Author + information
- Received June 6, 2012
- Revision received October 24, 2012
- Accepted November 8, 2012
- Published online April 1, 2013.
- Hitinder S. Gurm, MD⁎,⁎ (, )
- Dean Smith, PhD, MPH⁎,
- David Share, MD†,
- David Wohns, MD‡,
- John Collins, MD§,
- Mohan Madala, MD∥,
- Srinivas Koneru, MD¶,
- Dan Menees, MD⁎ and
- Stanley Chetcuti, MD⁎
- ↵⁎Reprint requests and correspondence:
Dr. Hitinder S. Gurm, University of Michigan Cardiovascular Center, Division of Cardiovascular Medicine, 1500 East Medical Center Drive, Room 2A394, Ann Arbor, Michigan 48109-5869
Objectives The purpose of this study was to assess the impact of manual versus automated contrast injection on renal complications in patients undergoing percutaneous coronary intervention (PCI).
Background Contrast volume is a major modifiable risk factor for contrast-induced nephropathy (CIN). Automated contrast injector systems (ACIS) are believed to be associated with a reduction in the total volume of contrast media use.
Methods We compared the outcome of 60,884 patients who underwent PCI at 28 hospitals in Michigan in 2008 to 2009 and assessed the outcome of those treated at hospitals that did not use ACIS (n = 24) and compared them with those that used ACIS (n = 4). Propensity matching was used to adjust for baseline differences.
Results The use of ACIS was associated with a statistically significant albeit clinically small difference in the average volume of contrast media use (mean 199 ± 84 ml vs. mean 204 ± 82 ml, p < 0.0001) with no difference in proportion of patients exceeding contrast volume/calculated creatinine clearance ratio of 3 (28.4% vs. 29.1%, p = 0.19). There was no difference in the incidence of CIN (3.11% vs. 3.42%, p = 0.15) or new need for dialysis (0.30% vs. 0.33%, p = 0.54), and these differences remained nonsignificant in propensity matched analysis. In fully adjusted, multivariate logistic analysis, patients treated with ACIS remained as likely to develop CIN (odds ratio: 0.96, 95% confidence interval: 0.83 to 1.11, p = 0.56) or new need for dialysis (odds ratio: 0.83, 95% confidence interval: 0.54 to 1.28, p = 0.40).
Conclusions Compared with hospitals using manual injection, institutions having ACIS used slightly less amount of contrast with no reduction in CIN. Use of ACIS is unlikely to impact contrast-induced renal complications in patients undergoing PCI.
- automated contrast injector system (ACIS)
- contrast-induced nephropathy (CIN)
- percutaneous coronary intervention (PCI)
Contrast-induced nephropathy (CIN) is a common complication in patients undergoing percutaneous coronary intervention (PCI) and is associated with increased morbidity, mortality, and healthcare expense (1–3). Multiple strategies have been advocated for prophylaxis of CIN, but the only proven strategies are adequate hydration, minimization of contrast dose, and the use of iso-osmolar or certain low-osmolar contrast media (4–8). The impact of contrast dose has been evaluated in multiple studies, and patients receiving high doses of contrast seem to be at greater risk of CIN and need for dialysis. Although multiple different thresholds have been explored for estimating safe dose of contrast media, there seems to be no dose of contrast that is free of risk, and a strategy of limiting contrast with as little as safely possible has been advocated (9). Practical strategies to limit contrast media include use of biplane angiography, selective avoidance of left ventriculography, and minimization of coronary injections. Automated contrast injector systems (ACIS) have been promoted as a strategy to reduce contrast use and are assumed to be effective in reducing renal complications in patients undergoing contrast-based procedures. However, this assumption is based on small single-center studies, and there is a paucity of data on the clinical effectiveness of ACIS with respect to reducing contrast use and associated improvement in clinical outcome (10–12). The goal of our study was to assess the clinical utility of ACIS across a broad population of patients undergoing PCI in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2)—a large multicenter quality improvement collaborative.
