and a pediatric lung model to measure P (aw), PEEP, and peak inspiratory pressure (PIP). Thirty-six HFOV setting combinations were studied, in random order. We analyzed the correlation between the pneumotachometer and HFJV measurements. In phase 2 we used the jet as the monitoring device during each of the same 36 combinations of HFOV settings, and recorded P (aw), PIP, and DeltaP. Then, for each combination of settings, the jet ventilator was placed in-line with a conventional ventilator and was set at the same rate and PIP as was monitored during HFOV. To determine the appropriate PEEP setting, we calculated the P (aw) contributed by the PIP, respiratory rate, and inspiratory time set for HFJV, and subtracted this from the goal P (aw). This value was the PEEP predicted for HFJV to match the HFOV P (aw). RESULTS: The correlation coefficient between the pneumotachometer and HFJV measurements was r = 0.99 (mean difference 0.62 +/- 0.30 cm H(2)O, p < 0.001). The predicted and actual PEEP required were highly correlated (r = 0.99, p < 0.001). The mean difference in these values is not statistically significantly different from zero (mean difference 0.25 +/- 1.02 cm H(2)O, p > 0.15). CONCLUSIONS: HFJV is an accurate monitor during HFOV. These measurements can be used to calculate the predicted PEEP necessary to match P (aw) on the 2 ventilators. Replicating the P (aw) with adequate PEEP on HFJV may help simplify transitioning between ventilators when clinically indicated.     

Monitoring of total positive end-expiratory pressure during mechanical ventilation by artificial neural networks

Ventilation treatment of acute lung injury (ALI) requires the application of positive airway pressure at the end of expiration (PEEP_app) to avoid lung collapse. However, the total pressure exerted on the alveolar walls (PEEP_tot) is the sum of PEEP_app and intrinsic PEEP (PEEP_i), a hidden component. To measure PEEP_tot, ventilation must be discontinued with an end-expiratory hold maneuver (EEHM). We hypothesized that artificial neural networks (ANN) could estimate the PEEP_tot from flow and pressure tracings during ongoing mechanical ventilation. Ten pigs were mechanically ventilated, and the time constant of their respiratory system (τ_RS) was measured. We shortened their expiratory time (TE) according to multiples of τ_RS, obtaining different respiratory patterns (R_pat). Pressure (P_AW) and flow (V′_AW) at the airway opening during ongoing mechanical ventilation were simultaneously recorded, with and without the addition of external resistance. The last breath of each R_pat included an EEHM, which was used to compute the reference PEEP_tot. The entire protocol was repeated after the induction of ALI with i.v. injection of oleic acid, and 382 tracings were obtained. The ANN had to extract the PEEP_tot, from the tracings without an EEHM. ANN agreement with reference PEEP_tot was assessed with the Bland–Altman method. Bland Altman analysis of estimation error by ANN showed ?0.40 ± 2.84 (expressed as bias ± precision) and ±5.58 as limits of agreement (data expressed as cmH₂O). The ANNs estimated the PEEP_tot well at different levels of PEEP_app under dynamic conditions, opening up new possibilities in monitoring PEEP_i in critically ill patients who require ventilator treatment.     

Paradoxical responses to positive end-expiratory pressure in patients with airway obstruction during controlled ventilation

OBJECTIVE: To reevaluate the clinical impact of external positive end-expiratory pressure (external-PEEP) application in patients with severe airway obstruction during controlled mechanical ventilation. The controversial occurrence of a paradoxic lung deflation promoted by PEEP was scrutinized. DESIGN: External-PEEP was applied stepwise (2 cm H(2)O, 5-min steps) from zero-PEEP to 150% of intrinsic-PEEP in patients already submitted to ventilatory settings minimizing overinflation. Two commonly used frequencies during permissive hypercapnia (6 and 9/min), combined with two different tidal volumes (VT: 6 and 9 mL/kg), were tested. SETTING: A hospital intensive care unit. PATIENTS: Eight patients were enrolled after confirmation of an obstructive lung disease (inspiratory resistance, >20 cm H(2)O/L per sec) and the presence of intrinsic-PEEP (> or =5 cm H(2)O) despite the use of very low minute ventilation. INTERVENTIONS: All patients were continuously monitored for intra-arterial blood gas values, cardiac output, lung mechanics, and lung volume with plethysmography. MEASUREMENTS AND MAIN RESULTS: Three different responses to external-PEEP were observed, which were independent of ventilatory settings. In the biphasic response, isovolume-expiratory flows and lung volumes remained constant during progressive PEEP steps until a threshold, beyond which overinflation ensued. In the classic overinflation response, any increment of external-PEEP caused a decrease in isovolume-expiratory flows, with evident overinflation. In the paradoxic response, a drop in functional residual capacity during external-PEEP application (when compared to zero-external-PEEP) was commonly accompanied by decreased plateau pressures and total-PEEP, with increased isovolume-expiratory flows. The paradoxic response was observed in five of the eight patients (three with asthma and two with chronic obstructive pulmonary disease) during at least one ventilator pattern. CONCLUSIONS: External-PEEP application may relieve overinflation in selected patients with airway obstruction during controlled mechanical ventilation. No a priori information about disease, mechanics, or ventilatory settings was predictive of the response. An empirical PEEP trial investigating plateau pressure response in these patients appears to be a reasonable strategy with minimal side effects.     

