Optimizing Kidney Replacement in Critical Care: SLED Can Play a Bigger Role in the ICU

SLED THERAPY UPDATE

Supplement featured in Nephrology Times, volume 13, number 3, April 2021.

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 sufficient 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 intermittent 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. The data that do exist are (SLED) and prolonged intermittent kidney There are no strictly defined standard largely observational correlating UF rates replacement therapy (PIKRT), was first parameters for prescribing SLED. during CKRT with outcomes and, notably, proposed as an easier to perform, more Prescribed treatments most often utilize have been contradictory. Higher net UF flexible, and less nurse-intensive therapy hemodialysis (diffusive clearance), i.e., rates have been associated with both compared to CKRT. Since that time, its SLED; but can be prescribed to perform decreased mortality,20,21 and increased utilization has been variable across the hemofiltration (convective clearance), i.e., mortality,22–25 suggesting the relation- United States with several large hospi- SLEDD-f; or hemodiafiltration (convective ship is likely variable.26 These data may tals and academic centers employing it and diffusive clearance) to achieve clinical be confounded by the well-established exclusively as their prolonged therapy of goals. In general, regardless of method of association between volume overload choice, instead of CKRT. clearance, SLED uses low blood flow (Qb), and mortality in AKI,27–31 as well as the with dialysate (Qd) flow rates and ultrafil- tendency for less ill patients to tolerate The primary aim of this article is to tration rates that are intermediate higher rates of net UF. Some experts have review the indications for and clinical between IHD and CKRT (Table 1). used these observational data to propose value of SLED therapy, provide guidance limits on net UF during CKRT to 1.75–2 for the prescribing of SLED, and review Data to guide the dosing of SLED are mL/kg/hr,32,33 though whether such limits additional considerations and historical limited, as the vast majority of data avail- or similar limits should apply to SLED are challenges. able on dosing of KRT for AKI or ESKD unclear. have been obtained with IHD or CKRT. Defining SLED Much like the data with CKRT, the few There are no data specifically on the studies comparing higher or lower doses optimal UF rates for SLED; however, the Multiple acronyms have been used to of KRT specific to SLED have generally extended treatment times that accompany describe KRT therapies with a duration yielded negative results relative to any the modality do allow for slower ultrafil- between that of IHD and CKRT. The benefit of higher dose therapy.14,15 Stan- tration compared to IHD, while achieving acronym SLED, and more recently PIKRT, dard Kt/V assessments used for IHD may metabolic clearance goals in considerably encompasses convective, diffusive and accurately quantify urea clearance with less time than CKRT. It is the opinion of hybrid methods. Treatments are delivered SLED and can be used to guide dosing to this group that it is more reasonable to using either standard outpatient IHD specific clinical targets, such as the target establish an upper limit for total hourly machinery with online dialysate genera- currently recommended by KDIGO for UF instead of net UF when prescribing tion or CKRT machines utilizing sterile, acute dialysis of three or more treatments SLED. Conservatively, a target total hourly pre-packaged dialysate.47–49 Examples per week, each with a Kt/V of 1.3 or greater. UF rate not to exceed 300mL/hr was of mid duration KRT include sustained 16,17 suggested, although it was noted that rates low-efficiency dialysis (SLED or SLEDD, exceeding this have been well tolerated if daily),50–52 sustained low-efficiency daily SLED can be prescribed using the same in some critically ill patients within this diafiltration (SLEDD-f),53 extended daily dialyzers typically used for IHD, with population. Until a larger body of clinical dialysis (EDD),54, accelerated venove- dialyzer choice being dictated by avail- evidence is available, this max UF rate nous hemofiltration (AVVH) and accel- ability and compatibility with available should likely remain site dependent, and erated venovenous hemodiafiltration KRT devices. The size of dialyzer appears customized to the individual patient. (AVVHDF).47 Typical treatment duration is to have only modest influence on clear- between 6 and 12 hours with dialysate flow ance during SLED as compared to Qd and The need for anticoagulation for SLED rates of 6 to 12 L/hr and blood flow 150 to treatment duration. Previous reports have treatments is significantly lower than 400 mL/min, or hemofiltration from 25 demonstrated that changing to small- that of CKRT14,34 with the majority of

DOC-0006767 Rev 01 CKRT SLED Risk Ratio Risk Ratio Study or subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

Kumar 2000 11 17 21 25 8.7% 0.77 [0.52, 1.14] Kumar 2004 20 28 14 26 8.0% 1.33 [0.87, 2.03] Berbece 2006 5 11 13 23 3.9% 0.80 [0.38, 1.69] Majumdar 2009 41 52 84 162 13.0% 1.52 [1.24, 1.87] Marinho 2009 44 59 3 14 2.4% 3.48 [1.26, 9.59] Abe 2010 11 30 5 30 2.8% 2.20 [0.87, 5.57] Feighen 2010 19 30 8 13 6.5% 1.03 [0.62, 1.71] Ferrer 2010 43 59 5 16 3.9% 2.33 [1.11, 4.90] Rittidesh 2010 9 12 11 15 7.6% 1.02 [0.65, 1.60] Wu 2010 45 63 18 38 9.1% 1.51 [1.04, 2.18] Abe 2011 9 25 5 25 2.7% 1.80 [0.70, 4.62] Schwenger 2012 65 117 57 115 12.0% 1.12 [0.88, 1.43] Badawy 2013 9 40 7 40 3.0% 1.29 [0.53, 3.12] Chen 2014 6 55 4 52 1.8% 1.42 [0.42, 4.74] Shafi 2014 10 27 18 34 5.5% 0.70 [0.39, 1.26] Sun 2014 29 65 37 80 9.3% 0.96 [0.67, 1.38] Total (95% CI) 690 708 100% 1.21 [1.02, 1.43] Total events 376 310 Heterogeneity: Tau2 = 0.05; Chi2 = 28.56, df = 15 (P = 0.02); I2 = 47% Test for overall effect: Z = 2.21 (P = 0.03) 0.1 0.2 0.5 1 2 5 10

FAVORS CKRT FAVORS SLED Figure 3 Overall Mortality in Patients Treated with Continuous Kidney Replacement Therapy (CKRT) Versus Sustained Low-Efficiency Dialysis (SLED).Kovacs 2017

80 CKRT p = 0.29 70 SLED

60 p = 0.32

50 p = 0.59

30 97 / 158 40 / 74 (61.4 %) (54.1 %)

