**Optimizing Perioperative Ventilation Support with Adequate Settings of Positive End-Expiratory Pressure**

Zhanqi Zhao1, Claudius Stahl2, Ullrich Müller-Lisse3, Inéz Frerichs4 and Knut Möller1

*1Department of Biomedical Engineering, Furtwangen University, 2Department of Anesthesiology, University Medical Center of Freiburg, 3Department of Radiology, University of Munich, 4Department of Anesthesiology and Intensive Care Medicine, University Medical Center of Schleswig-Holstein Campus Kiel, Germany* 

### **1. Introduction**

352 Front Lines of Thoracic Surgery

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#### **1.1 Mechanical ventilation**

Mechanical ventilation is often employed to replace spontaneous breathing of patients under general anesthesia. Even after operation, the patient still needs ventilation support until the respiratory muscles regain full function. A ventilator delivers a certain amount of air flow through a facial mask or tracheal tube to the patient whose respiratory system fails to function properly due to the effects of anesthetics or diseases. Based on the difference in breath initiation, mechanical ventilation can be divided into two categories: controlled ventilation and assisted ventilation. In this chapter, we focus on controlled mechanical ventilation, under which the patient is not able to trigger a valid breath and the ventilator overtakes all the workload of respiratory muscles. Respiratory parameters such as respiratory rate (RR), inspiratory–to-expiratory time ratio (I:E), tidal volume (Vt) (or minute volume) are controlled by the ventilator.

Traditionally, controlled mechanical ventilation can either be volume controlled (VCV) or pressure controlled (PCV). Ideal respiratory signals obtained in a healthy human during VCV and PCV are shown in Fig. 1. In the VCV mode, a patient receives constant flow from the ventilator until a preset Vt is reached. A severe drawback of VCV is missing control of the peak airway pressure. Airway pressure (Paw) depends on respiratory system compliance and resistance. In patients with certain lung diseases, such as acute lung injury (ALI), the same setting of Vt as in patients with healthy lungs may lead to a higher peak Paw with the potential to further injure the lung. Therefore, VCV is often applied with a pressure limitation. Once the peak Paw rises above this limit, the ventilator will stop delivering gas even if the preset Vt is not yet reached. In the PCV mode, a maximum airway pressure (Pmax) is defined. Inspiration ends when Pmax is reached i.e. the flow driven by the pressure difference decreases to zero. PCV may be superior to VCV in patients requiring one-lung

Optimizing Perioperative Ventilation Support with

order equation of motion:

and weight.

mechanics of the ventilator.

Adequate Settings of Positive End-Expiratory Pressure 355

To better understand the respiratory system, many mathematical models were proposed (Gillis and Lutchen, 1999, Lutchen and Costa, 1990). The simplest one is based on the first

where *Paw*, *V* and *V'* denote airway pressure, volume and airway flow, *Crs* and *Rrs* represent respiratory system compliance and resistance, respectively; *P0* is the pre-existing pressure in the lung. With the measured respiratory signals, lung mechanics (*Crs* and *Rrs*) can be calculated. These measures provide a better insight into the lung status and thereby help the

Fig. 2. Flow-volume curve of a patient with cystic fibrosis during forced respiration. The inspiration phase is depicted on the left side and expiration on the right side of the vertical axis. Rectangle points indicate maximal expiratory flow, expiratory flow at 75%, 50%, 25% of vital capacity and the end of expiration, from top to bottom respectively. The dashed-line shows the normal reference of expiratory flow rate with respect to this patient's age, height

At different locations i.e. the airway opening, the trachea or at the alveoli, pressure measurements are of interest. If the patient is intubated, tracheal pressure (Ptrach) is sometimes more desired than Paw since the endotracheal tube contributes significantly to total airflow resistance, and thus affects the Rrs calculation (Guttmann *et al.*, 1993). Alveolar pressure (Palv) is a decisive factor of alveolar recruitment/derecruitment. Palv is usually calculated by subtracting total resistive pressure from Paw or Ptrach. Typical examples of different pressure-volume curves based on Paw, Ptrach and Palv are plotted in Fig. 3. Note that at the start of inspiration and expiration, the signals are disturbed due to the non-ideal

physicians to establish diagnosis and make adequate therapeutical decisions.

<sup>0</sup> ( ) ( ) / '( ) *P t Vt C V t R P aw* = + ×+ *rs rs* (1)

anesthesia (Tuğrul *et al.*, 1997). However, the Vt is not controlled by the ventilator in the PCV mode, but determined by the preset maximum pressure and respiratory system mechanics. There is no guarantee that sufficient gas will be delivered into the lung. Hence, Vt and minute volume that the patient receives must be monitored. In reality, the respiratory signals measured by the ventilator do not look exactly like the ideal tracings shown in Fig. 1. Signals are subjected to various error sources, such as environmental noise, sense dysfunction, and calibration failure and they also depend on individual physiological or pathophysiological properties of the patient's respiratory system.