Data sources and study population
We examined the outcome of 60,884 patients who were treated in 2008 to 2009 at the hospitals participating in the BMC2 and assessed the outcome of those treated at hospitals that did not use ACIS (n = 24) and compared them with those that used ACIS (n = 4). Hospitals that initiated use of ACIS during the study period or used both ACIS and manual injection were excluded (n = 5). The details of the BMC2 and its data collection and auditing process have been described previously (13). The BMC2 is a physician-run quality improvement collaborative that is supported by but independent of the funding agency, Blue Cross Blue Shield of Michigan. A physician advisory committee is responsible for setting the quality goals and developing quality improvement efforts without any input from or sharing of data with the study sponsor. Procedural data on all consecutive patients undergoing PCI at participating hospitals are collected with standardized data collection forms. Baseline data include clinical, demographic, procedural, and angiographic characteristics as well as medications used before, during, and after the procedure and in-hospital outcomes. All data elements have been prospectively defined, and the protocol is approved by local institutional review boards at each hospitals. In addition to a random audit of 2% of all cases, medical records of all patients undergoing multiple procedures or coronary artery bypass grafting (CABG) and of patients who died in the hospital are reviewed routinely to ensure data accuracy. The study population for this analysis included all consecutive patients who underwent PCI between January 1, 2008, and December 31, 2009. Patients who were already on a dialysis regimen at the time of the procedure or those with missing serum creatinine pre- or post-procedure were excluded from outcome analysis. The type of contrast media and hydration protocols used were as per the operator preference guided by institutional policy and practice.
Our study had 3 endpoints for this analysis: procedural contrast volume, CIN, and nephropathy requiring dialysis (NRD). Contrast-induced nephropathy was defined as impairment in renal function resulting in ≥0.5 mg/dl absolute increase in serum creatinine from baseline (14). Baseline creatinine was collected within 1 month of the procedure. Among patients who had multiple assessments of serum creatinine in the 30 days before the procedure, the value closest to the time of the procedure was considered as the baseline value. Peak creatinine was defined as the highest value of creatinine in the week after the procedure and was ascertained as per local clinical practice. Peak creatinine was collected at least 1 day post-procedure but varied, depending on length of stay. Nephropathy requiring dialysis was defined as new, unplanned need for hemodialysis during the hospital stay due to worsening of renal function after PCI.
We separated patients into 2 categories: those treated at institutions that used ACIS universally; and those treated at institutions that did not have ACIS. Differences in discrete variables between patients treated with ACIS and those who were not were evaluated by the chi-square test and Fisher exact test. Continuous variables were expressed as mean ± SD, and discrete variables were expressed as frequency counts and percentages. Continuous variables were analyzed with the Student t test.
We compared the difference in total contrast volume and the proportion of patients exceeding a contrast volume/calculated creatinine clearance ratio of 3 among patients treated with ACIS versus those not treated with ACIS. We assessed the independent impact of ACIS use on outcome by multivariable adjustment for differences in baseline factors (but excluding contrast volume). Separate models were developed for CIN and NRD.
Furthermore, to account for the multiple differences between patients treated with and patients treated without ACIS, we used propensity matching. A propensity score for receiving ACIS was calculated with a non-parsimonious logistic regression model created from several pre-procedural patient characteristics. These patient characteristics included age, sex, serum creatinine, anemia, calculated creatinine clearance rate, smoking status, history of hypertension, diabetes, prior myocardial infarction, congestive heart failure, prior coronary revascularization (PCI or CABG), atrial fibrillation, peripheral vascular disease, history of stroke or transient ischemic attack, chronic obstructive pulmonary disease, left ventricular ejection function, and acuity of cardiac illness at presentation. Greedy matching technique was then used to match a patient receiving ACIS to a patient with the nearest propensity score who did not receive ACIS to permit adequate comparison of similar patients. Matching adequacy was confirmed by calculating the standardized differences for baseline variables among the matched subset with a standardized difference of <10% suggesting adequate matching and by assessing for differences in outcomes that would not be expected to be influenced by ACIS use (vascular complications and need for CABG). The study endpoints were then compared within this propensity-matched cohort with paired testing (15). We further evaluated differences in outcomes among several key, high-risk patient subgroups, including patients with abnormal renal function at baseline, diabetes, and anemia and patients treated with low osmolar contrast media. Glomerular filtration rate was estimated with the Modification of Diet in Renal Disease equation (16). The SAS software (version 9.2, SAS, Cary, North Carolina) was used for all analyses.
