PULMONARY OEDEMA: A REVIEW WILLIAM H. NOBLE ABSTRACT Pulmonary oedema results from derangement of a normal physiological process which is continuously producing and removing extravascular lung water according to principles stated by Starling's equation of fluid flow across semipermeable membranes. The parameters in Starling's equation cannot all be measured. However, experiments have suggested that increased pulmonary capillary hydrostatic pressure forces fluid extravascularly, diluting the colloid osmotic pressure of tissue fluids and increasing the hydrostatic pressure of lung tissue fluids. Once these reserves and the ability of puhnonary lymphatics to remove lung water are overcome, pulmonary oedema results. This oedema can also result from reduced colloid osmotic pressure in the pulmonary capillaries and increased capillary permeability, even at low pulmonary capillary hydrostatic l~ressure. Perhaps because of the reserve created by colloid osmotic pressure of tissue fluids, hy- drostatic pressure of lung tissue fluids and lymphatic drainage, pulmonary oedema accumu- lates at a slow rate initially, and at a much more rapid rate in later stages of oedema development. The rate of oedema formation may also relate to damage to the lung created by interstitial oedema, which opens the barrier to a later stage of alveolar oedema. While lung compliance is reduced with each successive increase in oedema formation, increased shunting and hypoxaemia do not result until alveolar oedema is present, in normal lung. The diagnosis of pulmonary oedema is best made by searching for causes of oedema and by chest radiographs. The management of pulmonary oedema must begin with maintenance of oxygenation of blood. This can best be achieved by applying continuous positive pressure ventilation (CPPV). CPPV does not remove lung water (in fact it may slightly increase it), but it does improve oxygenation by ventilating alveoli that were previously filled with fluid. The im- proved oxygenation buys time, so that therapy directed at the cause of pulmonary oedema (Starling's law) can be applied. Since current knowledge is inadequate we do not know how to reverse an increased capillary permeability, other than by removing its cause; or how to reduce tissue colloid osmotic pressure, or to increase the hydrostatic pressure of lung tissue fluids or the in- tracapillary colloid osmotic pressure or the lymphatic flow of fluid. This leaves only increasing intracapillary colloid osmotic pressure or decreasing pulmonary capillary hydrostatic pres- sure as the means available to reduce pulmonary oedema. In the face of a non-compliant left ventricle colloid infusions may be dangerous, as the attendant increase in blood volume may increase pulmonary capillary hydrostatic pressure and worsen pulmonary oedema. If in- creased capillary permeability is the cause of pulmonary oedema, colloids might leak ex- travasculady and draw fluid with them. Therefore the most important therapy in pulmonary oedema, regardless of cause, is to reduce pulmonary capillary hydrostatic pressure. Depend- ing on the cause of pulmonary oedema and the associated cardiac output, pulmonary capillary hydrostalic pressure may be decreased by reducing left ventricular preload, increasing myocardial contractility, reducing left ventricular after-load or some combination of these. The anaesthetic implications are that Starling reserves are large and pulmonary oedema should not occur in the normal patient. In the patient with pulmonary oedema or reduced cardio-pulmonary reserve preoperatively, every effort must be made to optimize Starling's forces before undertaking an anaesthetic in these life threatening situations. I Introduction Pathology II Pathophysiology Effects of pulmonary oedema Starling's Equation III Clinical Correlates of Pathophysiology normal values COP-r interaction of values Pmv Time course of pulmonary oedema P'r COPmv William H. Noble, M.D., F.R.C.P.(C), Associate Lymphatic removal of oedema Professor, University of Toronto; Department of Anaesthesia, St. Michael's Hospital, 30 Bond Street, Capillary permeability Toronto, Ontario, M5B 1W8. Cardiopulmonary bypass 286 Canad. Anaesth. Soc. J., vol. 27, no. 3, May 1980 NOBLE:PULMONARYOEDEMA 287 1V Diagnosis Gas Exchange history and physical examination Pao2 arterial partial pressure of oxygen CVP versus pulmonary artery Qs/Qt shunt fraction occluded pressure FRC functional residual capacity blood gases CPPV continuous positive pressure venti- lung compliance lation chest radiograph V/Q ventilation perfusion ratio V Management Pvoz mixed venous partial pressure of 1. MaintainOxygenation oxygen Flo z CPPV I INTRODUCTION 2. Lower Pmv lower ventricular preload PULMONARY OEDEMA may be defined as an ab- increase myocardial