Respiratory failure in acute pancreatitis: a possible role for triglycerides.

Respiratory failure is a frequent complication of acute pancreatitis. Two clinical studies of this association have demonstrated a high incidence of concomitant hypertriglyceridemia. Experimental studies were carried out using an ex vivo, isolated, perfused, ventilated, canine pulmonary lobe to evaluate the effects of triglyceride elevations on pulmonary mechanics and gas exchange. Control lobes perfused for a four hour period remained stable. When 5g and 10g of triglyceride were added to the perfusate, the lobes became grossly edematous and hemorrhagic. Intrapulmonary shunting developed (23 and 46%), weight gain occurred (130 and 189g), effective compliance decreased, and the pressure-volume deflation curves became abnormal. Free fatty acid (FFA) levels increased markedly during the perfusion periods. When small quantities of FFA were infused directly into the pulmonary artery, similar changes, but less severe, occurred. These studies demonstrate that triglyceride elevations are capable of adversely affecting pulmonary gas exchange and mechanics. Such changes probably occur secondary to FFA release. These data thus add support to the concept that the respiratory insufficiency that is seen in acute pancreatitis could be mediated through triglyceride elevations.     

Aspiration pneumonia: experimental evaluation of albumin and steroid therapy.

An experimental model using an ex vivo perfused ventilated canine pulmonary lobe was used to study aspiration pneumonia. After intrabronchial acid instillation, the lobe weight tripled, air way pressure and pulmonary artery pressure doubled, and intrapulmonary shunting increased from 5.5% to 53.4%. If large quantities of albumin were added to the lobe perfusate 5 minutes after intrabronchial acid instillation, weight gain, air way and pulmonary artery pressure, and intrapulmonary shunting were unchanged from control levels. If large quantities of steroid were added to the lobe perfusate 5 minutes after intrabronchial acid instillation, the lobe weight doubled but air way pressure and pulmonary artery pressure, and intrapulmonary shunting were not significantly different from control values. It is surmised that intrapulmonary acid aspiration causes an immediate and marked changed in pulmonary capillary permeability. Albumin administration by counteracting this permeability change, and steroid administration by modifying the permeability change, are both beneficial following acid aspiration.     

Different ventilation strategies affect lung function but do not increase tumor necrosis factor-alpha and prostacyclin production in lavaged rat lungs in vivo

BACKGROUND: Using an in vivo animal model of surfactant deficiency, the authors compared the effect of different ventilation strategies on oxygenation and inflammatory mediator release from the lung parenchyma. METHODS: In adult rats that were mechanically ventilated with 100% oxygen, acute lung injury was induced by repeated lung lavage to obtain an arterial oxygen partial pressure < 85 mmHg (peak pressure/positive end-expiratory pressure [PEEP] = 26/6 cm H2O). Animals were then randomly assigned to receive either exogenous surfactant therapy, partial liquid ventilation, ventilation with high PEEP (16 cm H2O), ventilation with low PEEP (8 cm H2O), or ventilation with an increase in peak inspiratory pressure (to 32 cm H2O; PEEP = 6 cm H2O). Two groups of healthy nonlavaged rats were ventilated at a peak pressure/PEEP of 32/6 and 32/0 cm H2O, respectively. Blood gases were measured. Prostacyclin (PGI2) and tumor necrosis factor-alpha (TNF-alpha) concentrations in serum and bronchoalveolar lavage fluid (BALF) as well as protein concentration in BALF were determined after 90 and 240 min and compared with mechanically ventilated and spontaneously breathing controls. RESULTS: Surfactant, partial liquid ventilation, and high PEEP improved oxygenation and reduced BALF protein levels. Ventilation with high PEEP at high mean airway pressure levels increased BALF PGI2 levels, whereas there was no difference in BALF TNF-alpha levels between groups. Serum PGI2 and TNF-alpha levels did not increase as a result of mechanical ventilation when compared with those of spontaneously breathing controls. CONCLUSIONS: Although alveolar protein concentration and oxygenation markedly differed with different ventilation strategies in this model of acute lung injury, there were no indications of ventilation-induced systemic PGI2 and TNF-alpha release, nor of pulmonary TNF-alpha release. Mechanical ventilation at high mean airway pressure levels increased PGI2 levels in the bronchoalveolar lavage-accessible space.     

