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936 PART 8: Renal and Metabolic Disorders

IHD while there was no change in MAP in the individuals receiving therapy selected accordingly. The most important point is that in
CVVHD. MAP at day 3 of RRT was higher in the CVVHD group centers where both intermittent and continuous modalities are avail-
versus the IHD group (79.9 ± 9.3 mm Hg vs 74.2 ± 10 mm Hg) despite able in the ICU, they are used as complementary therapies. Apart from
achieving a greater negative fluid balance over the first 3 days (median the special populations discussed below, such centers generally use
−4.005 L vs ±1.539 L; p < 0.001). 17 IHD for hemodynamically stable ICU patients, or when rapid removal
The Hemodiafe study group, a multicenter study consortium includ- of potassium, toxins, or fluid is desired and the patient is sufficiently
ing French medical centers, also conducted a randomized trial of hemodynamically stable to tolerate aggressive dialytic therapy, reserving
intermittent versus continuous renal replacement therapy. One hundred continuous modalities for periods of hemodynamic instability, particu-
eighty-four adult subjects were randomized to IHD and 175 individuals larly when associated with significant fluid overload. This personalized
were randomized to CVVHDF. Importantly, the study excluded individ- approach was successfully used in the ATN trial of RRT intensity (dose),
uals with a SAPS II score less than 37, focusing on individuals with AKI which is discussed below.
and multiorgan system failure in the ICU; however, no comment was
given with regard to exclusion of patients with hemodynamic instability. MODALITY OF RRT: SPECIAL CONSIDERATIONS
Similar to the results of previous studies, no difference in mortality was
seen between the two groups—41.8%, 31.5%, and 27.2% in the intermit- While the above literature suggests that both intermittent and continu-
tent group versus 38.9%, 32.6%, and 28.5% in the continuous group at ous therapies can be used in critically ill patients with AKI, a few clinical
28, 60, and 90 days, respectively; p = NS for all comparisons. Further, scenarios deserve special attention with regard to modality of therapy
there was no difference in frequency of hypotensive episodes (39% in and may represent situations where one modality is superior.
mean net fluid removal on days of therapy (2213 mL in the IHD group vs ■ ACUTE LIVER FAILURE
IHD group vs 35% in the CVVHDF group; p = 0.47), despite similar
2107 mL in the CVVHDF group). The total net fluid balance, accounting Acute liver failure (or fulminant hepatic failure) is characterized by labo-
for days not receiving therapy, was not reported. 18 ratory abnormalities suggestive of hepatocyte injury, impairment of liver
Finally, the Stuivenberg Hospital Acute Renal Failure (SHARF) function (manifested by increased prothrombin time [PT]/international
project also conducted a randomized trial of intermittent versus normalized ratio [INR] and bilirubin), and encephalopathy. Individuals
continuous renal replacement therapy. Similar to the study conducted by with fulminant hepatic failure are at risk for increased intracranial pres-
the Cleveland Clinic, randomization was according to severity of illness sure and cerebral herniation. Clearance of solutes and water via inter-
as determined by the SHARF severity of illness score. The investigators mittent RRT in the setting of AKI and fulminant hepatic failure may
randomized a total 316 adults, 144 to intermittent dialysis and 172 to have adverse effects on intracranial pressure, because rapid extracor-
CVVH. One hundred twenty-four of the eligible patients were excluded poreal clearance of uremic solutes causes acute plasma hypoosmolality,
from randomization due to “medical reasons”—primarily coagulation shifting water into the brain. In an observational study of nine patients
or hemodynamic disturbance. The groups at baseline were similar and with fulminant hepatic failure, increased intracranial pressure (ICP) and
hospital mortality was similar in the two groups—58.1% in the CVVH AKI treated with RRT, investigators compared the effect of IHD versus
group and 62.5% in the IHD group. 19 CRRT on ICP and cerebral perfusion. The mean ICP increased from
Taken together, the collective results of the clinical trials conducted to 9 ± 1.4 mm Hg to 13 ± 1.8 mm Hg (p < 0.05) in the first hour of an
date comparing intermittent versus continuous renal replacement therapy intermittent hemofiltration treatment versus no change in ICP (19 ± 4.8
