Page 1366 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 98: Renal Replacement Therapy in the Intensive Care Unit 939

was 28% versus 46% in the alternate-day hemodialysis group (p = 0.01). Ultimately, 1124 patients were randomized with 563 individuals in the
Importantly, while the prescribed dose of dialysis in both groups was to intensive strategy and 561 individuals in the standard strategy. Neither
achieve a Kt/V of 1.2, the delivered dose was lower in both groups (0.94 mortality (the primary end point) nor renal recovery differed between
in the alternate day group and 0.92 in the daily group) resulting in a the two groups—53.6% mortality in the intense therapy group versus
delivered dose of dialysis lower than the minimum established adequate 51.5% mortality in the standard therapy group, p = NS, and 75.8% of
dose. Whether the renal recovery and mortality benefits would persist individuals in the intense therapy group remained RRT dependent as
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if the both groups in this single-center study received at least a delivered compared to 72.6% of individuals in the standard therapy group, p = NS.
Kt/V of 1.2 per treatment is unclear. As one might expect, hypotension was more common in the intense
In examining the optimal dose of CRRT therapy and its effect on mor- strategy group (61.9% vs 48.6%; p < 0.05). 48
tality, Ronco and colleagues randomized individuals with AKI requir- Finally, the Randomized Evaluation of Normal Versus Augmented
ing CRRT to one of three treatment strategies (CVVH): prescribed Level (RENAL) Replacement Therapy Study represents the most recent,
dose of 20 mL/kg/h, 35 mL/kg/h, or 45 mL/kg/h. Individuals receiving randomized controlled trial assessing the effect of RRT dose on mortal-
the lowest dose of therapy, 20 mL/kg/h, had the highest mortality and ity. In this study of individuals receiving CRRT in 35 ICUs distributed
shortest median survival. Specifically, the mortality rates were 59% in throughout Australia and New Zealand, subjects were randomized to
the 20 mL/kg/h group, 43% in the 35 mL/kg/h group, and 42% in the a higher intensity therapy (CVVHDF with a prescribed dose of efflu-
45 mL/kg/h group (only the difference between the 20 mL/kg/h group ent of 40 mL/kg/h) versus a lower intensity therapy (CVVHDF with a
was statistically significantly compared with the other groups). The prescribed dose of effluent of 25 mL/kg/h). A total of 1508 patients were
median survival in the lowest dose group was 19 versus 33 days in the randomized and 721 individuals were in the higher intensity group and
intermediate dose group (p = 0.0007). All patients received ultrafiltra- 743 individuals were in the lower intensity group. Overall mortality was
tion rates greater than 85% of their prescribed dose. The results of this much lower than previous studies; however, no significant difference
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single-center study, which included preset filter changes and additional was observed in the two groups. Ninety-day mortality was 44.7% in both
treatment to ensure the dose prescribed was delivered, would require groups. Similarly, renal recovery did not differ between the two groups
further validation. with 14.4% and 6.8% of individuals in higher intensity therapy group
Finally, the study conducted by Saudan and colleagues found a sur- requiring RRT at 28 and 90 days, respectively versus 12.2% and 4.4% in
vival advantage to higher intensity CRRT in the 206 critically ill patients the lower intensity group, p = 0.31, 0.14. 49
with AKI at a single institution. Rather than strictly comparing two The results of the most recent and multicenter randomized controlled
doses of therapy, the study randomized individuals to a weight-based trials do not support a mortality or renal recovery benefit for those
CVVH therapy arm versus the same dose of CVVH plus an additional receiving higher-dose RRT for AKI. Meta-analyses similarly failed to
1 to 1.5 L/h dialysate therapy. The replacement fluid rate was calculated find any benefit of higher intensity RRT, with no improvement in sur-
as (0.6 × body weight in kg)/day and the dialysate fluid rate was 1 L/h vival or renal recovery. 50,51 Nevertheless, similar to the question of the
for individuals less than 70 kg and 1.5 L/h for individuals greater than optimal modality of RRT, the existing data appear to support that “one-
70 kg. Individuals receiving CVVH plus dialysis (CVVHDF) were more size-fits-all” dose of RRT is a flawed strategy. For many patients, as long