Comparison of exogenous surfactant therapy, mechanical ventilation with high end-expiratory pressure and partial liquid ventilation in a model of acute lung injury

We have compared three treatment strategies, that aim to prevent repetitive alveolar collapse, for their effect on gas exchange, lung mechanics, lung injury, protein transfer into the alveoli and surfactant system, in a model of acute lung injury. In adult rats, the lungs were ventilated mechanically with 100% oxygen and a PEEP of 6 cm H2O, and acute lung injury was induced by repeated lung lavage to obtain a PaO2 value < 13 kPa. Animals were then allocated randomly (n = 12 in each group) to receive exogenous surfactant therapy, ventilation with high PEEP (18 cm H2O), partial liquid ventilation or ventilation with low PEEP (8 cm H2O) (ventilated controls). Blood-gas values were measured hourly. At the end of the 4-h study, in six animals per group, pressure-volume curves were constructed and bronchoalveolar lavage (BAL) was performed, whereas in the remaining animals lung injury was assessed. In the ventilated control group, arterial oxygenation did not improve and protein concentration of BAL and conversion of active to non-active surfactant components increased significantly. In the three treatment groups, PaO2 increased rapidly to > 50 kPa and remained stable over the next 4 h. The protein concentration of BAL fluid increased significantly only in the partial liquid ventilation group. Conversion of active to non-active surfactant components increased significantly in the partial liquid ventilation group and in the group ventilated with high PEEP. In the surfactant group and partial liquid ventilation groups, less lung injury was found compared with the ventilated control group and the group ventilated with high PEEP. We conclude that although all three strategies improved PaO2 to > 50 kPa, the impact on protein transfer into the alveoli, surfactant system and lung injury differed markedly.      

Effect of mechanical ventilation on cytokine response to intratracheal lipopolysaccharide

BACKGROUND: Mechanical ventilation may cause lung injury through the excitation of an inflammatory response and the release of mediators, such as cytokines. The authors tested the hypothesis that intratracheal lipopolysaccharide amplifies the cytokine response to mechanical ventilation. METHODS: Rat lungs were intratracheally instilled with lipopolysaccharide followed by ex vivo mechanical ventilation for 2 h with low tidal volume of 7 ml/kg with 3 cm H2O positive end-expiratory pressure (PEEP), high tidal volume of 40 ml/kg with zero PEEP, medium tidal volume of 15 ml/kg with 3 cm H2O PEEP, or medium tidal volume and zero PEEP. RESULTS: In the absence of lipopolysaccharide, lung lavage concentrations of tumor necrosis factor and interleukin 1 beta but not macrophage inflammatory protein 2 were significantly higher in lungs ventilated at high tidal volume/zero PEEP than at low tidal volume. There was a marked increase in lavage tumor necrosis factor and macrophage inflammatory protein 2 concentrations in lungs ventilated at low tidal volume after exposure to intratracheal lipopolysaccharide at doses of 100 ng/ml or greater. However, in lungs ventilated at high tidal volume, this response to lipopolysaccharide was markedly reduced. In addition, the number of alveolar macrophages recovered in the lavage was significantly lower in lungs ventilated at high tidal volume. CONCLUSION: Ventilation strategy can modify lung cytokine responses to lipopolysaccharide, likely through an effect on the alveolar macrophage population.     

