Brar SS, Aharonian V, Mansukhani P, et al. Haemodynamic-guided fluid administration for the prevention of contrast-induced
acute kidney injury: The POSEIDON randomised controlled trial. Lancet 2014;383:1814-23.
The administration of intravenous fluid remains the cornerstone treatment for the
prevention of contrast-induced acute kidney injury (CI-AKI). Data from the Prevention
of Radiocontrast-Induced Nephropathy Clinical Evaluation (PRINCE) study indicate that
increasing the urine flow rate (>150 mL/h) reduces the toxic effect of contrast media
(CM). Volume expansion with normal saline might reduce contrast-mediated injury by
expanding plasma volume, reducing renin activation and loss of nitric oxide, reducing
production of reactive oxygen species, and through dilution of contrast within the
tubular lumen.[1] However, no well-defined protocols exist to guide fluid administration in this treatment.
In a randomised, parallel-group, comparator-controlled, single-blind phase 3 trial
published in the Lancet 2014, Brar et al., studied the efficacy of a new fluid protocol based on the left ventricular end-diastolic
pressure (LVEDP) for the prevention of CI-AKI in patients undergoing cardiac catheterization
(the POSEIDON trial). LVEDP is a haemodynamic parameter and can be used to establish
intravascular volume status. The primary outcome was the occurrence of CI-AKI, which
was defined as a greater than 25% or greater than 0.5 mg/dL increase in serum creatinine
concentration. Between Oct 10, 2010 and July 17, 2012, 396 patients aged 18 years
or older undergoing cardiac catheterisation with an estimated glomerular filtration
rate of 60 mL/min per 1.73 m2 or less and one or more of several risk factors (diabetes mellitus, history of congestive
heart failure, hypertension or age older than 75 years) were randomly allocated in
a 1:1 ratio to LVEDP-guided volume expansion (n = 196) or the control group (n = 200) who received a standard fluid administration protocol. Exclusion criteria
included inability to obtain consent from participants, emergency cardiac catheterisation
(e.g., primary percutaneous coronary intervention for ST-segment elevation myocardial
infarction), renal replacement therapy, exposure to radiographic contrast media within
the previous 2 days, allergy to radiographic contrast media, acute decompensated heart
failure, severe valvular heart disease, mechanical aortic prosthesis, left ventricular
thrombus, history of kidney or heart transplantation and change in estimated GFR of
7.5% or more per day or a cumulative change of 15% or more during the preceding 2
or more days. Patients and laboratory personnel were masked to treatment assignment,
but the physicians who did the procedures were not masked. N-acetylcysteine (NAC)
use was defined as 600 mg twice daily for 2 days, starting the day before the index
procedure, and use was at the discretion of the referring physician. If started, the
2-day course was completed.
Both groups received intravenous 0.9% sodium chloride at 3 mL/kg for 1 h before cardiac
catheterization. LVEDP was measured by an angled 5 French or 6 French pigtail catheter
placed in the mid cavity of the left ventricle and attached to standard haemodynamic
monitoring software. (Xper; Phillips, Melbourne, FL, USA). The fluid rate was adjusted
according to the LVEDP as follows: 5 mL/kg/h for LVEDP lower than 13 mmHg; 3 mL/kg/h
for LVEDP of 13-18 mmHg and 1.5 mL/kg/h for LVEDP higher than 18 mmHg. The control
group was hydrated at 1.5 mL/kg/h. The fluid rate was set at the start of the procedure
(before contrast exposure), continued for the duration of the procedure and for 4
h post-procedure in both groups. Analyses were by intention to treat. Adverse events
were assessed at 30 days and 6 months, and all such events were classified by staff
who was masked to treatment assignment. Serum creatinine was measured at 1-4 days
post procedure noting the highest value and 2-8 weeks after the index procedure.
