Höstman Staffan, Borges João Batista, Suarez-Sipmann Fernando, Ahlgren Kerstin M, Engström Joakim, Hedenstierna Göran, Larsson Anders
Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden.
Department of Surgical Sciences, Uppsala University Hospital, Entrance 70, 75185, Uppsala, Sweden.
Crit Care. 2015 Sep 17;19(1):331. doi: 10.1186/s13054-015-1040-4.
Low tidal volume (VT) ventilation is recommended in patients with acute respiratory distress syndrome (ARDS). This may increase arterial carbon dioxide tension (PaCO2), decrease pH, and augment pulmonary vascular resistance (PVR). We hypothesized that Tris(hydroxymethyl)aminomethane (THAM), a pure proton acceptor, would dampen these effects, preventing the increase in PVR.
A one-hit injury ARDS model was established by repeated lung lavages in 18 piglets. After ventilation with VT of 6 ml/kg to maintain normocapnia, VT was reduced to 3 ml/kg to induce hypercapnia. Six animals received THAM for 1 h, six for 3 h, and six serving as controls received no THAM. In all, the experiment continued for 6 h. The THAM dosage was calculated to normalize pH and exhibit a lasting effect. Gas exchange, pulmonary, and systemic hemodynamics were tracked. Inflammatory markers were obtained at the end of the experiment.
In the controls, the decrease in VT from 6 to 3 ml/kg increased PaCO2 from 6.0±0.5 to 13.8±1.5 kPa and lowered pH from 7.40±0.01 to 7.12±0.06, whereas base excess (BE) remained stable at 2.7±2.3 mEq/L to 3.4±3.2 mEq/L. In the THAM groups, PaCO2 decreased and pH increased above 7.4 during the infusions. After discontinuing the infusions, PaCO2 increased above the corresponding level of the controls (15.2±1.7 kPa and 22.6±3.3 kPa for 1-h and 3-h THAM infusions, respectively). Despite a marked increase in BE (13.8±3.5 and 31.2±2.2 for 1-h and 3-h THAM infusions, respectively), pH became similar to the corresponding levels of the controls. PVR was lower in the THAM groups (at 6 h, 329±77 dyn∙s/m(5) and 255±43 dyn∙s/m(5) in the 1-h and 3-h groups, respectively, compared with 450±141 dyn∙s/m(5) in the controls), as were pulmonary arterial pressures.
The pH in the THAM groups was similar to pH in the controls at 6 h, despite a marked increase in BE. This was due to an increase in PaCO2 after stopping the THAM infusion, possibly by intracellular release of CO2. Pulmonary arterial pressure and PVR were lower in the THAM-treated animals, indicating that THAM may be an option to reduce PVR in acute hypercapnia.
对于急性呼吸窘迫综合征（ARDS）患者，推荐采用低潮气量（VT）通气。这可能会增加动脉血二氧化碳分压（PaCO2），降低pH值，并增加肺血管阻力（PVR）。我们推测，三（羟甲基）氨基甲烷（THAM）作为一种纯质子受体，会减弱这些影响，防止PVR升高。
通过对18只仔猪反复进行肺灌洗建立一次性打击损伤ARDS模型。在以6 ml/kg的VT通气以维持正常碳酸血症后，将VT降至3 ml/kg以诱导高碳酸血症。6只动物接受THAM治疗1小时，6只接受3小时，6只作为对照未接受THAM。实验总共持续6小时。计算THAM剂量以使pH值正常化并产生持久效果。追踪气体交换、肺和全身血流动力学。在实验结束时获取炎症标志物。
在对照组中，VT从6 ml/kg降至3 ml/kg使PaCO2从6.0±0.5 kPa增加到13.8±1.5 kPa，pH值从7.40±0.01降至7.12±0.06，而碱剩余（BE）保持稳定，从2.7±2.3 mEq/L到3.4±3.2 mEq/L。在THAM组中，输注期间PaCO2降低，pH值升高至7.4以上。停止输注后，PaCO2升高至高于对照组相应水平（1小时和3小时THAM输注分别为15.2±1.7 kPa和22.6±3.3 kPa）。尽管BE显著增加（1小时和3小时THAM输注分别为13.8±3.5和31.2±2.2），但pH值变得与对照组相应水平相似。THAM组的PVR较低（在6小时时，1小时组和3小时组分别为329±77 dyn∙s/m(5)和255±43 dyn∙s/m(5)，而对照组为450±141 dyn∙s/m(5)），肺动脉压也是如此。
尽管BE显著增加，但THAM组在6小时时的pH值与对照组相似。这是由于停止THAM输注后PaCO2升高，可能是由于细胞内CO2释放。THAM治疗的动物肺动脉压和PVR较低，表明THAM可能是降低急性高碳酸血症中PVR的一种选择。
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