Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3764_Библиотеки_им_академика_М_И_Перельмана
.pdf
24
CHAPTER 24
CTO: How to Minimize ContrastAssociated Acute Kidney Injury
Luis Gruberg
Mather Hospital, Donald and Barbara Zucker School of Medicine, New York, NY, USA
Introduction
Contrast-associated acute kidney injury (CA-AKI) is
the acute impairment of renal function occurring
after any type of iodinated contrast-based procedures
[1–5]. This term implies a correlative diagnosis but
not a causal relationship between contrast medium
administration and a decrease in kidney function.
The formerly used term contrast-induced nephropathy implies a causal relationship between intravenous contrast media and the development of AKI,
hence the term contrast-induced. Use of the term
contrast-induced nephropathy in clinical practice can
be misleading because of the large fraction of falsepositive events (i.e., AKI related to concurrent nephrotoxic exposure or insults, medications, hypotension,
or atheroembolic events in proximity to the time of
contrast media administration). CA-AKI is the third
leading cause of hospital acquired renal failure (after
renal hypoperfusion and nephrotoxic drugs) and
accounts for approximately 11% of cases [4, 5]. While
this problem is not unique to cardiology, the number
of diagnostic and therapeutic cardiac angiograms performed annually in the United States and in the world
has markedly increased over the past few decades.
Percutaneous coronary intervention (PCI) is now the
preferred method for revascularization for most
patients with coronary artery disease. Furthermore,
technological and pharmacological advances have
allowed for the more widespread use of percutaneous
coronary artery revascularization even for patients
with multi-vessel disease and complex coronary
lesions. Coronary chronic total occlusion (CTO) is a
complete (100%) occlusion of a coronary artery with a
Thrombolysis in Myocardial Infarction (TIMI) flow 0
for at least 3 months. Approximately 1 in 4 patients
with obstructive coronary artery disease on coronary
angiography will have a CTO [6–12]. Percutaneous
revascularization of a CTO is now a well-established
procedure accounting for up to 10% of patients undergoing PCI. It is one of the most demanding procedures in interventional cardiology, and one that
requires extensive experience, specialized equipment
and techniques, and frequently the use of more contrast and radiation exposure [13]. Despite ongoing
technical advances and improved success rates, prolonged coronary angiography and the obligate use of
iodinated contrast media has become a common
cause of nephrotoxicity in these patients [6, 13–16].
Chronic total occlusions
Anatomically, CTOs consist of a hard fibrocalcific
proximal cap, a distal cap with less fibrotic material,
and a central area of organized thrombus [6]. The
highly calcific nature of these occlusions’ accounts for
the increased difficulty in successful percutaneous
recanalization. The success rate of CTO PCI in large
registries was traditionally lower than that of nonCTO intervention, predominately related to the difficulty in crossing the lesion. In the past decade success
rate has increased to 85–94% at experienced centers
with the implementation of an algorithmic approach
and technical advances [9]. Complications such as
major adverse cardiac events (1.6–3.3% vs 0.8–1.4%)
and mortality rates are also higher in these patients
(0.4–1.4% vs 0.3–0.7%) [17]. Technically, these procedures differ from other interventions in many ways,
including the time commitment of the operator, the
Chronic Total Occlusions: A Guide to Recanalization, Third Edition. Edited by Ron Waksman and Shigeru Saito.
© 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.
218
CHAPTER 24 CTO: How to Minimize Contrast-Associated Acute Kidney Injury 219
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
equipment used, the radiation exposure and, importantly, the total volume of contrast administered. The
amount of contrast used during CTO interventions
averages 200 ± 96 ml compared to 162 ± 65 ml used in
simpler lesions [13]. There are limited studies in a
small number of patients that have assessed the incidence of CA-AKI in chronic kidney disease (CKD)
patients undergoing CTO PCI. Azzalini and colleagues reported on 1,092 patients that underwent
CTO PCI at 5 centers in Europe. Only 214 of these
patients had pre-existing CKD and 878 did not have
CKD [18]. Patients with CKD received lower contrast
volume (272± 120 mL vs 319 ± 137 mL, P< 0.001),
although fluoroscopy time and total procedural time
were similar. CA-AKI developed in 9.1% of all
patients, 15.0% in patients with pre-existing renal disease, with significant lower procedural and technical
success and a 11.2% mortality rate at 24 months.
Subjects who developed CA-AKI had also higher incidence of major bleeding (2.1% vs 0.3%, P = 0.02),
vascular complications (6.2% vs 1.1%, P < 0.001), and
death (2.1% vs 0.1%, P = 0.001) [17]. A recent metaanalysis by Lee and colleagues that comprised six
cohort studies showed a high prevalence (25.5%) of
CKD in the CTO PCI population [19]. In the nonCKD group, outcomes were better with a lower rate of
CA-AKI, higher procedural success rate and lower
long-term mortality. The procedural success rate in
the CKD CTO PCI population was significantly lower
with a higher rate of CA-AKI and higher in-hospital
and long-term mortality rate, possible related to more
complex lesions and more comorbidities.
