Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial.

BACKGROUND: Delirium is a common and serious postoperative complication. Subanaesthetic ketamine is often administered intraoperatively for postoperative analgesia, and some evidence suggests that ketamine prevents delirium. The primary purpose of this trial was to assess the effectiveness of ketamine for prevention of postoperative delirium in older adults. METHODS: The Prevention of Delirium and Complications Associated with Surgical Treatments [PODCAST] study is a multicentre, international randomised trial that enrolled adults older than 60 years undergoing major cardiac and non-cardiac surgery under general anaesthesia. Using a computer-generated randomisation sequence we randomly assigned patients to one of three groups in blocks of 15 to receive placebo (normal saline), low-dose ketamine (0·5 mg/kg), or high dose ketamine (1·0 mg/kg) after induction of anaesthesia, before surgical incision. Participants, clinicians, and investigators were blinded to group assignment. Delirium was assessed twice daily in the first 3 postoperative days using the Confusion Assessment Method. We did analyses by intention-to-treat and assessed adverse events. This trial is registered with clinicaltrials.gov, number NCT01690988. FINDINGS: Between Feb 6, 2014, and June 26, 2016, 1360 patients were assessed, and 672 were randomly assigned, with 222 in the placebo group, 227 in the 0·5 mg/kg ketamine group, and 223 in the 1·0 mg/kg ketamine group. There was no difference in delirium incidence between patients in the combined ketamine groups and the placebo group (19·45% vs 19·82%, respectively; absolute difference 0·36%, 95% CI -6·07 to 7·38, p=0·92). There were more postoperative hallucinations (p=0·01) and nightmares (p=0·03) with increasing ketamine doses compared with placebo. Adverse events (cardiovascular, renal, infectious, gastrointestinal, and bleeding), whether viewed individually (p value for each >0·40) or collectively (36·9% in placebo, 39·6% in 0·5 mg/kg ketamine, and 40·8% in 1·0 mg/kg ketamine groups, p=0·69), did not differ significantly across groups. INTERPRETATION: A single subanaesthetic dose of ketamine did not decrease delirium in older adults after major surgery, and might cause harm by inducing negative experiences. FUNDING: National Institutes of Health and Cancer Center Support.

Scholarly productivity and national institutes of health funding of foundation for anesthesia education and research grant recipients: insights from a bibliometric analysis.

BACKGROUND: The Foundation for Anesthesia Education and Research (FAER) grant program provides fellows and junior faculty members with grant support to stimulate their careers. The authors conducted a bibliometric analysis of recipients of FAER grants since 1987. METHODS: Recipients were identified in the FAER alumni database. Each recipient's affiliation was identified using an Internet search (keyword "anesthesiology"). The duration of activity, publications, publication rate, citations, citation rate, h-index, and National Institutes of Health (NIH) funding for each recipient were obtained using the Scopus (Elsevier, USA) and NIH Research Portfolio Online Reporting Tools (National Institutes of Health, USA) databases. RESULTS: Three hundred ninety-seven individuals who received 430 FAER grants were analyzed, 79.1% of whom currently hold full-time academic appointments. Recipients published 19,647 papers with 548,563 citations and received 391 NIH grants totaling $448.44 million. Publications, citations, h-index, the number of NIH grants, and amount of support were dependent on academic rank and years of activity (P < 0.0001). Recipients who acquired NIH grants (40.3%) had greater scholarly output than those who did not. Recipients with more publications were also more likely to secure NIH grants. Women had fewer publications and lower h-index than men, but there were no gender-based differences in NIH funding. Scholarly output was similar in recipients with MD and PhD degrees versus those with MD degrees alone, but recipients with MD and PhD degrees were more likely to receive NIH funding than those with MDs alone. CONCLUSION: Most FAER alumni remain in academic anesthesiology and have established a consistent record of scholarly output that appears to exceed reported productivity for average faculty members identified in previous studies.

Remote ischemic preconditioning prevents deterioration of short-term postoperative cognitive function after cardiac surgery using cardiopulmonary bypass: results of a pilot investigation.