Percentage of Patients (%) of Patients Percentage 20 20 / 61 13 / 34 73 / 158 29 / 74 (32.8 %) (38.2 %) (46.2 %) (39.2 %) 10

0 30-day Mortality 30-day KRT Dependence Early Clinical Deterioration

Figure 4 30-day Mortality, KRT Dependence and Early Clinical Deterioration by KRT Modality. Kitchlu 2015

treatments able to be performed with no is 1.5x normal. Citrate anticoagulation patients that are particularly thrombo- anticoagulation. In cases where antico- has been performed successfully with genic and have either a contraindication to agulation is necessary, heparin protocols SLED therapy utilizing trisodium citrate or have failed heparin anticoagulation. combining a small bolus, approx. 1000 solutions.45 While effective, citrate does units, with a continuous rate of approx. add complexity and risk to the therapy.46 The Clinical Evidence for SLED and CKRT 500 units/hr. have been suggested 35,36 Given the generally low risk of clotting as effective starting doses with titra- with SLED therapy, it is the opinion of this To date, SLED has been shown to yield tion to effect or titration to a PTT that group that this may be best reserved for equivalent clinical outcomes compared

DOC-0006767 Rev 01 to CKRT across independent studies as Challenges with SLED Therapy eliminate the need to transfer patients out well as more rigorous systematic reviews to higher level of care facilities when these and meta-analyses. In terms of hemody- Although SLED offers many benefits, it patients are in their most critical state. namic tolerance, it has been demonstrated is not without challenges. First, there is that there is no statistically significant significant variability in clearance based In larger facilities currently using CKRT, difference between the two modalities in on the duration of therapy prescribed. SLED can improve practice patterns by hemodynamic variables including mean While there is no consensus on what the increasing surge capacity and allowing arterial pressure (MAP), heart rate (HR), ideal SLED treatment duration or dialy- for the adaptability to provide patients cardiac output (CO), and systemic vascular sate flow rate should be, some successful more optimal therapy instead of the resistance (SVR).37 Similar to CKRT, SLED SLED programs have addressed this by therapy that is available. Surge capacity can be used in hemodynamically unstable attempting to standardize the therapy to is increased with SLED because of the patients. Additionally, in a meta-analysis a specific duration, typically around 9–10 shorter treatment times, which allows a of both RCTs and observational studies hours, to allow two treatments per device single dialysis machine to be used for two by Zhang et al., no difference was seen per day. Aside from standardization, other critically ill patients per day (and poten- in days spent in the ICU, renal recovery, limitations center around the capabili- tially more, depending on treatment time). or fluid removal.38 This was echoed in the ties of the device or devices a facility has SLED also increases the ability to mobilize meta-analysis by Kovacs et al., which available. Using CKRT devices for hybrid patients earlier, which has been associated found no significant difference between therapies like SLED can be prohibitively with improved patient outcomes in the CKRT and SLED in the proportion of expensive due to the requirement for ICU.42 This would subsequently lead to renal recovery, time to renal recovery, sterile bags of dialysate. In addition, this shorter average lengths of stay in the ICU the number of hypotensive events, or the significantly increases nursing workload and allow for step-down therapy. number of vasopressors or the dose of intensity in treatment management and vasopressors needed.39 Finally, in RCTs may be limited in ability to achieve the Overall, no concrete guidance exists on mortality rates with SLED have not been target clearance in 6–12 hr. treatment what constitutes the best dialysis modality demonstrated to be inferior to those with times due to technical device constraints in the ICU setting for hemodynamically CKRT. 13,38 Evidence from observational and the inability to achieve clearance with unstable patients. SLED and CKRT have studies, however, have suggested that 12 hour thrice weekly therapy with CKRT demonstrated equivalence in tolerance SLED potentially has lower mortality risk devices. Reducing treatment time but from a hemodynamic perspective as well compared with CKRT.38,39 increasing dialysate flow rate on a CKRT as clinical outcomes such as renal recovery device does not reduce the cost or number and mortality. SLED does offer some Benefits of SLED Compared to CKRT of supplies needed to perform the therapy. advantages in terms of lower program Providing SLED therapy with traditional initiation cost and ongoing cost, allowing Interestingly, additional evidence has IHD devices that require portable water earlier patient mobilization, reduced need shown that SLED may potentially be purification systems can often lead to for anticoagulation and offering a more superior to CKRT in other aspects. Kiel- staffing challenges due to managing both robust treatment. stein et al. showed that acidosis was a complex dialysis device and a portable corrected faster with SLED compared with water purification system. In most cases, When considering SLED therapy, it is continuous therapy.37 SLED also offers this has required hemodialysis nurses to important to understand device capabil- more prescription flexibility which can manage the therapy or at least perform ities. Traditional IHD or CKRT machines facilitate other care needed for a critically the set up and monitor at frequent inter- pose certain challenges and may be ill patient, like proning those with severe vals.43 These models can potentially stress inefficient in the delivery of SLED, i.e., respiratory failure. By minimizing anti- a hospital’s limited hemodialysis nurse dependence on highly trained dialysis coagulation and overall drug exposure, resources and may lead to delays of IHD nurses, cost of supplies, and limited flow choosing SLED over CKRT may minimize treatments elsewhere in the hospital. rates. Careful evaluation of these criteria, the risk of errors in medication dosing in addition to a better understanding of and administration.12,19,34–36,40,41 SLED A final challenge is the lack of available the technological advancements that exist therapy also increases the likelihood of guidance on drug dosing when using in the market today, should be considered achieving clearance targets as procedures SLED.44 Guidance is available for some when starting a SLED program. Hospi- can be timed around dialysis instead of medications; however, guidance has been tals and healthcare systems offering KRT interrupting therapy for any procedure or limited by the wide variability of prescrip- must consider both financial and logistical test that is not dialysis. Although addi- tions associated with SLED. Opportuni- factors in addition to patient outcomes tional research is necessary to determine ties may exist to try to standardize the when selecting the best fit for their if SLED modalities are superior to CKRT, prescription and, as such, allow phar- facilities. Based on much of the available sufficient evidence is available in the liter- macists more consistent clearances from evidence, CKRT is more costly than SLED, ature to support the claim that SLED is, at which to calculate doses; however, this has and the current COVID-19 pandemic has minimum, equivalent to CKRT. not been common practice. Additionally, illustrated that it is also less adaptable newer technologies now available (see and less efficient. Flexibility in KRT will be In addition, as mobility has become a accompanying article on the following paramount to maintaining and expanding central focus in modern critical care pages) may also be of significant benefit capabilities in the ICU as we move through medicine, SLED facilitates earlier ambu- in addressing this challenge. the rest of the COVID-19 pandemic and lation of patients by allowing significant patient surges into the future. Mid-dura- “dialysis-free” time for nursing and Summary tion dialysis therapies like SLED have the therapy staff to work with the patient potential to provide this much-needed unrestrained by blood tubing and addi- For smaller facilities, a mid-duration KRT adaptability, especially if the histor- tional connections. Earlier mobilization such as SLED represents a way to effec- ical staffing challenges stemming from has been associated with reduction in both tively manage hemodynamically unstable device complexity can be overcome and ICU and overall length of stay (LOS) and patients, potentially with the same device standardization throughout hospital and has been associated with improved overall used for IHD. SLED also enables these healthcare systems can be established to outcomes.42 facilities to better handle patients who ensure more predictable clearance and decompensate and may greatly reduce or drug dosing.