Definition
Many definitions of CA-AKI are available in the literature. Historically, it was defined as an increase in
serum creatinine of 0.5 mg per deciliter (44 mol
per liter) or at least a 25% increase from the baseline level within 2 to 5 days after exposure to contrast material. The most current definition states
an increase in serum creatine of ≥0.3 mg/dL and/
or ≥50% relative increase in serum creatinine after
angiography compared with preprocedural levels
occurring up to 7 days after contrast administration
when no alternative etiology for AKI has been identified. In most patients, this rise occurs within the
first 24 hours, peaking 3–5 days after the procedure,
and is coupled with a reduction in creatinine
clearance [1, 3–5, 16, 20–22]. Unfortunately, serum
creatinine measurement is an insensitive method
to monitor renal function, as >50% reduction in
glomerular filtration rate may occur before any
increase is observed. Furthermore, plasma creatinine levels fluctuate according to hydration status
concomitant medications administered. Other
and
factors, such as hemodynamic status, atheroembolic
events, or medications administered can also cause
AKI after the administration of contrast media.
Multiple studies have established that a post-procedural rise in serum creatinine is associated with
increased mortality, myocardial infarction, target
vessel revascularization and accelerated progression
of underlying kidney disease and is now considered
a major procedural complication in the National
Cardiovascular Data Registry [23].
Pathophysiology
It has been hypothesized that CA-AKI is caused by
multiple pathologic processes, including vasoconstriction, direct nephrotoxicity, the formation of
reactive oxygen specifies, and impaired nitric oxide
production that affects mainly the tubular epithelium,
leading to loss of function, apoptosis, and necrosis
(Figure 24.1) [5, 24–26]. Immediately after injection
of contrast medium, there appears to be a transient
increase in renal blood flow which is followed by a
more prolonged period of arteriolar vasoconstriction
where renal blood flow is further decreased mediated
by potent vasoconstrictors such as endothelin, nitric
oxide, and prostaglandin [25–27]. Evidence suggests
that prolonged reductions in renal blood flow of up
to 50% occur for up to 4 hours after a contrast load
[27]. During this period of hypoperfusion, it seems
as though the outer medulla is at greatest risk for
ischemic damage [26]. In addition, a directly nephrotoxic effect of contrast media has been suggested
by the pathologic findings of cellular necrosis, interstitial inflammation, and epithelial cell vacuolization.
The degree of cytotoxicity is presumed to be directly
related to the length of exposure to contrast agents, and
thus, the importance of maintaining high urinary flow
rates periprocedurally. Also, the formation of oxygen
free radicals has been implicated in the apoptosis of
renal tubular cells and glomeruli in animal models.
In addition, contrast agents may increase blood viscosity, with subsequent changes in blood osmolality, a
reduction in microcirculatory flow further increasing
the risk of microvascular thrombosis.
Risk factors and risk calculators
The incidence of CA-AKI varies from 3.3 to 14.4% in
the available literature, depending on the patient
population studied and the definition. Multivariate
analysis have shown that the presence of renal
dysfunction at baseline, diabetes mellitus, congestive
heart failure, and higher doses of contrast media
increase that risk [5, 23, 28–30]. In the absence of risk
220 PART IV Wires Technique
Figure 24.1 Proposed mechanisms of contrast associated acute kidney injury. McCullough P, Choi J, Feghali G, et al.
Contrast-Induced Acute Kidney Injury. Reproduced with permission from ref. (25), © 2016, Elsevier.
factors, the overall incidence is low at 2–5% [26], but
in those with identifiable risk factors, the incidence
can vary between 11–50% [25–27]. Mehran and colleagues [31] identified multiple variables that were
independent predictors of CA-AKI and in 2004 developed a simple risk score that could predict the risk of
CA-AKI for patients undergoing PCI. The eight variables that were included in this risk calculator were
hypotension, the use of intra-aortic balloon pump,
heart failure, age > 75 years, anemia, diabetes, contrast
media volume, and serum creatinine > 1.5 mg/dL or
GFR < 60ml/min/1.73 m2. In this population, the rate
of CA-AKI increased exponentially with an increasing
risk score (8.4 and 55.9% for low and high-risk score,
respectively) [31]. Mehran and colleagues updated the
risk score calculator in 2021 (Mehran 2 CA-AKI Risk
Score) [32]. The updated model was based on data
from 14616 PCI patients in the United States,
including Model 1 with preoperative variables and
Model 2 with additional postoperative variables.
Compared with the original Mehran score, there was
higher discrimination, and it also included STEMI
patients. The new, updated, and contemporary risk
score also included only eight common and readily
available clinical variables (age, clinical presentation,
eGFR, congestive heart failure, diabetes, hemoglobin,
basal glucose, and left ventricular ejection fraction)
thereby allowing its practical routine use. Therefore, it
can be easily calculated at the bedside and incorporated into electronic medical records.
