SLED THERAPY UPDATE Supplement featured in Nephrology Times, volume 13, number 3, April 2021. Optimizing Kidney Replacement in Critical Care: SLED Can Play a Bigger Role in the ICU SLED and CKRT have demonstrated equivalence in tolerance from a hemodynamic perspective as well as clinical outcomes such as renal recovery and mortality. Sevag G. Demirjian, MD, Cleveland Clinic; J. Pedro Teixeira, MD, UNM Hospital; Bruce A. Mueller, PharmD, FCCP, FASN, FNKF, University of Michigan Hospital; William A. Rodriguez, MD, Austin Kidney Associates; Lenar T. Yessayan, MD, University of Michigan Hospital; Brendan T. Bowman, MD, UVA University Hospital; Reginald D. Gladish, MD, Decatur Morgan Hospital; Michael Aragon, MD Background substitute for, or a complement to CKRT, ICUs (~6 beds) may not offer dialysis or has been sporadic due to the challenges may have limited need for KRT in the The COVID-19 pandemic has illuminated related to operationalizing a SLED ICU setting. These facilities typically only many inefficiencies present in the health- program, the need to adjust drug dosing offer IHD with vasopressor support if care system, one of the most prominent for SLED and a lesser focus on value-based needed or, less commonly, may provide being the strain that can be placed on care compared to the current healthcare both IHD and prolonged intermittent intensive care units (ICUs) due to patient environment. With the more recent events kidney replacement therapy (PIKRT) or surges in the United States.1–3 Among the associated with the pandemic and patient sustained low efficiency dialysis (SLED). multitude of challenges identified, many surges, many facilities were forced to In contrast, larger tertiary care hospitals facilities experienced significant chal- deploy SLED programs to treat their most offer a mixture of intermittent hemodial- lenges in the delivery of dialysis due to unstable patients in order to meet patient ysis (IHD) along with continuous kidney insufficient supply of dialysis machines, demand and address supply shortages. replacement therapy (CKRT). sterile dialysate, and shortages of nursing This has generated a renewed interest staff trained to provide therapy.3 Due to in the modality’s value and potential to For smaller facilities, the startup costs the types of machines available, disrup- improve the efficiency in treatment of for CKRT can be prohibitive and include tions in supply chain related to high critically ill patients with AKI. the capital expense of investing in new demands, and the limited efficiency with machines, supply contracts and the which they can be used, the typical choices Understanding Acute Dialysis Delivery expenses related to initial and ongoing for kidney replacement therapy (KRT), support. Extensive time is required for continuous kidney replacement therapy Generally, hospitals and health systems initial training of nursing staff—both (CKRT) and intermittent hemodialysis select dialysis modalities that are best nephrology and ICU. Clinical support (IHD), have been unable to meet the needs suited to their individual operational and engineers require certification to provide of many facilities and have had a signif- logistical circumstances. These circum- maintenance on the new devices. Provided icant impact on ICUs’ ability to handle stances include factors such as annual that nephrologists have a working knowl- patient surges like those that are occurring treatment volume, staffing considerations, edge regarding CKRT therapy, ongoing with COVID-19.2,3 available technology and the accessi- costs are generally related to supplies and bility of ancillary support services such maintaining staff proficiency. If hospital Despite evidence of equivalent outcomes as clinical engineering and pharmacy. In ICU KRT volumes are not high enough to compared to CKRT, SLED uptake as a general, hospitals with smaller-volume maintain proficiency, nurses may quickly DOC-0006767 Rev 01 lose skills in CKRT. In addition to these CKRT > IKRT IKRT > CKRT obvious cost considerations, CKRT has certain “hidden” costs as well. A recent analysis demonstrated CKRT provision Northern Europe incurred significant storage and solution preparation costs above the acquisition Southern Europe costs. This can be quite variable depending on the degree of solution customization employed.4 North America It is not surprising, then, that a number of South America cost analyses have found IHD and SLED to be more cost effective than CKRT.5–8 For hospitals and health systems that Asia choose to utilize IHD- or SLED-based ICU therapy, this allows for standardization to a single device or set of devices. By utilizing a single platform, savings can be All regions expected in the areas related to decreased training costs, decreased supply and -500 -400 -300 -200 -100 0 100 200 300 400 500 storage costs and increased leverage in contracting. Depending on the technology, U.S. Dollars however, this model may still retain the complexity of necessitating specialized hemodialysis nursing staff to administer Figure 1 Median Difference and Range