Randomized Trial of the Effect of Mindfulness-Based Stress Reduction on Pain-Related Disability, Pain Intensity, Health-Related Quality of Life, and A1C in Patients With Painful Diabetic Peripheral Neuropathy.

IN BRIEF Painful diabetic peripheral neuropathy (PDPN) has a large negative impact on patients' physical and mental functioning, and pharmacological therapies rarely provide more than partial relief. Mindfulness-based stress reduction (MBSR) is a group psychosocial intervention that was developed for patients with chronic illness who were not responding to existing medical treatments. This study tested the effects of community-based MBSR courses for patients with PDPN. Among patients whose PDPN pharmacotherapy had been optimized in a chronic pain clinic, those randomly assigned to treatment with MBSR experienced improved function, better health-related quality of life, and reduced pain intensity, pain catastrophizing, and depression compared to those receiving usual care.

Clinical impact of neurocognitive deficits after cardiac surgery.

OBJECTIVES: Postoperative neurocognitive deficits (POCDs) have been found to occur frequently after cardiac surgery. Although POCDs have received significant attention in the medical literature and public media, the true clinical impact of these deficits on patient outcomes and quality of life (QOL) is not well defined. METHODS: Neuropsychometric testing was performed on 696 patients undergoing coronary artery bypass surgery using a battery of tests divided into 4 domains; memory, attention, speed, and psychomotor function. These were performed preoperatively, at hospital discharge, and at 3 months postoperatively. POCDs were defined as a drop in scores by 1 standard deviation in 1 domain or more. QOL was assessed using Short Form 36 and clinical outcomes were recorded. RESULTS: POCDs were identified in 265 (38%) patients at discharge and in 132 (19%) at 3 months. There was no observed difference in mortality or major morbidity in patients with or without POCDs. Predictors of POCDs at discharge were elevated preoperative creatinine (P = .04), increased cardiopulmonary bypass time (P = .005), and diabetes (P = .003). At 3 months, patients had improvements in both physical and mental components of QOL, independent of the occurrence of POCDs (P > .5). Independent predictors of improved QOL included younger age, severe preoperative anginal symptoms, normal left ventricular function, absence of postoperative wound infection, but not POCDs. CONCLUSIONS: Neurocognitive deficits can be frequently detected on comprehensive neuropsychometric testing after cardiac surgery. However, they are not associated with any clinically important differences in patient outcome or in QOL after surgery.

The clock drawing test is a poor screening tool for postoperative delirium and cognitive dysfunction after aortic repair.

BACKGROUND: The Clock Drawing Test (CDT) is a screening tool for dementia that tests a variety of cognitive domains. The CDT takes a maximum of two minutes to complete and might be helpful in identifying postoperative cognitive disorders at the bedside. The objective of this study was to evaluate the accuracy of the CDT in a population at high risk for postoperative cognitive disorders METHODS: In this prospective observational cohort study, patients were recruited who were ≥ 60 yr of age and scheduled for elective open repair of the abdominal aorta. Delirium was assessed using the Confusion Assessment Method (CAM) on postoperative days (POD) 2 and 4 and at discharge. Cognitive function was assessed with neuropsychometric tests before surgery and at discharge. Postoperative cognitive dysfunction (POCD) was determined using the Reliable Change Index. Clock Drawing Tests were administered at all time points. Agreement between the CDT and test for delirium or POCD was assessed with Cohen's Kappa statistic. RESULTS: Delirium was noted in 30 of 83 patients (36%; 95% confidence interval [CI] 26 to 46%) during their hospital stay, while POCD was noted in 48 of 78 patients (60%; 95% CI 51 to 72%) at discharge. Agreement between the CDT and CAM was poor at three intervals (Kappa 0.06 to 0.29), as was POCD at discharge (Kappa 0.46). Sensitivity of the CDT was <0.71 for both delirium and POCD at all intervals. False positives and negatives were common. CONCLUSION: Agreement between CDT and tests for delirium and POCD was poor; sensitivity was inadequate for a screening test. (ClinicalTrials.gov number, NCT00911677).