Respiratory signal analysis is helpful for the clinician and beneficial to the patient. Lung diseases influence tidal ventilation, which is reflected in the Paw, air flow and respiratory volume signals. Based on a shape analysis of respiratory signals, clinical diagnosis can be supported. For example, the flow-volume curve of a patient with cystic fibrosis during forced respiration, measured by body plethysmography, is plotted in Fig. 2. Low expiratory flow rates compared to the normal values at 75%, 50% and 25% of volume capacity indicate airway obstruction in this patient.

Fig. 1. Ideal respiratory signals (airway pressure, air flow and respiratory volume) of a healthy human under volume controlled (left) and pressure controlled (right) ventilation mode.

anesthesia (Tuğrul *et al.*, 1997). However, the Vt is not controlled by the ventilator in the PCV mode, but determined by the preset maximum pressure and respiratory system mechanics. There is no guarantee that sufficient gas will be delivered into the lung. Hence, Vt and minute volume that the patient receives must be monitored. In reality, the respiratory signals measured by the ventilator do not look exactly like the ideal tracings shown in Fig. 1. Signals are subjected to various error sources, such as environmental noise, sense dysfunction, and calibration failure and they also depend on individual physiological or

Respiratory signal analysis is helpful for the clinician and beneficial to the patient. Lung diseases influence tidal ventilation, which is reflected in the Paw, air flow and respiratory volume signals. Based on a shape analysis of respiratory signals, clinical diagnosis can be supported. For example, the flow-volume curve of a patient with cystic fibrosis during forced respiration, measured by body plethysmography, is plotted in Fig. 2. Low expiratory flow rates compared to the normal values at 75%, 50% and 25% of volume capacity indicate

 Fig. 1. Ideal respiratory signals (airway pressure, air flow and respiratory volume) of a healthy human under volume controlled (left) and pressure controlled (right) ventilation

pathophysiological properties of the patient's respiratory system.

airway obstruction in this patient.

mode.

To better understand the respiratory system, many mathematical models were proposed (Gillis and Lutchen, 1999, Lutchen and Costa, 1990). The simplest one is based on the first order equation of motion:

$$P\_{av}(t) = V(t) / \ulcorner C\_{rs} + V'(t) \times R\_{rs} + P\_0 \tag{1}$$

where *Paw*, *V* and *V'* denote airway pressure, volume and airway flow, *Crs* and *Rrs* represent respiratory system compliance and resistance, respectively; *P0* is the pre-existing pressure in the lung. With the measured respiratory signals, lung mechanics (*Crs* and *Rrs*) can be calculated. These measures provide a better insight into the lung status and thereby help the physicians to establish diagnosis and make adequate therapeutical decisions.

Fig. 2. Flow-volume curve of a patient with cystic fibrosis during forced respiration. The inspiration phase is depicted on the left side and expiration on the right side of the vertical axis. Rectangle points indicate maximal expiratory flow, expiratory flow at 75%, 50%, 25% of vital capacity and the end of expiration, from top to bottom respectively. The dashed-line shows the normal reference of expiratory flow rate with respect to this patient's age, height and weight.

At different locations i.e. the airway opening, the trachea or at the alveoli, pressure measurements are of interest. If the patient is intubated, tracheal pressure (Ptrach) is sometimes more desired than Paw since the endotracheal tube contributes significantly to total airflow resistance, and thus affects the Rrs calculation (Guttmann *et al.*, 1993). Alveolar pressure (Palv) is a decisive factor of alveolar recruitment/derecruitment. Palv is usually calculated by subtracting total resistive pressure from Paw or Ptrach. Typical examples of different pressure-volume curves based on Paw, Ptrach and Palv are plotted in Fig. 3. Note that at the start of inspiration and expiration, the signals are disturbed due to the non-ideal mechanics of the ventilator.

Optimizing Perioperative Ventilation Support with

oxygenation.

**2.1 History** 

effects.

drawbacks discussed.

**2. PEEP optimization** 

Adequate Settings of Positive End-Expiratory Pressure 357

thanks to the pulmonary surfactant. However, in patients with lung injury or with other types of lung disease as well as during thoracic surgery, some alveoli collapse at the end of expiration when the pressure drops below a critical value, and reopen in the next inspiration when the pressure rises above a certain opening pressure. To avoid cyclic recruitment/derecruitment (open/collapse) and to "keep the lung open", an adequate PEEP is applied (Fig. 4B). At the end of expiration, Paw doesn't drop to 0 cmH2O (relative to atmospheric pressure). Instead, the pressure is held by the ventilator at a preselected positive level. The recruited lung regions remain aerated, which leads to a better