of Dialysate and Replacement-Fluid Costs by Region. the therapy. The error bars represent the absolute range between the maximum fluid cost of CKRT and the minimum fluid cost of IKRT, and between the maximum fluid cost of IKRT and minimum fluid cost For large hospitals and health systems of CKRT. The box represents the 1st and 3rd quartiles of the fluid-cost range. The thick solid line with high ICU KRT volumes and special- represents the median difference in fluid costs for CKRT and IKRT across all centers in each region ty-specific ICUs, there is some economy in which data were available. Srisawat 2010 of scale with CKRT and possibly a small reduction in the ongoing training required to maintain proficiency. From a staffing standpoint, continuous therapies such as CKRT can be managed either completely by ICU nursing staff or with setup and troubleshooting services provided by CKRT > IKRT IKRT > CKRT experienced dialysis nurses with ICU staff monitoring during therapy. This frees dialysis nurses to provide typical acute Northern Europe hemodialysis treatments and improves staff efficiency; however, it does not Southern Europe address the significant supplies expense and logistical challenges, such as CKRT solution storage and preparation costs North America associated with the therapy. South America Aside from cost, the likely major driving force for continuous therapies in larger institutions remains entrenched in culture Asia and nephrologist/intensivist preference. CKRT remains the suggested modality for hemodynamically unstable patients in the most recent 2012 KDIGO guidelines for 9 All regions acute kidney injury (AKI). The authors of the KDIGO guidelines noted that -500 -400 -300 -200 -100 0 100 200 300 400 500 SLED is suitable for hemodynamically unstable patients but did not include it as U.S. Dollars a suggested modality, citing a lack of suffi- cient evidence which, in the subsequent 9 years, has continued to grow considerably. Figure 2 Median Difference and Range of Extracorporeal Circuit Costs by Region. The error Cited benefits of CKRT machines have bars represent the absolute range between the maximum extracorporeal circuit cost of CKRT been related to their compact nature. They and the minimum extracorporeal circuit cost of IKRT, and between the maximum extracorporeal do not require the bulky reverse osmosis circuit cost of IKRT and minimum extracorporeal circuit cost of CKRT. The box represents the devices needed with traditional hemodi- 1st and 3rd quartiles of the extracorporeal circuit-cost range. The thick solid line represents the alysis machines which may cramp already median difference in extracorporeal circuit costs for CKRT and IKRT across all centers in each tight ICU rooms. Additionally, in the rare region in which data were available. Srisawat 2010 case of intra-operative KRT needs, as in transplant or some cardiac surgeries, a compact, self-contained CKRT machine DOC-0006767 Rev 01 has been able to operate efficiently where to 100 mL/min. PIKRT can be performed er-sized dialyzers (to decrease risk of a traditional dialysis machine is not daily or 3 to 6 days per week. Clinical trials circuit clotting) had no appreciable change feasible due to the need for an external RO and observational studies have demon- in clearance or solute control.18,19 system. strated that SLED or PIKRT is non-inferior to CKRT regarding patient outcomes.55–57 In general, prescribing UF with KRT, Arguments for the cost-effectiveness Given the numerous acronyms to including SLED, requires serial assess- of CKRT over IHD generally rely on an describe this therapy, for consistency and ments of patient volume status and assumption of improved rates of dialysis simplicity, we will focus on the term SLED volume goals followed by adjustments liberation in the CKRT group. This yields in this manuscript to encompass all mid to meet those goals. Target fluid removal theoretical savings via decreased rates of duration therapies, as terms like EDD is prescribed as a total treatment net UF, CKD and ESKD.8,10,11 However, this possible infer that therapy is always provided daily. similar to IHD. Limited data exist evalu- benefit of CKRT over intermittent KRT with regard to improved renal recovery has only been demonstrated in a limited number of observational studies, has not been seen consistently in retrospective Typical Qb Typical Qd Typical Duration Typical Net Typical Therapy analyses and has never been demon- of Therapy UF Rate Frequency strated in a prospective randomized 12,13 trial. 150–300 mL/min 100–300 mL/min 6–12 hours Variable, 3–6 times 0–500 mL/hour per week In contrast, the use of existing inter- mittent hemodialysis machines to try to capture the advantages of CKRT began in Table 1 Typical SLED Prescribing Parameters the 1990s. By 2000, Kumar et al. reported PIKRT was as effective as continuous veno-venous hemofiltration (CVVH) in caring for hemodynamically unstable patients. EDD, also commonly referred The SLED Prescription ating optimal UF rate targets during any to as sustained low efficiency dialysis KRT for AKI.