OBJECTIVE: Remote ischemic preconditioning (RIPC) exerts neuroprotective effects in models of cerebral ischemia-reperfusion injury. The authors tested the hypothesis that RIPC decreases the incidence of postoperative delirium and prevents deterioration of short-term postoperative cognitive function in isoflurane-fentanyl-anesthetized patients undergoing cardiac surgery using cardiopulmonary bypass (CPB). DESIGN: Randomized, blinded, single-center pilot investigation. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: Thirty age- and education-matched men≥55 years of age undergoing elective coronary artery or valve surgery using CPB. Fifteen nonsurgical patients also were enrolled. INTERVENTIONS: RIPC was produced after induction of anesthesia using 4 cycles of brief (5 minutes) upper extremity ischemia (tourniquet inflation to 200 mmHg) interspersed with 5-minute periods of reperfusion (tourniquet deflation). MEASUREMENTS AND MAIN RESULTS: The Intensive Care Delirium Screening Checklist was used to assess delirium before and each day after surgery for as many as 5 consecutive days. Recent verbal and nonverbal memory and executive functions were assessed before and 1 week after surgery using a standard neuropsychometric test battery or at 1-week intervals in nonsurgical controls. The Geriatric Depression and the Hachinski Ischemia scales were used to identify the presence of clinical depression and vascular dementia, respectively. No differences in delirium scores were observed between RIPC and control groups (p=0.54). Baseline neurocognitive scores were similar in patients with versus without RIPC in all 3 cognitive domains. Significant declines in performance on 2 nonverbal memory tests (figure reconstruction and delayed figure reproduction; p=0.001 and p=0.003, respectively) and 1 verbal memory test (delayed story recall; p=0.0004) were observed 1 week after surgery in patients who were not treated with RIPC. There were no changes in performance of measures of executive function in this group. In contrast, performance on all cognitive tests was unchanged after compared with before surgery in patients receiving RIPC. At least a 1-standard deviation decline from baseline in cognitive performance was detected in figure reconstruction, delayed figure reproduction, immediate story recall, and delayed story recall in patients who were not exposed to RIPC. The incidence of at least a 1-standard deviation decline in neuropsychometric tests was observed in significantly fewer (1 v 9; p<0.0001) patients with versus without RIPC treatment based on composite Z-scores. Overall cognitive performance after surgery was better in patients treated with versus without RIPC (p=0.002). Clinical depression and vascular dementia were not detected in either group. CONCLUSION: The results of this pilot investigation indicated that RIPC prevented deterioration of short-term postoperative cognitive function but were unable to detect any difference in delirium in isoflurane-fentanyl-anesthetized patients undergoing cardiac surgery using CPB.

Aortic valve replacement reduces valvuloarterial impedance but does not affect systemic arterial compliance in elderly men with degenerative calcific trileaflet aortic valve stenosis.

OBJECTIVE: Standard methods of quantifying aortic valve stenosis (AS), which focus entirely on the valve itself, do not adequately characterize the magnitude, predict the onset, progression, and severity of symptoms, or identify the incidence of subsequent adverse events. Valvuloarterial impedance (Z(va)) is an index of global left ventricular (LV) afterload that incorporates valvular and arterial loads. The authors tested the hypothesis that aortic valve replacement (AVR) reduces Z(va) but does not affect the arterial component of LV afterload in elderly patients with degenerative calcific trileaflet AS. DESIGN: Observational study. SETTING: Veterans affairs medical center. PARTICIPANTS: Eight elderly (age, 79 ± 4 years) men with moderate-to-severe AS and normal preoperative LV function (ejection fraction, 61% ± 9%) scheduled for AVR with or without coronary artery bypass graft surgery were studied after institutional review board approval. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A comprehensive TEE examination was performed during isoflurane-fentanyl-rocuronium anesthesia. Doppler echocardiography was used to measure pressure gradients across the aortic valve, stroke volume (continuity equation), and aortic valve area using standard techniques. Z(va) was determined as (systolic arterial pressure+mean gradient)/stroke volume index. Energy loss index was calculated as (aortic area × aortic valve area)/([aortic area--aortic valve area]× body surface area). The stroke work loss was obtained as (mean gradient × 100/[systolic arterial pressure+mean gradient]). The ratio of stroke volume index to pulse pressure was used to measure systemic arterial compliance. Z(va), energy loss index, stroke work loss, and systemic arterial compliance were assessed before and 15 minutes after cardiopulmonary bypass. Systemic and pulmonary hemodynamics (invasive catheters) were similar after versus before AVR. Aortic valve area increased significantly (p<0.05) with AVR (0.92 ± 0.26 cm(2) to 1.94 ± 0.35 cm(2)), concomitant with decreases in peak and mean gradients (60 ± 17 mmHg to 15 ± 8 mmHg and 38 ± 11 mmHg to 8 ± 5 mmHg, respectively) and peak blood flow velocity (3.9 ± 0.5 m · s(-1) to 1.9 ± 0.5 m · s(-1)). AVR reduced Z(va) (4.6 ± 1.0 mmHg · mL(-1) · m(-2) to 3.5 ± 0.3 mmHg · mL(-1) · m(-2)) and improved energy loss index (0.55 ± 0.16 cm(2) · m(-2) to 1.58 ± 0.48 cm(2) · m(-2)) concomitant with a decline in stroke work loss (25% ± 6% to 7% ± 4%), but systemic arterial compliance remained unchanged (0.63 ± 0.13 compared with 0.70 ± 0.12 mL · mmHg(-1)· m(-2)). CONCLUSION: The current results showed that AVR acutely reduced Zva, improved energy loss index, and decreased stroke work loss, but did not affect systemic arterial compliance in elderly men with degenerative calcific trileaflet AS.