likely to survive at 28 days (59% vs 39%) as well as 90 days (59% vs 34%) as a minimum dose of therapy is achieved, which appears to be a deliv-
than those receiving CVVH alone. At face value, the trial results would ered dose of at least 20 mL/kg/h for CRRT and a single-pool Kt/V of 1.2
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suggest that higher dose therapy confers a significant survival advantage. for IHD, adequate support is given while not using excessive resources
However, the trial design was not established to directly compare two or causing unnecessary complications. Of course, this approach man-
doses of therapy as one group received not only a higher dose of therapy, dates careful prescription of RRT dose, and a commitment to monitor
but also dialysis in addition to ultrafiltration. While it is unclear whether and ensure actual dose delivery. Furthermore, selected patients may still
the outcome would differ if the study simply compared two doses of require higher dose RRT therapy (eg, those who are extremely catabolic,
CVVH, the conclusions drawn from the study must recognize this have refractory electrolyte or acid-base disturbances, or require toxin
potential limitation. Nevertheless, results do suggest that more therapy, removal); however, for the majority of patients, higher dose therapy
in the form of either additional hemofiltration or the addition of a dose does not appear to confer a benefit. Similar to deciding on the optimal
of dialysis, is beneficial. modality of therapy, an individual patient assessment is still necessary to
However, the majority of recent clinical trials have not shown a determine an optimal dose of therapy (see Table 98-3).
benefit of higher doses in AKI. Tolwani and colleagues performed a
single-center study consisting of 200 individuals randomized to “standard-
dose” CVVHDF with a prescribed rate of 20 mL/kg/h versus “high-dose” TECHNICAL ASPECTS
by presence of sepsis and oliguria. The investigators did not find a differ- ■ ACCESS
with a prescribed rate of 35 mL/kg/h. The randomization was stratified
ence in survival or renal recovery between the standard and high-dose Patients with AKI requiring RRT differ significantly from ESRD
groups. Specifically, the survival (to ICU discharge or 30 days) was 56% patients in that vascular access must be established urgently to initiate
in the standard dose group and 49% in the high-dose group (p = NS). RRT. Arteriovenous access has fallen out of favor for acute RRT, given
Renal recovery was 41% in the standard dose group and 29% in the the increased risk of complications resulting from arterial cannulation
high-dose group (p = NS). 47 with a large bore vascular catheter. Dual-lumen venous access serves as
Subsequently, Palevsky and colleagues performed the NIH ATN trial, an effective means of establishing vascular access that can be utilized
which was a randomized controlled trial of varying intensity of RRT in both intermittent and continuous forms of therapy. The optimal
across 27 institutions. Unique in its design, the study included indi- technique and site of placement of venous access has been examined.
viduals receiving both IHD, if hemodynamically stable, and, if hemo- Retrospective and prospective data suggest that real-time ultrasound
dynamically unstable, CRRT. Subjects were randomized to an intense guidance of temporary dialysis catheter placement, in both the internal
RRT strategy—6 days weekly of IHD or CVVHDF with a prescribed jugular vein and femoral vein, prevents complications and allows for
effluent rate of 35 mL/kg/h—or standard therapy—3 days per week of greater success. 52-54 The optimal site for dialysis access appears to be
IHD (alternate day except for Sunday) or CVVHDF with a prescribed more variable. It is generally accepted that the subclavian vein should
effluent rate of 20 mL/kg/h. IHD treatments were prescribed with a Kt/V be avoided when placing a large-bore venous catheter in a patient
of 1.2 to 1.4 and additional isolated ultrafiltration sessions were allowed who may require future maintenance hemodialysis as subclavian vein
in the standard therapy arm for volume management. A limited number catheter insertion can lead to subclavian stenosis, precluding future
of patients received slow low-efficiency dialysis in lieu of CVVHDF. ipsilateral arteriovenous access placement. Prospective studies have

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