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Background Pain expectancy may be an important variable that has been found to influence the effectiveness of treatments for pain. Much of the literature supports a self-fulfilment perspective where expectations for pain relief predict the actual pain experienced. However, in conditions such as neuropathic pain (NeP) where pain relief is difficult to attain, expectations for pain relief could be unrealistic. The objective of this study was to investigate the relationship between realistic/unrealistic expectations and 6-month, post-treatment outcomes. Methods We performed a retrospective analysis of a large cohort of patients with NeP (n = 789) attending tertiary care centres to determine the association between unrealistic (both positive and negative) and realistic expectations with outcomes after multidisciplinary treatment. An expectation variable with three categories was calculated: realistic expectations were those whose expected reduction in pain was similar to the observed mean group reduction in pain, while optimistic and pessimistic expectations were those who over- or under-estimated the expected response to treatment, respectively. The association between baseline realistic/unrealistic expectations and 6-month pain-related disability, catastrophizing and psychological distress was assessed. Results Univariable analyses suggested that realistic expectations were associated with lower levels of disability, catastrophizing and psychological distress, compared to unrealistic expectations. However, after adjustment for baseline symptom severity, multivariable analysis revealed that patients with optimistic expectations had lower levels of disability, than those with realistic expectations. Those with pessimistic expectations had higher levels of catastrophizing and psychological distress at follow-up. Conclusions These findings are largely congruent with the self-fulfilment perspective to expectations. Significance This study defined realistic pain expectations with patient data. Examining the relationship between expectations between pain and disability in a large cohort of patients with neuropathic pain.

Painful diabetic peripheral neuropathy (PDPN) is a chronic pain condition with modest response to pharmacotherapy. Participation in mindfulness-based stress reduction (MBSR) leads to improvements in pain-related outcomes but the mechanisms of change are unknown. The present study examined the mediators and moderators of change in 62 patients with PDPN who participated in a randomized controlled trial comparing MBSR to waitlist. Changes in mindfulness and pain catastrophizing were tested simultaneously as mediators. Increased mindfulness mediated the association between participation in MBSR and improved pain severity, pain interference, and the physical component of health-related quality of life (HRQoL) 3 months later. The mediation effect of pain catastrophizing was not significant. Linear moderated trends were also found. Post-hoc moderated mediation analyses suggested that MBSR patients with longer histories of diabetes might increase their mindfulness levels more, which in turn leads to improved pain severity and physical HRQoL. These results allow for a deeper understanding of pathways by which MBSR benefits patients with PDPN.

Background:Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers.Methods:Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction.Results:At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012).Conclusion:Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.

EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO) has been associated with a risk of neurologic injury that may be related to the precipitating event or to the ECMO therapy itself. In ECMO patients who progress into coma in particular, the use of extracorporeal circulation serves as a confounder because it increases the uncertainty surrounding the prediction of awakening and the potential for neurologic recovery. This uncertainty may lead to inappropriate decisions about continuation or withdrawal of life support even in cases in which the patient’s cardiopulmonary function has been re-established under ECMO. Auditory event-related potentials (ERPs) are neurophysiologic techniques that have been associated with higher-level cognitive functions, such as arousal or attention, and their recording during coma may identify those patients whose auditory preattentive memory remains active. Recent studies have documented that the mismatch negativity (MMN), an electrophysiologic marker of the auditory ERPs, can offer a valuable addition to routine clinical examination and other neurophysiologic methods in the early assessment and prediction of awakening from coma. The presence of MMN in the course of coma indicates the likelihood of awakening, and it may encourage the continuation of life support in those patients for whom clinical prognosis is uncertain. This report describes 2 comatose patients during ECMO, whose continuation of life support was questioned because of the uncertainty of their neurologic prognosis, and results of the MMN and other auditory evoked potentials (AEPs; brainstem and middlelatency) informed medical decisions about the continuation or withdrawal of intensive care after the patient’s cardiopulmonary function had improved under ECMO.

Chronic pain, including neuropathic pain, has a high prevalence and, therefore, its management is an important public health issue. Aggressive management guided by pain specialists can provide adequate pain relief; however, delays in access to these specialists can negatively impact patient’s well-being. The economic value of managing chronic neuropathic pain in academic centres is discussed, in addition to determining the long term outcomes of this type of pain management., BACKGROUND: The management of chronic pain, including neuropathic pain (NeP), is a major public health issue. However, there is a paucity of data evaluating pain management strategies in real-life settings. OBJECTIVE: To inform policy makers about the economic value of managing chronic NeP in academic centres by conducting a subeconomic assessment of a Canadian multicentre cohort study aimed at determining the long-term outcomes of the management of chronic NeP in academic pain centres. Specific questions regarding the economic value of this type of program were answered by a subset of patients to provide further information to policy makers. METHODS: Baseline demographic information and several pain-related measurements were collected at baseline, three, six and 12 months in the main study. A resource use questionnaire aimed at determining NeP-related costs and the EuroQoL-5 Dimension were collected in the subset study from consenting patients. Statistical analyses were conducted to compare outcomes over time and according to responder status. RESULTS: A total of 298 patients were evaluated in the present economic evaluation. The mean (± SD) age of the participants was 53.7±14.0 years, and 56% were female. At intake, the mean duration of NeP was >5 years. Statistically significant improvements in all pain and health-related quality of life outcomes were observed between the baseline and one-year visits. Use decreased over time for many health care resources (eg, visits to the emergency room decreased by one-half), which resulted in overall cost savings. CONCLUSION: The results suggest that increased access to academic pain centres should be facilitated in Canada.