Two of the greatest independent predictors of
CA-AKI are the presence of heart failure and preexisting renal insufficiency. The severity of renal impairment appears to be directly correlated with the
incidence of CA-AKI [1, 2, 21]. Rihal et al. retrospectively studied 7586 patients undergoing coronary
intervention. In that cohort, they found that CA-AKI
developed in 22.4% of patients with a baseline serum
creatinine between 2.0and 2.9 mg/dL and in 30.6% of
patients with a serum creatinine higher than 3.0m/
dL. In contrast, CA-AKI occurred in only 2.4% of
those with creatinine levels < 2.0 mg/dL [1].
Additionally, several studies have identified congestive
heart failure as an independent predictor of CA-AKI
[1, 2, 17]. The risk associated with CHF may be caused
by alterations in renal blood flow in the setting of a
low flow state or the administration of nephrotoxic
medications [3]. Diabetes mellitus is another strong
predictor of CA-AKI after coronary intervention.
Rihal and colleagues found that diabetic patients with
normal or mild renal impairment (defined as a serum
creatinine <2.0mg/dL) had a significantly higher risk
CHAPTER 24 CTO: How to Minimize Contrast-Associated Acute Kidney Injury 221
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
of CA-AKI when compared with nondiabetic patients
with similar renal function [1]. When patients with
serum creatinine levels above 2.0 mg/dL were analyzed, diabetics and nondiabetics had a higher and
statistically insignificant incidence of CA-AKI. These
results were confirmed by other investigators, showing that diabetic patients with mean serum creatinine
levels of 1.3 mg/dL had a higher rate of CA-AKI compared with nondiabetic patients [19]. Other reported
risk factors include a reduced intra-arterial volume,
the concurrent use of other nephrotoxic medications
such as nonsteroidal anti-inflammatory drugs or aminoglycosides, systemic hypertension, hyponatremia,
blood transfusion, older age, and hypoalbuminemia
[5, 29, 33].
Prophylactic measures and statins
Currently there is no available treatment to reverse
contrast induced nephropathy, and therapy is aimed
at prevention. Many preventative measures, including
diuretics, mannitol, dopamine, atrial natriuretic peptide, and endothelin receptor antagonists have failed
to show benefit in randomized, controlled trials. Few
measures have shown consistent benefit in the prevention of CA-AKI [34, 35]. Statins are drugs that
have been primarily used to lower low-density lipoprotein cholesterol. However, they also possess pleiotropic effects that include enhancement of endothelial
nitric oxide production, anti-inflammatory and antioxidative action with a significant benefit in primary
and secondary cardiovascular prevention. Therefore,
statins have been considered as promising candidate
agents for the prevention of CA-AKI and have been
the target of several studies. Li and colleagues performed a meta-analysis of seven randomized controlled studies with a total of 1399 patients using
high-dose statin (defined as a daily dose of 80mg or
40mg) versus low-dose statin treatment (defined as a
daily dose of 20mg or 10mg) or placebo [36]. The
overall results based on fixed-effect model showed
that the use of short-term high-dose statin treatment
was associated with a significant reduction in risk of
CA-AKI (RR = 0.51, 95% CI 0.34–0.76, p = 0.001). The
incidence of acute renal failure requiring dialysis was
very low and was not significant different after the use
of statin. However, the authors clearly stated that there
was marked clinical heterogeneity among these
studies, indicating the need for a large definitive
randomized controlled trial. Because high-intensity
statins are indicated for atherosclerotic disease
according to clinical practice guidelines, many
patients undergoing PCI will have an indication for
the initiation and maintenance therapy with these
agents. The implementation of high-dose statin in
patients without contraindications is a Class IIa recommendation, level of evidence A in the 2014 guidelines on myocardial revascularization [37].
Nephrotoxic drugs
Although intuitive, nephrotoxic medications should
be held for several days prior to any planned contrast
exposure. The general recommendation is to hold
metformin on the day of the procedure and 48 hours
after coronary angiography. The rationale for this recommendation is that patients with diabetes have a
high risk of CA-AKI and that patients who develop
AKI while on metformin have an increased risk of
metformin-induced lactic acidosis, which is characterized by an elevated blood lactate concentration,
decreased blood pH, increased anion gap, and higher
mortality. A Cochrane meta-analysis of 347 comparative trials and cohort studies, including 143 studies
that allowed for the inclusion of patients with renal
insufficiency, showed that there were no cases of fatal
or nonfatal lactic acidosis in 70490 patient-years of
metformin use [38]. Similar questions surround the
use of angiotensin converting enzyme inhibitors. Patel
et al. published a review of five trials which revealed
discordant results, showing no clear correlation between angiotensin converting enzyme inhibitors and
the occurrence of CA-AKI [39] (Figure 24.2). A more
contemporary study, The CAPTAIN trial (Angiotensin
Converting Enzyme Inhibitors and Contrast Induced
Nephropathy in Patients Receiving a Cardiac
Catheterization) showed that in patients with
moderate renal insufficiency, holding ACE inhibitors/
ARBs before coronary angiography lowered the incidence of CA-AKI (10.9% versus 18.4%; p=0.16) and
resulted in a lower rise in mean serum creatinine [40].