DOC-0006767 Rev 01 References renal failure. Canadian Journal of Anes- 20. Murugan R, Balakumar V, Kerti SJ, et al. thesia. 2005;52(3):327-332. doi:10.1007/ Net ultrafiltration intensity and mortality 1. Mittel AM, Panzer O, Wang DS, et al. BF03016071 in critically ill patients with fluid overload. Logistical Considerations and Clinical Critical Care. 2018;22(1). doi:10.1186/s13054- Outcomes Associated with Converting 11. Ethgen O, Schneider AG, Bagshaw SM, 018-2163-1 Operating Rooms into an Intensive Care Bellomo R, Kellum JA. Economics of dial- Unit during the Covid-19 Pandemic in ysis dependence following renal replace- 21. Tehranian S, Shawwa K, Kashani KB. a New York City Hospital. Anesthesia & ment therapy for critically ill acute kidney Net ultrafiltration rate and its impact on Analgesia Journal Publish Ahead of Print. injury patients. Nephrology Dialysis Trans- mortality in patients with acute kidney Published online 2020. doi:10.1213/ plantation. 2015;30(1):54-61. doi:10.1093/ injury receiving continuous renal replace- ANE.0000000000005301 ndt/gfu314 ment therapy. Clinical Kidney Journal. Published online December 17, 2019. 2. Arabi YM, Azoulay E, Al-Dorzi HM, et al. 12. Liang K v., Sileanu FE, Clermont G, et al. doi:10.1093/ckj/sfz179 How the COVID-19 pandemic will change Modality of KRT and recovery of kidney the future of critical care. Intensive Care function after AKI in patients surviving 22. Gleeson P, Crippa I, Sexton D, et al. Deter- Medicine. Published online February 22, to hospital discharge. Clinical Journal of the minants of renal recovery and mortality 2021. doi:10.1007/s00134-021-06352-y American Society of Nephrology. 2016;11(1):30- inpatients undergoing continuous renal 38. doi:10.2215/CJN.01290215 replacement therapy in the ICU. Inten- 3. Keene AB, Shiloh AL, Eisen L, et al. sive Care Medicine Experimental. 2015;3(S1). Critical Care Surge During the COVID-19 13. Nash DM, Przech S, Wald R, O’Reilly D. doi:10.1186/2197-425x-3-s1-a54 Pandemic: Implementation and Feed- Systematic review and meta-analysis of back From Frontline Providers. Journal of renal replacement therapy modalities for 23. Naorungroj T, Neto AS, Zwakman-Hes- Intensive Care Medicine. 2021;36(2):233-240. acute kidney injury in the intensive care sels L, et al. Mediators of the impact doi:10.1177/0885066620973175 unit. Journal of Critical Care. 2017;41:138- of hourly net ultrafiltration rate on 144. doi:10.1016/j.jcrc.2017.05.002 mortality in critically ill patients 4. Shaw AR, Chaijamorn W, Clark JS, receiving continuous renal replacement Mueller BA. Preparation times and 14. PM P, JH Z, TZ O, et al. Intensity of Renal therapy. Critical Care Medicine. Published costs for various solutions used for Support in Critically Ill Patients with online 2020:E934-E942. doi:10.1097/ continuous renal replacement therapy. Acute Kidney Injury. New England Journal CCM.0000000000004508 American Journal of Health-System Phar- of Medicine. 2008;359(1):7-20. doi:10.1056/ macy. 2018;75(11):808-815. doi:10.2146/ nejmoa0802639 24. Naorungroj T, Neto AS, Zwakman-Hes- ajhp160741 sels L, et al. Early net ultrafiltration rate 15. Faulhaber-Walter R, Hafer C, Jahr N, et al. and mortality in critically ill patients 5. Srisawat N, Lawsin L, Uchino S, Bellomo The Hannover Dialysis Outcome study: receiving continuous renal replacement R, Kellum JA. Cost of Acute Renal Replacement Comparison of standard versus intensi- therapy. Nephrology Dialysis Transplan- Therapy in the Intensive Care Unit: Results from fied SLED for treatment of patients with tation. Published online April 7, 2020. The Beginning and Ending Supportive Therapy acute kidney injury in the intensive care doi:10.1093/ndt/gfaa032 for the Kidney (BEST Kidney) Study.; 2010. unit. Nephrology Dialysis Transplantation. http://ccforum.com/content/14/2/R46 2009;24(7):2179-2186. doi:10.1093/ndt/ 25. Murugan R, Kerti SJ, Chang CCH, et al. gfp035 Association of Net Ultrafiltration Rate 6. Berbece AN, Richardson RMA. Sustained With Mortality Among Critically Ill Adults low-efficiency dialysis in the ICU: Cost, 16. Eloot S, van Biesen W, Dhondt A, et al. With Acute Kidney Injury Receiving anticoagulation, and solute removal. Impact of hemodialysis duration on the Continuous Venovenous Hemodiafil- Kidney International. 2006;70(5):963-968. removal of uremic retention solutes. tration: A Secondary Analysis of the doi:10.1038/sj.ki.5001700 Kidney International. 2008;73(6):765-770. Randomized Evaluation of Normal vs doi:10.1038/sj.ki.5002750 Augmented Level (RENAL) of Renal 7. James MT, Tonelli M. Financial aspects of Replacement Therapy Trial. JAMA network renal replacement therapy in acute kidney 17. Kellum JA, Lameire N, Aspelin P, et open. 2019;2(6):e195418. doi:10.1001/jama- injury. Seminars in Dialysis. 2011;24(2):215- al. Kidney disease: Improving global networkopen.2019.5418 219. doi:10.1111/j.1525-139X.2011.00836.x outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice 26. Serpa Neto A, Naorungroj T, Murugan 8. Manns B, Doig CJ, Lee H, et al. Cost of guideline for acute kidney injury. Kidney R, Kellum JA, Gallagher M, Bellomo R. acute renal failure requiring dialysis International Supplements. 2012;2(1):1-138. Heterogeneity of Effect of Net Ultra- in the intensive care unit: Clinical and doi:10.1038/kisup.2012.1 filtration Rate among Critically Ill resource implications of renal recovery. Adults Receiving Continuous Renal Critical Care Medicine. 2003;31(2):449-455. 18. Schlaeper C, Amerling R, Manns M, Replacement Therapy. Blood Purification. doi:10.1097/01.CCM.0000045182.90302. Levin NW. High clearance contin- Published online October 7, 2020:1-11. B3 uous renal replacement therapy with doi:10.1159/000510556 a modified dialysis machine.Kidney 9. Kellum JA, Lameire N, Aspelin P, et International, Supplement. 1999;56(72). 27. Wang N, Jiang L, Zhu B, Wen Y, Xi XM. al. Kidney disease: Improving global doi:10.1046/j.1523-1755.56.s72.13.x Fluid balance and mortality in critically outcomes (KDIGO) acute kidney injury ill patients with acute kidney injury: A work group. KDIGO clinical practice 19. Kumar VA, Yeun JY, Depner TA, Don multicenter prospective epidemiological guideline for acute kidney injury. Kidney BR. Extended daily dialysis vs. contin- study. Critical Care. 2015;19(1). doi:10.1186/ International Supplements. 2012;2(1):1-138. uous hemodialysis for ICU patients s13054-015-1085-4 doi:10.1038/kisup.2012.1 with acute renal failure: A two-year single center report. International Journal 28. Silversides JA, Pinto R, Kuint R, et al. Fluid 10. Jacka MJ, Ivancinova X, Gibney NRT. of Artificial Organs. 2004;27(5):371-379. balance, intradialytic hypotension, and Continuous renal replacement therapy doi:10.1177/039139880402700505 outcomes in critically ill patients under- improves renal recovery from acute going renal replacement therapy: A cohort

