ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
David H. Harpole, Jr
Mark F. Newman
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Grichnik, K. P.
Right arrow Articles by Newman, M. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Grichnik, K. P.
Right arrow Articles by Newman, M. F.

Ann Thorac Surg 1999;68:1786-1791
© 1999 The Society of Thoracic Surgeons

Original Articles

Cognitive decline after major noncardiac operations: a preliminary prospective study

Katherine P. Grichnik, MDa, Alexander J.J. Ijsselmuidena,b, Thomas A. D’Amico, MDa,b, David H. Harpole, Jr, MDa,b, William D. White, MPHa,b, James A. Blumenthal, PhDa,b, Mark F. Newman, MDa,b

a Division of Cardiothoracic Anesthesia, Department of Anesthesia, Duke University Medical Center, Durham, North Carolina, USA
b Division of Cardiothoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA

Address reprint requests to Dr Grichnik, Division of Cardiothoracic Anesthesia, Duke University Medical Center, Box 3094, Durham, NC 27710
e-mail: grich002{at}mc.duke.edu

Presented at the Thirty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 25–27, 1999.


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 References
 
Background. Cardiac operations frequently are complicated by postoperative cognitive decline. Less common and less studied is postoperative cognitive decline after noncardiac surgery, so we determined its incidence, severity, and possible predictors.

Methods. Twenty-nine patients who had thoracic and vascular procedures were studied. A neurocognitive test battery was administered preoperatively and 6 to 12 weeks postoperatively. A change score (preoperative minus postoperative) was calculated for each measure in each individual. Cognitive deficit (a measure of incidence) was defined as a 20% decrement in 20% or more of the completed tests. The average scores of all tests and the average decline (a measure of severity) were determined.

Results. The incidence of cognitive deficit was 44.8%. Overall the severity of the decline was an average of 15% decline. In the 44.8% of patients who had cognitive deficit, the severity was 24.7%. Multivariable predictors of cognitive decline were age (for incidence and severity) and years of education (for severity).

Conclusions. Cognitive decline after noncardiac operations is a frequent complication of surgical procedures. The severity could preclude successful return to a preoperative lifestyle.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 References
 
Cardiac operations frequently are complicated by postoperative cognitive decline [1, 2]. Cognitive dysfunction is most notable immediately after the operation, but it can persist. Cognitive impairment leads to longer hospitalization and increased acuity of hospitalization or discharge care. Further, there is great personal loss to patients who might not return to their baseline level of cognitive function, despite a successful surgical procedure. Cognitive decline after cardiac operations has been studied intensively; it is associated with age, baseline psychometric score, cerebral oxygenation, and years of education [3].

Cognitive decline after major noncardiac operations is not as well studied. Numerically, more noncardiac operations are performed each year, which could lead to a greater absolute number of patients who have cognitive impairment. Several reports indicated that cognitive dysfunction does occur, especially in the elderly [4–7]. The incidence of cognitive dysfunction has been reported to be between 1% and 60%, depending on the type of operation [5]. However, much of this dysfunction has been studied in the immediate postoperative period; the incidence of persistent cognitive decline has been less investigated. Further, the risk of cognitive dysfunction has not been well defined for major operations such as thoracic and vascular procedures. The purpose of this study was to define the incidence, severity, and predictors for cognitive dysfunction after major thoracic and vascular procedures in a preliminary, prospective manner.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 References
 
Fifty-one patients scheduled for elective major thoracic and vascular surgery were prospectively enrolled after investigational review board approval with written informed consent were obtained. Patients with symptomatic cerebrovascular disease, uncontrolled hypertension, alcoholism, psychiatric illness, renal insufficiency (creatinine > 2.0), or active liver disease were excluded. Pregnant women, patients unable to read, and patients with less than a seventh grade education were excluded. The intraoperative anesthetic care and perioperative care were standard for our institution. All patients were evaluated preoperatively; 6 to 12 week follow-up was obtained on 29 patients.