"The use of positive end-expiratory pressure in mechanical ventilation"

An improvement in oxygenation for patients who have acute respiratory failure using PEEP was described close to 40 years ago. Since then, a considerable amount of research has allowed clinicians to use this therapeutic modality in various ways. In patients receiving mechanical ventilation, the term positive end-expiratory pressure (PEEP) refers to pressure in the airway at the end of passive expiration that exceeds atmospheric pressure. The use of PEEP mainly has been reserved to recruit or stabilize lung units and improve oxygenation in patients who have hypoxemic respiratory failure. It has been shown that this helps the respiratory muscles to decrease the work of breathing and the amount of infiltrated-atelectatic tissues. The beneficial effects of the use of PEEP include: the improvement of oxygenation, recruitment of lung units, and improvement of compliance. Other effects can be adverse, like decreasing cardiac output, increased risk of barotrauma, and the interference with assessment of hemodynamic pressures.     

The effect of positive end-expiratory pressure ventilation on propofol concentrations during general anesthesia in humans

The present study investigated the effects of positive end-expiratory pressure (PEEP) on propofol concentrations in humans. Eleven patients undergoing elective surgery were enrolled in this study. Anesthesia was induced with propofol, then maintained using 60% nitrous oxide in oxygen, fentanyl 10-20 microg/kg and continuous infusion of propofol. Vecuronium was used to facilitate the artificial ventilation of the lungs. Propofol was administered to all subjects via target-controlled infusion to achieve a propofol concentration of 6.0 microg/mL at intubation and 2.0 microg/mL after intubation. Before, during and after PEEP level of 10 cmH(2)O, cardiac output (CO) and effective liver blood flow (LBF) was measured using indocyanine green as an indicator and blood propofol concentration was determined using high-performance liquid chromatography. Data are expressed as median and range. After PEEP of 10 cmH(2)O was applied, CO and effective LBF was significantly decreased from 5.5 (3.8-6.8) L/min to 4.5 (3.2-5.8) L/min (P < 0.05), 0.78 (0.65-1.21) L/min to 0.65 (0.50-0.89) L/min (P < 0.05), respectively. Propofol concentration was significantly increased from 2.21 (1.46-2.63) microg/mL to 2.45(1.79-2.89) microg/mL (P < 0.05). These data indicate that propofol concentrations can be increased by PEEP, suggesting the possibility of overdosing following PEEP.     

Bronchial blood flow reduction with positive end-expiratory pressure after acute lung injury in sheep

Smoke inhalation increases bronchial blood flow (Qbr) and produces edema of the airway system. This study investigates whether the increased Qbr seen 24 h after inhalation injury can be affected by mechanical ventilation with PEEP (5, 10, 15 cm H2O). Sheep (n = 8) previously prepared with cardiopulmonary catheters and ultrasonic transit time flow probes mounted around their bronchial arteries were insufflated with four sets of 12 breaths each of cotton smoke. Different levels of PEEP were added to the mechanical ventilation 24 h after injury; each PEEP level was applied for 45 min. There were significant increases in Qbr and lung lymph flow (QL) associated with a marked decrease in bronchial vascular resistance (BVR) 24 h after injury. However, no change was observed in mean arterial pressure (MAP) or cardiac index (CI). There was a substantial reduction in PaO2/FIO2 (P/F), which indicated a deterioration in arterial oxygenation. The application of varying levels of PEEP decreased Qbr (p less than .05) while BVR increased (p less than .05), but QL and P/F did not. CI and MAP were recorded. After removal of PEEP, none of the cardiopulmonary variables were significantly different from their postsmoke control values. These findings suggest that mechanical ventilation with PEEP markedly decreases the smoke-induced hyperemia edema frequently seen after inhalation injury without any significant alterations in MAP or CI.