Hydration
Volume expansion with oral and intravenous hydration
is the cornerstone for prevention of CA-AKI. The beneficial effects of saline hydration before and after contrast administration are thought to be due to a resultant
increase in effective renal blood flow and glomerular
filtration [3, 16, 30]. Isotonic bicarbonate, presumably
through the alkalinization of renal tubular fluid and a
subsequent reduction in free oxygen radicals, has
shown beneficial results (although mixed) in reducing
CA-AKI. A study by Merten et al. assessed the benefit
of hydration with sodium bicarbonate for the prevention of CA-AKI among patients undergoing diagnostic
or interventional procedures [41]. In this study, a total
of 119 patients were randomized to either a sodium
chloride solution or sodium bicarbonate in D5W. The
initial dose was a 3 mL/kg bolus for 1 hour immedi-
222 PART IV Wires Technique
CIN (% of Patients)
Cirit et al
35
Contrast Induced nephropathy (CIN)
Percentage of patients (%)
p=0.02
30
25
20
15
10
5
0
Figure 24.2 The rates of contrast-associated acute kidney injury (CA-AKI) in patients treated with angiotensin-converting
enzyme (green bar) and those in the control group (red bar). Adapted from Patel et al [40].)
ately before the procedure, followed by a 1 mL/kg/hour
infusion during the procedure, and lasting for 6 hours
afterwards. Despite a higher mean baseline serum creatinine level in patients randomized to the bicarbonate
arm, only 1.7% of these patients developed CA-AKI
compared to 13.6% of patients treated with sodium
chloride (p = 0.02) (Figure 24.3). Similarly, Ueda et al.
prospectively analyzed whether a bolus injection of
sodium bicarbonate given immediately before
emergent coronary angiography in patients with CKD
may prevent CA-AKI. In that trial, 59 patients were
randomized to bolus and infusion of sodium
bicarbonate or bolus and infusion of isotonic saline.
The incidence of CA-AKI was significantly lower in
the sodium bicarbonate group than in the sodium
chloride group (3.3% vs 27.6%, p = 0.01) [42].
In 2007, the Renal Insufficiency Following
Contrast Media Administration (REMEDIAL) trial
prospectively evaluated the efficacy of three preventive strategies for CA-AKI [43]. In this trial, 326
patients with chronic kidney disease scheduled for
coronary or peripheral angiography were randomly
assigned to the prophylactic administration of
29
ACE inhibitor Control
10.4
6
3.1
Gupta et al Toprak et al
normal saline infusion and N-acetylcysteine (NAC),
sodium bicarbonate infusion and NAC, or normal
saline in addition to NAC and ascorbic acid. Acute
kidney injury (CA-AKI) developed in 9.9% of the
saline and NAC group, and in 10.1% of the saline,
NAC, and ascorbic acid group (p = 1.0). In contrast,
only 1.9% of the patients assigned to the sodium
bicarbonate infusion given in conjunction with
NAC developed CA-AKI. Various meta-analysis of
randomized controlled trials have shown that intravenous bicarbonate in combination with NAC
reduced CA-AKI by 35% but did not reduce renal
failure that required dialysis in patients undergoing
catheterization or PCI [44]. The evidence that
sodium bicarbonate reduces the incidence of
CA-AKI is encouraging but more well-designed
randomized controlled trails are required to allow
definitive firm conclusion to be drawn.
In a study of 1620 patients randomized to intravenous hydration with either 0.9 or 0.45% saline at 1 ml/
kg/hr for 24 hours starting on the morning of
angioplasty [45], Mueller and colleagues found that
the incidence of CA-AKI after hydration with 0.9%
15.6
5.8
Figure 24.3 The in-hospital rates of contrast-associated acute kidney injury (CA-AKI) in patients treated with 0.9% saline
(red bar) vs those treated with bicarbonate (green bar). Adapted from Merten et al [42].)
15
10
5
0
13.6
Normal saline (n=60)
Bicarbonate (n=59)
1.7
CHAPTER 24 CTO: How to Minimize Contrast-Associated Acute Kidney Injury 223
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
saline was significantly lower (0.7 vs 2%, p = 0.04),
with the greatest benefit in women, diabetics, and
those receiving > 250 ml of contrast. Another study by
Clavijo et al. showed that the rapid administration of
1 liter of D5W given 5 minutes before coronary angiography reduced the incidence of CA-AKI from 5.7 to
1.4% (p = 0.03) [21].