Objectives: Several tools have been developed to screen for neuropathic pain. This study examined the sensitivity of the Douleur Neuropathique en 4 Questions (DN4) in screening for various neuropathic pain syndromes. Materials and methods: This prospective observational study was conducted in 7 Canadian academic pain centers between April 2008 and December 2011. All newly admitted patients (n=2199) were approached and 789 eligible participants form the sample for this analysis. Baseline data included demographics, disability, health-related quality of life, and pain characteristics. Diagnosis of probable or definite neuropathic pain was on the basis of history, neurological examination, and ancillary diagnostic tests. Results: The mean age of study participants was 53.5 years and 54.7% were female; 83% (n=652/789) screened positive on the DN4 (≥4/10). The sensitivity was highest for central neuropathic pain (92.5%, n=74/80) and generalized polyneuropathies (92.1%, n=139/151), and lowest for trigeminal neuralgia (69.2%, n=36/52). After controlling for confounders, the sensitivity of the DN4 remained significantly higher for individuals with generalized polyneuropathies (odds ratio [OR]=4.35; 95% confidence interval [CI]: 2.15, 8.81), central neuropathic pain (OR=3.76; 95% CI: 1.56, 9.07), and multifocal polyneuropathies (OR=1.72; 95% CI: 1.03, 2.85) compared with focal neuropathies. Discussion: The DN4 performed well; however, sensitivity varied by syndrome and the lowest sensitivity was found for trigeminal neuralgia. A positive DN4 was associated with greater pain catastrophizing, disability and anxiety/depression, which may be because of disease severity, and/or these scales may reflect magnification of sensory symptoms and findings. Future research should examine how the DN4 could be refined to improve its sensitivity for specific neuropathic pain conditions.

Catastrophizing is recognized as a key psychosocial factor associated with pain-related negative outcomes in individuals with chronic pain. Longitudinal studies are needed to better understand the temporal relationship between these constructs. The aim of this study was to determine if changes in catastrophizing early in treatment predicted subsequent changes in pain intensity and interference later in treatment, or alternately, if early changes in pain intensity and interference predicted subsequent changes in catastrophizing. A total of 538 patients with neuropathic pain were recruited from 6 multidisciplinary pain clinics across Canada. Study participants were asked to complete measures of catastrophizing, pain intensity, and interference when first seen in the clinic and then again at 3- and 6-month follow-ups. Cross-lagged panel analyses were used to determine the temporal associations among the study variables. The results showed that decreases in catastrophizing early in treatment prospectively predicted improvement in both pain intensity and interference later in treatment. Converse temporal relationships were also found, where a reduction in pain intensity and interference early in treatment predicted a subsequent diminishing of catastrophizing. All 4 unique cross-lagged correlations significantly accounted for an additional 4% to 7% of the total variance. The findings are consistent with theoretical models hypothesizing a causal impact of catastrophizing on pain, suggesting a mutual causation between these factors. The results support that treatments targeting catastrophizing may influence other pain-related outcomes, and conversely that treatments aiming to reduce pain could potentially influence catastrophizing. There may therefore be multiple paths to positive outcomes.

Background: Painful diabetic neuropathy (PDN) is a frequent complication of diabetes mellitus. Current treatment recommendations are based on short-term trials, generally of ≤3 months’ duration. Limited data are available on the long-term outcomes of this chronic disease. The objective of this study was to determine the long-term clinical effectiveness of the management of chronic PDN at tertiary pain centres. Methods: From a prospective observational cohort study of patients with chronic neuropathic non-cancer pain recruited from seven Canadian tertiary pain centres, 60 patients diagnosed with PDN were identified for analysis. Data were collected according to Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials guidelines including the Brief Pain Inventory. Results: At 12-month follow-up, 37.2% (95% confidence interval [CI], 23.0-53.3) of 43 patients with complete data achieved pain reduction of ≥30%, 51.2% (95% CI, 35.5-66.7) achieved functional improvement with a reduction of ≥1 on the Pain Interference Scale (0-10, Brief Pain Inventory) and 30.2% (95% CI, 17.2-46.1) had achieved both these measures. Symptom management included at least two medication classes in 55.3% and three medication classes in 25.5% (opioids, antidepressants, anticonvulsants). Conclusions: Almost one-third of patients being managed for PDN in a tertiary care setting achieve meaningful improvements in pain and function in the long term. Polypharmacy including analgesic antidepressants and anticonvulsants were the mainstays of effective symptom management.

Objective The mismatch negativity (MMN), an auditory event-related potential, has been identified as a good indicator of recovery of consciousness during coma. We explored the predictive value of the MMN and other auditory-evoked potentials including brainstem and middle-latency potentials for predicting awakening in comatose patients after cardiac arrest or cardiogenic shock. Materials and Methods Auditory brainstem, middle-latency (Pa wave), and event-related potentials (N100 and MMN waves) were recorded in 17 comatose patients and 9 surgical patients matched by age and coronary artery disease. Comatose patients were followed up daily to determine recovery of consciousness and classified as awakened and nonawakened. Results Among the auditory-evoked potentials, the presence or absence of MMN best discriminated between patients who awakened or those who did not. Mismatch negativity was present during coma in all patients who awakened (7/7) and in 2 of those (2/10) who did not awaken. In patients who awakened and in whom MMN was detected, 3 of those awakened between 2 and 3 days and 4 between 9 and 21 days after evoked potential examination. All awakened patients had intact N100 waves and identifiable brainstem and middle-latency waves. In nonawakened patients, N100 and Pa waves were detected in 5 cases (50%) and brainstem waves in 9 (90%). Conclusions The MMN is a good predictor of awakening in comatose patients after cardiac arrest and cardiogenic shock and can be measured days before awakening encouraging ongoing life support.