Neurocognitive (NC) testing was conducted preoperatively (baseline) and 6 to 12 weeks postoperatively. The following instruments assessed cognitive functioning, some cited previously [8].

  1. Randt Short Story Memory Test [8]: Subjects were required to recall a short story immediately after it had been read to them and after 30 minutes.
  2. Rey Auditory Verbal Learning Test [9]: This is a list learning task that assesses learning and memory. Scores used were sixth recall, delayed recall, and number of new words learned between the first and fifth trials.
  3. Modified Visual Reproduction Test from the Wechsler Memory Scale [10]: This test measures short- and long-term figural memory; subjects reproduce geometric shapes immediately and after 30 minutes.
  4. Wechsler Adult Intelligence Scale-Revised Test [Selected subtests, 8 and 10]:
  5. Digit Span: Subjects are required to repeat a series of digits that have been orally presented to them in forward and reverse order.
  6. Digit Symbol: Subjects are required to quickly reproduce as many coded symbols as possible in blank boxes beneath randomly generated digits, according to a preset coding scheme.
  7. Trail Making Test, Part B [8]: This tests processing speed and attention. Subjects connect a series of numbers and letters in sequence as quickly as possible.

Neurologic history and examination were completed preoperatively, on day 3 to 5 postoperatively, and 6 to 12 weeks postoperatively. The National Institutes of Health stroke scale was used to assess neurologic function [11].

Other predictors analyzed included age, education, marital status, chronic obstructive pulmonary disease (COPD), diabetes, baseline mean arterial pressure, hypertension (HTN), gender, type of operation, length of operation, intraoperative arterial oxygen saturation (SaO2), length of intensive care unit stay and hospital stay.

Cognitive deficit (incidence) was defined as a decline at 6 to 12 weeks postoperatively of at least 20% from baseline, in at least 20% of completed tests [12]. The average percentage decline from baseline over all tests (severity) was scored for each individual [12]. In this calculation, any improvement was counted as zero decline. For example, a patient whose scores decreased 12% on one test, dropped 20% on another, improved 10% on a third, and had no change on a fourth would show an average percentage decline over all tests of (12 + 20 + 0 + 0)/4 = 8%. This patient, with a 20% decline on one test of four (25%), would be characterized as having a cognitive deficit. Patients unable to complete every follow-up test were included in analyses for the tests that they did complete. Baseline cognitive function was summarized for each individual as the average of normalized scores (z scores) over all baseline tests.

To find potential predictors of cognitive dysfunction, univariable logistic regression was used; categoric deficit outcome and linear regression were used for the continuous severity measure. For primary multivariable hypothesis tests, predictors were limited to age and years of education, with baseline cognitive function as a covariate, because of the small sample size of this preliminary investigation. Nonsignificant effects were eliminated from the final model. Post-hoc subanalyses tested the univariate association of deficit and decline with other factors, including type of operation, history of hypertension, COPD, diabetes, length of operation, baseline mean arterial pressure, and postoperative length of stay. The Wilcoxon rank sum test was used to assess association with the severity index. Any factor with a significant univariate association was analyzed in the final multivariate model.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 References
 
The demographic characteristics of the study population are given in Table 1. The continuous demographic and perioperative measures are given in Table 2. The data in these tables were analyzed as possible predictors of cognitive decline. No differences were found between surgical procedures in the number of patients with cognitive decline (Table 3). The amount of cognitive decline per test was analyzed to determine whether one test was more difficult than another test for this population; no differences were found (Table 4). No patient had a stroke.