A prospective cohort study evaluating associations among delirium, postoperative cognitive dysfunction, and apolipoprotein E genotype following open aortic repair.

BACKGROUND: Patients undergoing major vascular surgery are at high risk of postoperative delirium and postoperative cognitive dysfunction (POCD). Apolipoprotein E (APOE) is involved in central acetylcholine synthesis, and patients bearing the ε4 genotype (APOE-ε4) are at increased risk of both vascular dementia and peripheral vascular disease. The purpose of this study was to evaluate the associations among delirium, POCD, and APOE-ε4 in patients undergoing open aortic repair. METHODS: Following Research Ethics Board approval and written informed consent, we recruited a cohort of patients ≥ 60 yr of age undergoing open aortic repair. Apolipoprotein E genotyping and a battery of nine neuropsychometric (NP) tests were performed prior to surgery. Delirium was assessed on postoperative days two, four, and discharge using the Confusion Assessment Method. Neuropsychometric testing was repeated at discharge and again three months following surgery. A group of non-surgical patients was used to adjust NP scores using reliable change index methodology. Logistic regression was used to evaluate independent predictors of both delirium and POCD. RESULTS: Eighty-eight patients underwent surgery, 78 completed NP testing on discharge, and sixty-nine completed NP testing at three months. Delirium was noted in 36% of patients after surgery, while POCD was noted in 62% at discharge and 6% at three months. Delirium predicted POCD at discharge (odds ratio 2.86; 95% confidence intervals 0.99 to 8.27) but not at three months. Apolipoprotein E-ε4 genotype was not associated with either delirium or POCD following adjustment for covariates. CONCLUSION: Both delirium and POCD are common following open aortic repair; however, the APOE genotype did not predict either condition. This trial has been registered with ClinicalTrials.gov (NCT00911677).

Cerebral emboli detected by transcranial Doppler during cardiopulmonary bypass are not correlated with postoperative cognitive deficits.

BACKGROUND AND PURPOSE: High-intensity transient signals (HITS) are the transcranial Doppler representation of both air and solid cerebral emboli. We studied the frequency of HITS associated with different surgical maneuvers during cardiopulmonary bypass for coronary artery bypass graft surgery and their association with postoperative cognitive dysfunction (POCD). METHODS: We combined 356 patients undergoing coronary artery bypass graft from 2 clinical trials who had both neuropsychological testing (before, 1 week and 3 months after surgery) and transcranial Doppler during cardiopulmonary bypass. HITS were grouped into periods that included: cannulation, cardiopulmonary bypass onset, aortic crossclamp-on, aortic crossclamp-off, side clamp-on, side clamp-off, and decannulation. POCD was defined by a decreased combined Z-score of at least 2.0 or reduction in Z-scores of at least 2.0 in 20% of the individual tests. RESULTS: Incidence of POCD was 47.3% and 6.3% at 1 week and 3 months after surgery. There was no association between cardiopulmonary bypass counts of HITS and POCD at 1 week (P=0.617) and 3 months (P=0.110). No differences in HITS counts were identified at any of the surgical periods between patients with and without POCD. Factors affecting HITS counts were surgical period (P<0.0001), blood flow velocity (P=0.012), cardiopulmonary bypass duration (P=0.040), and clinical study (P=0.048). CONCLUSIONS: Although cerebral microemboli have been implicated in the pathogenesis of POCD, in this study that included low-risk patients undergoing coronary artery bypass surgery, there was no demonstrable correlation between the counts of HITS and POCD.

Effects of mild hypothermia and rewarming on renal function after coronary artery bypass grafting.