Volume expansion has always been a concern, espe-
cially in an already volume overloaded heart failure
patient. The Prevention of Contrast Renal Injury with
Different Hydration Strategies (POSEIDON) trial
investigated different rates of fluid administration
guided by the left end-diastolic pressure in 396 patients
undergoing cardiac catheterization [46]. All patients
received a bolus of 0.9% normal saline 3
mL/kg for 1
hour prior to the procedure. Before the administration
of contrast, left end-diastolic pressure (LVEDP) was
measured and patients were randomized in a 1:1 ratio
to either LVEDP-guided therapy or a standard fluid
dose. In those patients randomized to the active arm
of the study, the fluid rate was 5 mL/kg/h for patients
with a LVEDP lower than 13 mm Hg, 3 mL/kg/h
for pressure of 13–18
pressure higher than 18
mm Hg, and 1.5 mL/kg/h for
mm Hg. The control group
was hydrated at 1 to 5 mL/kg per hour (n=200). The
authors concluded that CA-AKI occurred less frequently in patients in the LVEDP-guided group (6.7%)
than in the control group (16.3%) (relative risk 0.41,
95% CI: 0.22–0.79; p=0.005). Based on the results of
this trial, pre-procedural hydration in combination
with LVEDP-guided hydration has become the cornerstone for the prevention of CA-AKI. Despite
such recommendations, the A Maastricht ContrastInduced Nephropathy Guideline (AMACING) trial
challenged the notion of pre procedural hydration
for the prevention of CA-AKI [47]. The study randomly assigned 660 patients undergoing contrastenhanced procedures to receive either periprocedural
intravenous isotonic saline or no intravenous fluids.
The study was terminated prematurely and failed to
show a significant difference in the incidence of acute
kidney injury between the hydration group and the
no-hydration group (2.7% and 2.6%, respectively;
absolute difference, −0.1 percentage point; 95% CI,
−2.25 to 2.06). However, the validity of this finding
was diminished by substantial under enrollment,
low rates of intraarterial procedures (48%) and interventional procedures (16%), and moderate chronic
kidney disease in a majority of patients [47].
The use of a device that would permit a tailored
approach to hydration was tested in the recently
published Renal Insufficiency Following Contrast
Media Administration (REMEDIAL III) trial [48]. In
this study by Briguoni and colleagues, a total of 708
patients at high risk for CA-AKI were randomized to
either normal saline infusion rate adjusted according
to the LVEDP (LVEDP-guided group) or hydration
controlled by the RenalGuard System (RenalGuard
Solutions, Milford MA) in order to reach a urine
flow rate (UFR) ≥300
ml/h (UFR-guided group).
This device permits optimization of intravenous
hydration matching the patients’ urine output to
the infused volume after a fluid bolus and furosemide. By maintaining a high urine output, the renal
tubule is less exposed to contrast material (Figure
24.4). The UFR-guided hydration group received an
NS bolus followed by a weight-adjusted furosemide
bolus. Subsequent hydration was automatically regulated by the RenalGuard system. The total hydration
volume was higher in the UFR-guided group than
in the LVEDP-guided group (2,598 ± 1,349 ml vs.
1,709
± 1,116 ml; p < 0.001). The incidence of the
composite of CA-AKI and pulmonary edema was
significantly lower with the UFR-guided approach
compared with LVEDP-guided hydration (5.7% vs.
10.3%; risk ratio [RR]: 0.56; 95% confidence interval
[CI]: 0.39 to 0.79; p = 0.036). This finding was mainly
driven by prevention of CA-AKI [49]. However,
the system has not gained widespread acceptance
because of the logistic constraints involved with the
device and recent studies that failed to show a benefit
of the device in patients with moderate to severe
CKD requiring complex percutaneous coronary,
peripheral, and structural interventions [50]. Current
guidelines only recommend a reasonable hydration
regimen with isotonic crystalloid (1.0 to 1.5
mL/kg
per hour) for 3 to 12 hours before the procedure and
continuing for 6 to 24 hours after the procedure (class
of recommendation I, level of evidence B), however
most institutions have implemented more rigorous
hydration protocols.
Antioxidants
There have been over 25 studies evaluating the role of
the antioxidant N- acetylcysteine (NAC) in CA-AKI
prophylaxis. A recent meta-analysis of 13 trials with
1892 randomized patients showed a statistically nonsignificant 32% reduction in the risk for CA-AKI (RR
0.68, 95% CI 0.46–1.01) [51]. Published meta-analyses
documenting the heterogeneity between these studies
have limited the conclusions which have been drawn.
Most studies used a standard oral regimen of 600 mg
twice daily for 24 hours both on the day before and the
day of the procedure. One meta-analysis, however,
suggested a clear benefit. In a review of 26 randomized
trials involving NAC, Kelly et al. found a 38% relative
risk reduction of CA-AKI (RR 0.62; 95% CI 0.44–0.88)
[52]. However, the results were confounded by publication bias and the inclusion of trials with lower meth-
224 PART IV Wires Technique
Figure 24.4 Briguori C, D’Amore C, De Micco F, et al. Reproduced with permission from ref. (49), © 2020, Elsevier.
odological quality. More recently, the PRESERVE
(Prevention of Serious Adverse Events Following
Angiography) trial tested the efficacy of intravenous
sodium bicarbonate or oral acetylcysteine in preventing CIN [53]. This randomized controlled trial
included 5177 patients at high risk for renal complications who were scheduled for angiography. Using a
two-by-two factorial design, PRESERVE did not show
any benefit of intravenous sodium bicarbonate over
intravenous sodium chloride or of oral acetylcysteine
over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days.
