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 [6] .

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 [7] . The inflammation caused by cardiopulmonary bypass is related to perioperative capillary leak. Liu et al. [8] found independent factors of CLS were infection cycle time, type of cardiac malformation, the lowest temperature of operation, age and so on by analysis of 310 cases of congenital heart disease by the operation after cardiopulmonary bypass clinical data of patients.

Positive pressure mechanical ventilation itself can cause or worsen lung injury. Slutsky [9] indicated that the mechanical ventilation induced lung injury can demonstrate diffuse alveolar injury (alveolar epithelial and endothelial damage) induced by the gas leakage (i.e. stress injury) and non-cardiac source pulmonary edema.

Using of certain anticancer drugs, especially recombinant human interleukin (interleukin 2, IL-2) therapy, overdose will occur CLS [10] and after injection of interferon 1β in patients with multiple sclerosis also can cause CLS. With the increasing use of granulocyte colony-stimulating factor treatment in hematologic cancer and use of arsenic trioxide treatment for recurrence of acute promyelocytic leukemia, the side effects about CLS were increased [11] .

Oberholzer et al. [12] showed that TNF, IL-1, IL-8 and so on can accelerate the occurrence of CLS. Assier’s research shows that rat NK cells involve in the pathological process of CLS [13] . Chihara et al. [5] found that CLS patients had increased leukotriene B4 and this might be related to increased vascular permeability, plasma extravasation and others. Rafi found that IL-2 could enhance the cytotoxic T lymphocyte activity, increase fas ligand and perforin, Lymphocyte-activated killer cells and endothelial cells in close contact and start the autolysis to endothelial cell damage. Railan et al. [14] proposed that nitric oxide could lead to vascular endothelial cell injury and increase capillary permeability.

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 [19] that the happened pulmonary edema in recovery is more than that in acute leakage. Therefore, giving rehydration therapy should be in the premise of hemodynamic monitoring if condition is permitted.

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. [20] discovered that patients lacked of C4A genes added C4A gene-rich plasma before surgery and it was able to reduce the incidence of CLS after CPB.

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 [21] . With patients’ large capillary permeability and small molecular weight of liquid crystals, most of them can leak into the interstitial space and then systemic edema increases after infusion. So we should limit the volume of liquid crystals and avoid interstitial edema and cell swelling caused by excessive liquid crystals in the premise of ensuring the effective circulating blood volume. We need to prevent increased pulmonary edema, cardiac, thoracic and abdominal cavity effusion and added organ damage. Colloid hydroxyethyl starch as the generation of plasma in the traditional product is still the effective and available drug in clinical for CLS treatment. Tian et al. [22] thought that the newest plasma substitutes were hydroxyethyl starch of 130 × 10³ Da and 200 × 10³ Da molecular weight, polygeline of (27.5 - 39.5) × 10³ Da molecular weight and so on. In theory, they may have better expansion effect. When blood volume is restored, we use diuretics to reduce swelling of tissues and organs. In the leakage of the CLS, the human serum albumin can leak from capillaries, redistribute after entering into body and influence plasma colloid osmotic pressure in short time. Now we promote to use generation of plasma including new macromolecular plasma substitutes and don’t advocate adding FFP and/or human serum albumin for emergency treatment of CLS. At the recovery time, fluid intake should be strictly limited and increased diuresis with normal capillary permeability gradually returning and intravascular volume increasing.

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 [28] .

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 [29] , control SIRS symptoms, prevent the development of the disease to the MOD and improve the survival rate in critically ill patients. It also can make rapid absorption and removal of endotoxin in blood, correct acidosis and improve the body’s homeostasis. Meanwhile, CBP has a protective effect on vascular endothelial function [30] . CBP also can improve coagulation dysfunction in vivo because of heparin. It can reduce blood coagulation cascade [31] and play a role in the treatment CLS.