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DOI: 10.1148/radiol.2433060536
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(Radiology 2007;243:812-819.)
© RSNA, 2007

Neuroradiology

Complications of Diagnostic Cerebral Angiography: Evaluation of 19 826 Consecutive Patients1

Timothy J. Kaufmann, MD, John Huston, III, MD, Jay N. Mandrekar, PhD, Cathy D. Schleck, BS, Kent R. Thielen, MD, and David F. Kallmes, MD

1 From the Department of Radiology, Mayo Clinic, Mayo E2, 200 1st St SW, Rochester, MN 55905. Received March 25, 2006; revision requested May 26; revision received August 6; accepted September 7; final version accepted, October 19. Address correspondence to T.J.K. (e-mail: Kaufmann.timothy@mayo.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Purpose: To retrospectively evaluate the complications of diagnostic cerebral catheter angiography in 19 826 consecutive patients.

Materials and Methods: This HIPAA-compliant study had institutional review board approval, with waiver of informed consent. Demographic, procedural, and complication data in 19 826 consecutive patients undergoing diagnostic cerebral angiography at one institution from 1981 through 2003 were retrospectively reviewed. Neurologic, systemic, and local complications were recorded on the basis of clinical follow-up results after each angiographic examination. Events that occurred within 24 hours of angiography were considered to be complications of the procedure. Multivariable analysis was employed to identify patient and procedural factors significantly associated with neurologic complications.

Results: Neurologic complications occurred in 522 examinations (2.63%), and 27 of these (0.14%) were strokes with permanent disability. Twelve deaths occurred (0.06%). Access-site hematoma was the most common complication overall (4.2%). Factors independently associated with an increased risk of neurologic complication included the indication of atherosclerotic cerebrovascular disease (odds ratio [OR], 2.494), the indication of subarachnoid hemorrhage (OR, 2.523), and the comorbidity of frequent transient ischemic attack (OR, 1.674). Factors independently associated with a decreased risk of neurologic complication were increasing chronologic year in which the procedure was performed (OR, 0.659 per 5-year interval) and involvement of a trainee in the procedure (OR, 0.710).

Conclusion: In this review, diagnostic catheter cerebral angiography was found to have relatively low complication rates.

© RSNA, 2007


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Cerebral angiography has historically been central in the diagnosis, planning of treatment, and treatment of many central nervous system diseases. However, it is an invasive test with potentially severe complications, and the choice of an imaging test in the work-up of central nervous system disease should be accompanied by an accurate assessment of its complication risks.

Estimates of the complication rates of cerebral angiography published in approximately the past 20 years have been based on limited patient numbers (1–5). The largest of these referenced studies was based on 2899 consecutive examinations, and its authors also provide a concise summary of other published literature on cerebral angiography complications (4). A meta-analysis has been performed, combining data from 3517 patients (6). The purpose of our study was to retrospectively evaluate the complications of diagnostic catheter cerebral angiography on the basis of data in 19 826 consecutive patients.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Our Health Insurance Portability and Accountability Act–compliant study was approved by the institutional review board. Informed consent was waived by our institutional review board because we included only those patients who had previously provided authorization for use of their medical records for research. We retrospectively evaluated prospectively completed data forms for 23 416 consecutive diagnostic cerebral angiography examinations that were performed in 19 826 patients at our tertiary-quaternary medical center from 1981 through 2003. All patients undergoing diagnostic cerebral angiography in this period were included—both inpatients and outpatients. Interventional or therapeutic procedures, venography, and spinal angiography were not included.

Of these 23 416 examinations, 529 were associated with neurologic complications in 522 patients. For these 522 patients, only their first examination with a neurologic complication was included in the data set. For patients without a neurologic complication, only their first examination was included in the data set. The study data set then consisted of 19 826 examinations in 19 826 patients. These data included the first 1517 procedures, reported in 1984, in our institution (3), and the data sheets and methods of analysis are similar to those described in the previous publication. At our institution, nearly all patients referred for cerebral angiography have been evaluated by staff members of the neurology or neurosurgery services before the procedure.