At the present time, N- acetylcysteine does not offer a
significant benefit and is no longer recommended, furthermore, it’s a Class III indication in recent society
guidelines (no benefit) [54]. Occasionally it is still
being prescribed in very high-risk patients, particularly diabetic patients with chronic renal insufficiency.
The antioxidant ascorbic acid (Vitamin C) has been
shown to attenuate renal damage caused by a variety
of insults. In a randomized, double-blind, placebocontrolled trial of 231 patients treated with either
ascorbic acid or placebo, a significant reduction in the
incidence of CA-AKI was seen with the use of Vitamin
C [55]. These results were encouraging but were not
confirmed in larger clinical trials.
Contrast media type
As with various prophylactic measures, individual
contrast agents have also been evaluated to determine
their individual role in causing nephropathy.
Historically, contrast agents are composed of iodobenzene units with varying numbers of iodine molecules [3]. Increased iodine content allows for better
radiographic visualization and water solubility but
also increases the osmolarity. It is believed that certain
contrast media characteristics, such as osmolarity,
might influence the likelihood of CA-AKI in patients
at risk [3, 56, 57]. Multiple compounds with varying
properties and physiologic effects have been tested in
attempts to create radiocontrast media with high
attenuation while at the same time limiting nephrotoxicity. Early high-osmolar contrast media (HOCM)
(approximately 2000 mOsm/kg) were replaced by
low-osmolar contrast media (LOCM). While these
agents had an osmolarity 2–3 times lower than
HOCM (approximately 600–800mOsm/kg), they are
considered hyperosmolar in comparison to serum. In
a pooled analysis of 25 randomized trials, Barrett et al.
noted that HOCM posed a greater risk of CA-AKI
than LOCM in patients with pre-existing renal
dysfunction [58]. Interestingly, additional evidence
CHAPTER 24 CTO: How to Minimize Contrast-Associated Acute Kidney Injury 225
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
suggests that iso-osmolar contrast media (IOCM)
(290 mOsm/kg; iodixanol) may reduce the risk of
CA-AKI in high-risk patients even further. A metaanalysis of 16 randomized, controlled trials compared
changes in serum creatinine after administration of
the IOCM iodixanol in comparison to various LOCM
[30]. In this analysis, the overall incidence of CA-AKI
in the IOCM patients was 1.4% compared to 3.5% in
the LOCM group. The largest absolute difference was
found to be between patients with chronic kidney disease, diabetes mellitus, or a combination of the two.
As compared with high-osmolality contrast agents,
low-osmolality and iso-osmolality agents are associated with a lower risk of kidney injury and their use is
now recommended (class I recommendation, level of
evidence A) by the European Society of Cardiology
and the American Heart Association–American
College of Cardiology [37].
Contrast volume
Like osmolarity, the volume of contrast medium
administered during coronary angiography has been
found to correlate with the incidence of CA-AKI [1–
5, 22, 26, 27, 33]. In a study of 183 patients undergoing cardiac catheterization, Rich et al. found that
a contrast volume of > 200
risk factor for nephrotoxicity (RR 2.1, p = 0.005)
[29]. Many times, however, the total contrast volume
utilized is not found to be a statistically significant
univariate predictor of CA-AKI. The reason for this
may be related to a dose-dependent effect of intravenous contrast, which may differ in relation to
body weight and creatinine clearance. Cigarroa et al.
derived a formula to calculate a contrast “limit” (5
ml of contrast * kg of body weight)/ serum creatinine
(mg/dL)) [59]. This study found that the incidence
of CA-AKI is rare when adhering to this formula.
Morcos proposed that with the administration of
less nephrotoxic LOCM, the limits as defined by
the Cigarroa formula can be expanded by a factor
of 1.5 [60]. Similar findings have been documented
using other formulas, including the ratio of contrast
volume used to estimated glomerular filtration rates
(CV/eGFR) [45]. In a study by Liu et al., a CV/eGFR
> 2.39 was an independent predictor of CA-AKI after
PCI in patients with ST-elevation myocardial infarction (OR 4.24; 95% CI 1.23–14.66) [61]. Regardless,
multiple studies documenting the odds ratio for
contrast dose and nephropathy requiring hemodialysis found this risk to be very low [22, 33, 62]. Rihal
et al. noted in a study of 7586 patients, that for each
100 mL of contrast utilized during PCI, there was an
associated increased risk of acute renal failure with
an odds ratio of 1.12 [1]. A retrospective analysis of
ml was an independent
nearly 17,000 coronary interventions was performed
by Freeman et al. to define a weight and creatinine
adjusted maximum radiographic contrast dose
(MRCD) [33]. After adjustment for baseline risk
factors, contrast volume above a predefined MRCD
was the strongest independent predictor of nephropathy requiring dialysis (OR 6.2, 95% CI, 3.0–12.8).
