The Journal of ExtraCorporeal Technology No 56-3 | Page 27

102 A . Chevalier et al .: J Extra Corpor Technol 2024 , 56 , 101 – 107

Table 1 . Circuit components .

a Cortiva coating : heparin covalently bonded to polymer . b Bioline coating : covalently bonded recombinant human albumin and heparin .

is an effective and safe sedative that has been noted in multiple studies to be associated with a reduced risk of delirium compared with opioids and benzodiazepines [ 8 ]. Excess dexmedetomidine may cause bradycardia and hypotension [ 10 ]. While dexmedetomidine is significantly extracted by ECMO circuits in ex-vivo experiments [ 11 ], data guiding the use of dexmedetomidine in CRRT or the use of ketamine in ECMO or CRRT is limited [ 11 – 13 ]. Because few studies exist to guide the dosing of ketamine and dexmedetomidine for patients with ECLS , a study on the interactions of ketamine and dexmedetomidine with ECLS circuits is needed .

In this study , we quantify the degree of interaction of dexmedetomidine and ketamine with ECLS circuits using ex-vivo ECMO and CRRT experiments .

Materials and methods

Circuit-drug interactions were evaluated in closed-loop ECMO and CRRT circuits similar to previously published ex-vivo models [ 14 – 21 ]. Briefly , ECMO and CRRT circuits were constructed using common circuit components and a reservoir primed with a human blood and plasma mixture . Ketamine and dexmedetomidine were then injected into the circuits targeting a therapeutic concentration , and the percentage of the drug remaining was determined over time .

ECMO circuit setup

ECMO experiments were performed using a Maquet centrifugal pump with bioline coating ( Maquet , Rastatt , Germany ), Maquet Quadrox-iD oxygenator with bioline coating ( Maquet , Rastatt , Germany ), and Medtronic custom perfusion system tubing and reservoir ( Medtronic , Minneapolis , Minnesota ) ( Table 1 ). The reservoir was primed with 2 units of human red blood cells ( adenine saline added leukocytes reduced ), 1 unit of thawed human plasma frozen within 24 h after phlebotomy , 12.5 grams of 25 % albumin , 325 mg of calcium gluconate , 14 mEq of sodium bicarbonate , 1 gram of tromethamine ( THAM ), and 250 units of heparin sulfate . Additional THAM or carbon dioxide was added to the circuit prior to ketamine administration and as-needed hourly thereafter to maintain physiologic pH 7.20-7.45 as measured on an i-STAT Analyzer

( 300-G , Flextronics Manufacturing , Singapore ) using EG6 + cartridges ( 03P77-25 , Abbott Point of Care , Abbott Park , IL ). The temperature of the circuit was maintained at 37 degrees C using an ECMO Water Heater ( Cincinnati Sub-Zero , Cincinnati , OH ) connected to the Quadrox-iD integrated heat exchanger . Flow through the ECMO circuit was maintained at 1.0 L / min measured with an HT110 bypass flowmeter with an H8XL flow sensor ( Transonic , Davis , CA ). The flow was maintained at 1.0 L / min as this is approximately the flow that would be used for a 10 kg child flowing at a typical flow of 100 ml / kg / min .

CRRT circuit setup

CRRT experiments were performed using a Baxter Prismax system ( Baxter Healthcare , Deerfield , IL ) with a THERMAX blood warmer ( Baxter Healthcare , Deerfield , IL ) and HF1000 filter ( Baxter Healthcare , Deerfield , IL ) ( Table 1 ). A 500 ml Baxter EXACTAMIX ( Baxter Healthcare , Deerfield , IL ) bag was used as a reservoir for the circuit and was continuously stirred by an orbital shaker at 80 rpm . The reservoir was primed with 300 ml of human red blood cells ( adenine saline added leukocytes reduced ), 125 ml of thawed human plasma within frozen 24 h after phlebotomy , 12.5 grams of 25 % albumin , 180 mg of calcium gluconate , 7 mEq of sodium bicarbonate , 1.4 g of THAM , and 350 units of heparin sulfate , and this mixture was then connected to the circuit and pumped through the circuit . Additional THAM was added prior to ketamine or dexmedetomidine administration and hourly thereafter as needed to maintain physiologic pH 7.2-7.45 as measured on an i-STAT Analyzer using EG6 + cartridges . Temperature was maintained at 37.0 degrees C by the THERMAX blood warmer . Circuits ran in continuous venovenous hemodiafiltration ( CVVHDF ) circuit configuration with both dialysate and replacement fluids as this is the most common configuration used at our institution . Dialysis circuits used a blood flow rate of 80 ml / min , pre-blood pump ( PBP ) replacement fluid rate of 300 ml / h , post-filter replacement fluid rate of 100 ml / h , and dialysate fluid rate of 400 ml / h , with a net ultrafiltration rate of 0 ml / h . PrismaSATE 4 / 2.5 dialysis solution ( Baxter Healthcare , Deerfield , IL ) was used for dialysis , pre-blood pump , and replacement fluids . Due to premature circuit failure in two circuits , a total of 5 CRRT circuits were conducted for ketamine . Dexmedetomidine CRRT circuits were run in triplicate .