DOC-0006767 Rev 01 study. Critical Care. 2014;18(6). doi:10.1186/ 38. Zhang L, Yang J, Eastwood GM, Zhu G, 47. Gashti CN, Salcedo S, Robinson V, et al: s13054-014-0624-8 Tanaka A, Bellomo R. Extended Daily Dial- Accelerated venovenous hemofiltration: ysis Versus Continuous Renal Replace- early technical and clinical experience. Am 29. Correction Bellomo R, Cass A, Cole L, et ment Therapy for Acute Kidney Injury: A J Kidney Dis 2008; 51(5):804-810 al. An observational study fluid balance Meta-analysis. American Journal of Kidney and patient outcomes in the randomized Diseases. 2015;66(2):322-330. doi:10.1053/j. 48. Edrees F, Li T, Vijayan A: Prolonged Inter- evaluation of normal vs. augmented level ajkd.2015.02.328 mittent Renal Replacement Therapy. Adv of replacement therapy trial. Critical Care Chronic Kidney Dis 2016; 23(3):195-202 Medicine. 2012;40(6):1753-1760. doi:10.1097/ 39. Kovacs B, Sullivan KJ, Hiremath S, Patel R CCM.0b013e318246b9c6 v. Effect of sustained low efficient dialysis 49. Szamosfalvi B, Frinak S, Yee J: Sensors and versus continuous renal replacement hybrid therapies: a new approach with 30. Teixeira C, Garzotto F, Piccinni P, et therapy on renal recovery after acute automated citrate anticoagulation. Blood al. Fluid balance and urine volume are kidney injury in the intensive care unit: Purif 2012; 34(2):80-87 independent predictors of mortality in A systematic review and meta-analysis. acute kidney injury. Critical Care. 2013;17(1). Nephrology. 2017;22(5):343-353. doi:10.1111/ 50. Fiaccadori E, Regolisti G, Cademartiri C, doi:10.1186/cc12484 nep.13009 et al: Efficacy and safety of a citrate-based protocol for sustained low-efficiency 31. Vaara ST, Korhonen AM, Kaukonen KM, 40. Edrees F, Li T, Vijayan A. Prolonged dialysis in AKI using standard dialysis et al. Fluid overload is associated with Intermittent Renal Replacement equipment. Clin J Am Soc Nephrol 2013; an increased risk for 90-day mortality in Therapy. Advances in Chronic Kidney 8(10):1670-1678 critically ill patients with renal replace- Disease. 2016;23(3):195-202. doi:10.1053/j. ment therapy: Data from the prospective ackd.2016.03.003 51. Clark JA, Schulman G, Golper TA: Safety FINNAKI study. Critical Care. 2012;16(5). and efficacy of regional citrate anticoag- doi:10.1186/cc11682 41. Edrees FY, Katari S, Baty JD, Vijayan A. ulation during 8-hour sustained low-effi- A Pilot Study Evaluating the Effect of ciency dialysis. Clin J Am Soc Nephrol 2008; 32. Neyra JA, Yessayan L, Thompson Bastin Cooler Dialysate Temperature on Hemo- 3(3):736-742 ML, Wille K, Tolwani AJ. How to prescribe dynamic Stability During Prolonged and troubleshoot continuous renal Intermittent Renal Replacement Therapy 52. Berbece AN, Richardson RM: Sustained replacement therapy: A case-based review. in Acute Kidney Injury. Critical Care low-efficiency dialysis in the ICU: cost, Kidney360. Published online December Medicine. 2019;47(2):e74-e80. doi:10.1097/ anticoagulation, and solute removal. 14, 2020:10.34067/KID.0004912020. CCM.0000000000003508 Kidney Int 2006; 70(5):963-968 doi:10.34067/kid.0004912020 42. Morris PE, Goad A, Thompson C, et 53. Marshall MR, Ma T, Galler D, et al: 33. Murugan R, Bellomo R, Palevsky PM, al. Early intensive care unit mobility Sustained low-efficiency daily diafiltra- Kellum JA. Ultrafiltration in critically therapy in the treatment of acute respi- tion (SLEDD-f) for critically ill patients ill patients treated with kidney replace- ratory failure. Critical Care Medicine. requiring renal replacement therapy: ment therapy. Nature Reviews Nephrology. 2008;36(8):2238-2243. doi:10.1097/ towards an adequate therapy. Nephrol Dial Published online 2020. doi:10.1038/s41581- CCM.0b013e318180b90e Transplant 2004; 19(4):877-884 020-00358-3 43. Burgner A, Golper T. Walkaway PIKRT 54. Kumar VA, Craig M, Depner TA, et al: 34. Kitchlu A, Adhikari N, Burns KEA, et al. (as SLED) for Acute Kidney Injury. Extended daily dialysis: A new approach to Outcomes of sustained low efficiency dial- Clinical Journal of the American Society of renal replacement for acute renal failure ysis versus continuous renal replacement Nephrology. Published online September in the intensive care unit. Am J Kidney Dis therapy in critically ill adults with acute 11, 2020:CJN.07510520. doi:10.2215/ 2000; 36(2):294-300 kidney injury: A cohort study Dialysis cjn.07510520 and Transplantation. BMC Nephrology. 55. Schwenger V, Weigand MA, Hoffmann 2015;16(1). doi:10.1186/s12882-015-0123-4 44. Hoff BM, Maker JH, Dager WE, Heintz BH. O, et al: Sustained low efficiency dialysis Antibiotic Dosing for Critically Ill Adult using a single-pass batch system in acute 35. Marshall MR, Golper TA, Shaver MJ, Alam Patients Receiving Intermittent Hemo- kidney injury - a randomized inter- MG, Chatoth DK. Sustained low-efficiency dialysis, Prolonged Intermittent Renal ventional trial: the Renal Replacement dialysis for critically ill patients requiring Replacement Therapy, and Continuous Therapy Study in Intensive Care Unit renal replacement therapy. Kidney Inter- Renal Replacement Therapy: An Update. Patients. Crit Care 2012; 16(4):R140 national. 2001;60(2):777-785. doi:10.1046/ Ann Pharmacother. 2020 Jan;54(1):43-55. j.1523-1755.2001.060002777.x doi: 10.1177/1060028019865873. Epub 2019 56. Kitchlu A, Adhikari N, Burns KE, et al: Jul 25. PMID: 31342772. Outcomes of sustained low efficiency dial- 36. Kumar VA, Craig M, Depner TA, Yeun JY. ysis versus continuous renal replacement Extended daily dialysis: A new approach to 45. Finkel KW, Foringer JR. Safety of therapy in critically ill adults with acute renal replacement for acute renal failure regional citrate anticoagulation for kidney injury: a cohort study. BMC Nephrol in the intensive care unit. American Journal continuous sustained low efficiency 2015; 16:127 of Kidney Diseases. 2000;36(2):294-300. dialysis (C-SLED) in critically ill doi:10.1053/ajkd.2000.8973 patients. Ren Fail. 2005;27(5):541-5. doi: 57. Marshall MR, Creamer JM, Foster M, et al: 10.1080/08860220500198748. Mortality rate comparison after switching 37. Kielstein JT, Kretschmer U, Ernst T, et al. from continuous to prolonged intermit- Efficacy and Cardiovascular Tolerability of 46. Clark JA, Schulman G, Golper TA. Safety tent renal replacement for acute kidney SLED in Critically Ill Patients: A Random- and efficacy of regional citrate anticoag- injury in three intensive care units from ized Controlled Study. American Journal ulation during 8-hour sustained low-ef- different countries.Nephrology Dialysis of Kidney Diseases. 2004;43(2):342-349. ficiency dialysis. Clin J Am Soc Nephrol. Transplantation 2010; 26(7):2169-2175 doi:10.1053/j.ajkd.2003.10.021 2008 May;3(3):736-42. doi: 10.2215/ CJN.03460807. Epub 2008 Feb 13. PMID: Bryan Mayfield provided medical writing support. 18272829; PMCID: PMC2386695.