View this table:
[in this window]
[in a new window]
  		Table 1. Demographic Characteristics of Study Population (n = 29)

 

View this table:
[in this window]
[in a new window]
  		Table 2. Continuous Demographic and Perioperative Measures

 

View this table:
[in this window]
[in a new window]
  		Table 3. Surgical Procedures

 

View this table:
[in this window]
[in a new window]
  		Table 4. Amount of Cognitive Decline Per Test at 6 to 12 Weeks Postoperatively

 
Overall, 44.8% of subjects (13 of 29) showed cognitive deficit (incidence) at 6 to 12 weeks postoperatively. As a population estimate with our sample size, the 95% confidence limits were 26.5% to 64.3%. The average decline in test scores (severity) for all patients was 14.6% (standard deviation, 17.8%; range, 2.5% to 100%). In the 13 patients classified as having deficit, the average decline (severity) was 24.7% (standard deviation, 23%; range, 12.8% to 100%). One patient could not do any tests at 6 weeks, but had not had a stroke. For individual tests, the percentage of patients whose 6- to 12-week score decreased 20% or more below baseline ranged from 10.7% on the forward Digit Span to 35.7% on the immediate Visual Reproduction test (Table 4).

In the multivariable modeling of factors associated with the incidence of cognitive deficit, age was the only significant correlate (logistic regression, p = 0.02; c index [a measure of the fit of the model] = 0.813). The odds ratio associated with a 10-year increase in age was 2.09 (95% confidence limits, 1.19 to 4.30.) For the average decline measure of severity, age (p = 0.02) and years of education (p = 0.03) together were significantly associated (linear regression model p = 0.01; r2 = 0.29). The model estimates a 4% decrease in average decline per 10 years of age, but an improvement of 1.6% for each year of education. Baseline cognitive function was not significant for either outcome measure.

In the univariable subanalyses, there was no association between incidence of cognitive deficit or severity of decline with type or length of operation, baseline mean arterial pressure, postoperative length of stay, COPD, or diabetes. Hypertension appeared related to severity, but this association disappeared after accounting for age.

Continuous SaO2 data were available in 25 of 29 patients. One patient had an abnormally low SaO2, with a low of 50% and an average SaO2 of 82% for 125 minutes. Of the rest, 6 had at 1 to 4 minutes of SaO2 less than 90%. Arterial oxygen saturation in all patients was not associated with cognitive deficit or with average decline at 6 to 12 weeks (including and excluding the patient with significantly abnormal SaO2). Three of the 7 patients with any SaO2 less than 90% had cognitive deficit compared with 10 of 18 patients with no SaO2 less than 90%. The patient with the significantly abnormal SaO2 had cognitive deficit.


   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
References
 
Cognitive dysfunction can be devastating. Despite successful surgical intervention, a patient might not be able to return to their baseline status and could require more intensive care by the family or by a long-term care facility. Cognitive dysfunction can therefore create an enormous cost to society in suffering and consumption of resources. By identifying the incidence, severity, and predictors of cognitive dysfunction, we might prevent these adverse neuropsychologic outcomes.

Cognitive dysfunction after cardiac operations is a well-recognized and studied phenomenon. Up to 83% of patients exhibit cognitive dysfunction in the immediate postoperative period [3]. This dysfunction persists in 20% to 30% of patients. Predictors include age, baseline psychometric scores, largest cerebral arterial to venous (a-v) oxygen difference with rewarming, and years of education [1, 3]. These significant variables could predict only 10% to 40% of the variance in the model of cognitive dysfunction [3]. Thus, other unknown factors influence this decline in cognition, some of which might not be unique to cardiac operations.

The definition of cognitive dysfunction in the noncardiac literature varies. Prior studies focused on delirium, altered consciousness, altered psychomotor activity, disturbed sleep cycles, and depression. Consequently, the incidence of cognitive dysfunction reported has varied widely. Many studies also focused primarily on elderly patients, a population at high risk for neurocognitive problems [5]. Cataract operations were associated with a 1% to 3% incidence [13, 14], gastrointestinal operations with a 17% incidence [15], and orthopedic operations with a 28% to 62% [16–18] incidence of mental impairment. In contrast, Goldstein and associates [19] assessed 172 older surgical patients versus 190 nonsurgical patients and found no difference in cognitive dysfunction immediately postoperatively and at 10 months. However, they studied a relatively healthy population and had a large patient dropout rate by 10 months.

