Prolonged respiratory failure due to pulmonary embolism in a young woman: a case report

The pathophysiology of pulmonary edema (PE) is generally considered a result of elevated pulmonary capillary hydrostatic pressure due to increased left atrial pressure in consequence of a failing left ventricle [1], and pulmonary embolism is normally ruled out in the presence of PE. According to Starling’s equation,¹ fluid flux across the pulmonary capillary wall is determined by the permeability of the vessel wall and net transmural driving pressure, which is a balance of hydrostatic forces that tend to move fluid out of the capillary and colloid osmotic forces that tend to keep fluid in the capillary. PE develops when the amount of fluid crossing the pulmonary capillary endothelium exceeds the capacity of lymph fluid efflux in pulmonary interstitial space [2].

A 29-year-old Caucasian woman in respiratory distress was referred for initiation of parenteral nutrition because of chronic malabsorption and malnutrition. She had a history of bariatric gastric bypass surgery 10 years prior with multiple revisions over the following decade due to persisting steatorrhea. Her nutritional history revealed a voluntarily reduced protein intake of 25 g per day. She smoked one pack of cigarettes per day (13 pack years). Alcohol and recreational drugs were negated. Family history was insignificant.

Pulmonary capillary hydrostatic pressure varies with blood flow in the pulmonary circulation and with distribution of pulmonary vascular resistance between precapillary and postcapillary vessels. A pulmonary embolism increases precapillary resistance and hence is usually not associated with increases in pulmonary capillary pressure and development of PE. However, this applies only for areas of the pulmonary vascular bed directly affected by pulmonary embolism [5]. Blood flow is redirected from occluded vessels to open vessels in which increased pressure may be transmitted to the capillary bed. Moreover, pulmonary vascular resistance is directly related to the degree of vascular obstruction and location of the embolus [6, 7].

On the other hand, increased respiratory drive in hypoxemic respiratory failure seems to play a more relevant role in the pathophysiology of PE in the presented case, in addition to hyperadrenergic state causing peripheral vasoconstriction and increase in venous return [8]. Increased venous return may further increase pulmonary blood flow thus contributing to edema. Cyclic changes of alveolar pressures during respiration affect pulmonary capillary hydrostatic pressure. The profound negative intrathoracic pressure swings during respiratory failure lead to a rise of pulmonary transcapillary pressure, the pathophysiologic basis of negative pressure PE [9]. During respiratory efforts, intravascular pressure measured in pulmonary intrathoracic vessels decreases, but to a lesser extent than the esophageal or pleural pressure, resulting in increased transmural pulmonary vascular pressures. Our patient showed high respiratory drive with respiratory rates around 30 breaths per minute and tidal volumes (TVs) of 12.5 ml/kg predicted body weight during the 72 hours of NIV. Increased respiratory drive with the resulting increase of transmural pulmonary capillary pressures probably represents the underlying pathomechanism of patient self-inflicted lung injury due to prolonged application of non-invasive mechanical ventilation in hypoxemic respiratory failure, which seems to be one of the reasons for NIV failure and poor outcome of this patient group. As a consequence of negative pressure swings during experimentally increased respiratory resistance and during increased respiratory drive due to strenuous exercise, lung lymph flow was shown to double instantly. Increased transmural pulmonary vascular pressure in the context of an increased vascular permeability further increases the risk of PE through vascular leakage. Vascular permeability was shown to be increased in vascular injury inflicted by pulmonary embolism.

In addition to the described mechanisms favoring the development of PE, the counteracting determinant (that is, colloid osmotic pressure) was severely reduced in our patient, as serum albumin represents its main determinant. The effect of decreased albumin concentration on the development of PE is well known in experimental physiology. Low colloid osmotic pressure is considered a strong predictor in other lung diseases, such as acute respiratory distress syndrome (ARDS) [10]. The contribution of hypoalbuminemia to PE in clinical practice especially in the context of distinct negative pressure seems comprehensible, constituting hypalbuminemia as a risk factor for cardiogenic PE [11] and increased extravascular lung water in critically ill patients.

Finally, as the major determinant of interstitial fluid clearance is the pressure difference between the pulmonary interstitial space and the venous pressure at the junction of the thoracic duct and jugular vein, lymphatic flow may be significantly reduced in the setting of central pulmonary embolism and the associated rise in central venous pressure.

Negative pressure PE is another well-described etiology of PE [7], possibly of importance in severe acute respiratory failure. In conjunction with severe hypalbuminemia, even the negative intrathoracic pressure swings of respiratory distress may cause PE. Part of the mechanisms underlying patient self-inflicted lung injury may be excessive respiratory drive with resulting increases in pulmonary transmural vascular pressures. Detrimental consequences of NIV due to uncontrolled TV and pressure swings [12] need to be considered when treating patients in hypoxemic respiratory failure with low serum albumin.