DOC-0006767 Rev 01 ADAPTIVE THERAPY WITH TABLO

Tablo Hemodialysis System: Utilizing Adaptive Dialysis to Address the Challenges of ICU Kidney Replacement Therapy

Background The Tablo system contains three primary structure enables bedside dialysis in the components: acute setting, saving the time and expense In the United States, dialysis is a large, of transporting patients elsewhere for expensive sector of healthcare that has 1. Tablo Console: A compact, 35-inch tall, dialysis. Tablo’s clinical versatility and seen little technological innovation in easily transportable console with inte- effectiveness has been shown to achieve the last 30 years. The Tablo Hemodialysis grated water purification, on-demand clinical targets for clearance and volume System (Tablo) represents a significant dialysate production and touchscreen control across a wide range of settings, technological advancement, enabling interface. while patients treating on the device have novel, transformational dialysis care in reported experiencing fewer symptoms multiple care settings. 2. Tablo Cartridge: A proprietary, dispos- related to dialysis. 13 able, single-use, color–coded organizer Tablo is a next-generation, self-contained, with, pre-strung bloodlines compatible Adaptive Dialysis with Tablo enterprise solution hemodialysis system with any dialyzer that clicks into place, capable of delivering adaptive kidney minimizing steps, touchpoints and Outside of a global pandemic, for decades, replacement therapy, a term used to connections. dialysis in the ICU has been primarily describe the Tablo system’s unique ability isolated to two modalities: continuous to span a wide spectrum of treatment 3. TabloHub: Designed to bring data to kidney replacement therapy (CKRT) modalities from intermittent to prolonged dialysis and information to the care and intermittent hemodialysis (IHD). dialysis (2–24 hours daily), with or team, TabloHub is the web-based portal Sustained low efficiency dialysis (SLED) without ultrafiltration. This clinical versa- enabling Tablo to live in a connected therapy has been proposed as an alter- tility enables providers the ability to meet setting with 2-way wireless communi- native to continuous KRT since the early the hemodynamic needs of all patients cation, cloud-based system monitoring, 2000s, with evidence supporting equiv- and standardize dialysis with Tablo across treatment analytics, machine and clinical alent outcomes related to mortality, and the continuum of care, from hospital to recordkeeping that can be integrated with renal recovery, and potential benefits home. hospital EMRs. related to cost, reduction in the need for anticoagulation and potential to mobilize Designed to improve the dialysis experi- Tablo is an all-in-one dialysis machine patients earlier in their clinical course. ence for patients and help providers over- that combines consumer product It has been performed in some ICUs but come traditional care delivery challenges, simplicity, wireless connectivity, and has only rarely been offered alongside Tablo requires only an electrical outlet, real-time integrated water purification in CKRT and IHD to allow a full complement tap water and a drain to operate, freeing a compact unit. Its intuitive touchscreen of kidney replacement therapy options. providers from the burdensome infra- interface with step-by-step instructions While several possible reasons exist, the structure and costly supplies required to and 3-D animations is easy to learn and limitations of dialysis technologies have operate traditional dialysis machines. use. Tablo’s independence from infra- played a significant role as offering all

