The introduction of positive endexpiratory pressure into mechanical ventilation: a retrospective

Konrad J. Falke

The introduction of positive endexpiratory pressure into mechanical ventilation:

a retrospective

Continuous positive pressure breathing consisting of a pressure in the airways above the atmospheric level dur- ing spontaneous inspiration and expiration was used in the treatment of pulmonary edema and severe pneumo- nia even before World War II [1]. Positive endexpiratory airway pressure was also very commonly used in the ex- perimental laboratory in any open chest preparation in order to prevent expiratory lung collapse. An important precondition for the introduction of positive endexpirato- ry pressure (PEEP) in conjunction with mechanical ven- tilation was established by the experiments of Cournand et al. in 1948 [2]. They found, however, that, compared to mechanical ventilation with ambient endexpiratory pressure, mechanical ventilation with PEEP was associ- ated with a marked decrease in cardiac output due to re- duced venous return of blood to the heart. Possible nega- tive circulatory effects were the major concern in the early phase of clinical application of positive endexpira- tory pressure.

PEEP in conjunction with mechanical ventilation as it is used today first became possible with the introduction of the Engström mechanical ventilator in Sweden in the mid-1950s. This machine already had an attachment which allowed endexpiratory pressure to be increased above the atmospheric level. Presumably this option was

added by the inventors in order to prevent endexpiratory lung collapse during open chest surgery. The first report- ed clinically important use of PEEP was undertaken in the cardiac catheterization laboratory of the University Hospital in Zürich, Switzerland, by Bühlmann, Gattiker, and Hossli, who published their work in the Schweizer

strated very impressively in patients with mitral valve disease that mechanical ventilation with continuous posi- tive airway pressure led to a marked decrease in the pul- monary capillary wedge pressure despite the increase in alveolar pressure. This reflected the decrease in pulmo- nary vascular and cardiac transmural pressures which oc- curs when endexpiratory airway pressure is increased—a phenomenon which was elucidated years later by many studies, an example being the work of Qvist et al. in 1975 [4]. Bühlmann and his colleagues already found in their patients that continuous positive airway pressure ventilation led to improved mixed venous oxygen satura- tion despite a decrease in cardiac output, indicating a re- duction in pulmonary right-to-left shunt and an improve- ment in arterial oxygenation. However, because they could not measure arterial blood gases at that time, they did not recognize the clinical significance of this finding.

The first clinical evidence that PEEP increases lung volume in correlation with an improvement in arterial oxygenation was established by Frumin et al. in 1959 [5]

in anesthetized patients, although they too could only rely on O

saturation measurements. They explained the posi- tive effect of PEEP on the alveolar arterial O

difference by a possible recruitment of closed alveolar gas spaces.

They hypothesized that intermittent alveolar collapse with maintained perfusion might take place during endex- piration, a phenomenon which they called “shunt in time”

being reduced by the use of PEEP. (Much later this was

supported by the finding of marked swings of Pa

dur-

ing the respiratory cycle in left atrial blood, especially if

large tidal volumes and low respiratory frequencies were

used (present author's unpublished observation, 1971).

Hence, it was not until the mid-1960s, when Thomas Petty in Denver had learned how to determine arterial blood gases, that the potential of mechanical ventilation with PEEP to improve arterial oxygenation was recog- nized [6]. Petty and his colleagues first used an Engström anesthesia mechanical ventilator equipped with a device to produce PEEP. They discovered that in mechanically ventilated patients with hypoxic acute respiratory failure, which they termed “adult respiratory distress syndrome”

(ARDS), the addition of PEEP was capable of relieving severe life-threatening hypoxemia with cyanosis. Their famous paper [7], published in the Lancet in 1967 (after being rejected by three major US journals!), became a milestone in the evolution of respiratory intensive care medicine. The news spread very quickly, and in spring of 1969 a group of enthusiastic clinical researchers under the direction of Henning Pontoppidan (Fig. 1) and Myron B. Laver (Fig. 2) started to further investigate mechanical ventilation with PEEP in patients with severe acute lung disease [8]. Meanwhile, McIntyre et al. [9] had studied and published first results on using 5 cmH

O PEEP in five patients with acute lung disease. Both studies showed marked improvements in arterial P

. McIntyre et al. [9], who had studied the addition of 5 cmH

O PEEP, did not find a decrease in cardiac output, whereas Kumar et al. [8], using 13 cmH

O, showed a decrease in cardiac output averaging 15% of control.

On the basis of H.K. Beecher’s (1933!) finding of col- lapsed pulmonary gas spaces after upper abdominal sur- gery [10] and of the already mentioned investigations by Frumin et al. [5], Henning Pontoppidan at the Massachu- setts General Hospital in Boston hypothesized that the impaired pulmonary oxygenation in acute lung disease

might be due to reduced lung volume or functional resid- ual capacity (FRC), and that the improvement in arterial oxygenation with PEEP, which could indeed be quite dramatic, should correlate with changes in the FRC.

