Department of Pediatrics, University of Colorado/Children's Hospital Colorado, Aurora, Colorado.
Research Institute, Children's Hospital Colorado, Aurora, Colorado.
Shock. 2019 Mar;51(3):328-336. doi: 10.1097/SHK.0000000000001162.
Infant cardiopulmonary bypass (CPB) increases intestinal permeability leading to endotoxemia. Alkaline phosphatase (AP) reduces endotoxin toxicity in vitro but its effects on endotoxemia in human disease are poorly understood. We assessed the association between serum AP activity and endotoxemia in infants undergoing CPB and determined the effect of ex vivo addition of AP on endotoxemia.
Prospective cohort study of 62 infants ≤120 days of age undergoing CPB. AP activity and Endotoxin Activity Assay (EAA) were measured pre-operatively, during rewarming, and 24 h after cardiac intensive care unit admission. In 22 subjects, EAA was measured in pre-operative and rewarming whole blood samples with/without addition of 1,600 U/L of human liver AP.
AP activity decreased during CPB (mean decrease 94.8U/L; P < 0.0001). Median EAA was 0.41 pre-operation, rose to 0.52 (P < 0.05) during rewarming, and remained stably elevated at 24 h. Subjects with low pre-operative AP activity had significantly higher pre-operative (0.47 vs. 0.36; P < 0.05) and rewarming (0.59 vs. 0.43; P < 0.01) EAA with a trend toward higher EAA at 24 h (0.52 vs. 0.45; P = 0.12). Subjects with low rewarming AP activity showed similar differences that did not reach statistical significance. Ex vivo addition of human liver AP decreased pre-operative EAA by 29% (P < 0.001) and rewarming EAA by 51% (P < 0.0001).
Endotoxemia is common in infants undergoing CPB. Native AP activity and endotoxemia are inversely related and ex vivo addition of exogenous AP reduces whole blood EAA. Future research should evaluate AP as a therapy to reduce the harmful effects of endotoxemia following infant CPB.
婴儿心肺转流术（CPB）会增加肠通透性，导致内毒素血症。碱性磷酸酶（AP）可降低体外内毒素的毒性，但人们对内毒素血症在人类疾病中的作用知之甚少。我们评估了 CPB 婴儿血清 AP 活性与内毒素血症之间的相关性，并确定了外源性 AP 对内毒素血症的影响。
对 62 名年龄≤120 天的接受 CPB 的婴儿进行前瞻性队列研究。AP 活性和内毒素活性测定（EAA）分别于术前、复温时和心脏重症监护病房入院后 24 小时进行测量。在 22 名受试者中，在术前和复温时的全血样本中测量 EAA，同时加入/不加入 1600 U/L 的人肝 AP。
CPB 期间 AP 活性降低（平均降低 94.8U/L；P<0.0001）。术前中位 EAA 为 0.41，复温时升高至 0.52（P<0.05），24 小时时仍保持稳定升高。术前 AP 活性低的患者术前（0.47 比 0.36；P<0.05）和复温时（0.59 比 0.43；P<0.01）EAA 显著升高，24 小时时 EAA 呈升高趋势（0.52 比 0.45；P=0.12）。复温时 AP 活性低的患者也有类似但无统计学意义的差异。外源性人肝 AP 的添加可使术前 EAA 降低 29%（P<0.001），复温时 EAA 降低 51%（P<0.0001）。
CPB 婴儿内毒素血症常见。内源性 AP 活性与内毒素血症呈负相关，外源性 AP 的添加可降低全血 EAA。未来的研究应评估 AP 作为一种治疗方法，以减轻婴儿 CPB 后内毒素血症的有害影响。