preload normal collection of fluid in the extravascular reduce ventricular afterload tissues and spaces of the lung. It is important to (improve ventricular compliance) realise that the lungs have a dynamic and not a 3. Remove the cause of increased static water content. Water and proteins do move capillary permeability into the interstitial space and are returned to the 4. Increase COPmv (cautiously) venous circulation by an extensive network of VI Implications of Pulmonary Oedema for lymphatics. Once the capacity of the lymphatics the Anaesthetist: to remove excess fluids is exceeded, fluid ac- normal patients cumulates in the interstitial space and, if un- patients with pulmonary oed- checked, will lead to alveolar flooding. ema preoperatively Theoretically it should be possible to distin- patients with decreased cardio- guish between interstitial and alveolar oedema. pulmonary reserves However, an easy technique to detect small in- creases in extravascular water is not currently GLOSSARY OF TERMS available. Consequently little is known about the early interstitial phase of pulmonary oedema. In Haemodynamics animal experiments, determinations of volume and protein concentration of the lymphatic fluid Pmv pulmonary capillary hydrostatic from the lung or double indicator dilution tech- pressure niques to quantitate lung water are shedding PAO pulmonary artery occluded (wedge) some light on the process of extravascular lung pressure water formation in normal conditions and in dis- PPA pulmonary artery pressure ease. Since techniques to quantify lung water in LVEDP left ventricular end diastolic pressure patients are invasive, most of the patient data is LVEDV left ventricular end diastolic volume gathered in cardiac surgery settings. It is assumed CVP central venous pressure the principles learned there will apply to other Q cardiac output patients as well. Other clinical information usu- Lung Liquid Flow ally begins at the late alveolar oedema stage and Qf net transvascular flow of fluid makes assumptions about its cause. Kf fluid filtration coefficient In this review I will stress basic physiology and PT tissue fluid interstitial hydrostatic recent advances in knowledge of pulmonary pressure oedema. Gf reflection coefficient COPmv colloid osmotic pressure of plasma II PATHOPHYStOLOGY proteins COPr colloid osmotic pressure of tissue To understand the pathophysiology of pulmo- proteins nary oedema we should start by studying the ETV ~ extravascular thermal volume of lung physical forces and permeability properties that (a double indicator dilution mea- produce shifts in water from one compartment to sure of lung water) another. In 1896 Starling ~ stated the general 288 CANADIAN ANAESTHETISTS ~ SOCIETY JOURNAL transport equation for fluid flow across capillary ducts must return this fluid to the systemic ven- membranes: ous circulation or pulmonary oedema will result. If one variable in Starling's equation is Qf= Kf[(Pmv - P'r) - Gf(COPmv - COPT)] (I) changed, other variables will change. If an in- crease in hydrostatic pressure (Pmv) occurs fluid where Qfis the net transvascnlar flow of fluid, Kf will immediately move into the extravascular is the fluid filtration coefficient, Pray is the micro- lung and dilute the proteins (lymph proteins are vascular hydrostatic pressure, P,r is the tissue reduced in the presence of an increased Pray). 4 P~ interstitial fluid hydrostatic pressure, Gf is the changes have not been measured in pulmonary reflection coefficient describing the "effective" oedema, but data from Parker, et ol. 7 suggest an transvascular protein osmotic pressure differ- increase, lfwe assume these changes we obtain ence, COPmv is the colloid osmotic pressure of Qfof 3.6 as follows: plasma proteins, and COPy is the tissue fluid col- loid osmotic' pressure. Together Kt" and Gf de- Elevated Pray scribe pulmonary capillary permeability. Capillary Pray = 22 mm Hg COPmv = 25 mm Hg Examples of normal values and changes which lnterstitium P'r = 0 mm Hg COP.r = 2 mm Hg can occur in Starling's equation will clarify how oedema formation is affected. In the normal these Substituting in (1) results might apply. Kf is assumed to be 1 ml Qf= 1[(22 - o) - 0.8(25 - 2)] = 3.6 H20/mmHg. min -~ and is a property of the sys- tem that expresses how much water will flow This represents a small rise in the force,, across the membrane per unit change in pressure. favoring pulmonary oedema (3.6 versus 1.6 in th~ Gf is assumed to be 0.8, indicating that protein normal). The lung lymphatics should be able t~ can cross the pulmonary capillary membrane; but offset the development of pulmonary oedema bl the membrane is normally about 80 per ccnt ef- increasing lymph flow. But now the available t~s fective as a barrier to protein