Angiography Procedure
Information regarding the use of moderate sedation was not included in the data sheets, so exact tabulation of the number of patients receiving moderate sedation was not possible. However, from knowledge of general practice guidelines at our institution, most patients in the study period received moderate sedation, administered either by a radiology nurse or by the anesthesiology service, with intraprocedural cardiovascular monitoring. Cerebral angiography was performed by a staff neuroradiologist or by a resident physician or fellow under the direct supervision of a staff neuroradiologist. The angiographic technique has remained relatively unchanged over time, except that catheters and guidewires have been updated. Commonly used catheters have been 5-F 45° hockey stick–shaped, Simmons curve, vertebral, and pigtail catheters (the latter for aortic arch injections). A continuous catheter flush system with heparinized saline has been employed in our institution since 1990. The replacement of manual subtraction angiography by digital subtraction angiography began at our institution in 1993, and this transition was mostly completed by 1997.

Regarding the use of intravenous heparin boluses during angiography, the general clinical practice of angiographers over the study period was mixed. Some routinely administered a heparin bolus during angiography, and others did not. Exact tabulation of the use of intravenous heparin boluses was not possible because this was not recorded in the data sheets. Because the method of arteriotomy hemostasis was not included in the data sheets, exact tabulation of the number of patients who underwent manual groin compression relative to the number who underwent arteriotomy device closure was impossible. The general clinical practice at our institution, however, has been to use manual groin compression at the conclusion of diagnostic cerebral angiography.

Patients were monitored in a recovery area for 30–60 minutes after hemostasis was achieved and then were observed during flat bed rest for a total of 4 hours after hemostasis. Patients who were discharged on the day of the procedure underwent neurologic and peripheral vascular examination performed by staff members of the neuroradiology service at the time of discharge. For inpatients, the examination was performed on the morning after the procedure by staff members of the neuroradiology service and the referring service. Outpatients were telephoned at home by a registered nurse 1 day after the procedure to inquire about any complications.

Data Collection and Complications
Data sheets (Table 1) were begun for all patients at the time of angiography and were completed at the 24-hour evaluation unless there was a neurologic complication; in that instance, clinical follow-up was continued for at least 7 days after the procedure. Over the course of the study, data sheets were completed on weekdays mostly by one registered nurse whose job description included overseeing this database. During her absences, other radiology nurses would complete the data sheets. On weekends, radiology residents completed the sheets for all inpatients who had undergone angiography on the previous day.


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  		Table 1. Information on Cerebral Angiography Data Sheets

 
Any change in a patient's neurologic status, whether subjective or objective, and whether or not it was thought to be directly related to cerebral angiography, was recorded as a complication of angiography if it occurred within 24 hours of the examination. The medical charts of those patients who died within 24 hours of angiography were individually reviewed.

Statistical Analysis
Descriptive statistics of patient and procedural characteristics and complications were calculated. Univariate and multivariate analyses relating patient and procedural characteristics with complications were performed. Twenty of 19 826 patients had no listed birthdate and were excluded from multivariate models. Neurologic complications, including TIA, reversible ischemic neurologic deficit (RIND), stroke, and death related to a neurologic cause (10 of the 12 instances of death), were grouped as an outcome variable. The predictor variables of age, sex, individual risk factors, indication for the procedure, serum creatinine level, contrast agent type, contrast agent amount, number of catheters used, resident or fellow involvement, and date of procedure were tested for association with the outcome variable of neurologic complication in univariate logistic analysis. Odds ratios (ORs) were estimated, along with their 95% confidence intervals. The indication of tumor was the reference variable used for the indication for angiography. Of these predictor variables, those with a P value of less than .10 in univariate logistic analysis were considered as potential predictors in further multivariate logistic regression model building with neurologic complication as the outcome variable.