Effect of Mechanical Ventilation on Cytokine Response to Intratracheal Lipopolysaccharide

Background: Mechanical ventilation may cause lung injury through the excitation of an inflammatory response and the release of mediators, such as cytokines. The authors tested the hypothesis that intratracheal lipopolysaccharide amplifies the cytokine response to mechanical ventilation.

Methods: Rat lungs were intratracheally instilled with lipopolysaccharide followed by ex vivo mechanical ventilation for 2 h with low tidal volume of 7 ml/kg with 3 cm H2O positive end-expiratory pressure (PEEP), high tidal volume of 40 ml/kg with zero PEEP, medium tidal volume of 15 ml/kg with 3 cm H2O PEEP, or medium tidal volume and zero PEEP.

Results: In the absence of lipopolysaccharide, lung lavage concentrations of tumor necrosis factor and interleukin 1[beta] but not macrophage inflammatory protein 2 were significantly higher in lungs ventilated at high tidal volume/zero PEEP than at low tidal volume. There was a marked increase in lavage tumor necrosis factor and macrophage inflammatory protein 2 concentrations in lungs ventilated at low tidal volume after exposure to intratracheal lipopolysaccharide at doses of 100 ng/ml or greater. However, in lungs ventilated at high tidal volume, this response to lipopolysaccharide was markedly reduced. In addition, the number of alveolar macrophages recovered in the lavage was significantly lower in lungs ventilated at high tidal volume.     

Functional residual capacity and respiratory mechanics as indicators of aeration and collapse in experimental lung injury

Increased functional residual capacity (FRC) and compliance are two desirable, but seldom measured, effects of positive end-expiratory pressure (PEEP) in mechanically ventilated patients. To assess how these variables reflect the morphological lung perturbations during the evolution of acute lung injury and the morphological changes from altered PEEP, we correlated measurements of FRC and respiratory system mechanics to the degree of lung aeration and consolidation on computed tomography (CT). We used a porcine oleic acid model with FRC determinations by sulfur hexafluoride washin-washout and respiratory system mechanics measured during an inspiratory hold maneuver. Within the first hour, during constant volume-controlled ventilation with PEEP 5 cm H(2)O, FRC decreased by 45% +/- 15% (P = 0.005) and compliance decreased by 35% +/- 12% (P = 0.005). Resistance increased by 60% +/- 62% (P = 0.005). Only the FRC changes correlated significantly to the decreased aeration (R(2) = 0.56; P = 0.01) and the increased consolidation (R(2) = 0.43; P = 0.04) on CT. When the PEEP was changed to either 10 or 0 cm H(2)O, there were larger changes in FRC than in compliance. We conclude that, in our model, FRC was a more sensitive indicator of PEEP-induced aeration and recruitment of lung tissue and that FRC may be a useful adjunct to PaO(2) monitoring. IMPLICATIONS: Lung injury was quantified on computed tomography and related to monitored values of functional residual capacity and mechanical properties of the respiratory system. We found the functional residual capacity to be a more sensitive marker of the lung perturbations than the compliance. It might be of value to include functional residual capacity in the monitoring of acute lung injury.     

Effect of PEEP on the rate of thoracic duct lymph flow and clearance of bacteria from the peritoneal cavity

A nonvirulent strain of E. coli, type K¹²F-, that was labelled with chromium-51 was injected intraperitoneally. The thoracic duct was cannulated in the left side of the neck. Dogs were randomly divided into two groups. In Group A, six dogs were ventilated with a mechanical ventilator for 1 hour. They were then ventilated with PEEP (expiratory limb of the nonrebreathing system 10 cm below water level) for 1 hour, and finally ventilated without PEEP for another 30 minutes. In Group B, five dogs were initially ventilated with PEEP in the same manner employed in Group A for 1 hour, then were ventilated without PEEP for 1 hour, and finally were again ventilated with 10 cm PEEP for 30 minutes. Thoracic duct lymph was collected in 10 minute aliquots throughout the experiment.In Group A, when PEEP was instituted after a period of mechanical ventilation, there was significant diminution in the rate of lymph flow, but no significant change in bacterial clearance. When PEEP was discontinued, both lymph flow rate and bacterial clearance increased significantly. In Group B, when PEEP was removed, both lymph flow rate and bacterial clearance increased significantly. When PEEP was reinstituted, the rate of lymph flow significantly decreased, but the change in bacterial clearance was not significant.PEEP may exert a deleterious effect on the clearance of bacteria and particulate debris from the peritoneal cavity through the thoracic lymphatic vessels and should be used with caution in patients with abdominal sepsis.     

