Affiliations:
Ganga Prabhakar MD, Jaimela Dulaney MD, Leon S Barringer DVM, West Virginia University.Akella Chendrasekhar MD, Gregory A Timberlake MD, Department of Surgery Education, Iowa Methodist Medical Center.
Paper presented at The Eastern Association for the Surgery of Trauma Annual Meeting, Sanibel Island, Florida, January 1997.
Reprint requests should be sent to Akella Chendrasekhar MD, Department of Surgery Education, Iowa Methodist Medical Center, 1221 Pleasant St, Suite 550, Des Moines, IA 50309.

Adult respiratory distress syndrome (ARDS) has been defined as the spectrum of cellular damage resulting in lung injury with decreased respiratory compliance and increased resistance. The current working definition is one which classifies ARDS as a continuum of injury ranging from mild Acute Lung Injury (ALI) to the more severe ARDS ₁,₂,₃. In this continuum ALI is defined by a PaO2/FIO2 ratio of less than 300 without clinical signs of congestive heart failure and ARDS is defined similarly with a PaO2/FIO2 ratio of less than 200 and no signs of congestive heart failure (or if measured, a pulmonary capillary wedge pressure of less than 18 mmHg) 2.

Volume control ventilation with positive end expiratory pressure (PEEP) is currently accepted as one of the standard approaches for treatment of hypoxemia in respiratory failure due to acute lung injury (ALI) ₄,₅. Hemodynamic changes have been noted with PEEP values of greater than 10 mmHg, due to increased right ventricular impedance and subsequent reduction of cardiac output ₆. Positive pressure ventilation, specifically PEEP, has been shown to depress cardiovascular function as well as mesenteric blood flow ₇. This depression in mesenteric blood flow is not reversed by inotropes ₈.

External chest wall oscillation using a Hayek Oscillator (HO) is a new method of mechanical ventilation that provides negative pressure ventilation. Although negative pressure ventilation using the “Iron Lung” preceded the routine use of positive pressure ventilation, detailed studies of hemodynamic and splanchnic perfusion data are lacking. Our group has recently demonstrated that external chest wall oscillation (negative pressure ventilation) using a Hayek Oscillator results in enhancement of cardiac performance and normalization of splanchnic perfusion ₉,₁₀.

Systemic markers of perfusion, such as oxygen delivery and oxygen consumption, may not be able to accurately track shock states in certain situations ₁₁,₁₂. For this reason measurement of organ specific perfusion, specifically splanchnic perfusion, has been useful in tracking shock states where systemic markers have been insensitive (e.g. normotensive shock states). Gastric and intestinal tonometry, which are indirect methods to track intramucosal pH (pHi), have been shown to be relatively accurate markers of splanchnic perfusion 12,₁₃. Our group over the past 2 years has demonstrated that rectal mucosal surface pH correlates with gastric pHi as derived by gastric tonometry in animal models of hemorrhagic and endotoxic shock as well as trauma patients ₁₄-16.

The purpose of our study was to evaluate the effect of a Hayek Oscillator on splanchnic perfusion in an oleic acid model of acute lung injury (ALI). Our hypothesis was that external chest wall oscillation with the Hayek Oscillator (HO) ameliorates the deficit in splanchnic perfusion (as tracked by gastric tonometry, intestinal tonometry and rectal mucosal pH) seen with positive pressure ventilation in a porcine model of ALI.

MATERIALS AND METHODS

This protocol was approved by the University’s laboratory animal utilization committee. Animals were cared for in accordance with the current guidelines of the National Institutes of Health. Thirteen mixed breed adult swine, weighing 75 to 85 kg, were fasted overnight with free access to water. On the day of the experiment, the animals were initially anesthetized with intramuscular telazol (4 mg/kg) . Intravenous access was obtained by cannulation of an ear vein and anesthesia was continued with intravenous sodium pentobarbital (3-5 mg/kg/hour) . The animals were intubated endotracheally and mechanically ventilated. The ventilator was adjusted using positive end expiratory pressure (PEEP) and volume control ventilation to maintain eucarbia and a partial pressure of oxygen of at least 100 mmHg. Pulmonary artery and arterial catheters were placed via surgical cut downs. Gastric and small intestinal tonometers were placed at laparotomy. Rectal pH probe was placed next to the mucosa by palpation. The endotracheal tube was replaced with a surgical tracheostomy in order to facilitate the placement of a transesophageal echocardiography probe in the esophagus.

Transesophageal echocardiography was performed using an omniplane esophageal echocardiography probe (Hewlett-Packard, Andover, MA). We obtained left ventricular ejection fraction (LVEF) by averaging data from two planes to avoid any aberrance related to regional wall motion abnormalities.

Baseline measurements were obtained after placement of all catheters. ALI was induced by intravenous injection of oleic acid (0.03 ml/kg). Volume resuscitation was performed to maintain corrected pulmonary capillary wedge pressure (PCWP; adjusted for PEEP effect) at baseline levels. The lung injury was allowed to stabilize for 120 minutes prior to initial hemodynamic and tonometric data collection (ALI - 2 hrs). Minute volume and PEEP were adjusted to maintain eucarbia and oxygenation.

At this point the animals were randomly divided into 2 groups. The study group animals (n=6) were placed on a Hayek Oscillator (Breasy Medical Equipment, Charlotte, NC) in addition to positive pressure ventilation. The Hayek Oscillator was set at 35 breaths per minute with an inspiratory pressure of -35 cm H2O and an expiratory pressure of + 6 cm H2O. The control animals (n=7) continued on with positive pressure ventilation alone. Data were once again obtained one hour later in both groups.