Statistical tests were two sided, and P values less than .05 were considered to indicate a statistically significant difference. All of the statistical analyses were performed by using a commercially available software program (SAS, version 8.0; SAS Institute, Cary, NC).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Patients and Procedural Characteristics
Mean patient age was 52.9 years, and 54.7% of examinations involved male patients (Table 2). Overall, atherosclerotic cerebrovascular disease was the most common indication, for 38.4% of procedures. Hypertension was the most common comorbidity or risk factor, being present in 31.0% of patients. A trainee (resident and/or fellow) was present at 27.6% of examinations. The vast majority of approaches were retrograde femoral (97.8%). A single catheter was used in the majority of examinations (68.4%). Iopamidol (Isovue 4) and iothalamate meglumine (Conray 60) were the most common contrast medium types used (in 47.6% and 43.4% of procedures, respectively), although iohexol (Omnipaque 300) is what we currently use in nearly all examinations. The mean amount of contrast material used was 74.7 mL.


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  		Table 2. Patient and Procedure Characteristics

 
Complications
The most common complication was groin hematoma (4.2% of examinations); other, more serious groin complications were rare (Table 3). Nausea, vomiting, and/or transient hypotension was the most common systemic complication (1.2%), and anaphylaxis and death were rare (0.03% and 0.06%, respectively). Neurologic events occurred within 24 hours of the procedure in 2.63% of examinations, and they were considered to be complications of angiography for the purposes of this study by virtue of their timing. Of the 12 deaths, 10 were deemed to have a primary neurologic cause, although the majority of these patients had severe preprocedure neurologic morbidity, which was the indication for their angiographic examinations. The majority of neurologic complications were transient or reversible: TIA, 2.09%; RIND, 0.36%. Permanent stroke, without death, was seen after 0.14% of examinations.


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  		Table 3. Complications of 19 826 Cerebral Angiography Procedures

 
Hemiparesis was the most common neurologic complication, and aphasia the second most common, for TIA, RIND, and stroke (Table 4). The indication (Table 5) with the highest rate of neurologic complication was also the most common indication—namely, atherosclerotic cerebrovascular disease (4.0% of examinations in patients with this indication resulted in neurologic complications). Subarachnoid hemorrhage followed as the indication with the second-highest rate of neurologic complications (3.2% of examinations in patients with this indication resulted in neurologic complications). Neurologic complications were more likely to occur in the earlier time periods of the study than in the later time periods: Neurologic complications occurred in 342 of 9066 (3.8%) examinations performed between 1980 and 1988, in 162 of 7595 (2.1%) examinations performed between 1989 and 1996, and in 18 of 3165 (0.57%) examinations performed between 1997 and 2003.


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  		Table 4. Neurologic Complications of 19 826 Cerebral Angiography Procedures

 

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  		Table 5. Neurologic Complications of 19 826 Cerebral Angiography Procedures according to Indication

 
Predictor Variables
In univariate logistic regression models with neurologic complication (TIA, RIND, stroke, or death related to neurologic cause) as the outcome variable, the majority of the predictor variables were associated with the outcome variable with P values of less than .10 and were therefore included in further multivariate analysis. The most significant predictor variables (Table 6) positively associated with neurologic complications were the imaging indications of subarachnoid hemorrhage (OR, 2.523), atherosclerotic cerebrovascular disease (OR, 2.494), arteriovenous malformation (OR, 2.072), and "other" (OR, 1.935). The comorbidity of frequent TIAs was also significantly and positively associated with neurologic complications (OR, 1.674). Advancing patient age was also significantly associated with higher rates of neurologic complications, but the effect size for this variable was quite small (OR, 1.011).


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  		Table 6. ORs of Predictor Variables in Multivariable Models with Outcome Variable of Neurologic Complication

 
Two variables were associated with significantly decreased risk of neurologic outcome: involvement of a resident and/or fellow in the case (OR, 0.710) and increasing year of procedure (OR, 0.659 for 5-year intervals). Although associated with the outcome variable of neurologic complication with P values less than .10 in univariate analysis, the predictor variables of hypertension, elevated creatinine level, contrast agent volume, and particular type of contrast agents lost any significant association when covariance was controlled for in multivariable analysis.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ADVANCES IN KNOWLEDGE
 References
 
Our retrospective review of prospectively collected data for diagnostic cerebral angiography procedures in 19 826 consecutive patients reveals relatively low complication rates. A groin hematoma occurred in 4.2% of examinations and was the most common complication. Neurologic complications occurred within 24 hours of angiography in 2.63% of examinations, but the substantial majority of these complications were transient or reversible. Stroke with permanent disability occurred in 0.14% of examinations, and death occurred in 0.06% of examinations.