Hence the group in Boston went on to investigate how the stepwise increase of PEEP from zero to 5 and 10 and further on to 15 cmH

O would lead to an increase in the FRC and an associated improvement in Pa

[11]. They also hypothesized that if recruitment of closed gas spac- es in the lung takes place, this should be associated with an improvement in lung compliance. They found that this was indeed true; however, if the so-called dynamic or semistatic pulmonary compliance (C=V

/P

) was determined, it was found that this parameter would only increase with lower levels of PEEP—with higher levels lung and total thoracic compliance would fall, in- dicating overdistention of pulmonary gas spaces (Fig. 3) [11, 12]. In fact, they found that lung volume (FRC) was markedly decreased in ARDS, and on the basis of their findings on compliance they proposed that PEEP im- proves arterial oxygenation by recruitment of collapsed alveoli [11, 13]. However, they were surprised that im- provements in Pa

could go along with a decrease in compliance (Fig. 3). Today we understand that recruit- ment and overdistention of pulmonary gas spaces may take place simultaneously.

While the early PEEP studies in Boston were coming to an end, Peter Suter and Berrie Fairley in San Francis- co had also started working on the interactions of PEEP and compliance. They found that if mechanical ventila- tion takes place within the pulmonary pressure/volume range associated with maximum compliance, the nega- tive effect of PEEP on cardiac output is at its minimum.

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Fig. 1 Henning Pontoppidan M.D., Professor and Director of the Respiratory Intensive Care Unit at the Massachusetts Gen- eral Hospital, Harvard Medical School, in Boston in 1971. The graph shows his view of the changes in PaO₂and lung vol- umes with age (A) and with acute lung disease (B) based on the measurements of FRC us- ing helium dilution carried out in 1969–71 at the Massachu- setts General Hospital [13].

This was later characterized by Gattinoni and Pesenti [17] as the so-called “baby lung” in ARDS patients

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Fig. 2 Myron B. Laver MD as Professor at the Department of An- esthesia at the Massachusetts General Hospital in Boston around 1970. Later he became chairman at the Department of Anaesthesia at the Kantonsspital in Basel. He was very enthusiastic about the hemodynamic effects of PEEP, especially in cardiogenic pulmona- ry edema. He believed that PEEP should improve cardiac output due to reductions in pre- and afterload if left ventricular function is compromised. The graph shows all the measurements of cardiac

output carried out by Kumar et al. [8] and Falke et al. [11]. M.

Laver used to tell the story of the trumpet player whose cardiac angina was relieved when he played his trumpet, presumably due to the continuous positive airway/thoracic pressure applied. Today we know that PEEP usually does not increase cardiac output, but due to its decreasing effect on pre- and afterload, reducing myo- cardial wall stress, it may improve left ventricular function

Fig. 3 Pressure–volume loops with four levels of endexpiratory pressure (zero, 5, 10 and 15 cmH₂O) in three patients with ARDS [11]. The horizontal axis represents the transpulmonary pressure and the vertical axis the lung volume in liters or percent of pre- dicted. The FRC was measured with helium dilution technique, the∆FRC and the pressure–volume loops were determined using

pneumotachography. These examples all show increasing lung compliance in the lower parts and decreasing lung compliance in the upper parts of the pressure–volume relationships, the latter in- dicating overdistention of the lungs. Nevertheless PaO2 improved with all levels of PEEP

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In fact, in their group of patients the level of PEEP which led to the best compliance coincided with the maximum O

transport (cardiac output × arterial O

con- tent). They called this level of PEEP “best PEEP” [14].

In a later study they demonstrated that the combination of large tidal volumes with high levels of PEEP led to marked falls in compliance, indicating that such combi- nations of ventilator settings could be detrimental to lung function parameters [15].

The various studies by Falke et al. and Suter et al.

clearly showed more than 20 years ago that in ARDS pa- tients lung volume and compliance are markedly re- duced, and that mechanical ventilation with high tidal volumes applied on top of PEEP may lead to overdisten- tion of the lungs. Even at that time the conclusion should have been that low tidal volumes adjusted to the low lung volume in combination with relatively high PEEP are the settings of the ventilator which can be expected to be least detrimental to lung function. In fact, in the early 1970s MyronB. Laver had proposed the use of low tidal volumes together with relatively high PEEP and high respiratory frequencies, a type of mechanical venti- latory support which he called “pressure panting.” How- ever, at that time our attempts to lower tidal volumes in mechanically ventilated patients already suffering from severely compromised pulmonary oxygenation were in- hibited by the observation that the Pa

would fall even

further. This anecdotal observation was recently con- firmed by the US ARDS Network study on low versus high tidal volume. After 1980 pulmonary CT scanning of critically ill patients was introduced by Rommelsheim [16]. This new diagnostic approach helped to improve our understanding of the pathophysiological scenario of ARDS, which was very well characterized by Gattinoni and Pesenti in 1987 [17] as the so-called “baby lung con- cept.” Subsequently it became obvious that overdisten- tion of the lungs as indicated by a decreased compliance could be extremely harmful, contributing to what it is now called “ventilator-induced or ventilator-associated lung injury.” Another voice in the wilderness came from Theodor Kolobow and colleagues in 1980, who devel- oped the most consistent strategy of lung-protective res- piratory support, advocating “extracorporeal gas ex- change with low frequency (pressure limited) mechani- cal ventilation” [18]. Most recently, it was firmly estab- lished by the already mentioned large multicenter trial that low tidal volume in conjunction with PEEP is the only suitable approach by which to prevent iatrogenic lung injury [19]. Although today we believe we have ev- idence that mechanical ventilation is best tolerated if it takes place in between the lower and the upper inflection points of the static pressure volume relationship of the diseased lungs, the question of how to determine the op- timal level of PEEP is still disputed.

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