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Supplemental Digital Content is Available in the Text. None of the mindfulness-based clinical trials for chronic pain included in this review analyzed the interaction effects between mindfulness interventions and concomitant analgesic drug therapies., Most patients with chronic pain do not find adequate pain relief with a single treatment, and accumulating evidence points to the added benefits of rational combinations of different treatments. Given that psychological therapies, such as mindfulness-based interventions (MBIs), are often delivered in conjunction with concomitant analgesic drug therapies (CADTs), this systematic scoping review examines the evidence for any interactions between MBIs and CADTs. The protocol for this review has been published and registered. MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and PsycINFO databases were searched until July 2019. We included randomized controlled trials that evaluated the efficacy of MBIs for the treatment of chronic pain. A total of 40 randomized controlled trials (2978 participants) were included. Thirty-nine of 40 (97.5%) included mindfulness-based clinical trials allowed the use of CADTs. However, only 6 of these 39 (15.4%) trials provided adequate details of what these CADTs were, and only 4 (10.3%) trials controlled for CADTs. Of great relevance to this review, none of the included trials analyzed the interactions between MBIs and the CADTs to determine whether they have an additive, synergistic, or antagonistic effect on chronic pain. Adverse events were inconsistently reported, and no judgment could be made about safety. Future trials assessing the interactions between MBIs and CADTs, with better harms reporting, are needed to better define the role of MBIs in the management of chronic pain.

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.

Introduction:. Most current chronic pain treatment strategies have limitations in effectiveness and tolerability, and accumulating evidence points to the added benefits of rational combinations of different therapies. However, most published clinical trials of treatment combinations have involved combinations of 2 drugs, whereas very little research has been performed to characterize interactions between drug and nondrug interventions. Mindfulness-based interventions (MBIs) have been emerging as a safe and potentially effective treatment option in the management of chronic pain, but it is unclear how MBIs can and should be integrated with various other pain treatment interventions. Thus, we seek to review available clinical trials of MBIs for chronic pain to evaluate available evidence on the interactions between MBIs and various pharmacological treatments. Methods:. A detailed search of trials of MBIs for the treatment of chronic pain in adults will be conducted on the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO from their inception until the date the searches are run to identify relevant randomized controlled trials. Primary outcomes will include the following: (1) what concomitant analgesic drug therapies (CADTs) were allowed; (2) if and how trials controlled for CADTs and analyzed their interaction; and (3) results of available analyses of interactions between the MBI and CADT. Perspective:. This review is expected to synthesize available evidence describing the interactions between MBIs and various studied drug therapies for chronic pain. Available evidence may help inform the rational integration of MBIs with drug therapy for chronic 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.

Objective To evaluate the association between opioid dosage and ongoing therapy with physical function and disability in patients with neuropathic pain (NeP). Design Secondary analysis of a prospective cohort. Setting Multicenter clinical NeP registry. Subjects Seven hundred eighty-nine patients treated for various NeP diagnoses. Methods The following measures were included: dependent variables. 12-month self-reported physical function (pain disability index [PDI] and medical outcomes study short form-12 physical function [PCSS-12]); independent variables: baseline opioid dose (none, ≤200 mg and >200 mg of morphine equivalent), ongoing opioid use; potential confounding variables: age, sex, baseline pain intensity, and psychological distress (profile of mood states). Analysis of covariance models was created to examine the relationship between opioid therapy and both physical functioning outcomes with adjustment for confounding. Results Complete data was available for 535 patients (68%). Compared with the lower and high dose opioid groups, NeP patients not taking opioids had statistically lower disability and higher physical functioning scores, after adjusting for disease severity. Compared with patients prescribed opioid therapy on an ongoing basis, NeP patients who were not prescribed had statistically lower disability and higher physical functioning scores, after adjusting for disease severity. Improvements in disability and physical functioning scores from baseline and 12-months in all groups were modest and may not be clinically significant. Conclusions Physical functioning and disability did not improve in patients with NeP who were prescribed opioids compared with those who are not prescribed, even after adjusting for disease severity.

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.

BACKGROUND: It is important to determine the optimal hemoglobin (Hb) concentration for red blood cell (RBC) transfusion for patients undergoing cardiac surgery because increased mortality has been associated with the severity of anemia and exposure to RBCs. Because a definitive trial will require thousands of patients, and because there is variability in transfusion practices, a pilot study was undertaken to determine adherence to proposed strategies. STUDY DESIGN AND METHODS: A single-center parallel randomized controlled pilot trial was conducted in high-risk cardiac patients to assess adherence to two transfusion strategies. Fifty patients were randomly assigned either to a “restrictive” transfusion strategy (RBCs if their Hb concentration was 70 g/L or less intraoperatively during cardiopulmonary bypass [CPB] and 75 g/L or less postoperatively) or a “liberal” transfusion strategy (RBCs if their Hb concentration was 95 g/L or less during CPB and less than 100 g/L postoperatively). RESULTS: The percentage of adherence overall was 84% in the restrictive arm and 41% in the liberal arm. Twenty-two (88%) patients were transfused 99 units of RBCs in the liberal group compared to 13 patients who were transfused 50 units in the restrictive group (p

Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, spinal cord injury, or multiple sclerosis. These syndromes are much less common than peripheral etiologies, with less known regarding optimal treatment. The objective of this study was to determine the long-term clinical effectiveness of the management of central relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified from a prospective observational cohort from seven Canadian tertiary centers. Data regarding patient -characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome was the composite of reduced average pain intensity and pain interference. Secondary outcomes included assessments of function, mood, and quality-of-life. Results: At 12-month follow-up, 13.5% (95%CI,5.6-25.8) of patients achieved ≥30% reduction in pain, whereas 38.5% (95%CI,25.3-53.0) achieved a ≥1 point reduction in pain interference; 9.6% (95%CI,3.2-21.0) of patients achieving both these measures. Patients with peripheral neuropathic pain were more likely to achieve this primary outcome at 12-months (25.3% of patients; 95%CI,21.4-29.5) (p=.012). Conclusions: Patients with central neuropathic pain were less likely to achieve a meaningful improvement in pain and function compared to patients with peripheral neuropathic pain at 12-month follow-up.

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.

Recombinant activated factor VII (rFVIIa) is currently not approved by Health Canada or the Food and Drug Administration for treating excessive blood loss in nonhemophiliac patients undergoing on-pump cardiac surgery, but is increasingly being used “off-label” for this indication. A Canadian Consensus Conference was convened to generate recommendations for rFVIIa use in on-pump cardiac surgery. Methods: The panel undertook a literature review of the use of rFVIIa in both cardiac and non-cardiac surgery. Appropriateness, timing, and dosage considerations were addressed for three cardiac surgery indications: prophylactic, routine, and rescue uses. Recommendationswere based on evidencefromtheliterature and derived by consensus following recognized grading procedures. The panel recommended against prophylactic or routine use of rFVIIa, as there is no evidence at this time that the benefits of rFVIIa outweigh its potential risks compared with standard hemostatic therapies. On the other hand, the panel made a weak recommendation (grade 2C) for the use of rFVIIa (one to two doses of 35–70 μg·kg-1) as rescue therapy for blood loss that is refractory to standard hemostatic therapies, despite the lack of randomized controlled trial data for this indication. In cardiac surgery, the risks and benefits of rFVIIa are unclear, but current evidence suggests that its benefits may outweigh its risks for rescue therapy in selected patients. Methodologically rigorous studies are needed to clarify its risk-benefit profile in cardiac surgery patients. Le facteur VII active recombinant (rFVIIa) n’est actuellement approuve ni par Sante Canada ni par la Food and Drug Administration (FDA) pour le traitement du saignement excessif chez les patients non-hemophiles subissant une chirurgie cardiaque avec circulation extra-corporelle (CEC); neanmoins, il est de plus en plus utilise de maniere ‘non conforme’ pour cette indication. Une Conference canadienne de consensus s’est reunie afin de rediger des recommandations quant a l’utilisation du rFVIIa lors de la chirurgie cardiaque avec CEC. Le panel a entrepris une revue de la litterature traitant de l’utilisation du rFVIIa en chirurgies cardiaque et non cardiaque. Des considerations quant a la justification, au moment de l’administration et a la posologie ont ete evaluees pour trois indications en chirurgie cardiaque: les utilisations prophylactique, de routine ou de sauvetage. Les recommandations, basees sur des donnees probantes tirees de la litterature, ont ete interpretees par un consensus suivant des procedures de gradation reconnues. Le panel s’est prononce contre une utilisation prophylactique ou de routine du rFVIIa, etant donne qu’il n’existe actuellement pas de preuve que les bienfaits du rFVIIa l’emportent sur les risques potentiels encourus en comparaison des therapies hemostatiques standard. En revanche, le panel a enonce une recommandation faible (note 2C) en faveur de l’utilisation du rFVIIa (une a deux doses de 35–70 μg·kg-1) comme therapie de sauvetage en cas de saignement refractaire aux therapies hemostatiques standard et ce, malgre le manque de donnees d’etudes randomisees controlees concernant cette indication. En chirurgie cardiaque, les risques et bienfaits du rFVIIa ne sont pas clairs; toutefois, les donnees actuelles suggerent que ses bienfaits pourraient contrebalancer ses risques dans les cas de therapie de sauvetage chez certains patients. Des etudes methodologiquement rigoureuses sont necessaires afin de clarifier le profil risque/benefice du rFVIIa pour les patients de chirurgie cardiaque.

