Page 1361 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

934 PART 8: Renal and Metabolic Disorders

reduce the burden of the complications before they become acutely life surgery and combined liver and renal failure. Overall, the data appear to
threatening. Similarly, investigators have studied various criteria for support earlier RRT initiation. However, given the retrospective nature
5-8
the initiation of RRT to identify the optimal time of initiation, mostly of these studies, the variability in criteria used to define “early” versus
by conducting retrospective analyses of RRT datasets. Initial studies “late” timing, and the diversity of patient populations, it is impossible to
focused on the degree of azotemia at RRT initiation to compare “early” use this literature to provide a strong, evidence-based recommendation
versus “late” initiation of RRT. Uncontrolled data on “prophylactic” RRT for early initiation of RRT. The literature remains conflicting and the
in the setting of posttraumatic renal failure (initiation of dialysis prior primary limitations in study design have been the continued reliance
to blood urea nitrogen (BUN) reaching 200 mg/dL) suggested marked on markers of clearance to identify individuals with kidney injury and
improvement in survival as well as neuromuscular, metabolic, and the common practice of waiting for significant complications to develop
hematologic consequences of renal dysfunction. The first controlled prior to initiating RRT. Levels of certain serum chemistries (eg, potas-
2
trial by Conger and colleagues confirmed these findings; 18 individuals sium, phosphorus, bicarbonate) are affected by issues not directly related
with posttraumatic AKI were randomized to a more intensive hemodi- to the severity of AKI. They are also influenced by dietary intake, choice
alysis therapy to maintain BUN <60 mg/dL and serum creatinine (SCr) of fluid administration, and medication use; thus, their utility as thresh-
<5 mg/dL versus holding the initiation of hemodialysis until BUN olds for initiation of RRT is questionable (Table 98-2).
>150 mg/dL and SCr >10 mg/dL or other complications developed The goal of initiation of RRT should move beyond the notion of a
(hyperkalemia, volume overload, or uremic encephalopathy). Five simple “replacement therapy”, used reactively to remove the waste prod-
of eight patients (64%) in the intensive dialysis arm survived, versus 2 of ucts and excess fluid that accumulate in AKI. Rather, as Mehta writes,
10 patients (20%) in the conservative arm, a difference that did not the goal of RRT should be to provide “renal support” and facilitate the
reach statistical significance (p = 0.14). While the study was small, the other aspects of care of the critically ill patient including early nutri-
3
results were consistent with the retrospective findings, and supported tional support, restoration or preservation of euvolemia, maintenance
to the notion that “prophylactic” hemodialysis may be helpful to reduce of acid-base balance, maintenance of respiratory gas exchange, and pre-
the complications of kidney injury. vention of the accumulation of endogenous and exogenous (ie, medica-
Controlled trials regarding timing of initiation of RRT since the tions/metabolites and poisons) toxins. 9
initial study by Conger have been limited and the results have failed Unfortunately, the available literature does not provide specific,
to provide definitive direction on optimal timing. Rather than using objective guidelines for how to integrate these additional clinical factors
markers of azotemia as the strict criteria for randomization, Bouman (volume excess, nutritional support, etc) into the decision-making
and others conducted a more recent randomized controlled trial of process of initiating RRT. Nevertheless, the available literature does
initiation of RRT using a more comprehensive strategy. One hundred emphasize the potential deleterious effects of the complications of AKI
six adult subjects were randomized to one of three strategies: (a) early, and the potential benefits of full supportive measures. Specifically, data
high-volume hemofiltration, (b) early, low-volume hemofiltration, or from the PICARD study, a multicenter, prospective observational study
(c) late, low-volume hemofiltration. Patients were critically ill and eli- of patients with AKI in the setting of critical illness, observed that indi-
gible for randomization if they met the following criteria: urine output viduals with AKI and fluid overload (defined as >10% increase in fluid