Background The objective of this study was to compare the effect of thoracic paravertebral block (TPVB) and local anesthetic (LA) on persistent postoperative pain (PPP) 1 year following breast cancer surgery. Secondary objectives were to compare the effect on arm morbidity and quality of life. Methods Women scheduled for elective breast cancer surgery were randomly assigned to either TPVB or LA followed by general anesthesia. An NRS value of >3 at rest or with movement 1 year following surgery defined PPP. Blinded interim analysis suggested rates of PPP much lower than anticipated, making detection of the specified 20 % absolute reduction in the primary outcome impossible. Recruitment was stopped, and all enrolled patients were followed to 1 year. Results A total of 145 participants were recruited; 65 were randomized to TPVB and 64 to LA. Groups were similar with respect to demographic and treatment characteristics. Only 9 patients (8 %; 95 % CI 4–14 %) met criteria for PPP 1 year following surgery; 5 were in the TPVB and 4 in the LA group. Brief Pain Inventory severity and interference scores were low in both groups. Arm morbidity and quality of life were similar in both groups. The 9 patients with PPP reported shoulder-arm morbidity and reduced quality of life. Conclusions This study reports a low incidence of chronic pain 1 year following major breast cancer surgery. Although PPP was uncommon at 1 year, it had a large impact on the affected patients’ arm morbidity and quality of life.

Background Uncertainty regarding the long-term functional outcome of patients who awaken from coma after cardiac operations is difficult for families and physicians and may delay rehabilitation. We studied the long-term functional status of these patients to determine if duration of coma predicted outcome. Methods We followed 71 patients who underwent cardiac operations; recovered their ability to respond to verbal commands after coma associated with postoperative stroke, encephalopathy, and/or seizures; and were discharged from the hospital. The Glasgow Outcome Scale Extended (GOSE) was used to assess functional disability 2 to 4 years after discharge. Outcomes were classified as favorable (GOSE scores 7 and 8) and unfavorable (GOSE scores 1–6). Results Of 71 patients identified, 39 were interviewed, 15 died, 1 refused to be interviewed, and 16 were lost to follow-up. Of the 54 patients with completed GOSE evaluations, only 15 (28%) had favorable outcomes. Among patients with unfavorable outcomes, 15 (28%) died, 14 (26%) survived with moderate disabilities, and 10 (18%) had severe disabilities. Factors associated with unfavorable outcomes were increases in duration of coma ( p = 0.007), time in intensive care ( p = 0.006), length of hospitalization ( p = 0.004), and postoperative serum creatine kinase levels ( p = 0.006). Only duration of coma was an independent predictor of unfavorable outcome (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.008–1.537; p = 0.042). Patients with durations of coma greater than 4 days were more likely to have unfavorable outcomes (OR, 5.1; 95% CI, 1.3–21.3; p = 0.02). Conclusions Two thirds of comatose patients who survived to discharge after cardiac operations had unfavorable long-term functional outcomes. A longer duration of unconsciousness is a predictor of unfavorable outcome.

Background. Chronic pain (CP) accounts for 10–16% of emergency department (ED) visits, contributing to ED overcrowding and leading to adverse events.Objectives. To describe patients with CP attending the ED and identify factors contributing to their visit.Methods. We used a mixed-method design combining interviews and questionnaires addressing pain, psychological distress, signs of opioid misuse, and disability. Participants were adults who attended the EDs of a large academic tertiary care center for their CP problem.Results. Fifty-eight patients (66% women; mean age 46.5, SD = 16.9) completed the study. The most frequently cited reason (60%) for ED visits was inability to cope with pain. Mental health problems were common, including depression (61%) and anxiety (45%). Participants had questions about the etiology of their pain, concerns about severe pain-related impairment, and problems with medication renewals or efficacy and sometimes felt invalidated in the ED. Although most participants had a primary care physician, the ED was seen as the only or best option when pain became unmanageable.Conclusions. Patients with CP visiting the ED often present with complex difficulties that cannot be addressed in the ED. Better access to interdisciplinary pain treatment is needed to reduce the burden of CP on the ED.

Objectives To describe clinical and brain imaging characteristics of patients who recovered and did not recover consciousness from a coma after cardiac surgery and to investigate predictors of the duration of unconsciousness in those patients who ultimately recovered consciousness. Design A retrospective analysis from a cohort of patients who developed coma after cardiac surgery. Setting A single university hospital. Participants One hundred twelve patients with postoperative stroke, encephalopathy, and/or seizures who remained in coma longer than 24 hours after cardiac surgery. Interventions None. Measurements and Main Results The authors analyzed the patients' perioperative and intraoperative characteristics, laboratory values, noncontrast head computed tomography (CT) scans, and outcomes. Patients who did not recover consciousness (n = 16) were more likely to have been classified preoperatively as New York Heart Association class III/IV ( p = 0.037). In patients who recovered consciousness (n = 96), only increased preoperative serum creatinine was an independent predictor of a longer duration of unconsciousness ( p = 0.011). In patients who eventually recovered consciousness and had no acute findings on brain imaging, preoperative creatinine ( p = 0.014), the lowest postoperative hemoglobin ( p = 0.039), and surgical emergency ( p = 0.045) were independent predictors of the duration of unconsciousness ( p = 0.002). In patients who regained consciousness but had acute findings on brain imaging, cardiogenic shock ( p = 0.012) and the insertion of an intra-aortic balloon pump before or during surgery ( p = 0.025) predicted longer durations of unconsciousness ( p Conclusions In patients who ultimately recovered consciousness after being in a coma for at least 24 hours after cardiac surgery and have no abnormality on a brain CT scan, elevated preoperative serum creatinine, urgent cardiac surgery, and lower postoperative hemoglobin were correlated with an increased duration of unconsciousness.

ObjectivesModified ultrafiltration is a technique after cardiopulmonary bypass whereby blood withdrawn from the aortic cannula is passed across a semipermeable membrane to hemoconcentrate. Unblinded trials have suggested that modified ultrafiltration is efficacious for blood conservation. The objective of this trial was to assess the feasibility of a model testing modified ultrafiltration in which all members of the surgical team were blinded to the intervention.MethodsPatients (

Shed mediastinal blood during cardiopulmonary bypass (cardiotomy blood) contains fat, particulate matter, and vasoactive mediators that can adversely affect the pulmonary and systemic vasculature, as well as impair gas exchange. Our aim was to evaluate the effects of processing cardiotomy blood on cardiovascular and pulmonary function after cardiac surgery.Patients undergoing coronary artery bypass or aortic valve surgery, or both, using cardiopulmonary bypass were randomly allocated to receiving processed (treated, n = 132) or unprocessed shed blood (control, n = 134) In the treated group, shed blood was processed by centrifugation, washing, and additional filtration. Pulmonary function, arterial and venous blood gases, and hemodynamics were measured before, immediately after, and 2 hours after cardiopulmonary bypass in a consecutive subset of patients (n = 154). Patients and treating physicians were blinded to treatment assignment.Preoperative characteristics were similar between groups. There were no significant differences between groups in indexes of pulmonary mechanical function at any of the measured time points. Patients in the treated group demonstrated reduced pulmonary and systemic vascular resistance (both p0.01) as well as increased cardiac index in the perioperative period (2.6 +/- 0.07 versus 2.3 +/- 0.06 L . min(-1) . m(-2) at 2 hours after CPB, p = 0.004). Larger volumes of cardiotomy blood were associated with greater changes in systemic and pulmonary vascular resistance. Indicators of pulmonary gas exchange were similar between groups at all measured time points. Treated patients demonstrated a trend toward reduced length of ventilation (11.0 +/- 1.9 versus 13.9 +/- 2.4 hours, p = 0.12).Processing of shed mediastinal blood improves cardiopulmonary hemodynamics and may reduce ventilatory requirements after cardiac surgery.

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°C during aortic crossclamping and then randomized to rewarming to either 34°C or 37°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.

This study aims to examine if mindfulness is associated with pain catastrophizing, depression, disability, and health-related quality of life (HRQOL) in cancer survivors with chronic neuropathic pain (CNP). We conducted a cross-sectional survey with cancer survivors experiencing CNP. Participants (n = 76) were men (24 %) and women (76 %) with an average age of 56.5 years (SD = 9.4). Participants were at least 1 year post-treatment, with no evidence of cancer, and with symptoms of neuropathic pain for more than three months. Participants completed the Five Facets Mindfulness Questionnaire (FFMQ), along with measures of pain intensity, pain catastrophizing, pain interference, depression, and HRQOL. Mindfulness was negatively correlated with pain intensity, pain catastrophizing, pain interference, and depression, and it was positively correlated with mental health-related HRQOL. Regression analyses demonstrated that mindfulness was a negative predictor of pain intensity and depression and a positive predictor of mental HRQOL after controlling for pain catastrophizing, age, and gender. The two mindfulness facets that were most consistently associated with better outcomes were non-judging and acting with awareness. Mindfulness significantly moderated the relationships between pain intensity and pain catastrophizing and between pain intensity and pain interference. It appears that mindfulness mitigates the impact of pain experiences in cancer survivors experiencing CNP post-treatment. This study suggests that mindfulness is associated with better adjustment to CNP. This provides the foundation to explore whether mindfulness-based interventions improve quality of life among cancer survivors living with CNP.

This prospective observational cohort study addressed the long-term clinical effectiveness of the management of chronic neuropathic noncancer pain at 7 Canadian tertiary pain centers. Patients were treated according to standard guidelines and were followed at 3, 6, 12, 18, and 24 months. Standard outcome measures for pain, mood, quality of life, and overall treatment satisfaction were administered, with the primary outcome measure designated as the composite of 30% reduction in average pain intensity and 1-point decrease in the mean Interference Scale Score (0-10) of the Brief Pain Inventory at 12 months relative to baseline. Of 789 patients recruited, mean age was 53.5 ± 14.2 years (55% female) and mean duration of pain was 4.88 ± 5.82 years. Mean average pain intensity (0-10) at baseline was 6.1 ± 1.9. All standard outcome measures showed statistically significant improvement at 12 months relative to baseline (P < .001). However, only 23.7% attained clinically significant improvement in pain and function at 12 months as the primary outcome measure. Univariable analyses showed poorer outcomes at 12-month follow-up with longer duration of pain (P = .002), greater cigarette use (P = .01), more disability compensation (P = .001), and higher opioid doses at baseline and at 12 months (P < .02). Our present treatment modalities provide significant long-term benefit in only about a quarter of patients with neuropathic pain managed at tertiary care pain clinics. Opioid therapy may not be beneficial for the long term. Perspective: Evidence-based treatment of chronic neuropathic pain provides long-term benefit in only about one-quarter of patients seen in tertiary care centers. Opioid therapy may not be beneficial.

Background— Observational studies suggest that skeletonization of the internal thoracic artery (ITA) can improve conduit flow and length and reduce deep sternal infections and postoperative pain. We performed a randomized, double-blind, within-patient comparison of skeletonized and nonskeletonized ITAs in patients undergoing coronary surgery. Methods and Results— Patients (n=48) undergoing bilateral ITA harvest were randomized to receive 1 skeletonized and 1 nonskeletonized ITA. Intraoperatively, ITA flow was assessed directly and with a Doppler flow probe before and after topical application of papaverine. ITA harvest time and conduit length were recorded. A blinded assessment of pain (visual analog scale) and dysesthesia (physical examination) was performed at discharge, at 2 weeks, and at a 3-month follow-up. Sternal perfusion was assessed with nuclear imaging (n=7). Skeletonization required longer ITA harvest times (27±1 versus 24±1 minutes; P =0.04). There was a trend toward increased ITA length in the skeletonized group (18.2±0.3 versus 17.7±0.3 cm; P =0.09). In situ ITA flow was lower in skeletonized arteries (7.4±0.9 versus 10.1±1.0 mL/min; P = 0.01) and increased significantly after ITA division and papaverine application. Postanastomotic flows were similar between groups. Skeletonization was associated with decreased pain at the 3-month follow-up and a reduction in major sensory deficits at the 4-week and 3-month (17% versus 50%; P =0.002) follow-ups. Baseline adjusted sternal perfusion was significantly greater by 17±6% ( P =0.03) on the skeletonized side. Conclusions— Skeletonization results in reduced postoperative pain and dysesthesia and increased sternal perfusion at follow-up but does not produce increased conduit flow. ITA skeletonization may be a strategy for reducing morbidity after CABG.

Purpose: To report transesophageal echocardiographic (TEE) findings consistent with intraoperative acute diastolic dysfunction in a series of patients undergoing thoracoabdominal aortic aneurysm (TAAA) repair. Methods: A series of nine consecutive patients underwent TAAA repair with intraoperative TEE monitoring. Surgical repair was performed with the adjunct of a left atrio-femoral bypass. Invasive arterial and venous pressures were monitored. Intraoperative TEE was utilized to assess the diastolic function before, and during aortic cross clamping. Diastolic dysfunction was defined as a mitral inflow pulsed wave Doppler (E: A ratio) 1 (1.3 ± 0.08) before aortic cross clamping. During cross clamp, the E: A ratio decreased to 1 (1.2 ± 0.09). Three of the patients with intraoperative diastolic dysfunction developed postoperative myocardial infarction. Conclusions: Chronic diastolic dysfunction is a well-known entity. This report describes acute diastolic dysfunction, which was observed frequently in patients undergoing TAAA during aortic cross clamp. Further research is required to confirm this phenomenon and determine its possible association with increased postoperative cardiac morbidity. Objectif : Presenter les resultats de l’echocardiographie transœsophagienne (ETO) compatibles avec une dysfonction peroperatoire diastolique aigue chez une serie de patients operes pour un anevrysme aortique thoraco-abdominal (AATA). Methode : Neuf patients consecutifs ont subi la reparation d’un AATA sous monitorage peroperatoire avec ETO. Une derivation auriculo-femorale gauche et un monitorage endovasculaire des pressions arterielle et veineuse ont ete utilises. L’ETO peroperatoire a servi a evaluer la fonction diastolique avant et pendant le clampage de la crosse aortique. La dysfonction diastolique etait une onde Doppler pulsee d’entree mitrale (ratio E : A) < 1.

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 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.

The primary objective of this prospective cohort study was to assess the impact of ambulatory surgery on patient function one week and one month following surgery among surgical patients ≥ 65 yr of age. Secondary objectives were to determine whether changes in patient function were correlated with increased burden of care in the patient's primary caregiver and with patient assessments of postoperative pain and quality of life.Following Research Ethics Board approval, patients aged ≥ 65 yr undergoing elective ambulatory surgery and their caregivers were recruited. Patients completed the système de mesure de l'autonomie fonctionnelle (SMAF) and the Brief Pain Inventory. Primary caregivers completed the Zarit Burden Interview (ZBI). All measurements were obtained preoperatively and on postoperative days (POD) 7 and 30.Patient function decreased on POD 7 and had not returned to baseline on POD 30 (mean change in SMAF 6.9; 95% confidence interval (CI) 5.3 to 8.4 on POD 7 and mean change in SMAF 2.6; 95% CI 1.3 to 4.0 on POD 30). Interval changes in caregiver burden were not significant (mean change in ZBI -0.4; 95% CI -1.8 to 0.96 on POD 7 and mean change in ZBI -0.6; 95% CI -2.1 to 0.8 on POD 30). Decreased patient function was associated with increased caregiver burden at all time points (P0.001). Decreased caregiver function at baseline was also associated with higher ZBI (linear association 0.71; P = 0.02).Patients exhibited reduced function seven days following ambulatory surgery. Patient function largely recovered by POD 30. Caregiver burden was variable and influenced by both patient and caregiver function. This trial was registered with Clinical Trials.gov (NCT01382251).

Objective: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) and the Cardiac Anesthesia Risk Evaluation (CARE) score are risk indices designed in the mid-1990s to predict mortality after cardiac surgery. This study assesses their ability to provide risk-adjusted mortality in a contemporary cardiac surgical population. Methods: The mortality probability was estimated with the additive and logistic EuroSCORE, and CARE score, for 3818 patients undergoing cardiac surgery at one institution between 1 April 2006 and 31 March 2009. Model discrimination was obtained using the area under the receiver operating characteristics (ROC) curve and calibration using the appropriate chisquare goodness-of-fit test. Recalibration of risk models was obtained by logistic calibration, when needed. Calculation of risk-adjusted mortality was performed for the institution and eight surgeons, using each model before and when needed, after recalibration. Results: The area under the ROC curve is 0.72 (95% confidence interval (CI): 0.71—0.74) with the additive EuroSCORE, 0.84 (95% CI: 0.83—0.85) with the logistic EuroSCORE, and 0.79 (95% CI: 0.78—0.81) with the CARE score. The additive and logistic EuroSCORE have poor calibration, predicting a hospital mortality of 6.24% and 7.72%, respectively, versus an observed mortality of 3.25% (P < 0.001). Consequently, the risk-adjusted mortality obtained with those models is significantly underestimated for the institution and all surgeons. The CARE score has good calibration, predicting a mortality of 3.38% (P = 0.50). The hospital risk-adjusted mortality with the recalibrated additive and logistic EuroSCORE and CARE score is 3.24% (95% CI: 3.05— 3.43%), 3.25% (95% CI: 3.05—3.44%), and 3.12% (95% CI: 2.94—3.34%), respectively. The individual surgeons’ risk-adjusted mortality is similar with the recalibrated EuroSCORE models and CARE score, identifying two surgeons with higher rates than the hospital average mortality. Conclusions: The original additive and logistic EuroSCORE models significantly overestimate the risk of mortality after cardiac surgery. However, after recalibration both models provide reliable risk-adjusted mortality results. Despite its lower discrimination as compared with the logistic EuroSCORE, the CARE score remains calibrated a decade after its development. It is as robust as the recalibrated additive and logistic EuroSCORE to perform risk-adjusted mortality analysis. # 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Background: Mild to moderate systemic hypothermia is commonly used as a cerebral protective strategy during adult cardiac surgery. The benefits of this strategy for routine cardiac surgery have been questioned and the adverse effects of hyperthermia demonstrated. The purpose of the present study was to examine current temperature management and monitoring practices during adult cardiac surgery using CPB in Canada.Methods: Web-based survey referring to adult cases undergoing cardiac surgery using CPB without the use of deep hypothermic circulatory arrest. Thirty-two questionnaires were completed, representing a 100% response rate.Results: The usual management is to cool patients during CPB at 30 (94%) centers for low-risk (isolated primary CABG) cases and at 31 (97%) centers for high-risk (all other) cases. The average nadir temperature at the target site achieved on CPB is 34°C (range 28°C - 36°C). At 26 (81%) centers, patients are typically rewarmed to a target temperature between 36°C and 37°C before separation from CPB. Only 6 (19%) centers reported that thermistors and coupled devices used to monitor blood temperature are checked for accuracy or calibrated according to the product operating directive’s schedule or more often.Conclusions: Contemporary management of adult cardiac surgery under CPB still involves induction of mild to moderate systemic hypothermia. Significant practice variation exists across the country with respect to target temperatures for cooling and rewarming, as well as the site for temperature monitoring. This probably reflects the lack of definitive evidence. There is a need for well-conducted clinical trials to provide more robust evidence regarding temperature management.

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 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.

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 e4 genotype (APOE-e4) 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-e4 in patients undergoing open aortic repair. 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. 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-e4 genotype was not associated with either delirium or POCD following adjustment for covariates. 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).

We sought to determine the pharmacokinetic and pharmacodynamic behaviour of a continuous infusion of nifedipine given for prevention of myocardial ischaemia following coronary artery bypass graft (CABG) surgery. Patients scheduled for elective CABG, who had good left ventricular function, were included. Only normotensive patients who did not require treatment with vasoactive drugs and were bleeding less than 100 ml.hr-1 following surgery were included. The patients were randomly distributed into two groups: a control group not receiving any treatment and a treated group receiving a bolus (3 micrograms.kg-1.min-1 for 5 min) and maintenance (0.2 micrograms.kg-1.min-1) infusion of nifedipine, starting upon arrival in the recovery room and continuing for four hours. Patients given nifedipine were compared with control patients in order to determine the effects of nifedipine on haemodynamic function and on the postoperative incidence of hypotension, hypertension, myocardial ischaemia and infarction. Continuous 2-lead Holter monitoring was used to detect myocardial ischaemia. Infarction was diagnosed by 12-lead ECGs and by assessment of the MB-isoenzyme creatine kinase. The infusion of nifedipine rapidly achieved and maintained plasma concentrations between 30 and 40 ng.ml-1. The pharmacokinetic studies revealed a systemic clearance of nifedipine of 0.371 +/- 0.101 L.hr-1.kg-1, an apparent volume of distribution of 0.764 +/- 0.288 L.kg-1 and an elimination half-life of 1.4 +/- 0.6 hr. No correlation was found between plasma concentration of nifedipine and mean arterial pressure (MAP). The incidence of postoperative hypotension (MAP70 mmHg) and hypertension (MAP100 mmHg) was comparable between the groups. All haemodynamic variables were similar in both groups during the study period. Of 23 patients who received nifedipine, none showed evidence of ischaemia within six hours of starting the infusion. During the same period, five of 24 patients in the control group had ST-segment deviation suggestive of myocardial ischaemia (P = 0.05, Fisher's exact test). Three patients in the control group and none in the nifedipine group suffered perioperative myocardial infarction (P = NS). In conclusion, the continuous infusion of nifedipine used in this study is safe and reduces the incidence of myocardial ischaemia in normotensive patients with good left ventricular function following CABG. Further studies of larger number of patients are required to determine the role of calcium entry blockers following coronary artery surgery.

This study was undertaken in order to compare the effectiveness of amrinone and dobutamine as primary treatment of a low cardiac output (CO) after coronary artery bypass graft (CABG) surgery. Thirty patients with preoperative left ventricular dysfunction participated in this open-label randomized study. Patients were included if they failed to separate from cardiopulmonary bypass (CPB) without inotropic support or if they had a cardiac index (CI) less than 2.4 L/min/m2 after CPB regardless of the blood pressure, in the presence of adequate filling pressures. The treatment objectives were to separate from CPB and achieve a CIor = 2.4 L/min/m2 and a mean arterial pressureor = 70 mmHg. Patients treated with amrinone received 0.75 mg/kg followed by 10 micrograms/kg/min; when the objectives were not achieved within five minutes, another 0.75 mg/kg was given. Patients treated with dobutamine received an initial infusion of 5 micrograms/kg/min increased stepwise to 15 micrograms/kg/min if necessary. Eleven of 15 amrinone versus 6 of 15 dobutamine patients achieved the predefined treatment objectives with the test drug alone (P = NS). Comparisons of hemodynamics in patients treated solely with amrinone (n = 7) or dobutamine (n = 6) after CPB showed no significant differences between the treatment groups. The incidence of myocardial ischemia as detected by Holter monitor was 36% with amrinone and 33% with dobutamine. Two patients suffered ventricular fibrillation and two had significant supraventricular tachyarrhythmias (heart rate130/min) during treatment with dobutamine alone, whereas no significant arrhythmias occurred in the amrinone group (P = NS). Six dobutamine patients (40%) had postoperative myocardial infarction (MI) as opposed to none among the amrinone patients (P = 0.017). These results indicate that amrinone compares favorably with dobutamine as a primary treatment of low CO after CABG. Further study in a larger number of patients will be required in order to determine if the lower incidence of MI in the amrinone group was due to the treatment drug.

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.

The objective of this study was to determine if surface-modifying additive (SMA) cardiopulmonary bypass (CPB) circuits are associated with a lower rate of cerebral microemboli during CPB compared with standard circuits. In a 2 × 2 factorial design, patients undergoing coronary artery bypass graft surgery were randomized to SMA or standard CPB circuits (with and without methyl-prednisolone). Transcranial Doppler was used to detect high-intensity transient signals (HITS) in both middle cerebral arteries. HITS were counted from onset to end of CPB. Intervals of interest were as follows: period 1, from CPB onset to aortic cross-clamping; period 2, from aortic cross-clamping to immediately before de-clamping; period 3, from aortic de-clamping to before aortic side-clamping; period 4, from the application of the aortic side clamp to immediately before the release of the side clamp; period 5, from aortic side clamp release to the end of CPB. There were 14 patients in each circuit group. No significant differences were found on the partial and total counts of HITS (medians [25th, 75th percentile]) between patients exposed to standard (total count: 228 HITS [174, 280]) and SMA circuits (total count: 156 HITS [104, 356]; p = .427). The median of the sum of HITS per patient associated with perfusionist interventions was not different between both circuit groups (standard: 17 HITS [7, 80]; SMA: 43 HITS [13, 168]; p = .085). This study, with a sample size of 28 patients, indicates that it is unlikely to find any difference in the count of HITS during CPB that is greater than 117 HITS between the two CPB circuits. Moreover, our findings emphasize the relevance of minimizing additional sources of cerebral microembolization during CPB that are not directly related to the biocompatible nature of the SMA CPB circuit.

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.

Objective: Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used after coronary artery bypass surgery (CABG), yet their effects have seldom been evaluated in randomized controlled settings. The aim of this study was to examine the efficacy and safety of a commonly used NSAID, naproxen. We hypothesized that naproxen would reduce postoperative pain following CABG without increasing complications. Methods: Patients (NZ98) undergoing primary CABG were randomized to receive naproxen (500 mg q12h!5 doses via suppository started 1 h after operation, followed by oral 250 mg q8h!6 doses) or placebo. Standard analgesic and anti-emetic regimens were available to both patient groups. Interventions were double-blinded. Primary end-points were postoperative pain measured before and after chest physiotherapy by visual analog scale and pulmonary slow vital capacity (SVC). Results: Baseline characteristics were equivalent between the two groups. Over the first 4 postoperative days, naproxen decreased pain by 47G17% on average before chest physiotherapy (PZ0.034), and 44G13% after chest physiotherapy (PZ0.0092). Patients who received naproxen also had better preservation of SVC over the first 4 postoperative days (mean loss of SVC from baseline: 2.1G0.1 vs. 2.5G0.1 l, naproxen vs. placebo, PZ0.0032). This was concomitant with a lower white blood cell count observed in naproxen patients (9.2G0.3 vs. 12.7G1.5!10 9 /l, naproxen vs. placebo, PZ0.03). Patients who received naproxen had more chest tube drainage after 4 h postoperatively, but there was no difference in the incidence or amount of transfusions. There was no difference in medication use, length of stay, or in the incidence of atrial fibrillation, azotemia, and other complications. Conclusions: Naproxen is an effective and low-cost adjunct for optimization of pain control and lung recovery after CABG. Its use may result in increased chest tube drainage, but no apparent increase in other complications. q 2004 Published by Elsevier B.V.

To decrease the complications associated with cardiopulmonary bypass, novel biomaterials have been introduced that may be less thrombogenic than standard synthetic surfaces.Thirty-four patients undergoing coronary artery bypass grafting were randomized to bypass using either a control circuit or a circuit prepared "tip-to-tip" with a triblock-copolymer (polycaprolactone-polydimethylsiloxane-polycaprolactone).There was a progressive increase in thrombin generation in the control group during bypass, which was not seen in the test group. The test surface decreased the release of tissue plasminogen activator and plasmin-alpha2-antiplasmin complex formation (p0.005). There was also an increased platelet count and a decreased platelet activation in the test group, as detected by GMP-140 expression and beta-thromboglobulin release (p = 0.017). There was also significantly more debris that accumulated on the arterial filter in the control group, as confirmed by scanning electron microscopy.This clinical trial has demonstrated a significant difference in the hematologic effects of the test circuits, with evidence of platelet preservation, decreased fibrinolysis, and decreased thrombin generation. A larger trial would be necessary to establish the clinical relevance of these differences.

Laboratory studies demonstrate that mild degrees of brain cooling (2 degrees C to 5 degrees C) confer substantial protection from ischemic brain injury, and that mild elevation of brain temperature can be markedly deleterious. During hypothermic cardiopulmonary bypass (CPB) patients are made hypothermic and then rewarmed at a time when they are exposed to neurological insults. Our studies show that during rewarming, peak brain temperatures near 39 degrees C often are achieved inadvertently. We hypothesize that maintaining brain temperature < or = 34 degrees C during and after CPB will reduce the incidence of postoperative neuropsychological deficits. We present safety data from a study of 30 patients assigned either to conventional hypothermic CPB with rewarming or a protocol where brain temperature is raised only to 34 degrees C at the time of separation from CPB. There was no difference in bleeding, cardiac morbidity, or time to extubation between groups. We designed a neuropsychological test battery to detect postoperative neuropsychological deficits and tested its usefulness in a preliminary sample of 15 patients undergoing hypothermic CPB. We found patient acceptability and compliance were good. Sensitivity also seemed adequate in that 30% of patients were identified as having deteriorated at 1 week postoperatively compared to preoperatively, a result similar to that reported by others. Clinical trials of the efficacy of mild hypothermia in modulating brain injury in humans are needed before techniques of CPB can be designed to optimize neuroprotection.