The effect of prolonged inspiration time and PEEP on compliance and gas exchange in ventilated patients (author's transl)

The effect of prolonged inspiration time and PEEP on compliance, haemodynamics and gas exchange was studied on 15 patients, who were ventilated because of respiratory distress syndrome. The patients were ventilated by the Servoventilator 900 BR connected with a calculation unit. The inspiration time varied from 35 to 70%, the PEEP from 0 to 20 cm H2O. All patients were ventilated with constant tidal volumes (10-15 ml/kg b.w.). The compliance rose from 48 ml/H2O (ZEEP) to 61,5 ml/cm H2O (PEEP + 8 ml H2O). A further increase of PEEP caused a decrease of compliance to 48 ml/cm H2O (PEEP + 20 cm H2O). A prolongation of inspiration time of up to 53% showed an augmentation of compliance from 48 ml/cm H2O to 53 ml/cm H2O. Both modes of assisted ventilation caused an improvement of alveolar ventilation. The simultaneous consideration of various parameters of gas exchange, compliance and haemodynamics guaranteed the optimal mode of ventilation and minimal side effects.     

Different Ventilation Strategies Affect Lung Function but Do Not Increase Tumor Necrosis Factor-α and Prostacyclin Production in Lavaged Rat Lungs In Vivo

Background: Using an in vivo animal model of surfactant deficiency, the authors compared the effect of different ventilation strategies on oxygenation and inflammatory mediator release from the lung parenchyma.

Methods: In adult rats that were mechanically ventilated with 100% oxygen, acute lung injury was induced by repeated lung lavage to obtain an arterial oxygen partial pressure < 85 mmHg (peak pressure/positive end-expiratory pressure [PEEP] = 26/6 cm H2O). Animals were then randomly assigned to receive either exogenous surfactant therapy, partial liquid ventilation, ventilation with high PEEP (16 cm H2O), ventilation with low PEEP (8 cm H2O), or ventilation with an increase in peak inspiratory pressure (to 32 cm H2O; PEEP = 6 cm H2O). Two groups of healthy nonlavaged rats were ventilated at a peak pressure/PEEP of 32/6 and 32/0 cm H2O, respectively. Blood gases were measured. Prostacyclin (PGI2) and tumor necrosis factor-[alpha] (TNF-[alpha]) concentrations in serum and bronchoalveolar lavage fluid (BALF) as well as protein concentration in BALF were determined after 90 and 240 min and compared with mechanically ventilated and spontaneously breathing controls.

Results: Surfactant, partial liquid ventilation, and high PEEP improved oxygenation and reduced BALF protein levels. Ventilation with high PEEP at high mean airway pressure levels increased BALF PGI2 levels, whereas there was no difference in BALF TNF-[alpha] levels between groups. Serum PGI2 and TNF-[alpha] levels did not increase as a result of mechanical ventilation when compared with those of spontaneously breathing controls.     