A bibliometric analysis of geographic publication variations in the Journal of Cardiothoracic and Vascular Anesthesia from 1990 to 2011.

OBJECTIVE: The bibliometrics of the anesthesiology literature has shifted substantially during the past 3 decades. The present authors analyzed the Journal of Cardiothoracic and Vascular Anesthesia (JCVA) at selected time intervals from 1990 to 2011 to quantify temporal variations in geographic publication patterns. The authors also determined whether previously described reductions in North American research productivity were accompanied by similar decreases in the number of other forms of publication in JCVA. DESIGN: An observational study. SETTING: Internet analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The number of research articles, case reports and conferences, review articles, and letters in each issue of the journal were quantified in each of 4 time intervals consisting of consecutive 4-year periods (1990-1993, 1996-1999, 2002-2005, and 2008-2011). Forty-three countries published a total of 2,587 articles (ie, 1,141 research articles, 735 case reports, 175 review articles, and 536 letters) during the 4 time periods examined. Progressive decreases in the percentage of research articles, case reports, and letters, but not review articles, from North America were observed over time. Significant increases in the percentage of research articles and letters contributed by European authors in 2008 to 2011 were observed compared with 1990 to 1993. The percentage of all publications from the Middle East and Australasia increased significantly, whereas South America and Africa were relatively minor contributors to JCVA throughout the study period. CONCLUSIONS: The present bibliometric analysis indicates that JCVA has changed from a journal that primarily published work from countries in North America and Europe to one in which the Middle East and Australasia now make a substantial number of contributions. These results suggest that JCVA has evolved into a truly international journal since its inception in 1987.

Chronic pressure-overload hypertrophy attenuates vortex formation time in patients with severe aortic stenosis and preserved left ventricular systolic function undergoing aortic valve replacement.

OBJECTIVE: Transmitral blood flow produces a vortex ring that enhances the hydraulic efficiency of early left ventricular (LV) filling. The effect of pressure-overload hypertrophy on the duration of LV vortex ring formation (vortex formation time [VFT]) is unknown. The current investigation tested the hypothesis that chronic LV pressure-overload hypertrophy produced by severe aortic stenosis (AS) reduces VFT in patients with preserved LV systolic function undergoing aortic valve replacement. DESIGN: Observational study. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: After the Institutional Review Board's approval, 8 patients (7 men and 1 woman; age, 62±5 y; and ejection fraction, 59%±5%) with AS (peak pressure gradient, 81±22 mmHg; aortic valve area, 0.78±0.25 cm(2)) scheduled for aortic valve replacement were compared with 8 patients (all men; age, 63±3 y; and ejection fraction, 60%±7%) without AS undergoing coronary artery bypass graft surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Under general anesthesia, peak early LV filling (E) and atrial systole (A) blood flow velocities and their corresponding velocity-time integrals were obtained using pulse-wave Doppler echocardiography to determine E/A and atrial filling fraction (ß). Mitral valve diameter (D) was calculated as the average of minor and major axis lengths obtained in the midesophageal bicommissural and long-axis transesophageal echocardiography imaging planes, respectively. Posterior wall thickness (PWT) was measured at end-diastole using M-mode echocardiography. VFT was calculated as 4×(1-ß)×SV/πD(3), where SV = stroke volume measured using thermodilution. Systemic and pulmonary hemodynamics, LV diastolic function, PWT, and VFT were determined during steady-state conditions 30 minutes before cardiopulmonary bypass. Early LV filling was attenuated in patients with AS (eg, E/A, 0.77±0.11 compared with 1.23±0.13; ß, 0.43±0.09 compared with 0.35±0.02; p<0.05 for each). LV hypertrophy was observed (PWT, 1.4±0.1 cm compared with 1.1±0.2 cm; p<0.05) and VFT was lower (3.0±0.9 v 4.3±0.5; p<0.05) in patients with versus without AS. Linear regression analysis showed a significant correlation between VFT and PWT (VFT = -2.57 ×PWT + 6.81; r(2) = 0.345; p = 0.017). CONCLUSION: The results indicated that pressure-overload hypertrophy produced by AS reduced VFT in patients with normal LV systolic function undergoing aortic valve replacement.