In addition, in-hospital mortality was significantly
higher in patients who exceeded the MRCD compared with those who did not. This “threshold”
effect, rather than a linear dose effect, has been
noted in other studies as well [59]. Gurm and colleagues from the Blue Cross Blue Shield of Michigan
Cardiovascular Consortium registry assessed the
association between calculated creatine clearance
and the risk of CA-AKI. The risk for CA-AKI and
the need for dialysis approached significance when
the ratio of contrast volume/calculated creatine
clearance (CV/CCC) exceeded 2 and was dramatically elevated in patients the ratio of 3 (adjusted OR
for CA-AKI: 1.46, 95% CI: 1.27 to 1.66) [63]. Because
creatinine clearance and glomerular filtration rate
are now routinely calculated for hospitalized patients
undergoing invasive cardiac procedures, the use of
the CV/CCC ratio can be easily incorporated into
clinical practice and should be used routinely in all
patients undergoing contrast-based procedures.
Ultra-low and zero contrast volume
Recent studies have assessed the feasibility and safety
of ultra-low contrast volumes, usually defined as contrast volume less than or equal to the patients’ estimated creatinine clearance (CV/eCC<1). In a
retrospective analysis of 75,393 patients undergoing
PCI between July 2014 and June 2017 from the Blue
Cross Blue Shield of Michigan Cardiovascular
Consortium registry, the use of ultra-low volume of
contrast was associated with a meaningful reduction
in CA-AKI when compared with patients treated with
a low CV/eCC (1–3) or high CV/eCC (>3) (1.5% vs.
2.3% vs. 7.7%) and the need for dialysis replacement
therapy [64] (Figure 24.5). The use of minimal contrast volumes or even no contrast (zero contrast PCI)
using intravascular ultrasound and intracoronary
physiology to guide successful stent implantation has
also shown encouraging results [65, 66]. A meta-analysis of four studies that comprised 1975 patients
showed that intravascular ultrasound-guided CTOPCI had similar all-cause mortality, major adverse
cardiac events and cardiovascular mortality when
compared with angiography-guided CTO-PCI [67].
Furthermore, it was associated with lower risk of stent
thrombosis, shorter procedure time and less contrast
volume use (P<0.001). The idea of using intravascular
226 PART IV Wires Technique
DialysisAcute Kidney Injury
ACUTE KIDNEY INJURY
Percentage of Patients
9
8
7
6
5
4
3
2
1
0
Figure 24.5 The rates of CA-AKI and dialysis in patients treated with different contrast volumes. Ultra-low volume of
contrast to estimated creatinine clearance (CV/eCC) (Blue bars); low CV/eCC (1-3) (red bars) or high CV/eCC (>3) (green
bars). Contrast associated acute kidney injury (CA-AKI). Adapted from Merten et al [42].
P<0.0001 p=0.009
1.47
CV/eCC <1 CV/eCC 1-3 CV/eCC >3
7.69
2.27
0.1
1.4
0.2
ultrasound-guided low-contrast coronary interventions can be applied not only to the population with
CKD but also to other patients who have risk factors
to develop CA-AKI after PCI. Thus, patients having
either advanced age, diabetes mellitus, intra-aortic
balloon pump use, cardiogenic shock, or a high
number of revascularized vessels could potentially
benefit from minimum- or zero-contrast intravascular ultrasound-guided PCI.
Hemofiltration
Continuous veno-venous hemofiltration is a form of
renal-replacement therapy used in acute renal failure
patients and has been evaluated as an alternative
strategy for the prevention of CA-AKI in high-risk
patients. In a randomized study by Marenzi and colleagues, 114 consecutive patients with chronic renal
failure (serum creatinine >2mg/dL) undergoing coronary interventions were randomly assigned to either
hemofiltration or isotonic-saline hydration at a rate of
1ml/kg per hour [68]. Treatment was initiated 4 to 8
hours before the coronary intervention and continued
for 18 to 24 hours after the procedure was completed.
An increase in the serum creatinine concentration of
more than 25% from the base-line value occurred less
frequently among the patients in the hemofiltration
group than among the control patients (5% vs. 50%,
p<0.001). Temporary renal-replacement therapy
(hemodialysis or hemofiltration) was required in 25%
of the control patients and in 3 percent of the patients
in the hemofiltration group. This data was corroborated by other studies in high-risk populations by the
same group of investigators. However, a systematic
review of nine randomized controlled and 2 nonrandomized trials (8 using hemodialysis and 3 hemofiltration) that comprised a total of 1010 patients did not
show a benefit or a reduction in the incidence of
CA-AKI when compared with standard medical
therapy [69]. Because of lack of definite data, neither
acute dialysis nor continuous renal replacement
therapy should be performed prior to PCI, regardless
of residual kidney function, and are currently considered a Class III indication, level of evidence B [37].
