The modern paradigm recognizes that AKI is an independent risk factor for death14,15,16 and that the aggressive management of RRT may affect outcomes and reduce mortality.17,18,19 However, there is no consensus on the optimal time to initiate RRT. This has led to a wide variation in clinical practice. Traditionally the indication for RRT20 has been based on or a combination of the following: volume overload, such as pulmonary edema that is not controlled with diuretic use, hyperkalemia-induced arrhythmias, uncontrolled metabolic acidosis, intoxication with a dialyzable drug or toxin, and overt uremic signs such as encephalopathy, pericarditis, or even uremic bleeding diathesis.
The optimal access for hemodialysis are arteriovenous fistulas (AVFs) that provide high blood flow (> 500 mL/min), durable long-term vascular access, relatively low thrombosis rates, and low infection rates. AVFs require months to mature and be functional, making them unsuitable for patients with AKI. AVFs cannot withstand prolonged cannulation associated with CCRT. Therefore with CVVH a temporary central venous catheter is needed. These catheters are generally noncuffed, nontunneled, double lumen with a large diameter of 12 to 15 Fr, providing a flow between 200 and 500 mL/min. They contain a venous and an “arterial” lumen although both lumens are in the same vein. The arterial lumen (typically red) withdraws blood from the patient and carries it to the CVVH machine, while the venous lumen (typically blue) returns blood to the patient from the machine. These catheters are typically constructed of materials such as polyurethane and are relatively stiff at room temperature, but become pliable at body temperature. They are inserted at the bedside. The internal jugular or femoral veins are preferred, over the subclavian vein due to the risk of developing venous stenosis after placement precluding future placement of an AVF in the ipsilateral arm.
Despite the widespread use of CRRT, there is little consensus regarding the optimum delivery of RRT, resulting in wide variations in clinical practice.21 Some studies have suggested survival benefit from delivery of higher-intensity CRRT to patients with AKI, whereas other studies have been inconsistent in their results. CRRT is most often prescribed based on the body weight to effluent flow rate target of 20 to 25 mL/kg/h. Recent studies have shown that effluent flow rate higher than 25 mL/kg/h does not improve outcomes in ICU patients.22 In our institution, the typical rates used for CVVH are a blood flow rate of 200 mL/min and RF rate of 2 L/h with ultrafiltration rate based on the individual need for fluid balance. This rate is variable and changes every hour depending on the total input and output of the previous hour. For example, if the desired fluid balance is –50 mL/h with a total input of 200 mL and output of 100 mL from the previous hour, the balance is +100 mL, therefore the ultrafiltration rate will be set at 150 mL/h.
Although CRRT can be run without anticoagulation, filters last much longer if some form of anticoagulation is used. Their fibers are prone to thrombosis, as removal of fluid through ultrafiltration leads to hemoconcentration at the distal end. Anticoagulation is generally recommended, as the clotting cascades are activated when the blood touches the nonendothelial surfaces of the tubing and filter. Multiple options exist for anticoagulation including heparin, prostacyclin, citrate, and even direct thrombin inhibitors. Unfractionated heparin is most commonly used, but can result in systemic anticoagulation and may be contraindicated in patients with active hemorrhage or heparin-induced thrombocytopenia (HIT). Any dose less than 5 units/kg/h is considered low-dose prefilter unfractionated heparin. This dose is reported to have minimal effect on the activated partial thromboplastin time (aPTT). A dose between 8 and 10 units/kg/h is considered medium-dose prefilter unfractionated heparin. This dose mildly elevates the aPTT and is recommended for patients with minimal risk of bleeding. Heparin may be administered using a pump integrated into the CRRT machine, or via a separate volumetric pump. Systemic unfractionated heparin is reserved for patients with other indications for systemic anticoagulation and is administered intravenously and titrated to achieve a target aPTT of about 1.5 to 2.5 times above the patient’s baseline. For patients with high risk of bleeding regional unfractionated heparin to the CVVH blood circuit may be used. In this technique, a prefilter dose of 1500 units/h of heparin combined with administration of protamine postfilter at a dose of 10 to 12 mg/h is used. This approach is monitored with the aPTT to keep it as close to normal as possible. Another option for these patients is the use of citrate. Citrate regional anticoagulation is widely used and has become the primary mode of anticoagulation in many centers. Citrate infused in the arterial limb of the CRRT circuit prevents hemofilter thrombosis by chelating calcium, a critical component of the clotting cascade. Calcium chloride infused into the venous line of the system restores normal systemic calcium levels. This approach appears to reduce the risk of hemorrhage and extend hemofilter patency.23 In addition, citrate can be used for patients with HIT. Serum and ionized calcium levels should be carefully monitored, especially in patients with significant liver dysfunction, and the calcium infusion appropriately adjusted. Citrate is hepatically metabolized into bicarbonate and can cause metabolic alkalosis. In the setting of hepatic failure, citrate accumulation results in elevated serum but low ionized calcium levels, reflecting increased circulating calcium bound to citrate.
Semipermeable membranes are the basis of all blood purification therapies. The surface area of the membrane depends on the number and length of these fibers. Membrane surface area affects solute clearance and ultrafiltration. Membrane size or surface area varies with the specific model of hemodialyzer or hemofilter. Larger dialysis cartridges are used for patients with a larger surface area or those needing high solute clearances. They allow water and some solutes to pass through the membrane, while cellular components and other solutes remain behind. The water and solutes that pass through the membrane are called the ultrafiltrate. Pore dimensions determine the size selectivity of molecular flux across the membrane, typically pore size membranes are 30,000 Da. Low-flux (< 500 Da) membranes clear small molecules (urea, potassium, and creatinine), but do not clear the larger “middle molecules” that may act as toxins. High-flux membranes (< 20,000 Da) clear middle molecules, such as β2-microglobulin and perhaps inflammatory cytokines generated by AKI and MOSF. There are 2 types of membranes used in RRT: cellulose and synthetic. Synthetic membranes are biocompatible, high flux, which allow clearance of larger molecules causing less trauma to platelets and white blood cells (WBCs), and are thus primarily used in CRRT. Filters are changed when they become contaminated, clogged, or according to individual hospital protocols.