do not demonstrate a mortality benefit or a significant impact on recovery to 18 ± 4 mm Hg) in the first hour of treatment with CAVH. Further,
of renal function for either modality. Even when other effects of RRT are MAP also significantly declined in the first hour of intermittent hemo-
assessed, that is fluid balance and adequacy of clearance, the benefits of filtration treatment (93 ± 2 to 82 ± 2.1 mm Hg), whereas there was no
CRRT do not translate into mortality differences. The implications of the change in MAP in individuals receiving CAVH. Overall, the cerebral
study results for clinicians are unclear. Should the results guide clinicians perfusion pressure (MAP – ICP) declined approximately 27% in the
to only use IHD in that it allows more patient mobility and has lower cost? individuals receiving intermittent hemofiltration versus no change in
Have the conducted studies been adequately powered to demonstrate a the group receiving CAVH. The study was not designed to demonstrate
mortality difference when the overall mortality in the studies is lower a mortality difference between the groups and no significant difference
than observed mortality in nonexperimental trials? Further complicat- was observed. The small study population, single center, and relative
21
ing our assessment of the findings of experimental trials, the results of a severity of disease (individuals already had evidence of increased ICP)
meta-analysis conducted in 2002 utilizing 13 studies and 1400 individuals limit the generalizability of the study findings. Additionally given the
including both observational and experimental designs concluded, after limited data describing the effects of CRRT on ICP in the setting of
adjusting for severity of illness and quality of study, the relative risk of hepatic failure, studies such as this one which utilized the outdated
mortality was lower in patients receiving CRRT. 20 modality of CAVH technology still guide therapy. Nevertheless, cerebral
Rather than a nihilistic approach, an alternative method of interpret- perfusion pressure is a critical parameter in the setting of fulminant
ing the data is simply that we are studying the wrong question. Applying hepatic failure and interventions that risk cerebral perfusion pressure
a “one-size-fits-all” approach to studying modality of RRT is flawed. In should be avoided if possible. The hemodynamic benefits of CRRT in
centers where both modalities—IHD and CRRT—are available, choice the setting of AKI and liver failure were further documented in a small,
of therapy will be influenced by both patient and nonpatient factors that randomized trial conducted at the same center as the study above.
are not included in randomized controlled trials (ie, catheter function, Thirty-two patients with fulminant hepatic failure, intracranial pressure
safety of anticoagulation, patient mobility, nurse staffing, etc). Most monitoring, and oliguric AKI were randomized to intermittent hemofil-
importantly, the results of the available studies suggest that with use tration or CRRT. Ultimately, 12 patients were randomized to intermittent
of either modality of RRT, practicing physicians are “doing no harm.” therapy and 20 patients were randomized to CRRT (8 received CAVH,
Individuals with severe hemodynamic instability or certain other 12 received CAVHD). Hemodynamic parameters including right atrial
special conditions outlined below may still benefit from use of CRRT pressure, systemic vascular resistance (SVR), cardiac index (CI), and
over intermittent therapy. However, for the majority of individuals, tissue oxygen delivery (D O 2 ) were assessed along with ICP. During the
even in the setting of multiorgan system failure, intermittent dialysis first hour of intermittent hemofiltration, CI fell 15 ± 2% versus no change
can adequately achieve solute clearance and control of volume balance. in the CRRT arm (3 ± 3%). CI did return back to the index value during the
Rather than focusing on selecting one modality for all individuals, the course of the intermittent treatment. MAP also fell during the intermit-
goals of therapy—large amounts of volume removal, removal of ingested tent treatment, 82 mm Hg to 74 mm Hg, p < 0.05, versus no change
toxins, clearance of uremic solutes, etc, should be kept in mind and the in the CRRT arm, 74 mm Hg to 74 mm Hg. Correspondingly, oxygen

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