Recent trends in publication of basic science and clinical research by United States investigators in anesthesia journals.

BACKGROUND: United States anesthesia research production declined sharply from 1980-2005. Whether this trend has continued despite recent calls to improve output is unknown. We conducted an observational internet analysis to quantify American basic science and clinical anesthesia research output in 14 anesthesia journals with impact factors greater than one at three-year intervals during the past decade. RESULTS: American investigators published 1,486 (21.7%) of the total of 6,845 research articles identified in anesthesia journals in 2001, 2004, 2007, and 2010. Approximately two-thirds of all US articles were published in Anesthesiology and Anesthesia and Analgesia. There was a significant correlation (r2 = 0.316; P = 0.036) between the number of articles published by American authors in each anesthesia journal and the corresponding journal's impact factor in 2010. Significantly (P < 0.05; Pearson's Chi-square) fewer basic science articles were published in 2007 and 2010 compared with 2001. US clinical research output also declined in 2007 (201; 15.7%) compared with 2001 (266; 19.1%) and 2004, but an increase occurred in 2010 (279; 21.8%, P < 0.05 versus 2007). CONCLUSIONS: The results indicate that US anesthesia research output continued to decrease from 2001 to 2007. An increase in clinical but not basic science research was observed in 2010 compared with 2007, suggesting that a modest recovery in clinical research production may have begun.

Cardiopulmonary bypass transiently inhibits intraventricular vortex ring formation in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: Transmitral blood flow during early left ventricular (LV) filling produces an intraventricular rotational body of fluid known as a "vortex ring" that enhances the hydraulic efficiency of early LV filling. The authors tested the hypothesis that exposure to cardiopulmonary bypass (CPB) attenuates intraventricular vortex formation time (VFT) in patients with normal preoperative LV systolic and diastolic function undergoing coronary artery bypass graft (CABG) surgery. DESIGN: A prospective, observational study. PARTICIPANTS: Ten men (65 ± 4 years, 91 ± 11 kg, and 175 ± 8 cm) with a normal preoperative LV ejection fraction (58% ± 6%) scheduled for elective CABG surgery were studied after institutional review board approval. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Anesthesia was induced with etomidate, fentanyl, and rocuronium and maintained with isoflurane. Myocardial protection during CPB consisted of antegrade and retrograde cold blood cardioplegia administered at 15-minute intervals, systemic and topical hypothermia, and warm continuous antegrade cardioplegia before aortic cross-clamp removal. The peak early LV filling and atrial systole blood flow velocities (E and A, respectively) and corresponding velocity-time integrals (VTI-E and VTI-A, respectively) were obtained with pulse-wave Doppler echocardiography and used to determine E/A and atrial filling fraction (ß, VTI-A/[VTI-E + VTI-A]), respectively. Mitral valve diameter (D) was calculated as the average of minor and major axis lengths obtained in the midesophageal bicommissural and long-axis transesophageal echocardiographic imaging planes, respectively. VFT was calculated 30 minutes before and 15, 30, and 60 minutes after CPB as 4 × (1 - ß) × stroke volume (SV)/πD(3), where SV is the stroke volume measured using thermodilution. All patients separated from CPB in sinus rhythm without pacing or vasoactive drug support. Systemic and pulmonary hemodynamics were similar before compared with all times after CPB. CPB significantly (p < 0.05) reduced VFT (5.3 ± 1.8 to 4.0 ± 1.5 15 minutes after CPB); the recovery of VFT (to 4.7 ± 1.6, p > 0.05 v baseline) was noted 60 minutes after CPB. A reduction in E/A (1.26 ± 0.22 to 0.96 ± 0.27) and an increase in ß (0.33 ± 0.04 to 0.41 ± 0.07) occurred 15 minutes after CPB. E/A and ß also recovered gradually toward control values after CPB (1.25 ± 0.22 and 0.36 ± 0.04, respectively, 60 minutes after CPB; p > 0.05 v. baseline). CONCLUSIONS: The results indicated that CPB transiently attenuate VFT in patients with normal preoperative LV systolic and diastolic function undergoing CABG surgery. These data suggest that CPB adversely affects diastolic transmitral flow efficiency by reducing intraventricular vortex ring formation in vivo.

Comparison of pre-existing cognitive impairment, amnesic mild cognitive impairment, and multiple domain mild cognitive impairment in men scheduled for coronary artery surgery.