DOC-0006767 Rev 01 therapies required at least 3 different tional efficiencies, including reducing the is within 50mL/hr of accuracy and can be devices and usually involved coordination cost of their ICU dialysis programs by up set as high as 2L per hour or programmed of 2 different nursing groups, ICU RNs to 65%.14 to disallow UF above a certain volume per and HD RNs, as well as pharmacy and hour to avoid inadvertently high UF rates biomedical engineering staff, making this See Table 1, Therapeutic Capabilities of the that could impact hemodynamics. 10,11 option too complex for all but the most Tablo Hemodialysis System, for full prescrip- sophisticated academic centers. tion ranges. Prescribing SLED Therapy with Tablo

Tablo’s ability to streamline delivery of Prescribing Intermittent Hemodialysis Compared to conventional dialysis most dialysis modalities into a single with Tablo devices, Tablo allows SLED to be deliv- device and single workflow makes the ered with a single device as opposed to full complement of treatment times and Tablo has demonstrated, at a maximum needing a dialysis machine and a portable options a reality for today’s hospital dialysate flow rate of 300mL/min, the water filtration system. This not only systems. With the option of hemodial- ability to achieve comparable clearance has the advantage of a much smaller ysis, isolated ultrafiltration and sequen- and clinical target adequacy in stan- footprint in the normally very tight ICU tial therapy (mixed HD and UF mode) dard treatment times.6,7,8 At a dialysate setting but eliminates the complexity therapy and the ability to use any dialyzer, flow rate of 300mL/min, a typical IHD of managing two different devices. the right combination of metabolic and prescription on Tablo utilizes a blood flow This has allowed ICU nursing staff at volume clearance and the appropriate rate between 300–400mL/min and is typi- numerous hospital systems throughout of removal can be achieved. Tablo allows cally 3–4 hours in duration. Estimated the US to quickly adopt SLED therapy prescribers to choose the right duration URR difference compared to higher flow with Tablo and has greatly reduced, and and intensity of therapy to meet each rates is approximately 3–5%. For patients in many cases eliminated, the additional patient’s metabolic and clearance needs, where additional clearance is needed, an burden SLED has previously placed on while utilizing the same staff and staffing increase in time by 15 mins. or a larger Hemodialysis nursing staff.9,12 Compared ratio to provide the treatment. Tablo dialyzer can be utilized to achieve higher to CKRT devices, Tablo is able to achieve utilizes consistent, familiar prescription clearance goals. Unlike CKRT devices, the clinical goals for clearance at a signifi- orders to provide therapy of any duration. Tablo allows thrice-weekly ICU IHD to be cantly lower cartridge cost while elimi- Whether prescribing 24-hour or 4-hour performed with the same device that is nating the complexity and cost associated therapy, the same order set can be used used for 24-hour therapy. Tablo is compat- with attempting to transport and hang for all treatments. Meaningful evidence ible with any commercially available high over 60 liters of dialysate fluid for each has been generated to demonstrate that flux dialyzer and can utilize a wide range SLED treatment. Tablo adaptive dialysis providers can realize significant opera- of dialysate compositions. Ultrafiltration allows SLED to be performed in a more

1. WIRELESS CONNECTIVITY Two way data communication can automatically send treatment data to the cloud.

2. TREATMENT MODALITIES Flexible kidney replacement therapy 3 options including extended therapy (XT), SLED, IHD, and UF only

3. TOUCHSCREEN GUIDANCE Animations and conversational instructions make Tablo easy to learn and use 4

4. TABLO CARTRIDGE Minimizes setup and takedown time by removing manual steps

5. SENSOR-BASED AUTOMATION

Tablo sensors help to automate much 6 of the setup, treatment management and maintenance

6. DIALYSATE ON DEMAND 7 Purifies water and produces dialysate in real-time

7. MOBILITY All you need is an electrical Figure 1 Tablo Hemodialysis System outlet and tap water Main Components and Features

DOC-0006767 Rev 01 Therapy Typical Tx length (hours) When used

Hemodialysis IHD 0–6 Hemodynamically stable SLED 6–12 High acuity unstable patients XT up to 24 High acuity unstable patients

UF-Only 0–6hr Isolated volume removal in hemodynamically stable AKI or ESRD >6hr (SCUF) Slow isolated volume removal in the hemodynamically unstable patient

Sequential Therapy (Mixed Sequential IHD 0–6 Dialysis initiation in vol overloaded mode HD and UF therapies) Sequential SLED 6–12 Slow UF with reduction in metabolic clearance Sequential XT up to 24 Slow UF with reduction in metabolic clearance

