Strategic leukocyte depletion reduces pulmonary microvascular pressure and improves pulmonary status post-cardiopulmonary bypass

Abstract

Cardiopulmonary bypass (CPB) precipitates inflammation that causes marked pulmonary dysfunction. Leukocyte filtration has been proposed to reduce these deleterious effects. Other studies show an improvement with aprotinin. We proposed that a combination of these two therapies would synergistically improve pulmonary outcomes. Two hundred and twenty-five patients participated in a randomized prospective study comparing pulmonary microvascular function and pulmonary shunt fraction postcoronary artery bypass grafting (CABG). The study group underwent leukocyte depletion with aprotinin during the procedure. Pulmonary microvascular function was assessed by pulmonary microvascular pressure (PMVP), a measure of pulmonary capillary edema, and pulmonary function was evaluated by comparing pulmonary shunt fractions. Elevated PMVP and increased pulmonary shunting compromise pulmonary performance. The leukocyte-depleted group had significantly reduced PMVP and pulmonary shunt fraction for at least the first 24 hours postbypass. The combination of strategic leukocyte filtration and aprotinin therapy can effectively reduce postoperative decline in pulmonary function. Cardiopulmonary bypass precipitates a variety of inflammatory effects that can cause marked pulmonary dysfunction to the point of respiratory failure, necessitating prolonged mechanical ventilation. Leukocyte filtration has been investigated previously and appears to be beneficial in improving pulmonary outcome by preventing direct neutrophil-induced inflammatory injury. Recent studies of leukocyte reduction profiles suggest that leukoreduction via leukofiltration is short lived with filter saturation occurring 30-45 minutes after onset of filtration. This phenomenon may explain the limited utility observed with higher risk patients. These patients typically require longer pump runs, so leukocyte reduction capability is suboptimal at the time of pulmonary vascular reperfusion. To more effectively protect the lung from reperfusion injury, leukocyte filtration can be delayed so that reduction of activated neutrophils is maximal at the time of pulmonary vascular reperfusion. It is, thus, conceivable that a timely use of arterial line leukoreducing filters may improve, more substantially, pulmonary function postbypass. Two hundred and twenty-five isolated coronary revascularization patients participated in this prospective, randomized trial. The patients received moderately hypothermic CBP alone (control group: n = 110) or combined with leukocyte depletion, initiated 30 minutes before crossclamp release, with filters placed in the bypass circuit (study group: n = 115). All patients also received full Hammersmith aprotinin dosing during the operation. Pulmonary microvascular pressures were lower in the study group at three hours postbypass, and continued to fall until 24 hours postbypass. In contrast, the control group measured a rise in PMVP and a continued plateau throughout 24 hours postbypass (p < 0.028). The calculated pulmonary shunt fraction also was reduced sign...

The effects of various leukocyte filtration strategies in cardiac surgery

“…Hayashi et al n/a n/a n/a n/a n/a [84] (1) C vs (2) n/a n/a n/a n/a n/a [87] (1) C vs (2) TLC + Aprot. 1 n/a 1 F n/a n/a 120 55 65 --n/a n/a --n/a [29] (1) Aprot. vs (2) have demonstrated a significantly lower maximum dose of inotrope at weaning of CPB in the leukodepleted group, but in their later study could only replicate this in patients who had extended aortic cross clamp time [73].…”

“…In 2003 the same group studied the impact of this combined approach on post-bypass pulmonary function and found a statistically significant benefit in pulmonary artery pressure and pulmonary microvascular pressure at 24 h, and in shunt fraction at 6 h postoperatively. They have also reported reductions in ventilation time, hospital stay and cost, but no statistical significance was assigned to this [29]. The 2004 study by the same group assessed the combined outcomes of the first two studies, namely atrial fibrillation and pulmonary dysfunction.…”

“…Initially work focused on molecular inflammatory mediators and a wide variety of markers of neutrophil activation [17,22,23]. However, later work measured biochemical markers of organ injury [24][25][26] and examined the impact of leukodepletion on post-operative clinical course and the hospital costs [11,[27][28][29][30].…”

Systemic Leukofiltration Does Not Attenuate Pulmonary Injury after Cardiopulmonary Bypass

“…2,10, 65 We studied six outcomes, and found systemic leukofiltration only to have an effect on two: early PaO 2 /FiO 2 ratio and duration of intubation post-CPB cessation. Furthermore, the clinical significance of the effect is likely to be minimal in both cases.…”

Os leucócitos e a resposta inflamatória na lesão de isquemia-reperfusão

“…Initial clinical studies showed beneficial effects of LDF on CPB, with lower release of leukocyte enzymes, improvement in clinical recovery, a shorter stay in the intensive care unit (ICU) and lower costs [50][51][52]. However, other authors showed that the use of FDL seemed to be less effective than expected, and its effectiveness diminished over surgical time [53][54][55].…”