The cognitive consequences of major noncardiac operations compared with cardiac operations have also been studied, and results have varied. Treasure and colleagues [20] examined 76 patients who had cardiac operations compared with 29 patients who had other major (abdominal aortic aneurysm and noncardiac thoracic) operations and found that 73% of cardiac patients had neuropsychologic dysfunction at 8 days, which improved to 37% at 8 weeks. However, similar neuropsychologic changes also occurred in 50% of the control group, which did not improve by 8 weeks. Shaw and associates [21] studied 312 cardiac surgical patients compared with 50 patients who had operations for peripheral vascular disease. At discharge, 38% of the cardiac patients had significant neuropsychologic symptoms compared with 31% of the patients with peripheral vascular disease, who showed neuropsychologic impairment on only one or two subtest scores. As a separate measure, intellectual dysfunction was not seen in patients with peripheral vascular disease in contrast to 24% of cardiac patients. Hammeke and Hastings [22] showed that both cardiac and peripheral vascular disease patients declined on neuropsychologic testing postoperatively (24% and 7%, respectively) compared with a nonoperative control group of patients with coronary artery disease whose cognitive function did not decline. Similarly, Heyer and coworkers [23] found that the noncardiac control patients had significant rates of neuropsychologic test abnormalities perioperatively and at 4 to 6 weeks. In large studies of mixed noncardiac surgical populations, Moller and associates [24] and Marcantonio and associates [7] studied 1218 and 1341 patients, respectively. Moller and associates found a 26% incidence of cognitive dysfunction at 1 week postoperatively and a 10% incidence at 3 months. Marcantonio and associates found a 7% incidence of delirium perioperatively; aortic aneurysm and noncardiac thoracic operations were found to be high-risk procedures for delirium. A subset of those patients had persistent dysfunction [7].

Few previous studies have focused on thoracic and vascular surgical patients as a primary study group with a long-term follow-up. We examined patients who had major thoracic and vascular procedures and who were hospitalized for at least 36 hours. The objective measures of attention, short-term memory, concentration, and speed of mental and motor responses have been found to be the most persistent in dysfunction in prior studies; thus they were examined 6 to 12 weeks postoperatively [1, 3, 25].

We found a 44% incidence of cognitive dysfunction. The average decline in test scores (severity) for all patients was 14.6% and for the subgroup with a cognitive deficit was 24.7%. This astonishingly large amount of impairment might not be recognized by the clinician. The severity index suggests that patients can still function in activities of daily living, although not to the same degree and perhaps not as independently as preoperatively. The old adage "Granny has not been the same since her operation" is reflected in these findings [5].

Multiple etiologies, including age, preexisting cerebrovascular disease, prior functional and American Society of Anesthesiology (ASA) status, urgency of operation, general versus regional anesthesia, have been proposed to explain cognitive dysfunction but the causative factors are unknown and the severity of dysfunction is unpredictable [7, 17, 25, 26].

We found that age predicted incidence and severity of cognitive dysfunction, which is consistent with prior studies. Age and years of education also predicted the severity of the cognitive dysfunction. Aging might lead to reduced tolerance for the stress of anesthesia, the operation, and postoperative events such that when cognition is impaired, it is more severe with increasing age. More years of education were protective, which might reflect the educated patient’s test taking skill or could imply a greater tolerance for perioperative stress.