CONTEXT: Preoperative cognitive impairment (PreCI), amnesic mild cognitive impairment (aMCI; a risk factor for Alzheimer's disease) and multiple domain MCI with amnesia (mdMCI+a) identify preoperative cognitive abnormalities in patients scheduled for coronary artery bypass graft surgery (CABG). OBJECTIVES: Preoperative cognitive function is important in determining the incidence and severity of postoperative cognitive dysfunction, but the methods used to measure preoperative cognition are diverse. The incidence of preoperative cognitive abnormalities in cardiac surgical patients is unknown. DESIGN: Observational study. SETTING: Veteran Administration Medical Center in the United States of America. PARTICIPANTS: Elective CABG surgery patients and nonsurgical controls. MAIN OUTCOME MEASURES: Recent verbal and nonverbal memory and executive functions were assessed using psychometric tests. Associations were determined using multivariate regression analysis. We quantified the incidences of PreCI, aMCI and mdMCI+a in patients before elective CABG surgery. RESULTS: Patients (n = 100) scheduled for surgery had lower cognitive scores compared with nonsurgical controls (n = 100) on eight of 10 psychometric tests. Differences between patients and controls were 'large' for the Immediate and Delayed Story Recall tests (Cohen's d; wherein d is defined as a difference between two means divided by the pooled SD for those two means), 'medium' for the Immediate Word List Recall test and 'small' for five other tests. Twenty-five, 20, and 21 patients satisfied the criteria for PreCI, aMCI and mdMCI+a, respectively. Fifteen patients satisfied the criteria for both PreCI and mdMCI+a, whereas only five did so for both PreCI and aMCI. PreCI was not significantly associated with aMCI (P > 0.05), but was significantly associated with mdMCI+a (P < 0.00001). CONCLUSION: PreCI, aMCI and mdMCI+a identified preoperative cognitive abnormalities in different groups of patients scheduled for CABG surgery. The findings emphasise that identification of patients with preoperative cognitive dysfunction is methodology-dependent. The optimal approach to subsequently identify patients who may be at greatest risk of progressive cognitive deterioration after CABG surgery remains to be determined.

Scholarly productivity of united states academic cardiothoracic anesthesiologists: influence of fellowship accreditation and transesophageal echocardiographic credentials on h-index and other citation bibliometrics.

OBJECTIVE: The h-index allows the evaluation of scholarly output in academics, but this bibliometric statistic has not been applied extensively to measure productivity in anesthesiology. The authors tested the hypothesis that the h-index is dependent on academic rank, American College of Graduate Medical Education (ACGME) accreditation of the training program, and National Board of Echocardiography credentials in perioperative transesophageal echocardiography (TEE) in United States academic cardiothoracic anesthesiologists. DESIGN: Observational. SETTING: Internet analysis. PARTICIPANTS: United States academic cardiothoracic anesthesiologists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Faculty members from 30 randomly selected fellowship programs with or without accreditation were identified using the Society of Cardiovascular Anesthesiologists web site. The status of each faculty member's credentials in perioperative TEE was defined using the "verify certification" function on the National Board of Echocardiography web site. Publications, citations, citations/publication, and the h-index for each faculty member were obtained using Scopus. Two hundred fifty-nine cardiothoracic anesthesiologists (204 men and 55 women) were identified (8 instructors [3%], 123 assistant professors [48%], 56 associate professors [22%], 63 professors [24%], and 9 chairpersons [3%]). The average cardiothoracic anesthesiologist had an h-index of 6 ± 7 with 28 ± 46 publications, 499 ± 988 total citations, and 13 ± 18 citations per publication. The h-index increased significantly (p < 0.05) among ranks (instructors [1 ± 1], assistant professors [3 ± 3], associate professors [7 ± 5], professors [12 ± 8], and chairpersons [18 ± 13]). Significant differences in the number of publications and total citations also were observed among ranks. Differences in the h-index among ranks were observed regardless of program accreditation status or transesophageal echocardiographic credentials. Faculty members working in American College of Graduate Medical Education-accredited programs had more publications and citations and higher h-indices than their counterparts in programs that were not accredited. Except for program directors, the scholarly output of academic cardiothoracic anesthesiologists with or without transesophageal echocardiographic credentials was similar within each academic rank. CONCLUSIONS: The results show that the h-index increases progressively with academic rank and is dependent on fellowship program accreditation status but not transesophageal echocardiographic credentials in United States academic cardiothoracic anesthesiologists.

Metabolic syndrome exacerbates short-term postoperative cognitive dysfunction in patients undergoing cardiac surgery: results of a pilot study.

