Ferrari Fiorenza, Benegni Simona, Marinari Eleonora, Haiberger Roberta, Garisto Cristiana, Rizza Alessandra, Giorni Chiara, Quattrone Maria Giovanna, Arpicco Silvia, Muntoni Elisabetta, Milla Paola, Ricci Zaccaria
Intensive Care Unit, I.R.C.C.S. Fondazione Policlinico San Matteo, Pavia, Italy.
Department of Cardiology and Cardiac Surgery, Pediatric Cardiac Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Perfusion. 2022 Sep;37(6):553-561. doi: 10.1177/02676591211006828. Epub 2021 Mar 31.
Few data are available regarding intraoperative plasma concentrations of vancomycin administered as prophylaxis in pediatric cardiac surgery. The aims of this study were to investigate during pediatric cardiac surgery with cardiopulmonary bypass(CPB) the attainment of the area-under-the-curve of the vancomycin serum concentrations versus time over surgery to minimum inhibitory concentration ratio(AUC/MIC) of 400 (mg × h)/l and/or a target concentration of 15-20 mg/l.
In a prospective study, 40 patients divided into four subgroups (neonates, infants, children <10 years-old, ⩾10 years-old) undergoing cardiac surgery with cardiopulmonary bypass (CPB) were enrolled. A slow vancomycin bolus of 20 mg/kg, up to a maximum dose of 1000 mg was administered before skin incision and a further dose of 10 mg/kg (up to 500 mg) at CPB start. Vancomycin samples were collected intraoperatively at four time points.
The median (interquartile range) age was 241.5 days (47-3898) and the median weight was 7.1 kg (3.1-37). The median AUC/MIC was 254.73 (165.89-508.06). In 11 patients the AUC/MIC target was not reached. Neonates displayed the lowest AUC/MIC values, and these were significantly lower than those of children ⩾10 years old (p = 0.02). Vancomycin concentrations were above the maximal target of 20 mg/l in 82.5% and 80% of patients at surgery and CPB start, respectively. At CPB and surgery end, 42.5% of patients showed vancomycin concentrations above 20 mg/l and 42.5% below 15 mg/l. Patients⩾10 years old showed the highest peak values whereas neonates were those with the lowest troughs. AUC/MIC correlated with age(r:0.36, p = 0.02), weight(r:0.35, p = 0.03), intraoperative protein value(r:0.40, p = 0.01), CPB priming volume/kg(r:-0.33, p = 0.04), CPB duration(r:0.36, p = 0.02) and vancomycin troughs(r:0.35, p = 0.04).
An AUC/MIC ⩾400 target was not reached in one-quarter of children undergoing heart surgery. Vancomycin peaked before the start of surgery and neonates were those with the lowest troughs. Vancomycin concentrations are affected by CPB hemodilution and by patients' age and weight.
关于小儿心脏手术中预防性使用万古霉素的术中血浆浓度，可用数据较少。本研究的目的是在小儿体外循环（CPB）心脏手术期间，研究万古霉素血清浓度随时间变化的曲线下面积与最低抑菌浓度之比（AUC/MIC）达到400（mg×h）/l和/或目标浓度15 - 20mg/l的情况。
在一项前瞻性研究中，纳入了40例接受体外循环（CPB）心脏手术的患者，分为四个亚组（新生儿、婴儿、<10岁儿童、≥10岁儿童）。在皮肤切开前给予20mg/kg的万古霉素缓慢推注，最大剂量为1000mg，在CPB开始时再给予10mg/kg（最大500mg）的剂量。术中在四个时间点采集万古霉素样本。
中位（四分位间距）年龄为241.5天（47 - 3898天），中位体重为7.1kg（3.1 - 37kg）。中位AUC/MIC为254.73（165.89 - 508.06）。11例患者未达到AUC/MIC目标。新生儿的AUC/MIC值最低，且显著低于≥10岁儿童（p = 0.02）。在手术时和CPB开始时，分别有82.5%和80%的患者万古霉素浓度高于20mg/l的最大目标值。在CPB结束和手术结束时，42.5%的患者万古霉素浓度高于20mg/l，42.5%低于15mg/l。≥10岁的患者峰值最高，而新生儿谷值最低。AUC/MIC与年龄（r：0.36，p = 0.02）、体重（r：0.35，p = 0.03）、术中蛋白值（r：0.40，p = 0.01）、CPB预充量/kg（r： - 0.33，p = 0.04）、CPB持续时间（r：0.36，p = 0.02）和万古霉素谷值（r：0.35，p = 0.04）相关。
四分之一接受心脏手术的儿童未达到AUC/MIC≥400的目标。万古霉素在手术开始前达到峰值，新生儿谷值最低。万古霉素浓度受CPB血液稀释以及患者年龄和体重的影响。