The lack of other predictors of cognitive dysfunction was surprising. One-lung anesthesia should cause transient hypoxia, which could be associated with cognitive dysfunction. However, we found no association of intraoperative oxygenation with cognitive dysfunction. This finding is consistent with Moller’s study of 1218 elderly patients at 1 week and 3 months after noncardiac operations [24]. They found that age (but not hypoxemia or hypotension) was the only risk factor for late cognitive dysfunction. In our study, COPD also was not a predictor for cognitive dysfunction. Similarly, Isoaho and associates [27] found no differences in cognitive impairment in ambulatory patients with and without COPD in a community setting. However, chronic hypoxia in advanced COPD could result in mental dysfunction, which can be reversed with oxygen therapy [28, 29]. A second procedure-specific cause of cognitive dysfunction in the vascular surgical population might be related to the clamping of major arteries, which we did not examine. This maneuver could result in cardiac dysfunction with impaired cerebral perfusion and oxygenation. To examine this more closely, one would have to compare major abdominal operations with abdominal aortic grafting operations. Ongoing studies are addressing thoracic and vascular operations separately. Larger numbers of patients are being examined to confirm our findings and to seek causes specific for each type of operation.

This preliminary prospective study was limited by the small sample size and by the combination of thoracic and vascular surgical patients as a noncardiac surgical group. The sample size limits the power of our study to detect effects on cognitive deficit and decline and limits the number of predictors that can be tested reliably. The likelihood of an overly influential single observation is high. Furthermore, follow-up was at 6 to 12 weeks postoperatively. To determine the true incidence, severity, and impact of cognitive dysfunction, studies at 6 to 12 months are also needed. Then the effects of persistent cognitive dysfunction on return to baseline functional status can be determined.

Perhaps the biggest limitation of the study was the loss to follow-up of 22 subjects. If subjects lost to follow-up differed from those evaluated, our conclusions could be unfounded. The baseline characteristics of those followed up and those lost to follow-up were compared; there were no significant differences between groups, including all demographic characteristics and all individual baseline cognitive test scores. Thus, we have neither evidence nor reason to believe that the follow-up group is not representative of the group as a whole.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 