Contrast removal
Most of the contrast medium injected into the coronary arteries during coronary angiography is thought
to drain into the coronary sinus. Although still exper-
CHAPTER 24 CTO: How to Minimize Contrast-Associated Acute Kidney Injury 227
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
imental, novel methods are being devised to enable
cannulation of the coronary sinus and to detect,
capture, and remove contrast material before it enters
the systemic circulation and reaches the kidneys [70,
71]. The first human study of this kind was published
by Danenberg et al. [72]. In this original study, seven
patients with chronic kidney disease (serum creatinine 2.96±0.63mg/dl) referred for coronary angiography underwent cannulation of the coronary sinus
with a two-lumen, balloon-tipped 7 F Reverse Berman
Catheter (Arrow International Inc., Reading, PA). In
four patients, adequate positioning of the Reverse
Berman catheter within the coronary sinus was not
possible. In the other three patients, however, the
authors were able to retrieve 44% of the injected contrast material. Furthermore, they reported an additive
effect of coronary sinus blockade allowing for a
smaller volume of contrast material to be used. The
increased venous pressure associated with coronary
sinus occlusion at the time of contrast injection
reduced coronary flow rates, allowing for the use of
smaller contrast volumes. A more contemporary
study by Ali Diab and colleagues, in 18 high-risk
patients that underwent coronary sinus aspiration,
there was only one case of CA-AKI (5.6%) compared
with 9 (36%) out of 25 control subjects matched cases
[73]. The DyeVert™ Plus EZ Contrast Reduction
System (Osprey Medical, Minnetonka, MN, USA) is a
medical device designed to reduce contrast volume
administered to patients during cardiac catheterization. The device has a valve that automatically diverts
some of the contrast material away from the patient
and into a reservoir chamber when the manual injection pressure exceeds a threshold. Published studies
have demonstrated that the DyeVert™ System effectively reduces the volume of contrast delivered to
patients undergoing coronary angiography and/or
PCI while preserving adequate image quality [74]. A
recent review of 17 studies involving 1731 cases where
the DyeVert™ System was used demonstrated an absolute risk reduction in the incidence CA-AKI of 5.0%
(95% CI, 0.40–9.80%; P = 0.03) and a relative risk 0.60
(95% CI, 0.40–0.90; P = 0.01) when compared with
1387 cases where the system was not used [75].
Ongoing studies will provide more data on the potential benefits of this device.
New horizons: Impella and
percutaneous left ventricular
support devices
Short-term support with percutaneous left ventricular
assist devices is emerging as an effective strategy to
maintain hemodynamic stability and protect endorgan function during high-risk PCI. Flaherty and
colleagues initially reported on 230 patients that
underwent high-risk PCI with partial hemodynamic
support provided by the continuous flow, microaxial
Impella 2.5 (Abiomed Inc., Danvers, MA) [76]. In this
analysis, CA-AKI occurred in 6 (5.2%) Impellasupported patients and 32 (27.8%) patients without
Impella support. The Global cVAD Renal Protection
Study assessed the impact of the Impella in 223 prospectively treated patients who underwent high-risk
PCI and were deemed to be at high risk for CA-AKI
(any increase in serum creatinine ≥0.3 mg/dL or a 1.5to 2.0-fold relative increase from baseline at 48 hours)
[77]. Impella support significantly reduced the occurrence of CA-AKI in patients with CKD and severely
reduced left ventricular systolic function. CA-AKI
occurred in 4.9% of the patients compared with predicted rate of ~22% for this patient population.
Remarkably, this represents a 77.6% lower CA-AKI
rate relative to the predicted rate by Mehran risk scoring (p<0.0001). The renal protective effect of Impella
support persisted with a 50% lower risk of CA-AKI
observed in those patients at the highest risk for AKI
with a Mehran score≥16 (28.6% observed AKI incidence vs. 57.3% predicted, p=0.008). Despite these
encouraging results, currently there is no clear evidence that short-term hemodynamic support with
percutaneous left ventricular assist devices is sufficient
to protect against CA-AKI during high-risk PCI.
Summary
A decline in kidney function following contrast-based
angiography and percutaneous interventions is still
a major cause of morbidity and mortality. Patients
undergoing CTO-PCI are not exempt. On the contrary, because of the complex nature of the disease
and procedure, they may be at a higher risk of getting
exposed to a higher volume of contrast and radiation.
Therefore, every effort should be made to identify
patients that may be at heightened risk of developing
CA-AKI, preferably using the Mehran CA-AKI risk
calculator. There are multiple options as seen in
Figure 24.6 [78]. However, how can we minimize the
risk of CA-AKI in patients undergoing CTO-PCI? First,
adequate protocol-guided, pre-procedural volume
expansion with normal saline in combination with
intra-procedural LVEDP-guided fluid administration
has become the cornerstone for the prevention of
CA-AKI. Second, every effort should be made to use
the lowest possible contrast volume, ideally ultra-low
contrast volume, defined as contrast volume less than
or equal to the estimated creatinine clearance or eGFR.
The implementation of high-dose statin before diagnostic catheterization has been shown to reduce the
incidence of CA-AKI and should also be considered,
Соседние файлы в папке Библиотека им академика М.И. Перельмана