OBJECTIVE: The authors tested the hypothesis that patients with metabolic syndrome are more likely to develop short-term cognitive dysfunction after cardiac surgery with cardiopulmonary bypass. DESIGN: A prospective study. SETTING: Veterans Affairs medical center. PARTICIPANTS: Fifty-six age- and education-balanced patients undergoing elective cardiac surgery with cardiopulmonary bypass (28 patients with and without metabolic syndrome in two separate groups) and 28 nonsurgical controls were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Recent verbal and nonverbal memory and executive functions were assessed using a psychometric test battery before and 1 week after cardiac surgery or at 1-week intervals in nonsurgical controls. Neurocognitive scores under the baseline condition were at least 1 z score (1 standard deviation) worse in surgical patients with compared without metabolic syndrome in all 3 cognitive areas (nonverbal and verbal recent memory and executive functions). Neurocognitive performance further deteriorated after surgery by at least 1 z score on 3 tests in the verbal memory modality (Immediate and Delayed Story Recall and Delayed Word List Recall). Overall cognitive performance (composite z score) after surgery was significantly (p = 0.03) worse in metabolic syndrome patients compared with those who did not have the disorder. CONCLUSIONS: The results indicate that short-term cognitive functions were more profoundly impaired in patients with metabolic syndrome undergoing cardiac surgery with cardiopulmonary bypass compared with their healthier counterparts.

Postoperative delirium and short-term cognitive dysfunction occur more frequently in patients undergoing valve surgery with or without coronary artery bypass graft surgery compared with coronary artery bypass graft surgery alone: results of a pilot study.

OBJECTIVE: The authors tested the hypothesis that patients undergoing valve repair or replacement surgery with or without coronary artery bypass graft (CABG) surgery using cardiopulmonary bypass (CPB) had a greater incidence of postoperative delirium and cognitive dysfunction compared with patients undergoing CABG surgery alone. DESIGN: Prospective study. SETTING: Veterans Affairs medical center. PARTICIPANTS: Forty-four age- and education-balanced male patients (≥ 55 years of age) undergoing elective cardiac surgery with CPB (n = 22 valve ± CABG surgery and n = 22 CABG surgery alone) and nonsurgical controls (n = 22) were recruited. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Delirium was assessed with the Intensive Care Delirium Screening Checklist before and for 5 consecutive days after surgery. Recent verbal and nonverbal memory and executive functions were assessed using a psychometric test battery before and 1 week after cardiac surgery or at 1-week intervals in nonsurgical controls. Intensive care unit stay, hospital stay, and 30-day readmission were significantly (p = 0.03, p = 0.01, and p = 0.04, respectively) longer in patients undergoing valve surgery ± CABG surgery versus CABG surgery alone. Postoperative delirium occurred more frequently (p = 0.01) in patients undergoing valve ± CABG surgery versus CABG surgery alone. Overall cognitive performance (composite z score) after surgery also was impaired significantly (p = 0.004) in patients undergoing valve ± CABG surgery compared with CABG surgery alone. The composite z score after surgery decreased by at least 1.5 standard deviations in 11 patients (50%) versus 1 patient (5%) without valve surgery compared with nonsurgical controls (p = 0.001, Fisher's exact test). The presence of delirium predicted a composite z score decrease of 1.2 points (odds ratio = 0.30; 95% confidence interval, 0.13-0.68). CONCLUSIONS: The results indicated that patients undergoing valve surgery with or without CABG surgery have a higher incidence of postoperative delirium and cognitive dysfunction 1 week after surgery compared with those undergoing CABG surgery alone.

Elevated postoperative inflammatory biomarkers are associated with short- and medium-term cognitive dysfunction after coronary artery surgery.

PURPOSE: We tested the hypothesis that elevated postoperative interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations are associated with short- and medium-term impairment of cognitive functions in patients after coronary artery surgery using cardiopulmonary bypass. METHODS: Eighty-six age- and education-balanced patients ≥55 years of age undergoing elective coronary artery bypass surgery with cardiopulmonary bypass and 28 nonsurgical controls with coronary artery disease were enrolled. Recent verbal and nonverbal memory and executive functions were assessed before surgery and at 1 week and 3 months after surgery using a cognitive test battery. IL-6 concentrations were measured before surgery and 4 h after cardiopulmonary bypass, and CRP concentrations were measured before surgery and at 24 and 72 h after anesthetic induction. Overall cognitive function between high and low biomarker concentration groups was analyzed by the Wilcoxon rank-sum test. RESULTS: Recent memory was at least 1 standard deviation (SD) impaired at 1 week and 3 months in the high-CRP compared with low-CRP and in the high-IL-6 compared with low-IL-6 concentration groups. Overall cognitive function was significantly (P = 0.04 and P = 0.01, respectively) different between the high- and low-CRP concentration groups (CRP assayed 24 h after anesthetic induction) at both 1 week and 3 months. Overall cognitive function was also significantly (P = 0.04) different between the high and low-IL-6 concentration groups at 1 week after surgery. CONCLUSION: The results suggest that elevated postoperative IL-6 and CRP concentrations are associated with the subsequent development of short- and medium-term impairment of cognitive functions after coronary artery surgery.