Our study cohort comprised 60,884 patients, of whom 9,995 were treated at institutions with ACIS, and 50,889 were treated at institutions that did not use ACIS. The baseline demographic characteristics, comorbidities, and select laboratory variables are presented in Table 1. Patients treated with ACIS were slightly younger, less likely to have hypertension, and more likely to have had a recent myocardial infarction. There was no difference in the baseline serum creatinine. The fluoroscopic time was shorter in patients treated with ACIS.
The mean contrast volume in the ACIS group was 199 ± 84 ml compared with a mean of 204 ± 82 ml in patients treated without ACIS (p < 0.0001). The proportion of patients exceeding contrast volume/calculated creatinine clearance of 3 was similar at institutions using ACIS (28.4% vs. 29.1%, p = 0.19). There was no difference in the incidence of CIN (3.11% vs. 3.42%, p = 0.15) or NRD (0.30% vs. 0.33%, p = 0.54). No difference was noted with respect to in-hospital mortality or need for CABG (Fig. 1).
After multivariate adjustment, there was no difference in the odds of CIN (odds ratio: 0.96, 95% confidence interval: 0.83 to 1.11, p = 0.56) or new need for dialysis (odds ratio: 0.83, 95% confidence interval: 0.54 to 1.28, p = 0.40) with ACIS compared with no ACIS.
The baseline comparison of the propensity-matched cohort is provided in Table 2. The 2 groups (ACIS vs. no ACIS) were wellmatched, and no major differences were noted with respect to any of the variables. The use of ACIS was associated with a similar incidence of CIN (3.17% vs. 2.91%, p = 0.34) and a similar incidence of NRD (0.28 vs. 0.18, p = 0.17). There was no difference in the propensity-matched group with respect to death (1.35% vs. 1.13%, p = 0.14), CABG (1.14% vs. 0.90%, p = 0.10), or transfusion (4.44% vs. 3.93%, p = 0.08), but a higher incidence of vascular complications was noted in patients treated with ACIS (2.63% vs. 1.84%, p = 0.0002).
When we evaluated the outcome in the different pre-specified subgroups, a reduction in CIN with ACIS was identified in patients who were treated with iodixanol, whereas an increase in CIN was identified in patients with moderately impaired renal function (Fig. 2). The number of events was too low for a reliable subgroup analysis for NRD.
Finally, when we assessed the renal outcomes in the unmatched data (results not shown) or in the matched data by stratifying patients by length of stay, there was no difference in CIN among patients with length of stay of 2 days (0.52% vs. 0.65%, p = 0.40), those discharged after a length of stay of 3 days (1.70% vs. 2.04%, p = 0.52), and those whose hospital stay exceeded 3 days (10.25% vs. 12.22%, p = 0.07).
The key finding of our study is that use of ACIS in our study population is not associated with a clinically meaningful reduction in the volume of contrast media or in reduction in the incidence of CIN or NRD. The outcomes in patients treated with ACIS were broadly similar to those in patients treated with manual injection and there was only a marginal suggestion of benefit of 1 versus the other strategy in certain subgroups.
Our findings are important for many reasons. Automated contrast injector systems have been promoted as a means to reduce the total amount of contrast used at a given institution and per patient. Although our study cannot evaluate the amount of total contrast consumption at a given institution, we did not find a clinically relevant reduction in contrast dose for the average patients with ACIS. These findings call into question the utility of the ACIS as a renal-protective strategy.