  1. Croughwell N.D., Newman M.F., Blumenthal J.A., et al. Jugular bulb saturation and cognitive dysfunction after cardiopulmonary bypass. Ann Thorac Surg 1994;58:1702-1708.[Abstract]
  2. Hammon J.W., Jr, Stump D.A., Kon N.D., et al. Risk factors and solutions for the development of neurobehavioral changes after coronary artery bypass grafting. Ann Thorac Surg 1997;63:1613-1618.[Abstract/Free Full Text]
  3. Newman M.F., Croughwell N.D., Blumenthal J.A., et al. Predictors of cognitive decline after cardiac operation. Ann Thorac Surg 1995;59:1326-1330.[Abstract/Free Full Text]
  4. Williams-Russo P., Sharrock N.E., Matis S., Szatrowski T.P., Charlson M.E. Cognitive effects after epidural vs. general anesthesia in older adults. JAMA 1995;274:44-50.[Abstract/Free Full Text]
  5. Parikh S.S., Chung F. Postoperative delirium in the elderly. Anesth Analg 1995;80:1223-1232.[Abstract]
  6. Cryns A.G., Gorey K.M., Goldstein M.Z. Effects of surgery on the mental status of older persons. A meta-analytic review. J Geriatr Psychiatry Neurol 1990;3:184-191.
  7. Marcantonio E.R., Goldman L., Mangione C.M., et al. A clinical prediction rule for delirium after elective noncardiac surgery. JAMA 1994;271:134-139.[Abstract/Free Full Text]
  8. Newman M.F., Croughwell N.D., Blumenthal J.A., et al. Effect of aging on cerebral autoregulation during cardiopulmonary bypass. Association with postoperative cognitive dysfunction. Circulation 1994;90:II243-II249.
  9. Rey A. L’examen clinique en psychologie. Paris: Presses Universitaires de France, 1964.
  10. Wechsler D. The Wechsler Adult Intelligence Scale—revised. New York: Psychological Corporation, 1981.
  11. Goldstein L.B., Samsa G.P. Reliability of the National Institutes of Health stroke scale. Extension to non-neurologists in the contest of a clinical trial. Stroke 1997;28:307-310.[Abstract/Free Full Text]
  12. Mahanna E.P., Blumenthal J.A., White W.D., et al. Defining neuropsychological dysfunction after coronary artery bypass grafting. Ann Thorac Surg 1996;61:1295-1296.[Free Full Text]
  13. Linn L., Kahn R.L., Coles R., et al. Patterns of behavior disturbance following cataract operation. Am J Psychiatry 1953;110:281-289.[Abstract/Free Full Text]
  14. Chung F., Lavelle P.A., McDonald S., et al. Cognitive impairment after neuroleptanalgesia in cataract surgery. Anesth Analg 1989;68:614-618.[Abstract/Free Full Text]
  15. Kaneko T., Takahashi S., Nako T., et al. Postoperative delirium following gastrointestinal surgery in elderly patients. Surg Today 1997;27:107-111.[Medline]
  16. Rogers M.P., Liang M.H., Daltroy L.H., et al. Delirium after elective orthopedic surgery. Int J Psychiatry Med 1989;19:109-121.[Medline]
  17. Williams-Russo P., Urquhart B.L., Sharrock N.E., Charlson M.E. Postoperative delirium. J Am Geriatr Soc 1992;40:759-767.[Medline]
  18. Gustafson Y., Brannstrom B., Berggren D., et al. A geriatric-anesthesiologic program to reduce acute confusional states in elderly patients treated for femoral neck fractures. J Am Geriatr Soc 1991;39:655-662.[Medline]
  19. Goldstein M.Z., Fogel B.S., Young B.L. Effect of elective surgery under general anesthesia on mental status variables in elderly men and women. Int Psychogeriatr 1996;8:135-149.[Medline]
  20. Treasure T., Smith P.L., Newman S., et al. Impairment of cerebral function following cardiac and other major surgery. Eur J Cardiothorac Surg 1989;3:216-221.[Abstract]
  21. Shaw P.J., Bates D., Cartidge N.E., et al. Neurologic and neuropsychological morbidity following major surgery. Stroke 1987;18:700-707.[Abstract/Free Full Text]
  22. Hammeke T.A., Hastings J.E. Neuropsychologic alterations after cardiac operations. J Thorac Cardiovasc Surg 1988;96:326-331.[Abstract]
  23. Heyer E.J., Delphin E., Adams D.C., et al. Cerebral dysfunction after cardiac operations in elderly patients. Ann Thorac Surg 1995;60:1716-1722.[Abstract/Free Full Text]
  24. Moller J.T., Cluitmans P., Rasmussen L.S., et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. Lancet 1998;351:1888-1889.[Medline]
  25. Fisher B.W., Flowerdrew G. A simple model for predicting postoperative delirium in older patients undergoing elective orthopedic surgery. J Am Geriatr Soc 1995;43:175-178.[Medline]
  26. Chung F., Meier R., Lautenschlager E., Carmichael F.J., Chung A. General or spinal anesthesia. Anesthesiology 1987;67:422-427.[Medline]
  27. Isoaho R., Puolijok H., Huhti E., Laippala P., Kivela S.L. Chronic obstructive pulmonary disease and cognitive impairment in the elderly. Int Psychogeriatr 1996;8:113-125.[Medline]
  28. Prigatano G.P., Wright E.C., Levin D., et al. Quality of life and its predictors in patients with mild hypoxemia and chronic obstructive pulmonary disease. Arch Intern Med 1984;144:1613-1619.[Abstract/Free Full Text]
  29. Block A.J. Neuropsychological aspects of oxygen therapy. Respir Care 1983;28:885-888.



This article has been cited by other articles:


Home page
 Anesth. Analg.Home page
D. J. Cook and G. A. Rooke
Priorities in Perioperative Geriatrics
Anesth. Analg., June 1, 2003; 96(6): 1823 - 1836.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
David H. Harpole, Jr
Mark F. Newman
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Grichnik, K. P.
Right arrow Articles by Newman, M. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Grichnik, K. P.
Right arrow Articles by Newman, M. F.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS