Chapter 1: Physiologic Effects of Mechanical Ventilation

Ventilators used in adult acute care use positive pressure applied to the airway opening to inflate the lungs. Although positive pressure is responsible for the beneficial effects of mechanical ventilation, it is also responsible for many potentially deleterious side effects. Application of mechanical ventilation requires an understanding of both its beneficial and adverse effects. In the care of an individual patient, this demands application of strategies that maximize the potential benefit of mechanical ventilation while minimizing the potential for harm. Due to the homeostatic interactions between the lungs and other body systems, mechanical ventilation can affect nearly every organ system of the body. This chapter provides an overview of the beneficial and adverse physiologic effects of mechanical ventilation.

During normal spontaneous breathing, intrathoracic pressure is negative throughout the ventilatory cycle. Intrapleural pressure varies from about –5 cm H₂O during exhalation to –8 cm H₂O during inhalation. Alveolar pressure fluctuates from +1 cm H₂O during exhalation to –1 cm H₂O during inhalation. The decrease in intrapleural pressure during inhalation facilitates lung inflation and venous return. Transpulmonary pressure is the difference between proximal airway pressure and intrapleural pressure. The greatest static transpulmonary pressure that can be generated normally during spontaneous inspiration is less than 35 cm H₂O.

Intrathoracic pressure fluctuations during positive pressure ventilation are opposite to those that occur during spontaneous breathing. During positive pressure ventilation, the mean intrathoracic pressure is usually positive. Intrathoracic pressure increases during inhalation and decreases during exhalation. Thus, venous return is greatest during exhalation and it may be decreased if expiratory time is too short or mean alveolar pressure is too high.

Many of the beneficial and adverse effects associated with mechanical ventilation are related to mean airway pressure. Mean airway pressure is the average pressure applied to the airway during the ventilatory cycle. It is related to both the amount and duration of pressure applied during the inspiratory phase (peak inspiratory pressure, inspiratory pressure waveform, and inspiratory time) and the expiratory phase (positive end-expiratory pressure [PEEP] and respiratory rate).

Shunt

Shunt is perfusion (blood flow) without ventilation (Figure 1-1). Pulmonary shunt occurs when blood flows from the right heart to the left heart without participating in gas exchange. The result of shunt is hypoxemia. Shunt can be either capillary shunt or anatomic shunt. Capillary shunt results when blood flows past unventilated alveoli. Examples of capillary shunt are atelectasis, pneumonia, pulmonary edema, and acute respiratory distress syndrome (ARDS). Anatomic shunt occurs when blood flows from the right heart to the left heart and completely bypasses the lungs. Normal anatomical shunt occurs due to the Thebesian veins and the bronchial circulation. Abnormal anatomic shunt occurs with congenital cardiac defects. Total shunt is the sum of the capillary and anatomic shunt.

Positive pressure ventilation usually decreases shunt and improves arterial oxygenation. An inspiratory pressure that exceeds the alveolar opening pressure expands a collapsed alveolus, and an expiratory pressure greater than alveolar closing pressure prevents its collapse. By maintaining alveolar recruitment with an adequate expiratory pressure setting, arterial oxygenation is improved. However, if positive pressure ventilation produces overdistention of some lung units, this may result in redistribution of pulmonary blood flow to unventilated regions (Figure 1-2). In this case, positive pressure ventilation paradoxically results in hypoxemia.

Although positive pressure ventilation may improve capillary shunt, it may worsen anatomic shunt. An increase in alveolar pressure may increase pulmonary vascular resistance, which could result in increased flow through the anatomic shunt, decreased flow through the lungs, and worsening hypoxemia. Thus, mean airway pressure should be kept as low as possible if an anatomic right-to-left shunt is present.

A relative shunt effect can occur with poor distribution of ventilation, such as might result from airway disease. With poor distribution of ventilation, some alveoli are underventilated relative to perfusion (shunt-like effect and low ventilation-perfusion ratio), whereas other alveoli are overventilated (dead space effect and high ventilation-perfusion ratio). Positive pressure ventilation may improve the distribution of ventilation, particularly by improving the ventilation of previously underventilated areas of the lungs.

Ventilation

Ventilation is the movement of gas into and out of the lungs. Tidal volume (V_T) is the amount of gas inhaled or exhaled with a single breath and minute ventilation (V̇_E) is the volume of gas breathed in 1 minute. Minute ventilation is the product of tidal volume (V_T) and respiratory frequency (f_b):

Ventilation can be either dead space ventilation (V̇_D) or alveolar ventilation (V̇_A). Minute ventilation is the sum of dead space ventilation and alveolar ventilation:

Alveolar ventilation participates in gas exchange (Figure 1-3), whereas dead space ventilation does not. In other words, dead space is ventilation without perfusion. Anatomic dead space is the volume of the conducting airways of the lungs, and is about 150 mL in normal adults. Alveolar dead space refers to alveoli that are ventilated but not perfused, and is increased by any condition that decreases pulmonary blood flow. Total physiologic dead space fraction (V_D/V_T) is normally about one-third of the V̇_E. Mechanical dead space refers to the rebreathed volume of the ventilator circuit and acts as an extension of the anatomic dead space. Due to the fixed anatomic dead space, a low tidal volume increases the dead space fraction and decreases alveolar ventilation. An increased dead space fraction will require a greater minute ventilation to maintain alveolar ventilation (and PaCO₂).

Because mechanical ventilators provide a tidal volume and respiratory rate, any desired level of ventilation can be provided. The level of ventilation required depends upon the desired PaCO₂, alveolar ventilation, and tissue CO₂ production (V̇co₂). This is illustrated by the following relationships (note that the factor 0.863 is not used if the measurements are made at the same conditions and using the same units):

and

A higher V̇_E will be required to maintain Paco₂ if V̇co₂ is increased, such as occurs with fever and sepsis. If dead space is increased, a higher V̇_E is required to maintain the same level of V̇_A and Paco₂. If this level of ventilation is undesirable due to its injurious effects on the lungs and hemodynamics, Paco₂ can be allowed to increase (permissive hypercapnia). Mechanical ventilation can produce overdistention of normal alveoli, resulting in alveolar dead space. Mechanical ventilation can also distend airways, increasing anatomic dead space.

Atelectasis

Atelectasis is a common complication of mechanical ventilation. This can be the result of preferential ventilation of nondependent lung zones with passive ventilation, the weight of the lungs causing compression of dependent regions or airway obstruction. Breathing 100% oxygen may produce absorption atelectasis, and should be avoided if possible. Use of PEEP to maintain lung volume is effective in preventing atelectasis.

Barotrauma

Barotrauma is alveolar rupture due to overdistention. Barotrauma can lead to pulmonary interstitial emphysema, pneumomediastinum, pneumopericardium, subcutaneous emphysema, and pneumothorax (Figure 1-4). Pneumothorax is of greatest clinical concern, because it can progress rapidly to life-threatening tension pneumothorax. Pneumomediastinum and subcutaneous emphysema rarely have major clinical consequences.

Ventilator-Induced Lung Injury

Alveolar overdistention causes acute lung injury. Alveolar distention is determined by the difference between intra-alveolar pressure and the intrapleural pressure. The peak alveolar pressure (end-inspiratory plateau pressure) should ideally be as low as possible and less than 30 cm H₂O. Alveolar distention is also affected by intrapleural pressure. Thus, a stiff chest wall may be protective against alveolar overdistention. Overdistention is minimized by limiting tidal volume (eg, 4-8 mL/kg ideal body weight) and alveolar distending pressure (< 25 cm H₂O). Ventilator-induced lung injury can also result from cyclical alveolar collapse during exhalation and re-opening during subsequent inhalation. This injury is ameliorated by the application of PEEP to avoid alveolar derecruitment. Ventilating the lungs in a manner that promotes alveolar overdistention and derecruitment increases inflammation in the lungs (biotrauma). Inflammatory mediators may translocate into the pulmonary circulation, resulting in systemic inflammation. An important characteristic of the lungs of mechanically ventilated patients is heterogeneity; that is, some lung units are prone to overdistention and others are prone to collapse.

Pneumonia

Ventilator-associated pneumonia (VAP) can occur during mechanical ventilation; this is more common during invasive ventilation than with noninvasive ventilation. VAP most often results from aspiration of oropharyngeal secretions around the cuff of the endotracheal tube. A number of prevention strategies can be bundled to reduce the risk of VAP.

Hyperventilation and Hypoventilation

Hyperventilation lowers Paco₂ and increases arterial pH. This should be avoided because of the injurious effects of alveolar overdistention and an alkalotic pH. Respiratory alkalosis causes hypokalemia, decreased ionized calcium, and increased affinity of hemoglobin for oxygen (left shift of the oxyhemoglobin dissociation curve). Relative hyperventilation can occur when mechanical ventilation is provided for patients with chronic compensated respiratory acidosis; if a normal Paco₂ is established in such patients, the result is an elevated pH. Hypercapnia during mechanical ventilation may be less injurious than the traumatic effects of high levels of ventilation to normalize the Paco₂. A modest elevation of Paco₂ (50-70 mm Hg) may not be injurious and a pH as low as 7.20 is well tolerated by most patients.

Oxygen Toxicity

A high inspired oxygen concentration is considered toxic. What is less clear is the level of oxygen that is toxic. Oxygen toxicity is probably related to Fio₂ as well as the amount of time that the elevated Fio₂ is breathed. Although the clinical evidence is weak, it is commonly recommended that an Fio₂ greater than 0.6 be avoided, particularly if breathed for a period more than 48 hours. High Fio₂ levels can result in a higher than normal PaO₂. A high Pao₂ may produce an elevation in Paco₂ due to the Haldane effect (ie, unloading CO₂ from hemoglobin), due to improving blood flow to low-ventilation lung units (ie, relaxing hypoxic pulmonary vasoconstriction), and due to suppression of ventilation (less likely). However, this is usually not an issue during mechanical ventilation because ventilation can be controlled. A high Pao₂ can produce retinopathy of prematurity in neonates, but this is not known to occur in adults.

