From the *Department of Anesthesiology, Critical Care and Pain Medicine, Steward St. Elizabeth's Medical Center; †Harvard Medical School, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center; ‡Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Steward St. Elizabeth's Medical Center; and §Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Anesth Analg. 2013 Dec;117(6):1313-8. doi: 10.1213/ANE.0b013e3182a76f3b.
IV infusion systems can be configured with manifolds connecting multiple drug infusion lines to transcutaneous catheters. Prior in vitro studies suggest that there may be significant lag times for drug delivery to reflect changes in infusion rates set at the pump, especially with low drug and carrier flows and larger infusion system dead-volumes. Drug manifolds allow multiple infusions to connect to a single catheter port but add dead-volume. We hypothesized that the time course of physiological responses to drug infusion in vivo reflects the impact of dead-volume on drug delivery.
The kinetic response to starting and stopping epinephrine infusion ([3 mL/h] with constant carrier flow [10 mL/h]) was compared for high- and low-dead-volume manifolds in vitro and in vivo. A manifold consisting of 4 sequential stopcocks with drug entering at the most upstream port was contrasted with a novel design comprising a tube with separate coaxial channels meeting at the downstream connector to the catheter, which virtually eliminates the manifold contribution to the dead-volume. The time to 50% (T50) and 90% (T90) increase or decrease in drug delivery in vitro or contractile response in a swine model in vivo were calculated for initiation and cessation of drug infusion.
The time to steady state after initiation and cessation of drug infusion both in vitro and in vivo was much less with the coaxial low-dead-volume manifold than with the high-volume design. Drug delivery after initiation in vitro reached 50% and 90% of steady state in 1.4 ± 0.12 and 2.2 ± 0.42 minutes with the low-dead-volume manifold and in 7.1 ± 0.58 and 9.8 ± 1.6 minutes with the high-dead-volume manifold, respectively. The contractility in vivo reached 50% and 90% of the full response after drug initiation in 4.3 ± 1.3 and 9.9 ± 3.9 minutes with the low-dead-volume manifold and 11 ± 1.2 and 17 ± 2.6 minutes with the high-dead-volume manifold, respectively. Drug delivery in vitro decreased by 50% and 90% after drug cessation in 1.9 ± 0.17 and 3.5 ± 0.61 minutes with the low-dead-volume manifold and 10.0 ± 1.0 and 17.0 ± 2.8 minutes with the high-dead-volume manifold, respectively. The contractility in vivo decreased by 50% and 90% with drug cessation in 4.1 ± 1.1 and 14 ± 5.2 with the low-dead-volume manifold and 12 ± 2.7 and 23 ± 5.6 minutes with the high-dead-volume manifold, respectively.
The architecture of the manifold impacts the in vivo biologic response, and the drug delivery rate, to changes in drug infusion rate set at the pump.
静脉输液系统可以通过连接多个药物输注管路和经皮导管的歧管进行配置。先前的体外研究表明，药物输送到反映输液泵设定的输液速率变化可能存在显著的滞后时间，尤其是在低药物和载体流速以及较大的输液系统死腔体积的情况下。药物歧管允许多个输注连接到单个导管端口，但会增加死腔体积。我们假设，体内药物输注引起的生理反应的时间过程反映了死腔体积对药物输送的影响。
在体外和体内比较了高和低死腔体积歧管中开始和停止肾上腺素输注（[3 mL/h]，恒速载体流[10 mL/h]）时的动力学反应。与由 4 个顺序的旋塞组成的歧管（药物从最上游端口进入）相比，一种新型设计由带有单独同轴通道的管组成，这些通道在下游连接器处交汇至导管，这实际上消除了歧管对死腔体积的贡献。计算了在体外药物输送达到 50%（T50）和 90%（T90）的增加或减少或在体内猪模型中的收缩反应的时间，用于药物输注的开始和停止。
在体外和体内，无论是在药物输注开始还是停止后，稳态的达到时间都明显少于同轴低死腔体积歧管。体外药物输送达到 50%和 90%的稳态分别在低死腔体积歧管中需要 1.4 ± 0.12 分钟和 2.2 ± 0.42 分钟，而在高死腔体积歧管中需要 7.1 ± 0.58 分钟和 9.8 ± 1.6 分钟。体内的收缩性在低死腔体积歧管中分别在 4.3 ± 1.3 分钟和 9.9 ± 3.9 分钟达到药物起始时的 50%和 90%的全反应，而在高死腔体积歧管中分别在 11 ± 1.2 分钟和 17 ± 2.6 分钟达到药物起始时的 50%和 90%的全反应。体外药物输送在低死腔体积歧管中分别在药物停止后 1.9 ± 0.17 分钟和 3.5 ± 0.61 分钟下降了 50%和 90%，而在高死腔体积歧管中分别在药物停止后 10.0 ± 1.0 分钟和 17.0 ± 2.8 分钟下降了 50%和 90%。体内的收缩性在低死腔体积歧管中分别在药物停止后 4.1 ± 1.1 分钟和 14 ± 5.2 分钟下降了 50%和 90%，而在高死腔体积歧管中分别在药物停止后 12 ± 2.7 分钟和 23 ± 5.6 分钟下降了 50%和 90%。
歧管的结构会影响体内生物学反应以及泵设定的输液速率变化时的药物输送率。