<30 mL/h for more than 6 hours despite adequate circulatory support as compared to admission weight) had greater mortality: in-hospital—
(central venous pressure [CVP] or pulmonary artery occlusion pressure 48% versus 35%, p = 0.01, 30-day—37% versus 25%, p = 0.02, and
[PAOP] >12 mm Hg), addition of any dose of norepinephrine or phos- 60-day—46% versus 32%, p = 0.006. An observational study of more
10
phodiesterase inhibitors or >5 µg/kg/min of dobutamine or dopamine than 17,000 individuals with AKI and concomitant critical illness, using
and challenge with high-dose diuretics (>500 mg of furosemide in multivariate stepwise logistic regression the use of enteral nutritional
<6 hours), creatinine clearance (CrCl) of <20 mL/min in a 3-hour support, compared to all other nutritional support options, was associ-
urine collection and receiving mechanical ventilation. Individuals with ated with improved survival (OR 0.86; p < 0.001). 11
preexisting chronic kidney disease (Cockroft-Gault estimated creatinine Guidelines regarding initiation of RRT in the setting of AKI and
clearance <30 mL/min), AKI secondary to glomerulonephritis, tubu- critical illness should, therefore, take into account the complete aspects
lointerstitial nephritis, post-renal obstruction, surgical renal artery of treating these complex patients as well as objective definitions of
occlusion, or preexisting advanced liver disease or AIDS were excluded. AKI. It is likely that until the development and acceptance of standard-
Early initiation was defined as initiation of CRRT within 12 hours of ized and reproducible criteria to initiate RRT, the standard approach
meeting inclusion criteria. Late initiation was defined as implementa- to timing of RRT initiation will continue to be individualized without
tion once conventional criteria for RRT were met (BUN >112 mg/dL, use of standardized criteria, and accordingly there will be a high degree
potassium >6.5 mmol/L or severe cardiogenic pulmonary edema of practice variability.
requiring high-level ventilatory support). The study also compared dose
of therapy—high volume defined as blood flow rate of 200 mL/min and MODALITY OF RRT: INTERMITTENT vERSUS
hemofiltration rate of >3 L/h and low volume defined as blood flow rate CONTINUOUS DELIvERY
of 150 mL/min and hemofiltration rate of 1 to 1.5 L/h. The mean time
from meeting inclusion criteria to initiation of CRRT was 7 hours in the The widespread availability of sophisticated modern dialysis technologies
early group and 42 hours in the late group. There was no baseline differ- including tunneled and temporary venous catheters; blood pumps that are
ence in severity of illness scores (at ICU admission or study inclusion), able to maintain adequate blood flows to prevent thrombosis; standard-
vasoactive support or creatinine clearance (at study inclusion) between ized, portable dialysate and replacement solutions; and RRT equipment
the early and late groups. The investigators found no difference in platforms that can be operated by well-trained nursing staff without a
survival (ICU, hospital, or 28-day) or duration of renal failure, mechani- dedicated dialysis background has increased the popularity of continuous
cal ventilation, or hospitalization between the early and late groups. modalities of RRT (CRRT). In the study conducted by the BEST Kidney
Although this was a very small and underpowered trial, and essentially a investigators of AKI in the ICU, 1006/1258 (80%) of individuals received
pilot study, it remains the only prospective, randomized, controlled trial CRRT. Nevertheless, the optimal choice of modality remains controver-
1
of RRT initiation timing in the modern era. 4 sial, and may be limited by resources available at a given institution.
Despite the absence of convincing data supporting or refuting The rationale for the use of continuous modalities is based primar-
early initiation of RRT, further prospective trials have been lacking. ily on the common presence of hemodynamic instability of critically
Additional data supporting the early initiation of RRT come from ill patients with AKI, which is often exacerbated by IHD. Initially
retrospective, observational studies examining the use of RRT in AKI described in clinical use in 1977, continuous arteriovenous hemofiltra-
occurring in a variety of clinical settings, including sepsis, post-cardiac tion (CAVH) provided a means of fluid and solute removal in patients

section08.indd 934 1/14/2015 8:27:59 AM