Effect of positive end-expiratory-pressure on regional ventilation in patients with acute lung injury evaluated by electrical impedance tomography

BACKGROUND AND OBJECTIVE: For the treatment of patients with adult respiratory distress syndrome and acute lung injury bedside measurements of regional lung ventilation should be considered for optimizing ventilatory settings. The aim was to investigate the effect of positive end-expiratory pressure (PEEP) on regional ventilation in mechanically ventilated patients at the bedside by electrical impedance tomography. METHODS: Eight mechanically ventilated patients were included in the study. PEEP levels were increased from 0 to 5, 10, 15 mbar and back to 0 mbar. Regional ventilation in 912 regions of the thorax was investigated at each PEEP by electrical impedance tomography. The obtained regions were divided in four groups: none (none and poorly ventilated regions including chest wall and mediastinum), bad, moderate and well-ventilated regions. RESULTS: Increasing the PEEP stepwise from 0 to 15 mbar decreased the non-ventilated regions (none: 540 regions at PEEP 0 and 406 regions at PEEP 15). In contrast, the other regions increased (bad: 316 regions at PEEP 0 and 380 regions at PEEP 15; moderate: 40 regions at PEEP 0 and 100 regions at PEEP 15; well: 0 region at PEEP 0 and 34 regions at PEEP 15 (median values)) indicating an improvement of regional ventilation. CONCLUSIONS: Increasing PEEP in mechanically ventilated patients reduces none ventilated regions (atelectasis). Furthermore, it leads to a shift from none and bad ventilated regions to moderately and well-ventilated regions. Electrical impedance tomography is a bedside technique and might be an alternative to computed tomography scan to assess aerated lung regions.     

Relation of the static compliance curve and positive end-expiratory pressure to oxygenation during one-lung ventilation.

BACKGROUND: Positive end-expiratory pressure (PEEP) is commonly applied to the ventilated lung to try to improve oxygenation during one-lung ventilation but is an unreliable therapy and occasionally causes arterial oxygen partial pressure (PaO(2)) to decrease further. The current study examined whether the effects of PEEP on oxygenation depend on the static compliance curve of the lung to which it is applied. METHODS: Forty-two adults undergoing thoracic surgery were studied during stable, open-chest, one-lung ventilation. Arterial blood gases were measured during two-lung ventilation and one-lung ventilation before, during, and after the application of 5 cm H(2)O PEEP to the ventilated lung. The plateau end-expiratory pressure and static compliance curve of the ventilated lung were measured with and without applied PEEP, and the lower inflection point was determined from the compliance curve. RESULTS: Mean (+/- SD) PaO(2) values, with a fraction of inspired oxygen of 1.0, were not different during one-lung ventilation before (192 +/- 91 mmHg), during (190 +/- 90), or after ( 205 +/- 79) the addition of 5 cm H(2)O PEEP. The mean plateau end-expiratory pressure increased from 4.2 to 6.8 cm H(2)O with the application of 5 cm H(2)O PEEP and decreased to 4.5 cm H(2)O when 5 cm H(2)O PEEP was removed. Six patients showed a clinically useful (> 20%) increase in PaO(2) with 5 cm H(2)O PEEP, and nine patients had a greater than 20% decrease in PaO(2). The change in PaO(2) with the application of 5 cm H(2)O PEEP correlated in an inverse fashion with the change in the gradient between the end-expiratory pressure and the pressure at the lower inflection point (r = 0.76). The subgroup of patients with a PaO(2) during two-lung ventilation that was less than the mean (365 mmHg) and an end-expiratory pressure during one-lung ventilation without applied PEEP less than the mean were more likely to have an increase in PaO(2) when 5 cm H(2)O PEEP was applied. CONCLUSIONS: The effects of the application of external 5 cm H(2)O PEEP on oxygenation during one-lung ventilation correspond to individual changes in the relation between the plateau end-expiratory pressure and the inflection point of the static compliance curve. When the application of PEEP causes the end-expiratory pressure to increase from a low level toward the inflection point, oxygenation is likely to improve. Conversely, if the addition of PEEP causes an increased inflation of the ventilated lung that raises the equilibrium end-expiratory pressure beyond the inflection point, oxygenation is likely to deteriorate.     