Table 1 Therapeutic Capabilities of the Tablo Hemodialysis System

cost effective, staff efficient manner with the same low Qb mentioned above with the same dialyzer and dialysate while allowing dialysis programs to and would be recommended to have a Qd flow rate provides consistent clear- standardize the clearance achieved with of approximately 200ml/min to provide ance across devices. In addition, Tablo’s SLED and maintain the clinical flexibility sufficient clearance during a 6-hour treat- sequential or “Mixed mode” therapy needed by nephrologists and intensivists ment. allows the delivered dose of metabolic to care for the critically ill. Total UF, dialysate composition and clearance with SLED to be consistently dialyzer would be patient specific and prescribed and delivered while allowing When ordering SLED with Tablo, the site dependent. ultrafiltration to be adjusted based on prescription stays very much the same the individual patient’s need. For many with slower flow rates to balance the With Tablo, 10–12 hour SLED treatments patients, sequential therapy allows the longer duration therapy and the potential can allow 2 patients to be treated with a prescription of 4-hour dialysis therapy for hemodynamic instability: single device per day and allow for slower with the predictable clearance and drug ultrafiltration in highly unstable patients. dosing that accompanies IHD treatment, Tablo’s simple take-down and set-up then conversion to isolated ultrafiltration Blood Flow 150–250mL/min allow efficient transition between ICU for whatever duration is needed to achieve patients, maximizing time when patients volume management goals. This can be Duration 6–12 hours are receiving treatment and minimizing preprogrammed as part of the initial time spent in tear down, transportation prescription or added at any time during Dialyzer Any High Flux and set up. Dialysate flow rates for 10–12 treatment. With onboard water purifica- hour therapy are suggested to be low, as tion and dialysis on demand the switch Qd 100–200ml/min there is potential for over-dialysis with between modes is immediate. SLED therapy of this duration. A Qd of UF Total volume to be removed 100mL/min provides 6 liters of diffusive While further data is needed, the clear- therapy per hour in addition to convec- ance of medications and removal of elec- tion achieved through ultrafiltration and trolytes during isolated ultrafiltration is Recommended considerations for removal of any pre or post filter replace- considerably lower than during diffusive prescribing SLED in general, and more ment fluid. Dialysate composition can therapy and should greatly reduce elec- specifically with Tablo, are to strongly often utilize a 4K bath or conversion to trolyte replacement and drug clearance consider standardizing SLED treatment a 4K bath during therapy. Prescribed variability previously encountered in time and dialysate flow rate. Ideally SLED Total Buffer will vary based on the degree SLED programs. can be utilized to care for 2–3 patients of acidosis present. Ultrafiltration is with a single device per day, and dialysis prescribed as a Total UF goal for the Prescribing Sequential Therapy times and flow rates could be protocoled to entire treatment, based on assessment of with Tablo provide more predictable treatments and volume status and anticipated volume to clearances. be received. Unanticipated volume given Sequential therapy was developed in part- throughout the day (blood products, medi- nership with ICU nephrologists and early Six-hour SLED treatments could poten- cations, drips, etc.) can be added at any Tablo clinical sites. An identified limita- tially allow 3 patient treatments per device time to the total goal and will be removed tion of prior therapy models, ICU kidney in one day and be beneficial in times of evenly over the remaining treatment time replacement therapy is often prescribed patient surges where demand is high; to minimize variability in hourly volume primarily for volume management but however, shorter SLED treatments may removal and potential impact on hemody- results in requisite metabolic clearance involve ultrafiltration rates that may be namics. that may not be desirable. In clinical higher than desired in highly unstable practice, this results in recurrent episodes patients (see the prior accompanying From a standardization and drug-dosing of hypophosphatemia, hypomagnesemia article, “Optimizing Kidney Replacement perspective, a single device across all ICUs and hypokalemia. These electrolyte in Critical Care: SLED Can Play a Bigger with a single user group offers unprece- deficiencies in the ICU have not only been Role in the ICU”, for UF recommenda- dented opportunity to simplify and proto- associated with adverse events in critically tions). Six-hour therapy can be ordered colize SLED delivery. Tablo prescribed ill patients but also have been associated

DOC-0006767 Rev 01 with delays in extubation, increases in volumes (50–200mls/flush), which will be has enabled nurses to manage critical length of stay and delays in renal recovery. automatically administered and adjusted treatment parameters remotely, from an 1–5 Sequential therapy allows prescribing for by the device. This allows prescribers online dashboard accessible through any of hemodialysis for the number of hours additional anticoagulation strategy connected device, thereby ensuring staff needed to accomplish metabolic clear- options outside of pharmacotherapy to safety and reducing PPE use, while main- ance goals, then an automated conversion minimize clotting without complicating taining a high quality of patient care. to isolated ultrafiltration mode to allow the nursing workflow. continuation of slow volume removal Summary without additional metabolic clearance. Tablo is compatible with heparin and has Prescriptions can start in either mode and been used with regional citrate anticoag- Specifically designed to simplify dialysis switch at any point during therapy, for any ulation (RCA) as well. Heparin is typically treatment for patients and providers, duration therapy up to 24 hours. Prescrip- prescribed as a bolus through the injec- the Tablo Hemodialysis System is a tion parameters such as ultrafiltration tion port on the cartridge (Tablo does not first-of-its-kind enterprise solution that goal and blood flow can be kept constant have an incorporated heparin pump) at is approved for use across the entire through both modes or individualized on the initiation of treatment for IHD and continuum of care—from hospital to a per segment basis. Conversion between has been delivered as a continuous drip home. Capable of providing dialysis modes occurs automatically without for longer duration therapy (see the prior of any duration for any level of patient nursing intervention and is recorded auto- accompanying article, “Optimizing Kidney acuity, Tablo allows physicians and hospi- matically on the treatment flowsheet for Replacement in Critical Care: SLED Can tals to expand their clinical capabilities to documentation purposes. Play a Bigger Role in the ICU”, for dosing include 24-hour and intermediate-dura- suggestions). Anecdotally, RCA has been tion SLED therapies, without the cost and Prescribing Beyond 12 Hours used effectively with Tablo using site- complexity that has typically accompa- based protocols. nied this type of expansion. A significant benefit of adaptive therapy is the ability to span all potential treatment Final Note: Tablo’s Critical Role Prescribing on Tablo is familiar and times. Tablo’s 24-hour therapy (XT) allows in the COVID-19 Response consistent across all therapeutic ranges, slow, continuous hemodialysis over an with an adaptive dialysis model that entire prescribing period with a dialysate Tablo’s unique advantages enabled allows achievement of metabolic clear- flow rate of 50mL/min, providing 3L/hr of providers that adopted the technology ance and volume management goals in diffusive clearance in addition to convec- the ability to navigate a complex clinical single-mode or mixed-mode therapies tion achieved through ultrafiltration and environment compounded by surges of which can help standardize prescribing removal of any pre- or post-filter replace- COVID-19-positive patients. Facilitated by and potentially minimize the complexity ment fluid. Blood flow rates remain low its design and data capabilities, including of electrolyte replacement and drug at 150–250mL/min. UF is prescribed as Remote Monitoring, Tablo has helped dosing in ICU kidney replacement. The total UF with the ability to adjust as often enhance operational versatility, clinical Tablo Hemodialysis System’s adaptive as hourly, based on site-based protocols. flexibility and safety that have proven therapy model allows clinicians and Unlike traditional CKRT, Tablo XT allows anecdotally to be invaluable in the setting facilities the opportunity (even under the on-demand rapid adjustment to dialysate of COVID-19 patient surges. Outlined pressures of the COVID-19 pandemic) sodium and buffer. This contrasts with below are a few examples of benefits expe- to expand their current KRT capabili- other devices that require sterile, prepack- rienced by Tablo customers responding to ties while reducing cost and potentially aged dialysate which can be limited and/ these unprecedented circumstances: reducing complications and outcomes in or require compounding in the pharmacy, patients requiring KRT in the ICU. lending to the potential for medication Highly mobile and compact, Tablo has error. With Tablo, adjustments to dialysate helped providers to quickly repurpose potassium and calcium are made through existing locations, and enabled an increase References simple bedside changes in dialysate in bedside dialysis (without needing an concentrates, greatly simplifying the dial- external RO), to deliver isolation treat- 1. Hendrix RJ, Hastings MC, Samarin ysate changes, compared to the process ments to COVID-infected patients while at M, Hudson JQ. Predictors of Hypo- required to stop treatment, order, change, the same time easing pressure on usual 1:1 phosphatemia and Outcomes during and hang liters of sterile dialysate bags patient-to-staff ratios and decreasing staff Continuous Renal Replacement Therapy. every time these parameters are adjusted. exposure—in any area of the hospital. Blood Purif. 2020;49(6):700-707. doi: 10.1159/000507421. Epub 2020 Apr 22. Prescribing Anticoagulation on Tablo Step-by step-instructions and onscreen PMID: 32320987. animations have allowed providers to The Tablo system was designed to mini- expedite the completion of Tablo training 2. Lim C, Tan HK, Kaushik M. Hypophospha- mize the blood-air interface by efficiently in roughly 4 hours, and leverage the pool temia in critically ill patients with acute removing air from the system during the of nurses and technicians being freed by kidney injury treated with hemodialysis automated priming sequence. This allows the reduction of elective procedures to is associated with adverse events. Clin many treatments performed with Tablo manage and/or support treatments. Kidney J. 2017;10(3):341-347. doi:10.1093/ in the acute and chronic environments to ckj/sfw120 be performed without anticoagulation. Offering a broad range of treatment Tablo does allow a manual dialyzer flush modalities and enabling an adaptive 3. Song YH, Seo EH, Yoo YS, Jo YI. Phosphate to be performed with a simple button approach to therapy, providers have found supplementation for hypophosphatemia press at any point during therapy and will that by shifting from Extended Therapy during continuous renal replacement account for that flush by adjusting the (XT) to SLED in the ICU has helped therapy in adults. Ren Fail. 2019;41(1):72- treatment UF goal to ensure the patient balance the individual patient need with 79. doi:10.1080/0886022X.2018.1561374 volume removal remains as prescribed. the increased demand for treatments, Tablo also offers the ability to prescribe machines and supplies. 4. João Matias P, Azevedo A, Laranjinha recurrent scheduled dialyzer flushes at a I, Navarro D, Mendes M, Ferreira C, wide range of intervals (5–60 mins) and Tablo’s Remote Monitoring capability Amaral T, Jorge C, Aires I, Gil C, Ferreira