Postoperative cognitive dysfunction after noncardiac surgery: effects of metabolic syndrome.

PURPOSE: Vascular risk factors, including metabolic syndrome, are known to contribute to the development of cognitive dysfunction. We tested the hypothesis that patients with metabolic syndrome are more likely to develop cognitive dysfunction after noncardiac surgery. METHODS: Age- and education-balanced patients (n = 60) undergoing elective noncardiac surgery with and without metabolic syndrome and 30 nonsurgical controls were enrolled. Recent verbal and nonverbal memory and executive functions were assessed using a psychometric test battery before and 1 month after noncardiac surgery or at a 1-month interval in nonsurgical controls. RESULTS: Neurocognitive scores under baseline conditions were similar in surgical patients with versus without metabolic syndrome in all examined cognitive modalities (recent nonverbal and verbal memory, executive functions). Pronounced reductions in tests of verbal memory (delayed story recall, immediate and delayed word list recall) and executive function (backward digit span) were observed in patients with versus without metabolic syndrome after surgery. Overall cognitive performance after surgery was also significantly (P = 0.03) more impaired in patients with versus without metabolic syndrome. The prevalence rate of POCD wasdifferent in the studied groups (17/30 [corrected] and 8/30 in patientswith versus without metabolic syndrome; P < 0.02). CONCLUSIONS: The results indicate that cognitive functions were more profoundly impaired in patients with metabolic syndrome undergoing noncardiac surgery compared with their healthier counterparts.

History of post-traumatic stress disorder is associated with impaired neuropsychometric performance after coronary artery surgery.

OBJECTIVE: To determine if preoperative history of post-traumatic stress disorder (PTSD) is associated with postoperative cognitive impairment. DESIGN: An observational study. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: Cardiac surgical patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age- and education-balanced patients (≥55 years of age) undergoing cardiac surgery (n = 30 with a history of PTSD+, n = 56 without a history of PTSD-) and nonsurgical controls (n = 28) were recruited. Recent verbal and nonverbal memory and executive functions were assessed before and 1 week after cardiac surgery or at 1-week intervals in nonsurgical controls. Demographic and medical parameters were similar between groups with the exception of preoperative depression and a history of alcohol dependence. Preoperative depression scores were significantly (p = 0.02) higher in PTSD+ compared with PTSD- groups. Immediate Word List Recall and Delayed Word List Recall under baseline conditions were worse in PTSD+ compared with PTSD- patients. Cognitive performance after surgery decreased by at least 1 standard deviation in 27 PTSD- patients (48%) and in 25 PTSD+ patients (83%) (p = 0.002) versus nonsurgical controls. Multivariate regression analysis (including a history of depression and alcohol dependence) revealed that a history of PTSD was significantly associated with overall (including nonverbal recent memory, verbal recent memory, and executive functions) postoperative cognitive dysfunction (p = 0.005). CONCLUSIONS: The current findings suggest that patients with a history of PTSD undergoing coronary artery surgery using cardiopulmonary bypass may be especially vulnerable to postoperative cognitive impairment.

Preoperative dispositional optimism correlates with a reduced incidence of postoperative delirium and recovery of postoperative cognitive function in cardiac surgical patients.