Patients being imaged for the indications of subarachnoid hemorrhage and atherosclerotic cerebrovascular disease were 2.5 times more likely than patients with the reference indication of tumor to have a neurologic complication within 24 hours. Patients with a history of frequent TIAs were 67% more likely than those without such history to have a neurologic complication. However, the participation of a trainee in an angiographic examination appears to have been protective, with neurologic complications 29% less likely to occur. The rate of neurologic complications decreased significantly with time over the 24-year duration of this study; a neurologic complication was 34% less likely to occur with each 5-year progression in time. Neurologic complications occurred in 3.8% of examinations during the first one-third of the study and in 0.57% of examinations during the last one-third.

Our discovered rate of neurologic complications associated with cerebral angiography, 2.63%, is similar to that found by other researchers, who have reported rates of 0.9%–4% (1–5,7–10). Our discovered rate of stroke with permanent disability or death in approximately 0.2% of cerebral angiographic examinations is slightly lower than that of other researchers, who have reported rates of 0.3%–1.3% (1–5,7–10). This could be reflective of differences in clinical follow-up between the current study and previously reported studies or of differences in patient populations or clinical practice. Our findings of an increased rate of neurologic complications in patients known to have or suspected of having atherosclerotic cerebrovascular disease and in patients with a history of frequent TIAs is consistent with the findings of other authors (1,3,4,6).

Neurologic complications have significantly decreased in more recent years, which could potentially represent an improvement in equipment, angiographer skill, or both. Patient selection variables have certainly changed with time (eg, angiography for diagnostic tumor evaluation is now substantially less common than previously), but the decreased rate of neurologic complications over time persisted even when the major patient selection criteria were controlled for in multivariate analysis. Heparinized saline catheter flush systems entered standard use in approximately 1990 and could be protective against neurologic complications. The shift from manual subtraction angiography to digital subtraction angiography began in 1993 at our institution and was mostly complete by approximately 1997, and associated decreases in injection volumes and rates could potentially be related to decreased neurologic complication rates.

We realize there were potential limitations of our study. Its data accuracy depended very strongly on the reliability of our clinical follow-up. There were very few missing data points, which may relate to the presence of a single, highly reliable nurse overseeing clinical follow-up data collection for the majority of the time period of the study. The collection of clinical follow-up data on weekdays was performed by or directly overseen by this nurse, but on weekends was dependent on residents performing rounds on inpatients and was therefore less person specific. Clinical follow-up on weekends may have been performed by individuals less experienced in evaluating medical records or in examining patients.

Another potential limitation of our data collection was that patients were evaluated clinically at 24 hours, and data sheets were completed at that time for patients who did not have new neurologic deficits. Therefore, we could potentially have missed neurologic complications occurring more than 24 hours after angiography that have been reported to occur (2). Also, our estimation of the rate of contrast material–induced nephropathy, which may manifest more than 24 hours after angiography, may thus be falsely low.

A limitation of our data collection with converse effects on results would be that adverse clinical outcomes were considered to be complications of cerebral angiography solely on the basis of the timing of their occurrence. Patients with a history of frequent TIAs, for example, had relatively more neurologic events in the first 24 hours after cerebral angiography than did patients without this history, but it is conceivable that at least some of these neurologic events would have occurred in these patients whether or not they underwent angiography. Another example of the bias created by the underlying disease is that, at chart review of the 10 neurologically related patient deaths, at least half of these patients were noted to have had severe morbidity before angiography that indeed was the indication for the angiography and that may have caused the patient's death within the same time frame, with or without angiography.

