O'Connor Sean, Zhang Yan Ling, Christians Uwe, Morrison John E, Friesen Robert H
Department of Anesthesiology, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO, USA.
Paediatr Anaesth. 2016 Jul;26(7):703-9. doi: 10.1111/pan.12917. Epub 2016 May 5.
Propofol and remifentanil can be combined to deliver total intravenous anesthesia (TIVA). Propofol and remifentanil are sometimes mixed in the same syringe. Since remifentanil is a solution and propofol is an emulsion, we hypothesized that they would separate over time when mixed in the same syringe.
Nine 60-ml polypropylene syringes were prepared as follows: Group A: 1.25 ml of remifentanil solution (1 mg·ml(-1) ) was added to 48.75 ml of propofol (10 mg·ml(-1) ) in three syringes. Group B: 2.5 ml of remifentanil (1 mg·ml(-1) ) was added to 47.5 ml of propofol (10 mg·ml(-1) ) in three syringes. Group C: 5 ml of remifentanil (1 mg·ml(-1) ) was added to 45 ml of propofol (10 mg·ml(-1) ) in three syringes. The remifentanil lyophilized powder was reconstituted with sterile water and added to the propofol by injection through the port on the bottom of the syringe. The syringe was then inverted five times in succession to mix the drugs. The syringes were mounted in an upright vertical position (plunger on top, port on bottom) with wire on a pegboard. Samples of the mixture were taken from the bottom port (via a 3-way stopcock) and from the top of the syringe (via a stopcock on an 18-gauge needle placed 5 mm through the plunger) at the following time intervals (min) from baseline: T0, T10, T30, T60, T120, T180, T240, T300. Remifentanil and propofol were quantified using specific and validated HPLC/MS/MS assays with automated online sample preparation.
Concentrations of remifentanil were significantly greater at the top than the bottom of the syringes in groups A and B. Concentrations of propofol were significantly greater at the bottom than the top of the syringes in all groups.
Our data indicate that remifentanil solution and propofol emulsion are immiscible: remifentanil separates from propofol and rises to the top. Thus, concentrations of remifentanil and propofol delivered to patients from the same syringe during TIVA are not those expected and cannot be reliable. Remifentanil and propofol should be administered in separate syringes when used in combination for TIVA.
丙泊酚和瑞芬太尼可联合用于实施全静脉麻醉（TIVA）。丙泊酚和瑞芬太尼有时会混合在同一注射器中。由于瑞芬太尼是溶液，丙泊酚是乳剂，我们推测当它们混合在同一注射器中时会随时间分离。
制备9支60毫升聚丙烯注射器，如下所示：A组：在3支注射器中，将1.25毫升瑞芬太尼溶液（1毫克·毫升⁻¹）加入48.75毫升丙泊酚（10毫克·毫升⁻¹）中。B组：在3支注射器中，将2.5毫升瑞芬太尼（1毫克·毫升⁻¹）加入47.5毫升丙泊酚（10毫克·毫升⁻¹）中。C组：在3支注射器中，将5毫升瑞芬太尼（1毫克·毫升⁻¹）加入45毫升丙泊酚（10毫克·毫升⁻¹）中。将瑞芬太尼冻干粉末用无菌水复溶，并通过注射器底部端口注入加入丙泊酚中。然后将注射器连续倒置5次以混合药物。将注射器垂直放置（活塞在上，端口在下），用金属丝固定在钉板上。在以下时间间隔（分钟）从基线开始，从底部端口（通过三通旋塞）和注射器顶部（通过位于活塞5毫米处的18号针头的旋塞）采集混合液样本：T0、T10、T30、T60、T120、T180、T240、T300。使用经过验证的特定高效液相色谱/串联质谱法（HPLC/MS/MS）并结合自动在线样品制备对瑞芬太尼和丙泊酚进行定量分析。
A组和B组中，注射器顶部的瑞芬太尼浓度显著高于底部。所有组中，注射器底部的丙泊酚浓度显著高于顶部。
我们的数据表明瑞芬太尼溶液和丙泊酚乳剂互不相溶：瑞芬太尼与丙泊酚分离并升至顶部。因此，在TIVA期间从同一注射器给予患者的瑞芬太尼和丙泊酚浓度并非预期浓度，且不可靠。瑞芬太尼和丙泊酚联合用于TIVA时应分别用不同注射器给药。