Expiratory flow limitation in morbidly obese postoperative mechanically ventilated patients

Although obesity promotes tidal expiratory flow limitation (EFL), with concurrent dynamic hyperinflation (DH), intrinsic PEEP (PEEPi) and risk of low lung volume injury, the prevalence and magnitude of EFL, DH and PEEPi have not yet been studied in mechanically ventilated morbidly obese subjects. In 15 postoperative mechanically ventilated morbidly obese subjects, we assessed the prevalence of EFL [using the negative expiratory pressure (NEP) technique], PEEPi, DH, respiratory mechanics, arterial oxygenation and PEEPi inequality index as well as the levels of PEEP required to abolish EFL. In supine position at zero PEEP, 10 patients exhibited EFL with a significantly higher PEEPi and DH and a significantly lower PEEPi inequality index than found in the five non-EFL (NEFL) subjects. Impaired gas exchange was found in all cases without significant differences between the EFL and NEFL subjects. Application of 7.5 +/- 2.5 cm H2O of PEEP (range: 4-16) abolished EFL with a reduction of PEEPi and DH and an increase in FRC and the PEEPi inequality index but no significant effect on gas exchange. The present study indicates that: (a) on zero PEEP, EFL is present in most postoperative mechanically ventilated morbidly obese subjects; (b) EFL (and concurrent risk of low lung volume injury) is abolished with appropriate levels of PEEP; and (c) impaired gas exchange is common in these patients, probably mainly due to atelectasis.     

Cardiopulmonary effects of oleic acid-induced pulmonary edema and mechanical ventilation

In order to define the mechanisms whereby cardiac output and arterial oxygen transport are reduced by acute permeability pulmonary edema and by positive end-expiratory pressure (PEEP), hemodynamic, respiratory, and lung water changes were measured in 12 mechanically ventilated dogs prior to the injection of oleic acid and at 1, 2.5, and 4 hr after the injection. Measurements were performed at each interval before and after the addition of 20 cm H2O PEEP. Positive end-expiratory pressure was not continued between measurements. One hour after the oleic acid injection, the lung water content and the pulmonary vascular resistance had increased more than 100% while the right ventricular (RV) volume, RV stroke volume, and PaO2 had decreased more than 35%. Each application of PEEP increased the PaO2 to control levels. However, PEEP also significantly increased the lung water content and pulmonary vascular resistance, and decreased the RV volume and stroke volume by 33%. The extravasation of fluid from the intravascular to the interstitial and alveolar spaces of the lung with oleic acid pulmonary edema is associated with substantial decreases in right ventricular volume and stroke volume and significant increases in the pulmonary vascular resistance. Treatment with 20 cm H2O PEEP further increases the lung water content and pulmonary vascular resistance and substantially reduces the right ventricular volume and stroke volume.     

Effects of sternotomy on heart-lung interaction in patients undergoing cardiac surgery receiving pressure-controlled mechanical ventilation

BACKGROUND: The key concept underlying the dynamic indexes of preload dependence is the physiological heart-lung interaction. During sternotomy this interaction undergoes various changes, some of which remain unclear. Our primary aim was to investigate how the interaction changes during sternotomy by evaluating pulse pressure variations (PPV) with the chest closed and after sternotomy in patients ventilated using the pressure-controlled mode. METHODS: We prospectively studied 25 patients undergoing coronary artery bypass grafting (CABG) receiving pressure-controlled ventilation. Standard hemodynamic data, PPV and tidal volume delivered were recorded before and after sternotomy, and, with the chest open, before and after positive end-expiratory pressure (PEEP) was applied and inspiratory pressure was increased. RESULTS: Sternotomy left all variables statistically unchanged from values before thoracotomy although in the subgroup of patients with a PPV > 8% (56%) sternotomy significantly reduced PPV (from 14.4 +/- 5.2% to 8.9 +/- 4.5%). With the chest open, when PEEP was applied at 5 cm H(2)O, tidal volume decreased (from 643 +/- 83 to 587 +/- 104 ml) and stroke volume decreased (from 77 +/- 17 to 72 +/- 15 ml) but PPV remained unchanged. When PEEP was discontinued and inspiratory pressure was increased by 5 cm H(2)O, tidal volume increased (from 643 +/- 83 to 814 +/- 89 ml) and PPV increased (from 8.2 +/- 3.9% to 12.3 +/- 6.8%) but stroke volume remained unchanged. CONCLUSIONS: In patients ventilated in the pressure-controlled mode, except those with a pre-sternotomy PPV > 8% (fluid responders), sternotomy leaves standard hemodynamic data and PPV unchanged. When the chest wall is open, cyclic changes (tidal volume) but not continuous changes (PEEP) in intrathoracic pressure directly influence PPV.     

Pulmonary responses of unilateral positive end expiratory pressure (PEEP) on experimental fat embolism.

The role of positive end expiratory pressure (PEEP) was evaluated in preventing the deleterious mechanical respiratory effects of fatty acid pulmonary embolism. One group of animals had ventilation without PEEP, while the second group had PEEP of 10 cm H2O applied only to the right lung. In the right lung, PEEP slightly reduced the blood flow, increased the vascular resistance, but reduced intersititial edema and reduced the degree of shunting to almost normal. Hypoxemia was prevented in the right pulmonary venous system, but was prominent in the left. The hypoxemia and shunting in the left lung were comparable to the Group I animals without PEEP to either lung. These studies confirm the value of PEEP in the therapy of the pulmonary manifestations of fat embolism which are the lethal factors in the fatty embolism syndrome.     

The effect of incremental positive end-expiratory pressure on right ventricular hemodynamics and ejection fraction

The effects of incremental positive end-expiratory pressure (PEEP) on right ventricular (RV) function were evaluated in 36 (n = 36) ventilated patients. Positive end-expiratory pressure was increased from 0 (baseline) to 20 cm H2O in 5-cm H2O increments and RV hemodynamics and thermally derived right ventricular ejection fraction (RVEF), right ventricular end-diastolic volume index (RVEDVI), and right ventricular end-systolic volume index (RVESVI) were computed. Right ventricular contractility was determined from the analysis of RV systolic pressure-volume relations. Right ventricular ejection fraction declined from 42 +/- 8% at baseline to 30 +/- 9% at 20 cm H2O PEEP. Right ventricular end-diastolic volume index declined between 0 and 5 cm H2O PEEP (103 +/- 42 to 92 +/- 34 ml.m-2) and then increased to 113 +/- 40 at 20 cm H2O PEEP. Right ventricular end-systolic volume index increased from 60 +/- 31 ml.m-2 at baseline to 79 +/- 34 ml.m-2 at 20 cm H2O PEEP. The slope (E) of the relation of RV peak systolic pressure to RV end-systolic volume index decreased from 0.26 mm Hg.m2.ml-1 between PEEP of 0-15 cm H2O to 0.05 mm Hg.m2.m-1 at PEEP greater than 15 cm H2O. It is concluded that low levels of PEEP have a predominant preload reducing effect on the RV. Above 15 cm H2O PEEP, RV volumes increase and E decreases, consistent with increased RV afterload and a decline in RV contractility.     

The acute effects of intralipid on lung function

To determine whether the oleic acid contained in intralipid injures the lung, we measured fractional lobar perfusion, lobar shunt, and edema (wet to dry weight ratios, W/D) in 20 open-chested mechanically ventilated dogs. Five dogs received oleic acid 0.03 g/kg injected into a lower lobe pulmonary artery. Ten received 0.5 cc/kg of 20% intralipid which contains the equivalent amount of oleic acid, five of these animals being heparinized. The same dose of oleic acid was also suspended in intralipid and administered to five heparinized dogs. Shunt and edema were measured in another five heparinized closed-chested dogs receiving 2 g/kg of intralipid IV over 1 hr. Half hour after intralipid or oleic acid, shunts did not change. At 2 1/2 hr, oleic acid alone increased lobar shunt from 4.6 +/- 1.4 to 40.8 +/- 24.9% while intralipid shunt remained unchanged with and without heparin. Lobar perfusion fell significantly with oleic acid from 29.3 +/- 2.3 to 17.8 +/- 5.6% while showing no change in the lobes not receiving oleic acid. When oleic acid was suspended in intralipid, shunt and perfusion changed less than with oleic acid alone. Mean W/D of the oleic acid lower lobe exceeded (P less than 0.05) W/D of the other lobes, including the lobe receiving oleic acid suspended in intralipid which had a W/D greater than the lobes receiving intralipid only. We conclude that intralipid has no acute deleterious effects on pulmonary gas exchange, blood flow distribution, or edema. Our data suggest that intralipid may protect the lung from the deleterious effects of fatty acids.     

Relation of the Static Compliance Curve and Positive End-expiratory Pressure to Oxygenation during One-lung Ventilation

Background : Positive end-expiratory pressure (PEEP) is commonly applied to the ventilated lung to try to improve oxygenation during one-lung ventilation but is an unreliable therapy and occasionally causes arterial oxygen partial pressure (Pao2) to decrease further. The current study examined whether the effects of PEEP on oxygenation depend on the static compliance curve of the lung to which it is applied.

Methods : Forty-two adults undergoing thoracic surgery were studied during stable, open-chest, one-lung ventilation. Arterial blood gasses were measured during two-lung ventilation and one-lung ventilation before, during, and after the application of 5 cm H2O PEEP to the ventilated lung. The plateau end-expiratory pressure and static compliance curve of the ventilated lung were measured with and without applied PEEP, and the lower inflection point was determined from the compliance curve.

Results : Mean (+/- SD) Pao2 values, with a fraction of inspired oxygen of 1.0, were not different during one-lung ventilation before (192 +/- 91 mmHg), during (190 +/- 90), or after ( 205 +/- 79) the addition of 5 cm H2O PEEP. The mean plateau end-expiratory pressure increased from 4.2 to 6.8 cm H2O with the application of 5 cm H2O PEEP and decreased to 4.5 cm H2O when 5 cm H2O PEEP was removed. Six patients showed a clinically useful (> 20%) increase in Pao2 with 5 cm H2O PEEP, and nine patients had a greater than 20% decrease in Pao2. The change in Pao2 with the application of 5 cm H2O PEEP correlated in an inverse fashion with the change in the gradient between the end-expiratory pressure and the pressure at the lower inflection point (r = 0.76). The subgroup of patients with a Pao2 during two-lung ventilation that was less than the mean (365 mmHg) and an end-expiratory pressure during one-lung ventilation without applied PEEP less than the mean were more likely to have an increase in Pao2 when 5 cm H2O PEEP was applied.     

HIGH PEEP DECREASES HYALINE MEMBRANE FORMATION IN SURFACTANT DEFICIENT LUNGS

Lung lav age was performed in 16 anaesthetized rabbits to producesurfactant-deficient lungs. This resulted in alveolar collapse,an arterial Po₂ of less than 15kPa on 100% oxygen and an inflectionpoint on the inspirator/ limb of the pressure-volume curve atan airway pressure of 8–10 mm Hg. One group of eight animalswas then ventilated with a positive end-expiratory pressure(PEEP) equal to the pressure at the inflection point, whilstthe second group of eight was ventilated with a PEEP 5 mm Hgless than the inflection point. Animals in the high PEEP grouphad a significantly greater arterial P02 than those in the lowPEEP group, but the mean survival time for each group was similar.However, there was a significantly greater incidence of hyalinemembranes in the low PEEP group. Various mechanisms to explainthese findings are discussed.