BACKGROUND: Hypothermia is a potential strategy for visceral organ protection during cardiopulmonary bypass (CPB). We report data from two randomized studies evaluating mild hypothermia and rewarming on postoperative renal function in cardiac surgical patients. METHODS: Patients undergoing nonemergency, isolated coronary artery bypass grafting were enrolled into two studies. In the first, 223 patients were cooled to 32 degrees C during CPB and randomly assigned to rewarming to 37 degrees C (RW-37 degrees) or 34 degrees C (RW-34 degrees). The second study randomized 267 patients to sustained mild hypothermia at 34 degrees C (S-34 degrees) or normothermia (S-37 degrees) without rewarming. Serum creatinine levels were measured. Creatinine clearance was calculated. Significant renal dysfunction was defined as a 25% increase in serum creatinine or a 25% decrease in creatinine clearance postoperatively. RESULTS: Postoperative serum creatinine levels were persistently higher in the RW-37 degrees patients than in the RW-34 degrees group (p < 0.01). RW-37 degrees patients had a higher incidence of renal dysfunction (17%) than RW-34 degrees patients (9%, p = 0.07). Sustained mild hypothermia had no beneficial effect on postoperative serum creatinine levels (p = 0.44) or significant renal dysfunction: S-34 degrees, 20% vs S-37 degrees, 15% (p = 0.28). Diabetes (odds ratio [OR], 1.6; 95% confidence interval [CI] 1.3 to 2.1), prolonged CPB time (OR, 1.1; 95% CI, 1.0 to 1.2), and rewarming (OR, 1.4; 95% CI, 1.0 to 1.9) were independent risk factors for significant renal dysfunction. Renal dysfunction was associated with longer hospital stay (8.4 +/- 0.8 vs 6.8 +/- 04 days, p < 0.001). CONCLUSIONS: Sustained mild hypothermia does not improve renal outcome. However, rewarming on CPB is associated with increased renal injury and should be avoided.

Effects of sustained mild hypothermia on neurocognitive function after coronary artery bypass surgery: a randomized, double-blind study.

OBJECTIVE: Neurocognitive deficits occur frequently in patients undergoing cardiac surgery and may be caused, in part, by ischemic cerebral injury. Cerebral hypothermia has been proposed as a neuroprotective strategy to reduce ischemic injury in animal studies, in postcardiac arrest, and during cardiac surgery. We sought to evaluate the effects of sustained mild intraoperative hypothermia, without rewarming, on neurocognitive function after coronary artery bypass surgery. METHODS: Patients (aged >/= 60 years) undergoing non-urgent coronary surgery were randomized to an intraoperative nasopharyngeal temperature of 34 degrees C (hypothermic; n = 133) or 37 degrees C (normothermic; n = 134), maintained using water-circulating thermal control pads. No active rewarming was used. Transcranial Doppler was used intraoperatively to monitor middle cerebral artery emboli. Neuropsychometric testing, consisting of a battery of 16 tests, was performed by blinded observers preoperatively, before discharge, and at 3 months, and tests were divided into 4 cognitive domains. A deficit was prospectively defined as a 1 standard deviation decrease in individual scores from baseline in 1 or more domains. RESULTS: The number of intraoperative cerebral emboli was similar between the control and the treated groups (188 [115-331] vs 182 [100-305], P = .71). At discharge, neurocognitive deficits were present in 45% of control patients and in 49% of treated patients (P = .49) and at 3 months decreased to 8% in control patients and 4% in treated patients (P = .28). There was no correlation between the total number of cerebral emboli and the occurrence of neurocognitive deficits (r = -0.01; P = .88). Hypothermic patients demonstrated trends toward reduced intensive care unit stay (1.4 +/- 1.0 days vs 1.2 +/- 0.7 days, P = .06) and increased chest tube output (655 +/- 327 mL/24 h vs 584 +/- 325 mL/24 h, P = .09). CONCLUSIONS: Mild intraoperative hypothermia has no major adverse effects but does not decrease the incidence of neurocognitive deficits in patients undergoing coronary artery bypass surgery. In the absence of rewarming and cerebral hyperthermia, sustained mild hypothermia does not improve cognitive outcome.

The cardiotomy trial: a randomized, double-blind study to assess the effect of processing of shed blood during cardiopulmonary bypass on transfusion and neurocognitive function.

BACKGROUND: Reinfusion of unprocessed cardiotomy blood during cardiac surgery can introduce particulate material into the cardiopulmonary bypass circuit, which may contribute to postoperative cognitive dysfunction. On the other hand, processing of this blood by centrifugation and filtration removes coagulation factors and may potentially contribute to coagulopathy. We sought to evaluate the effects of cardiotomy blood processing on blood product use and neurocognitive functioning after cardiac surgery. METHODS AND RESULTS: Patients undergoing coronary and/or aortic valve surgery using cardiopulmonary bypass were randomized to receive unprocessed blood (control, n=134) or cardiotomy blood that had been processed by centrifugal washing and lipid filtration (treatment, n=132). Patients and treating physicians were blinded to treatment assignment. A strict transfusion protocol was followed. Blood transfusion data were analyzed using Poisson regression models. The treatment group received more intraoperative red blood cell transfusions (0.23+/-0.69 U versus 0.08+/-0.34 U, P=0.004). Both red blood cell and nonred blood cell blood product use was greater in the treatment group and postoperative bleeding was greater in the treatment group. Patients were monitored intraoperatively by transcranial Doppler and they underwent neuropsychometric testing before surgery and at 5 days and 3 months after surgery. There was no difference in the incidence of postoperative cognitive dysfunction in the 2 groups (relative risk: 1.16, 95% CI: 0.86 to 1.57 at 5 days postoperatively; relative risk: 1.05, 95% CI: 0.58 to 1.90 at 3 months). There was no difference in the quality of life nor was there a difference in the number of emboli detected in the 2 groups. CONCLUSIONS: Contrary to expectations, processing of cardiotomy blood before reinfusion results in greater blood product use with greater postoperative bleeding in patients undergoing cardiac surgery. There is no clinical evidence of any neurologic benefit with this approach in terms of postoperative cognitive function.

Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass: five-year follow-up of a randomized trial.

OBJECTIVE: In a randomized trial of 223 patients undergoing coronary artery surgery with cardiopulmonary bypass, we have reported a neuroprotective effect of mild hypothermia. To determine whether the beneficial effect of mild hypothermia was long-lasting, we repeated the psychometric tests in 131 patients after 5 years. METHODS: Patients were cooled to 32 degrees C during aortic crossclamping and then randomized to rewarming to either 34 degrees C or 37 degrees C, with no further rewarming until arrival in intensive care unit. Cognitive function was measured preoperatively and 1 week and 5 years postoperatively with a battery of 11 psychometric tests interrogating verbal memory, attention, and psychomotor speed and dexterity. RESULTS: Patients who had greater cognitive decline 1 week after surgery showed poorer performance 5 years later. The magnitude of cognitive decline over 5 years was modest. The incidence of deficits defined as a 1 standard deviation [SD] decline in at least 1 of 3 factors was not different between temperature groups. Fewer patients in the hypothermic group had deficits that persisted over the 5 years, but this difference did not attain statistical significance (RR = 0.64, P = .16). CONCLUSIONS: The effect of surgery on cognitive function observed early after surgery is an important predictor of cognitive performance 5 years later. Although there was evidence of a neuroprotective effect of mild hypothermia early after surgery in the original cohort, the results after 5 years were inconclusive. In general, the magnitude of cognitive changes over 5 years was modest. We believe that further trials investigating the efficacy of mild hypothermia in patients having cardiac surgery are warranted.

Research awards program of the Canadian Anesthesiologists' Society/Canadian Anesthesia Research Foundation: survey of past recipients.

PURPOSE: To review the effectiveness of the Research Grants, Career Scientist Award and Fellowship Program (RGCSFP) of the Canadian Anesthesiologists' Society (CAS)/Canadian Anesthesia Research Foundation (CARF) by surveying past recipients. METHODS: The CAS Research Committee database of past RGCSFP recipients was reviewed to identify all past award recipients from the time of program inception in 1985 until the year 2005. A questionnaire was mailed to all past recipients with retrievable addresses. The questionnaire asked specific questions regarding past and current research, publications, grant procurement and mentoring of trainees. In addition, opinions regarding the program's effectiveness were solicited. RESULTS: Of the 100 mailed survey forms, 66 (66%) were completed and returned. The number of original published articles per respondent was 30.1 +/- 28.5 (mean +/- SD) at the time of the survey, and the life-time number of all publication types was 38.5 +/- 34.6. Cumulative research funding increased in relation to the number of years in research, and amongst past recipients with > 15 years in research, individual research funding from all sources was $585,747 +/- $773,716. Ninety-six percent of respondents agreed or strongly agreed that the program was valuable. CONCLUSIONS: The RGCSFP has supported a large number of new and established anesthesia investigators in Canada, and these individuals have demonstrated high research productivity. The program is considered to be very valuable according to past recipients.

Predictors of early neurocognitive deficits in low-risk patients undergoing on-pump coronary artery bypass surgery.

BACKGROUND: Postoperative cognitive deficits (POCDs) are a source of morbidity and occur frequently even in low-risk patients undergoing cardiac surgery. Predictors of neurocognitive deficits can identify potentially modifiable risk factors as well as high-risk patients in whom alternate revascularization strategies may be considered. METHODS AND RESULTS: 448 patients undergoing coronary surgery (coronary artery bypass graft [CABG]) underwent standardized preoperative and postoperative neurocognitive testing as part of 2 randomized trials evaluating the effects of mild hypothermia during coronary surgery. Prospectively collected data were used to identify univariate predictors of POCDs and multivariable logistic regression models were constructed. Models were bootstrapped 1000 times. POCDs occurred in 59% of patients. Significant univariate predictors included intraoperative normothermia, impaired left ventricular (LV) function, higher educational level, elevated serum creatinine and reduced creatinine clearance, prolonged intubation time, intensive care unit (ICU) stay, and hospital stay. Advanced age, presence of carotid disease, and cardiopulmonary bypass time were not associated with increased POCDs in this cohort. Multivariable modeling identified intraoperative normothermia (odds ratio [95% confidence interval] -1.15 [1.01, 1.31]), poor LV function (1.53 [1.02, 2.30]), and elevated preoperative creatinine (1.01 [1.00 to 1.03] for every 1 mmol/L increase), prolonged (>24 hours) ICU stay (1.88 [1.27 to 2.79]), and higher educational level (1.52 [1.01 to 2.28]) as independent predictors of POCD occurrence. CONCLUSIONS: Mild hypothermia, in the intraoperative and perioperative period, may be a protective strategy for the prevention of POCDs. Patients with elevated pre-operative creatinine and poor LV function carry a higher risk of POCDs and may benefit from revascularization strategies other than conventional on-pump CABG.

Effects of methylprednisolone and a biocompatible copolymer circuit on blood activation during cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) induces derangements in physiology characterized by activation of blood pathways that may contribute to multiorgan dysfunction. This trial addresses the efficacy of a biocompatible surface alone and in combination with steroids in inhibiting these changes. METHODS: In a factorial design, patients undergoing coronary artery bypass grafting were randomized (four groups; n = 17 per group) to CPB utilizing control circuits or a circuit prepared with a surface modifying active copolymer (SMA-CPB), with or without methylprednisolone (MPSS, 1 g intravenous). Leukocyte and complement activation, cytokine release, and bradykinin generation were measured. Clinical outcomes (blood loss, transfusion, arterial pressure response, and postoperative cardiac and pulmonary functions) were also examined. RESULTS: The SMA-CPB was associated with a significant inhibition of elastase release (p = 0.026) and bradykinin generation (p = 0.027) during CPB. Terminal complement complex (TCC) generation was inhibited as an effect of SMA-CPB (p = 0.047). There was an interaction of SMA-CPB and MPSS to decrease both TCC (p = 0.042) and bradykinin generation (p = 0.028). There were strong effects of MPSS in inhibiting release of interleukin 6 (IL-6) (p = 0.007) and IL-8 (p < 0.001) and tissue plasminogen activator over time (p = 0.009) as well as decreasing peak day 1 creatine kinase (CK, p = 0.015) levels. Clinical effects of MPSS included decreased atrial fibrillation (p = 0.02), improved cardiac index over time, increased pulmonary compliance, and increased insulin need. CONCLUSIONS: This trial suggests a potential beneficial effect for combined strategies to minimize inflammation after CPB. The specific effect of MPSS in decreasing postoperative atrial fibrillation and CK warrants further investigation of its role as a potential myocardial protective agent.