The main findings of the POSEIDON trial were that CI-AKI occurred less frequently
in patients in the LVEDP group (6.7% [12/178]) than in the control group (16.3% [28/172];
relative risk 0.41, 95% CI 0.22-0.79; P = 0.005). In patients with stable renal insufficiency undergoing cardiac catheterisation
and followed up for 6 months post-procedure, LVEDP-guided fluid administration as
compared with standard treatment resulted in a significant 68% relative reduction
(9.5% absolute reduction) in the primary endpoint of CI-AKI and a significant 59%
relative reduction (6.4% absolute reduction) in major adverse clinical events. Hydration
treatment was terminated prematurely because of shortness of breath (safety endpoint)
in three patients in each group. They concluded that LVEDP-guided fluid administration
was safe and effective in preventing CI-AKI in patients undergoing cardiac catheterisation.[2]
The POSEIDON trial has been criticized for its emphasis on patients with medium risk
category for AKI. Also, more than 50% of patients had normal LVEDP and only 15% had
high values.[3] Further studies are warranted to examine the effect of LVEDP-guided fluid administration
in patients with high LVEDP, therefore, targeting the dysfunctional heart, where the
normal Frank Starling mechanisms would not apply.
Some studies have shown the advantages of CI-AKI prophylaxis with NAC and sodium bicarbonate
solution. The Renal Insufficiency After Contrast Media Administration Trial I (REMEDIAL
I) trial showed that the combined strategy of volume supplementation with sodium bicarbonate
and NAC was better than normal saline and NAC alone or a combination of normal saline,
ascorbic acid, and NAC in preventing CI-AKI inpatients at low to medium risk. However,
in high-risk patients, the rate of CI-AKI remained high.[4]
The randomised, multicenter, investigator-driven REMEDIAL II trial by Briguori et al., showed that RenalGuard therapy was found superior to sodium bicarbonate and NAC
in preventing CI-AKI in high-risk patients. The RenalGuard System, which creates high
urine output and fluid balancing, may be beneficial in preventing CI-AKI. Patients
with an estimated glomerular filtration rate ≤ 30 mL/min/1.73 m2 and/or a risk score ≥ 11 were randomly assigned to sodium bicarbonate solution and
NAC (control group) or hydration with saline and NAC controlled by the RenalGuard
System and furosemide (RenalGuard group). The primary end point was an increase of
≥0.3 mg/dL in the serum creatinine concentration at 48 hours after the procedure.
CI-AKI occurred in 16 of 146 patients in the RenalGuard group (11%) and in 30 of 146
patients in the control group (20.5%; odds ratio, 0.47; 95% confidence interval, 0.24-0.92).
There were 142 patients (48.5%) with an estimated glomerular filtration rate ≤ 30
mL/min/1.73 m2 and 149 patients (51.5%) with only a risk score ≥ 11. Subgroup analysis according
to inclusion criteria showed a similarly lower risk of adverse events (estimated glomerular
filtration rate ≤ 30 mL/min/1.73 m2 odds ratio, 0.44; risk score ≥ 11: odds ratio, 0.45; P for interaction = 0.97. The rate of in-hospital dialysis (4.1% versus 0.7%; P = 0.056) were higher in the control group.[5] Further studies are needed to compare LVEDP-guided versus RenalGuard system-guided
hydration regimens.
A recent study examined the role of vitamin E (tocopherol) in preventing CI-AKI and
concluded that prophylactic oral α- or γ-tocopherol with 0.9% saline protected against
CI-AKI in patients with chronic kidney disease (CKD) undergoing coronary procedures.
In this study, 305 patients were randomly assigned to prophylaxis administration with
0.9% saline infusions plus daily oral medication comprised of either (i) placebo (n = 101), (ii) α-tocopherol (n = 102) or (iii) γ-tocopherol (n = 102) starting 5 days before and ending 2 days after coronary procedures. CI-AKI
developed in 14.9% in the placebo group, 4.9% in the α-tocopherol group (P = 0.02 versus the placebo group) and 5.9% in the γ-tocopherol group (P = 0.04 versus the placebo group). In patients with diabetes, hypertension, anaemia,
aged over 55 years, males or with contrast agent dosages >120 mL, α-tocopherol showed
a greater effect than γ-tocopherol when compared with the placebo group (P < 0.05).[6] This strategy should be compared to the abovementioned strategies to ascertain its
effect vis-a-vis fluid protocols and NAC use for preventing CI-AKI in elective radiographic
procedures.