We did not record the use of intravenous heparin boluses in our database, which would have been an interesting variable to study with regard to neurologic complications (11). Also in this study we did not collect diffusion-weighted magnetic resonance imaging data, which in other studies have shown subclinical ischemic injuries in 9% or less of examinations to as many as 26% of examinations (12–15). We allow that subtle neurologic deficits could have been missed in the patients' clinical follow-up.

In conclusion, results of our retrospective study of prospectively gathered data in 19 826 consecutive patients show a relatively low rate of complications of diagnostic cerebral angiography.


   ADVANCES IN KNOWLEDGE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
References
 


   FOOTNOTES
 

Abbreviations: OR = odds ratio • RIND = reversible ischemic neurologic deficit • TIA = transient ischemic attack

Authors stated no financial relationship to disclose.

Author contributions: Guarantor of integrity of entire study, T.J.K.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, T.J.K.; clinical studies, T.J.K., J.H., K.R.T.; statistical analysis, T.J.K., J.N.M., C.D.S.; and manuscript editing, all authors


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 

  1. Heiserman JE, Dean BL, Hodak JA, et al. Neurologic complications of cerebral angiography. AJNR Am J Neuroradiol 1994;15:1401–1407.[Abstract]
  2. Dion JE, Gates PC, Fox AJ, Barnett HJ, Blom RJ. Clinical events following neuroangiography: a prospective study. Stroke 1987;18:997–1004.[Abstract/Free Full Text]
  3. Earnest F 4th, Forbes G, Sandok BA, et al. Complications of cerebral angiography: prospective assessment of risk. AJR Am J Roentgenol 1984;142:247–253.[Abstract/Free Full Text]
  4. Willinsky RA, Taylor SM, TerBrugge K, Farb RI, Tomlinson G, Montanera W. Neurologic complications of cerebral angiography: prospective analysis of 2,899 procedures and review of the literature. Radiology 2003;227:522–528.[Abstract/Free Full Text]
  5. Waugh JR, Sacharias N. Arteriographic complications in the DSA era. Radiology 1992;182:243–246.[Abstract/Free Full Text]
  6. Cloft HJ, Joseph GJ, Dion JE. Risk of cerebral angiography in patients with subarachnoid hemorrhage, cerebral aneurysm, and arteriovenous malformation: a meta-analysis. Stroke 1999;30:317–320.[Abstract/Free Full Text]
  7. Hankey GJ, Warlow CP, Sellar RJ. Cerebral angiographic risk in mild cerebrovascular disease. Stroke 1990;21:209–222.[Abstract/Free Full Text]
  8. Hankey GJ, Warlow CP, Molyneux AJ. Complications of cerebral angiography for patients with mild carotid territory ischaemia being considered for carotid endarterectomy. J Neurol Neurosurg Psychiatry 1990;53:542–548.[Abstract/Free Full Text]
  9. Leffers AM, Wagner A. Neurologic complications of cerebral angiography: a retrospective study of complication rate and patient risk factors. Acta Radiol 2000;41:204–210.[CrossRef][Medline]
  10. Johnston DC, Chapman KM, Goldstein LB. Low rate of complications of cerebral angiography in routine clinical practice. Neurology 2001;57:2012–2014.[Abstract/Free Full Text]
  11. Bendszus M, Koltzenburg M, Bartsch AJ, et al. Heparin and air filters reduce embolic events caused by intra-arterial cerebral angiography: a prospective, randomized trial. Circulation 2004;110:2210–2215.[Abstract/Free Full Text]
  12. Bendszus M, Koltzenburg M, Burger R, Warmuth-Metz M, Hofmann E, Solymosi L. Silent embolism in diagnostic cerebral angiography and neurointerventional procedures: a prospective study. Lancet 1999;354:1594–1597.[CrossRef][Medline]
  13. Britt PM, Heiserman JE, Snider RM, Shill HA, Bird CR, Wallace RC. Incidence of postangiographic abnormalities revealed by diffusion-weighted MR imaging. AJNR Am J Neuroradiol 2000;21:55–59.[Abstract/Free Full Text]
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