We administered sodium nitroprusside (SNP) or nifedipine intravenously to patients who became hypertensive after elective coronary revascularization and compared their effects on hemodynamics and the electrocardiogram in a parallel, randomized, open-label study. Four of 21 patients treated with nifedipine required the addition of SNP to maintain mean arterial pressure less than 90 mm Hg, compared with 4 of 28 patients in the SNP group who required the addition of nifedipine. The success rates of nifedipine (81%) and SNP (86%) were not significantly different. There was no difference in the incidence of adverse ST-segment changes during drug infusion (4% versus 5%) or perioperative myocardial infarction (9.5% versus 10.7%) in the nifedipine versus SNP groups, respectively. The plasma nifedipine concentration (mean value +/- SD) at steady state for 21 patients receiving nifedipine was 119 +/- 42.5 ng/mL. The pharmacokinetic variables for nifedipine were as follows (mean values +/- SD): systemic clearance, 0.525 +/- 0.228 L.h-1.kg-1; apparent volume of distribution, 0.738 +/- 0.446 L/kg; and elimination half-life, 1.02 +/- 0.51 h. These values are similar to those reported previously in healthy volunteers. We conclude that intravenous nifedipine can be used safely to control hypertension after coronary revascularization but were unable to demonstrate an advantage of nifedipine compared with SNP in preventing postoperative ischemia or infarction in this group of patients who had good left ventricular function.

The effect of nitrous oxide (N2O) on ischaemic myocardium was investigated in the presence of beta-receptor blockade. Three anaesthetics were compared in each of six dogs: isoflurane 1.8% alone, isoflurane 1.4% with 50% N2O, and isoflurane 1.8% with 50% N2O. Heart rate (HR), systolic aortic blood pressure (SBP), and left atrial pressure (LAP) were held constant during the three treatments. The left anterior descending coronary artery (LAD) was cannulated and perfused with an autoperfusion circuit. Systolic segment length was measured with a sonomicrometer in the LAD and circumflex regions. Regional myocardial blood flow was measured using radioactive microspheres. Propranolol was administered intravenously and then measurements were made during imposition of a stenosis on the perfusion circuit sufficient to decrease systolic shortening by 30%. The substitution of 50% N2O for 0.4% isoflurane had no effect on systolic shortening or transmural myocardial blood flow in the ischaemic or normal region. When N2O was added to 1.8% isoflurane, systolic shortening decreased by 34.6% in the ischaemic and 57.3% in the normally perfused region, while transmural myocardial blood flow distribution did not change significantly. The decrease in shortening was therefore not due to increased ischaemia. These results were similar to those of a previous experiment which was identical except that beta-blockade was absent. It is concluded that beta-receptor blockade does not markedly alter the response of normal or ischaemic myocardium to N2O.

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°C (hypothermic; n=133) or 37°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.

Two equipotent anesthetic regimens, isoflurane 1.8% in 50% nitrogen/oxygen and isoflurane 1.4% in 50% nitrous oxide/oxygen, were compared to test if nitrous oxide, without changing the depth of anesthesia, can affect myocardial function, blood flow, and metabolism in an ischemic region of the heart. In 14 dogs, anesthesia was induced with sodium thiopental. Following tracheal intubation, they were ventilated with isoflurane in oxygen. The chest was opened, the LAD coronary artery cannulated, and flow to it controlled with an autoperfusion circuit. Systolic shortening in the LAD and circumflex regions was measured with a sonomicrometer via pairs of piezo-electric crystals placed in the subendocardium. Regional myocardial blood flow was measured with radioactive microspheres injected into the left atrium. Regional myocardial lactate metabolism was assessed by withdrawing blood from a catheter placed in the anterior cardiac vein. Measurements were made during the imposition of a stenosis on the perfusion circuit sufficient to decrease systolic shortening by 10-20%. The same stenosis was imposed three times in a randomized and balanced crossover design. Treatment with nitrous oxide was associated with small increases in heart rate and systolic blood pressure (5 and 8%, respectively), as well as a 19% reduction in systolic shortening and a 30% fall in endo/epi blood flow ratio in the hypoperfused LAD region distal to the stenosis. Lactate extraction was low or negative during both anesthetics, but differences were not statistically significant. The data indicate that the substitution of 50% nitrous oxide for 0.4% isoflurane caused a reduction in mechanical function and a further maldistribution of blood flow in ischemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was designed to determine if nitrous oxide can worsen myocardial ischemia by directly affecting coronary tone in the absence of changes in myocardial oxygen consumption. Three anesthetics were compared in each animal: isoflurane 1.8% alone, isoflurane 1.4% with 50% nitrous oxide, and isoflurane 1.8% with 50% nitrous oxide. Heart rate, systolic aortic pressure and left atrial pressure were held constant during the three treatments. In 12 isoflurane-anesthetized dogs the chest was opened and the left anterior descending (LAD) coronary artery cannulated and perfused with an autoperfusion circuit. Systolic segment shortening was measured in the LAD and circumflex regions of the heart with a sonomicrometer. Regional myocardial blood flow was measured with radioactive microspheres. Measurements were made during imposition of a stenosis on the perfusion circuit sufficient to decrease systolic shortening by 30–50%. The same stenosis was imposed three times in a randomized and balanced crossover design. When heart rate, blood pressure, and left atrial pressure were held constant, the substitution of 50% nitrous oxide for 0.4% isoflurane had no effect on myocardial blood flow or function in the ischemic or normal region. When nitrous oxide was added to 1.8% isoflurane, systolic shortening decreased by 35% in the ischemic and 27% in the normally perfused region, but myocardial blood flow was unaffected. The decrease in shortening was therefore not due to increased ischemia. The effects of nitrous oxide on ischemic myocardium can be explained by its well-known hemodynamic and direct myocardial actions. These results suggest that nitrous oxide does not have important direct effects on the coronary circulation.

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.