Capillary Leak Syndrome (CLS) in patients with severe course of disease is more and more common, and the clinical manifestations of CLS include systemic edema, hypoproteinemia, effective circulating blood volume reduction and hemoconcentration. The common pathogenies are sepsis, severe trauma, cardiopulmonary bypass and so on. Clinically, CLS is usually divided into leakage period and recovery period, with different pathophysiologic process, clinical manifestation and treatment in different period respectively. Although there are more treatments, they are not effective treatment measures. There have been so many studies about improvement of endothelial function, macromolecular colloid liquid applications, and continuous blood purification treatment. Systematic understanding of the pathological mechanism, clinical manifestations and staging, diagnosis and treatment of the CLS has a guiding value.
Capillary Leak Syndrome (CLS) is a syndrome of hypoproteinemia, hypovolemic shock, acute renal ischemia in clinical manifestations and the main reasons are the cell injury of capillary endothelial , increased vascular permeability, and a large number of plasma proteins leaking into the tissues of small molecule clearance. [
Diagnostic criteria of CLS [
Critically ill patients with CLS will influence their prognosis. So incidence, risk factors and the impact on function of the important organs of CLS will get more and more concern by critical medicine physicians. According to reports [
According to internal and external osmotic pressure vessel changes, water and electrolytes can access to the tissue space freely through the capillary barrier and the plasma protein and other ingredients cannot be under normal physiological conditions. Body can cause series of CLS clinical manifestations in the pathological state, for example, severe trauma, sepsis, the operation after cardiopulmonary bypass (particularly in infants and young children) and reperfusion injury, snakebite, acute lung injury or acute respiratory distress syndrome, burns, toxic effects of drugs (recombinant IL-2 and docetaxel) and so on will cause increased capillary permeability by exudating materials of molecular weight less than 20 × 103 Da and even molecular weight of 90 × 103 Da in serious condition [
These pathogenic factors can cause systemic inflammatory response syndrome by excessive activation of mononuclear macrophage system and release of inflammatory mediator. Under the function of inflammatory mediator, endothelial cell and capillary walls damage, cell junction separation and cracks appear, capillary transport channel diameter and vascular permeability increase, small protein in the blood leaks into the interstitial space by causing the interstitial colloid osmotic pressure, interstitial edema, such as body height of edema, ascites and pleural fluids and the effective circulating blood volume decrease. Interstitial pulmonary edema leads to hypoxemia, tissue hypoxia increases cell damage and then causing MODS [
In the operation of cardiopulmonary bypass, systemic inflammatory response can be caused by the blood surface contact with the pump pipe, non-physiological perfusion, surgical trauma, ischemia reperfusion injury, and changes in body temperature [
Positive pressure mechanical ventilation itself can cause or worsen lung injury. Slutsky [
Using of certain anticancer drugs, especially recombinant human interleukin (interleukin 2, IL-2) therapy, overdose will occur CLS [
Oberholzer et al. [
CLS can be divided into capillary leakage stage and recovery stage.
With the increased pulmonary capillary permeability, plasma proteins and other small molecules ooze from the vascular permeability to pulmonary interstitial rapidly, pulmonary effusion changes and leads to hypoxemia. Patients in serious condition will be in pulmonary edema [
Small proteins of plasma leaks to extravascular, plasma colloid osmotic pressure decreases, effective circulating blood volume reduces and then decreased blood pressure may occur. Pericardial effusion as well as cardiac tamponade [
Large amount of liquid leaks from the capillary wall and will cause ascites under abdominal wall, gastrointestinal wall and peritoneal edema, then anorexia, nausea, vomiting, abdominal distension, and luminal expansion. Pancreatic tissue edema and trypsin penetrates into the abdominal cavity will make damage increased. Liver cell congestion, edema, degeneration and other pathological changes will impaire liver function and acute liver injury appears.
The formation of massive proteinuria will make the plasma colloid osmotic pressure decreased and tissue edema [
Brain capillary permeability increases, a large number of white matter intercellular fluid accumulates (extracellular space expansion) and is rich in protein, glial elements around gray matter blood vessels and neurons swells (glial cell edema), brain size and weight increase, gyrus is wide and flat, sulci becomes narrow, ventricles reduce and the performance of intracranial hypertension appears. Severe cerebral edema can cause herniation [
Increased capillary permeability makes small proteins in plasma penetrate into tissue space. And then decreaseing of plasma colloid osmotic pressure, increased interstitial fluid colloid osmotic pressure, serious edema of systemic mucocutaneous, conjunctival edema, increasing tears overflow in plasma samples and pain of limbs muscle show.
In the recovery stage of CLS, there are two ways for interstitial fluid to reflux. When it reabsorbs from the venous capillaries and drains into the right atrium through lymphatic, gradually capillary permeability returns normally and blood volume tends to restore. Leakage of plasma proteins to the organization cannot return to capillaries and the colloid osmotic pressure in tissue fluid is still high because of normal capillary permeability. Edema in patients will hardly disappear with normal serum albumin levels and sometimes may last longer. If continuing to offer a lot of fluid at this time, acute pulmonary edema, alveolar atrophy, gas diffusion barriers, increased arterial and venous blood shunt and decreased arterial partial pressure of oxygen will become. Rapid increasing in cardiac preload will induce acute left ventricular failure easily and lead to repeated illness. Some studies have shown [
Currently, there are many researches about CLS therapy with no specific treatment. The following treatment is in favor of shortening the duration of capillary leakage and improving the successful rescue rate except for active treatment and removal of the primary disease inducing predisposing factors.
Tahirkhel et al. reported that terbutaline and aminophylline were effective drugs to prevent occurrence of CLS. Terbutaline (β agonist) and aminophylline (phosphodiesterase inhibitor) can loose endothelial cells and improve capillary permeability. In addition, terbutaline has anti-inflammatory effect and can adjust the production of cytokines. Zhang et al. [
The key point of fluid therapy in CLS is maintaining the effective circulating blood volume and avoiding shock. For a long time, liquid crystal or colloid treatment is controversial to CLS patients [
It can widely inhibit inflammatory reaction and decrease capillary permeability. In the acute phase, using small doses of hormones can control the inflammatory mediated vascular endothelial injury effectively and reduce the clinical symptoms. It should not be used as a preventive treatment because of the side effects of steroid restrictions.
It can promote injury repair and regeneration of capillaries [
It can protect IL-2 induced rat model of CLS by dose-dependent and reduce the CLS severity and mortality [
Studies have shown that [
In the leakage of CLS, for a large number of fluid in capillaries leaks to interstitial lung with making lung compliance, increased airway resistance, decreased ventilatory function and severe hypoxemia may occur. Mechanical ventilation improves lung compliance and ventilation or perfusion ratio, decreases airway resistance, improves oxygenation and reduces pulmonary effusion by increasing positive end expiratory pressure. Mechanical ventilation can effectively increase the oxygen supply of tissues and organs and has great help in improving body environment and treatment of primary disease [
CBP treatment can enhance clearance of inflammatory mediators, improve pulmonary gas exchange, keep hemodynamics stable control of azotemia, reduce fluid overloading because of entering macromolecular synthetic colloids, be convenient for nutrition support, improve oxygen metabolism or tissue perfusion in patients [
Currently, there is no specific prevention and treatment for critically ill patients in CLS. We should restore blood volume as soon as possible, improve hypoxemia and capillary permeability and reduce the degree of capillary leakage at the same time of active treatment of primary disease. With the pathogenesis deepening research of CLS and the comprehensive application of various prevention methods, the incidence of CLS will reduce, the survival rate will increase and patients’ prognosis will improve.