OBJECTIVE: To determine if preoperative psychosocial factors including dispositional optimism, perceived social support, and perceived stress correlate with the recovery of postoperative cognition. DESIGN: Observational study. SETTING: Veterans Affairs medical center. PARTICIPANTS: Cardiac surgical patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age- and education-balanced patients (> or =55 years of age) undergoing cardiac surgery (n = 40) and nonsurgical controls (n = 40) were recruited. A psychosocial evaluation for dispositional optimism, perceived social support, perceived stress, and depression was performed before surgery using standardized questionnaires. Delirium was assessed with the Intensive Care Delirium Screening Checklist before and for 5 consecutive days after surgery. Recent verbal and nonverbal memory and executive functions were assessed before and 1 week after cardiac surgery or at 1-week intervals in nonsurgical controls. Preoperative perceived stress significantly (p < 0.01) correlated with preoperative depression scores. Preoperative dispositional optimism significantly (p < 0.05) correlated with preoperative perceived social support. A multiple logistic regression revealed that dispositional optimism significantly (p < 0.02) predicted the absence of postoperative delirium within 5 days of surgery. Patients who showed high levels of dispositional optimism suffered a significantly (p < 0.03) lower incidence of postoperative delirium. Preoperative dispositional optimism also significantly (p < 0.001) correlated with a postoperative cognitive performance determined by composite z scores. A stepwise multiple regression analysis revealed that dispositional optimism significantly (p < 0.05, R(2) = 35%) predicted postoperative cognitive function. CONCLUSIONS: Preoperative dispositional optimism, but not perceived social support, perceived stress, and depression positively correlated with a reduced incidence of postoperative delirium within 5 days and recovery of cognitive performance 1 week after cardiac surgery.

Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: To determine if ketamine attenuates postoperative delirium concomitant with an anti-inflammatory effect in patients undergoing cardiac surgery using cardiopulmonary bypass. DESIGN: A prospective randomized study. SETTING: A Veterans Affairs medical center. PARTICIPANTS: Cardiac surgical patients. INTERVENTIONS: Patients at least 55 years of age randomly received placebo (0.9% saline, n = 29) or an intravenous bolus of ketamine (0.5 mg/kg intravenously, n = 29) during anesthetic induction in the presence of fentanyl and etomidate. MEASUREMENTS AND MAIN RESULTS: Delirium was assessed by using the Intensive Care Delirium Screening Checklist before and after surgery. Serum C-reactive protein concentrations were determined before and 1 day after surgery. The incidence of postoperative delirium was lower (p = 0.01, Fisher exact test) in patients receiving ketamine (3%) compared with placebo (31%). Postoperative C-reactive protein concentration was also lower (p < 0.05) in the ketamine-treated patients compared with the placebo-treated patients. The odds of developing postoperative delirium were greater for patients receiving placebo compared with ketamine treatment (odds ratio = 12.6; 95% confidence interval, 1.5-107.5; logistic regression). CONCLUSIONS: After cardiac surgery using cardiopulmonary bypass, ketamine attenuates postoperative delirium concomitant with an anti-inflammatory effect.

Postoperative delirium is associated with postoperative cognitive dysfunction at one week after cardiac surgery with cardiopulmonary bypass.

Postoperative delirium with cognitive impairment frequently occurs after cardiac surgery. It was hypothesized that delirium is associated with residual postoperative cognitive dysfunction in patients after surgery using cardiopulmonary bypass. Male cardiac surgical patients (M age = 66 yr., SD = 8; M education = 13 yr., SD = 2) and nonsurgical controls (M age = 62, SD = 7; M education = 12, SD = 2) 55 years of age or older were balanced on age and education. Delirium was assessed by the Intensive Care Delirium Screening Checklist preoperatively and for up to 5 days postoperatively. Recent verbal and nonverbal memory and executive functions were assessed (as scores on particular tests) before and 1 wk. after surgery. In 56 patients studied (n = 28 Surgery; n = 28 Nonsurgery), nine patients from the Surgery group developed delirium. In the Surgery group, the proportion of patients having postoperative cognitive dysfunction was significantly greater in those who experienced delirium (89%) compared with those who did not (37%). The odds of developing this dysfunction in patients with delirium were 14 times greater than those who did not. Postoperative delirium is associated with scores for residual postoperative cognitive dysfunction 1 wk. after cardiac surgery.

Cognitive function in older diabetic subjects with a history of alcohol abuse.

Either diabetes or alcohol abuse can impair cognitive function, especially at older ages. Whether a history of alcohol abuse increases the risk for cognitive impairment in diabetic patients has not been examined. Cognitive function of type 2 diabetic subjects with a history of alcohol abuse was expected to be more impaired than that of subjects with either diabetes or alcohol abuse alone. Men, 55 years of age, were categorized as 15 alcoholic-diabetic; 15 alcoholic-nondiabetic; 15 nonalcoholic-diabetic; 15 nonalcoholic-nondiabetic, and matched on age, sex, and education. Participants' verbal memory, visuospatial memory, and executive functions were assessed using a neurocognitive test battery. Significant interactions of diabetes and alcoholism for Visual Delayed Recall, Story Immediate Recall, and Story Delayed Recall implied that diabetes and alcohol abuse enhanced each other's effect in lowering cognitive test scores. Alcohol abuse history in older diabetic subjects presents an increased risk for cognitive impairment.