Statistical analysis was performed using the averaged values for each stage of the hemorrhagic shock model. Each stage values were compared with baseline values using a one way analysis of variance with repeated measures. As part of the analysis of variance, the Student-Newman-Keuls test was used for the multiple comparisons. Statistical significance threshold was p < 0.05.

RESULTS

All the animals tolerated the experimental procedure. All animals were started off with a baseline PEEP of 5 cm H2O. There was a significant increase in the PEEP applied in both the control and study animals with the onset of lung injury. The extent of lung injury as quantified by PaO2/FIO2 ratio was 190 + 22 and 204 + 19 for the study animals and control animals respectively (p=n.s.) The lung injury created by this model has been documented in previous studies as well as our own unpublished data to be stable for 5-6 hours. The mean arterial pressure and the pulmonary capillary wedge pressure and the mean arterial pressure were kept at baseline values as per the design of the experiment. The cardiac index was depressed with the onset of lung injury by intravenous injection of oleic acid. This depression persisted in the control animals with positive pressure ventilation alone and was normalized in the animals that were placed on the Hayek Oscillator (Table 1). There was a significant drop in systemic vascular resistance in the animals that were placed on the Hayek Oscillator as compared to control animals. There was also a significant drop in LV ejection fraction with the onset of lung injury that persisted in control animals and was ameliorated in the study animals (Table 2). The drop in splanchnic perfusion as detected by gastric pHi , intestinal pHi and rectal mucosal pH persisted in the control animals while it was corrected in the study animals (Table 1).

Table 1: Hemodynamic, Tonometric and Rectal pH data

Table 2: Hemodynamic, Respiratory, and Transesophageal echo data.

• Mean + SD as compared to baseline levels, *p < 0.05, +p = n.s.

• MAP = Mean arterial pressure (mmHg)

• LV EF = Left ventricular ejection fraction (%)

• SVRI = Systemic vascular resistance index (Dyne sec/cm5/m2)

• PCWP = Pulmonary capillary wedge pressure (mmHg)

• PEEP = Positive end expiratory pressure (cm H2O)

• ALI(2 hrs) = 2 hours after induction of acute lung injury

• ALI(3 hrs) = 3 hours after induction of acute lung injury

DISCUSSION

Depression of cardiovascular function in acute lung injury treated with positive pressure ventilation has been well documented in the literature 6,16,₁₇. However this was predominantly thought to be related to an increase in right ventricular impedance secondary to PEEP and reduction in the filling of the left ventricle resulting in a decreased cardiac output 6,16,17. Our data regarding cardiac index and LV ejection fraction shows an LV afterload problem which may be related to PEEP. The systemic vascular resistance which is an indirect measure of afterload was shown to be increased when preload was normalized in oleic acid induced lung injury. We eliminated the preload effect related to PEEP by volume loading the animals to maintain a corrected PCWP of approximately ₁₅ mmHg. The drop in cardiac index and LV ejection fraction may also be related to the model used in this experiment. Oleic acid has been thought to depress cardiac function ₁₈,₁₉. However in our previous work with this model we found oleic acid injection, with adequate volume resuscitation in the absence of PEEP, failed to produce a significant depression in cardiac function 9.

The Hayek Oscillator presents a new application of an old physiologic standard. The concept of negative pressure ventilation predates positive pressure ventilation. The similarity in physiology to spontaneous respiration was intuitive. The old “Iron lung” ventilators were extensively used in the polio epidemic of 1950 only to be supplanted by positive pressure ventilators due to ease of use and ease of production. The Biphasic approach (active inspiratory and expiratory cycles) of a Hayek Oscillator allows for better control of ventilation as compared to a pure negative pressure ventilator ₂₀,₂₁. We had previously documented improvement in LV function when the Hayek Oscillator was used as a primary ventilator in a porcine model of acute lung injury 9. The implication from that study was that the Hayek oscillator was able to acutely reduce afterload despite a lack of synchronization with the cardiac cycle. This led us to the next step, how does the Hayek oscillator perform when used in conjunction with positive pressure ventilation ? Clearly the oscillator improves cardiac performance not only with respect to both cardiac index and LV ejection fraction.

Love et al. revealed that PEEP does lower mesenteric flow and in a subsequent study this group also found that the flow deficit is not corrected by the use of inotropes 7,8. We also had similar findings in our study. We found that splanchnic flow as determined by several modalities (gastric and intestinal pHi as well as rectal mucosal pH) is depressed in acute lung injury treated by PEEP. The Hayek Oscillator corrected the flow deficit created by the PEEP in the study animals as compared to the control animals where the flow deficit persisted. The data imply that the Hayek Oscillator is reducing afterload despite a lack of synchrony with the cardiac cycle. We also considered the possibility that the Hayek Oscillator may be producing a sympathetic discharge in our animals with a subsequent improvement in cardiac output due to release of intrinsic catecholamines. However this theory fails with regard to the lack of rise in systolic blood pressure and lack of rise in heart rate. Another more likely explanation is the negative pressure oscillation causing release of an intrinsic vasodilator such as atrial natriuretic peptide. Our data only evaluates the short term effect of the Hayek Oscillator on cardiac function and splanchnic perfusion in a porcine model of lung injury. Clearly further studies on longer term effects of the Hayek Oscillator as well as clinical studies evaluating its utility in patients are needed.