The prior work related to use of ACIS is restricted to few small studies, and the results were substantively different from those observed in our study. Anne et al. (10) randomized 453 patients to manual injection versus ACIS and found a substantial decrease in the amount of contrast used for both patients who underwent diagnostic angiography only (mean 130 ± 60 ml vs. 257 ± 64 ml) and those who underwent diagnostic catheterization and PCI (mean 228 ± 90 ml vs. 350 ± 94 ml). It is noteworthy that the average amount of contrast used in the manual injection arm of this study was significantly higher than the amount used in our patient population. Furthermore, Brosh et al. (11) demonstrated that the difference between the total amounts of contrast used was driven in large part by a difference in amount of contrast wasted, although they also noted slightly lower contrast administered to patients undergoing diagnostic angiography with ACIS but not in those undergoing PCI. The impact of using ACIS on clinical outcomes was assessed by Call et al. (12). They compared the incidence of CIN among 1,798 patients treated at their institution over a 2-year period before the introduction of ACIS with 377 patients who were treated after the introduction of ACIS. They noticed a decline in total contrast use from an average of 204 to 146 ml and a corresponding decline in CIN from 19.3% to 13.3%.
The results of our study are in distinct contrast with the findings from these studies. The findings of our study suggest that the old-fashioned manual injection is equally effective at controlling the amount of contrast use in this patient population. Substantial reduction in the amount of contrast used/case requires forgoing procedures, such as left ventriculography or aortography, and limiting the total number of contrast injections. It is unlikely that the total amount used/injection can make a significant difference to the total contrast use, provided the aforementioned measures are used. Finally, the BMC2 collaborative has been engaged in a long-standing effort to reduce procedural complications, including CIN, and it is possible that most institutions and operators were actively working toward minimizing contrast use. Such efforts would translate into reduction in use of contrast in all patients and would minimize any expected benefit of ACIS.
Although observational data in general cannot supplant clinical trials, large studies such as ours can be helpful in complementing randomized trials, particularly when the randomized studies are small or reflect experience of select centers. The results of our study suggest that institutional use of ACIS does not automatically translate into a reduction in renal complications, and similar outcomes can be obtained with manual injection. Automated contrast injector systems might have other benefits, such as allowing use of smaller bore catheters for diagnostic angiography and cost savings in association with reduction in total amount of contrast used. However, the use of ACIS cannot be recommended specifically for renal protection.
Our subgroup analysis did find significant differences in 2 groups of patients, a higher risk of CIN with ACIS in those with a creatinine clearance of 30 to 60 ml/min/m2 and a lower risk in those treated with iodixanol. The most likely reason for this is that this simply reflects a chance finding, because no adjustment for multiple comparisons was performed. However, these subgroups might be worthy of further study.
The BMC2-PCI registry is a regional database with an active focus on multicentric quality improvement and might or might not be representative of the wider population of patients undergoing PCI in the United States (17). Nevertheless, the registry is comprehensive in that it includes almost all PCIs performed in the state of Michigan. The study was also subject to unmeasured residual confounding, despite propensity-matched analyses that might influence any of the noted associations. We did notice a difference in vascular complications in the propensity-matched groups that might suggest differences in practice or inability to fully adjust for patient-level factors. There might be variance in other aspects of care, such as differences in hydration policies, staging of procedures, or use of left ventriculography or aortography across the 2 hospital cohorts that were not adjusted for. Finally, the term CIN implies that contrast media are solely responsible for all cases of renal dysfunction occurring in this population, although this is probably incorrect. We elected to use this term, because there is no widely accepted alternative.
Compared with hospitals using manual injection, institutions having ACIS used slightly lower amount of contrast with no difference in CIN or NRD. Use of ACIS is unlikely to impact contrast-induced renal complications in patients undergoing PCI.
The Blue Cross Blue Shield of Michigan Cardiovascular Consortium registry is funded by Blue Cross Blue Shield of Michigan. The sponsor had no role in analysis, study design, or decision to publish these results. Dr. Gurm receives research funding from Blue Cross Blue Shield of Michigan and the National Institutes of Health. Dr. Share is employed by Blue Cross Blue Shield of Michigan. Dr. Chetcuti has received funding for the multicenter study Core Valve Pivotal Study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- automated contrast injector systems
- coronary artery bypass grafting
- contrast-induced nephropathy
- nephropathy requiring dialysis
- percutaneous coronary intervention
- Received June 6, 2012.
- Revision received October 24, 2012.
- Accepted November 8, 2012.
- American College of Cardiology Foundation
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