Positive pressure ventilation can decrease cardiac output, resulting in hypotension and potential tissue hypoxia. This effect is greatest with high mean airway pressure, high lung compliance, and low circulating blood volume. Increased intrathoracic pressure decreases venous return and right heart filling, which may reduce cardiac output. With spontaneous breathing, venous return to the right atrium is greatest during inhalation, when the intrathoracic pressure is lowest. During positive pressure ventilation, venous return is greatest during exhalation.

Positive pressure ventilation may increase pulmonary vascular resistance. The increase in alveolar pressure, particularly with PEEP, has a constricting effect on the pulmonary vasculature. The increase in pulmonary vascular resistance decreases left ventricular filling and cardiac output. Increased right ventricular afterload can result in right ventricular hypertrophy, with ventricular septal shift and compromise of left ventricular function. Increased pulmonary vascular resistance with PEEP produces a West Zone 1 effect, which increases dead space, and thus results in less alveolar ventilation and a higher Paco₂.

The adverse cardiac effects of positive pressure ventilation are ameliorated by lower mean airway pressure. When high mean airway pressure is necessary, circulatory volume loading and administration of vasopressors may be necessary to maintain cardiac output and arterial blood pressure.

Urine output can decrease secondary to mechanical ventilation. This is partially related to decreased renal perfusion due to decreased cardiac output, and may also be related to elevations in plasma antidiuretic hormone and reductions in atrial natriuretic peptide that occur with mechanical ventilation. Fluid overload frequently occurs during mechanical ventilation, due to decreased urine output, excessive intravenous fluid administration, and elimination of insensible water loss from the respiratory tract due to humidification of the inspired gas.

Patients being mechanically ventilated may develop gastric distention (meteorism). Stress ulcer formation and gastrointestinal bleeding can also occur in mechanically ventilated patients, and stress ulcer prophylaxis should be provided.

Appropriate nutritional support is problematic in mechanically ventilated patients. Underfeeding can result in respiratory muscle catabolism and increases the risk of pneumonia and pulmonary edema. Overfeeding increases metabolic rate and thus increases the required minute ventilation. Overfeeding with carbohydrates increases V̇co₂, further increasing the ventilation requirement.

In patients with head injury, positive pressure ventilation might increase intracranial pressure. This is related to a decrease in venous return, which increases intracranial blood volume and pressure. If high mean airway pressure is used, cerebral perfusion can also be compromised due to arterial hypotension.

Delirium is common in mechanically ventilated patients. The mnemonic ABCDE has been proposed to remind clinicians of important steps of care in mechanically ventilated patients (Awakening and Breathing, Choice of sedative and analgesic, Delirium monitoring, and Early mobilization). Such an evidence-based protocol may improve patient outcome, including mortality. Benzodiazepine-based sedation may increase the risk of delirium, when compared with agents such as dexmedetomidine.

Mechanically ventilated patients are at increased risk of critical illness and weakness (polyneuropathy and polymyopathy). If the respiratory muscles are not used during mechanical ventilation (ie, paralysis), ventilator-induced diaphragm dysfunction can occur. On the other extreme, excessive respiratory muscle activity can result in muscle fatigue. Thus, an appropriate balance between respiratory muscle activity and support from the ventilator is important. Mobilization of mechanically ventilated patients is used increasingly to address generalized weakness in this patient population.

PEEP can reduce portal blood flow. However, the clinical importance of the effects of positive pressure ventilation on hepatosplanchnic perfusion is unclear.

Critically ill patients are usually mechanically ventilated through an endotracheal or tracheostomy tube. This puts these patients at risk for all of the complications of artificial airways such as laryngeal edema, tracheal mucosal trauma, contamination of the lower respiratory tract, sinusitis, loss of the humidifying function of the upper airway, and communication problems.

Mechanically ventilated patients may not have normal sleep patterns. Sleep deprivation can produce delirium, patient-ventilator asynchrony, and sedation-induced ventilator dependency.

Lack of synchrony between the breathing efforts of the patient and the ventilator may be due to poor trigger sensitivity, auto-PEEP, incorrect inspiratory flow or time setting, inappropriate tidal volume, or inappropriate mode. Asynchrony can also be caused by nonventilator issues such as pain, anxiety, and acidosis.

A variety of mechanical complications can occur during mechanical ventilation. These include accidental disconnection, leaks in the ventilator circuit, loss of electrical power, and loss of gas pressure. The mechanical ventilator system should be monitored frequently to prevent mechanical malfunctions.