In 1960's, Ashbaugh *et al.* proposed the use of PEEP to improve oxygenation in a clinical syndrome characterized by atelectasis and hypoxemia (Ashbaugh *et al.*, 1967). The use of PEEP has become widespread ever since that study. Suter and his colleagues later published the concept of "optimal" PEEP (Suter *et al.*, 1975). Because at that time, cardiac output and blood gas measurements were not always available, they suggested that maximizing tidal compliance could be used to identify a PEEP level, at which oxygen delivery was optimized. In the past three decades, a multitude of physicians and scientists dedicated themselves to identify the best PEEP levels for patients under surgeries (Beiderlinden *et al.*, 2003, Berendes *et al.*, 1996, Bensenor *et al.*, 2007), as well as patients with variable diseases, such as ALI or ARDS (Badet *et al.*, 2009, Huh *et al.*, 2009), morbid obesity (Bohm *et al.*, 2009, Erlandsson *et al.*, 2006), chronic obstructive pulmonary disease (COPD) (Glerant *et al.*, 2005, Mancebo *et al.*, 2000), brain-injury (Shapiro and Marshall, 1978, Huynh *et al.*, 2002), including infants (Greenough *et al.*, 1992, Dimitriou *et al.*, 1999). Although different terminologies and endpoints for optimizing PEEP were used (Villar, 2005), most of the approaches tried to obtain the best oxygenation while minimizing VILI as outcome. A lower mortality rate and a better quality of life would be the most desirable goals of therapies. While PEEP has experimentally been shown to reduce VILI, there is no consent in the literature if a suitable PEEP is able to reduce mortality (Miller *et al.*, 1992, DiRusso *et al.*, 1995, Brower *et al.*, 2004),

due to the fact that the effect of PEEP is hard to be assessed independently.

It remains under debate how to titrate an adequate PEEP level in individual patients, despite the widely used application of PEEP in clinical practice (Rouby *et al.*, 2002). Increase of PEEP may prevent alveolar derecruitment in dependent areas but may lead to hyperinflation in the non-dependent areas, which may trigger pulmonary inflammation (Terragni *et al.*, 2007). Besides, high PEEP levels may reduce cardiac output (Baigorri *et al.*, 1994) and impair the hemodynamic stability (Herff *et al.*, 2008). Therefore, as also stated by Rouby and Brochard in an editorial (Rouby and Brochard, 2007), one goal of setting PEEP is to find a suitable level, high enough to keep the lung open while minimizing adverse side

Generally speaking, the current available methods of PEEP titration can be mainly divided into three categories: They are based on 1) arterial blood gases such as partial pressure of oxygen in arterial blood (PaO2) and oxygen saturation (SpO2); 2) lung mechanics such as dynamic compliance and static pressure-volume (P/V) curve; 3) imaging techniques such as computed tomography (CT) and electrical impedance tomography (EIT). In the following, representative methods within these three categories are introduced and their assets and

Fig. 3. Three pressure-volume curves obtained in a lung healthy patient undergoing orthopedic surgery. Paw (blue line): airway pressure; Ptrach (red circle): tracheal pressure; Palv (black dashed line): alveolar pressure.

#### **1.2 Lung protective ventilation strategy**

When patients are generally anesthetized, the alveoli in the dependent lung regions may collapse while non-dependent regions remain open. With the help of sufficient external pressure delivered by a ventilator during inspiration, some of the collapsed lung regions may be opened up (i.e. they are recruited) but already open regions may be overinflated. Neither atelectasis nor hyperinflation of lung regions is beneficial in most clinical cases, however, one or the other or a mixture of both processes is inevitable to a certain degree. During expiration, while gas is exhaled, the alveolar pressure drops, which may lead to alveolar collapse (i.e. derecruitment) of the dependent lung regions. Different types of ventilator-induced lung injury (VILI) are therefore observed during mechanical ventilation (Dreyfuss and Saumon, 1998, Uhlig and Frerichs, 2008), such as shear stress trauma caused by cyclic recruitment/derecruitment, barotrauma and pulmonary edema caused by high ventilation pressure. As one of many perioperative complications, acute respiratory distress syndrome (ARDS) was found developed in 3.1% of patients after thoracic surgery and carrying a high mortality rate of over 30% (Grichnik and D'Amico, 2004, Phua *et at.*, 2009). Various lung protective ventilation strategies have therefore been proposed, including high positive end-expiratory pressure (PEEP) combined with low Vt (Brower *et al.*, 2004, Brochard *et al.*, 1998, The Acute Respiratory Distress Syndrome Network, 2000), permissive hypercapnia (Hickling *et al.*, 1990), and recruitment maneuvers (Lachmann, 1992), to reduce the adverse consequences of mechanical ventilation. In this chapter, we focus on optimization of PEEP.

PEEP was introduced to maintain the once recruited atelectatic areas open and thereby reduce the risk of hypoxemia, cyclic recruitment/derecruitment and biotrauma (Gattinoni *et al.*, 2001, Slutsky and Tremblay, 1998). Figure 4 illustrates the effect of PEEP on keeping the lung open. In healthy subjects, although the pulmonary alveoli increase their size at the end of inspiration and decrease at the end of expiration, the shape of alveoli doesn't change thanks to the pulmonary surfactant. However, in patients with lung injury or with other types of lung disease as well as during thoracic surgery, some alveoli collapse at the end of expiration when the pressure drops below a critical value, and reopen in the next inspiration when the pressure rises above a certain opening pressure. To avoid cyclic recruitment/derecruitment (open/collapse) and to "keep the lung open", an adequate PEEP is applied (Fig. 4B). At the end of expiration, Paw doesn't drop to 0 cmH2O (relative to atmospheric pressure). Instead, the pressure is held by the ventilator at a preselected positive level. The recruited lung regions remain aerated, which leads to a better oxygenation.