DOC-0006767 Rev 01 A. Lower serum magnesium is associ- ≥ 500 mL/min.” Presented at the 25th New Hemodialysis System Using a Flow ated with cardiovascular risk factors International Conference on Advances Balancing Technique.” Presented at and mortality in haemodialysis patients. in Critical Care Nephrology AKI & CRRT the 24th International Conference on Blood Purif. 2014;38(3-4):244-52. doi: 2020; Feb 24-27, 2020; San Diego, CA. Advances in Critical Care Nephrology AKI 10.1159/000366124. Epub 2015 Jan 6. & CRRT 2019; Feb 26–March 1, 2019; San PMID: 25573320. 8. Augustin, Dimitri A, et al. “In-Vivo Diego, CA. Dialysis Kinetics of 300 mL/min and 500 5. Alves SC, Tomasi CD, Constantino L, mL/min Dialysate Flows.” Journal of the 12. Moore, K. et al. “Single Center Expe- Giombelli V, Candal R, Bristot Mde L, American Society of Nephrology, vol. 29, rience: Conversion to Tablo Dialysis Topanotti MF, Burdmann EA, Dal-Pizzol Abstract Edition (http://www.asn-online. System. Presented at the 26th International F, Fraga CM, Ritter C. Hypomagnesemia org/education/kidneyweek/archives/). Oct. Conference on Advances in Critical Care as a risk factor for the non-recovery of the 2018, p. 620. Nephrology AKI & CRRT 2021; Feb 28– renal function in critically ill patients with March 5, 2021; Virtual Conference. acute kidney injury. Nephrol Dial Trans- 9. Aragon, Michael, et al. “Urgent Training plant. 2013 Apr;28(4):910-6. doi: 10.1093/ with the Tablo Hemodialysis System in 13. Troy J. Plumb, Luis Alvarez, Dennis L. ndt/gfs268. Epub 2012 Jul 4. PMID: Response to COVID-19.” Journal of the Ross, et al “Safety and efficacy of the Tablo 22764195. American Society of Nephrology, vol. 31, hemodialysis system for in-center and no. Abstract Edition (http://www.asn-on- home hemodialysis” Hemodialysis Interna- 6. Sylvia-Reardon, Mary H, et al. “A Single line.org/education/kidneyweek/archives/), tional 2020; 24:22-28 Center Experience Piloting the TABLO Oct. 2020, p. 304 Hemodialysis System for Intermittent 14. Sevag Demirjian, Matthew Lane, Glen (IHD) in an Acute Hospital Setting – a 10. Aragon, Michael, et al. “Ultrafiltration Chertow, Luis Alvarez “Early Experience Quality Improvement Project.” Journal of Accuracy of the Tablo Hemodialysis with a Novel Hemodialysis System used the American Society of Nephrology, vol. System During 24-hour Therapy.” Journal for PIRRT Demonstrates Clinical Manage- 30, Abstract Edition (http://www.asn-on- of the American Society of Nephrology, ment at Lower Cost than CRRT and IHD”, line.org/education/kidneyweek/archives/), vol. 31, no. Abstract Edition (http://www. poster presentation AKI/CRRT 2018. Oct. 2019, p. 560. asn-online.org/education/kidneyweek/ archives/), Oct. 2020, p. 403 7. Aragon, Michael, et al. “Single Center Case Study on Acute Dialysis with a Dialysate 11. Lingam, Gopi, and Michael Aragon. Flow Rate of 300 mL/min compared to “Volume Management Accuracy in a

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DOC-0006767 Rev 01