OBJECTIVE To compare the ability of the signal relative-intensity and sample-volume-length (SVL) to discriminate air bubbles from solid spheres in an in-vitro model using two different carrier frequencies of the Doppler transducer. METHODS A gel ultrasound phantom was connected to a circuit in which blood-mimicking fluid circulated. Air bubbles (100-140 microm) and latex spheres (125 +/- 10 microm) were injected into the circuit and interrogated using 1- and 2-MHz transducers. High-intensity-transient-signals (HITS) were recorded with a dual-gated transcranial Doppler (TCD) system. Receiver-Operating-Characteristic curves determined the best cut-off points that would distinguish between embolic materials. RESULTS HITS from air bubbles had higher intensities and longer SVL than solid spheres with either transducer (P < .0001). Air bubbles (P < .0001) and microspheres (P= .049) showed higher intensities with the 1-MHz relative to the 2-MHz transducer. The intensity increase with the 1-MHz transducer was greater for air bubbles than microspheres (P < .0001). The discriminating efficacy of both the relative-intensity and SVL was similar between transducers (intensity, P= .201; SVL, P= .98). CONCLUSIONS The relative-intensity and SVL are equally effective to distinguish solid from air emboli using 1- and 2-MHz transducers. Our study indicates that using a lower carrier frequency does not improve the discrimination of air from solid emboli.

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.

Patients with coronary disease and related health care providers are faced with confusing and often conflicting information with regards to the neurocognitive impact of different strategies for coronary revascularization. Studies involving the measurement of postoperative cognitive deficit (POCD) have significant limitations that may ultimately impact on their interpretation and clinical relevance. In this review, we have described the origin of these tests and delineated the rationale for the design of testing that is commonly used in cardiac surgery patients. In general, neurocognitive tests assess domains of memory/new learning, psychomotor speed/dexterity and attentional capacity/mental control. Pre- and post-intervention tests in each domain can be evaluated either by the measurement of mean change scores (Group Comparison Model) for the entire group as continuous data, or by using categorical or continuous data to examine patterns of individual decline (Individual Comparison Model). This latter approach requires a specific definition of what constitutes a decline, which can be criticized as being arbitrary. There are limitations to each of these approaches that necessitate that critical information in trial design is available to the reviewer to facilitate interpretation. For example, the impact of factors such as test/re-test reliability and practice effect can be mitigated by the use of an appropriately chosen control population. Liberal parlance of neurocognitive outcome as a rationale for therapeutic choice must be tempered by wise interpretation of these tests. It is only through the understanding of their limitations and the implications of trial design that we can translate these results to provide the best therapeutic options for our patients in unbiased manner. Perfusion (2007) 22, 185—192.

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.

Objective: When the right atrium (RA) cannula is connected to the venous return line of the cardiopulmonary bypass (CPB) circuit, air is often introduced. Air in the venous cannula may increase cerebral air embolization at initiation of CPB despite the arterial line filter. We measured the volume of air present in the venous cannula after cannulation of the RA. Transcranial Doppler quantified emboli as high-intensity transient-signals (HITS) in both middle-cerebral arteries (MCA) at the beginning of CPB. Methods: After RA cannulation, the air column in the venous line was measured and the total volume calculated using the known lumen diameter. CPB onset was defined as the instant when the CPB machine started moving the patient’s blood from the RA into the venous reservoir. Starting from CPB onset, HITS were counted: (a) until completion of the first minute on CPB (1-min count) and (b) until aortic cross clamping (pre-clamping count). Results: We studied 135 patients during coronary artery bypass surgery operated on by 10 cardiac surgeons. HITS during onset of CPB were detected in 95% of patients. Median counts were 10 HITS (25th, 75th percentiles: 3, 26) at 1-min and 21 HITS (8, 51) during pre-clamping. A significant correlation was found between the volume of air in the venous cannula and the HITS counts (r = 0.524, p < 0.0001). Absence of retained air was associated with lower HITS counts [3 HITS (1, 11)] compared with any amount of air [13 HITS (4, 29), p = 0.002)]. The volume of air in the venous cannula, the MCA mean blood flow velocity and the pre-clamping time were the only independent predictors of the pre-clamping HITS counts (p < 0.001). Conclusion: Air in the venous cannula can result in HITS in the MCA. Minimizing the volume of air introduced into the venous cannula after cannulation of the RA can decrease cerebral air embolization at the beginning of CPB. # 2005 Elsevier B.V. All rights reserved.

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.

Introduction: Despite major advances in biomaterial research and blood conservation, bleeding is still a common complication after cardiopulmonary bypass and cardiac surgery remains a major consumer of blood products. Although the underlying mechanisms for these effects are not fully established, two proposed major etiologies are the hemodilution associated with the use of the heart-lung machine and the impact of reinfusion of shed cardiotomy blood. Therapeutic strategies that primarily encompass the use of devices or technologies to overcome these effects may result in improved clinical outcomes. Objective: To determine the extent to which 1) lipid/leukocyte filtration and centrifugal processing of cardiotomy blood, and 2) modified ultrafiltration (MUF) are currently applied in adult cardiac surgery in Canada. Methods: A questionnaire was mailed to the chief perfusionist at all adult cardiac surgical centers in Canada, addressing details regarding the frequency of use of cardiotomy blood processing and MUF. Results: All questionnaires (36, 100%) were completed and returned. With regards to cardiotomy blood management, in 21 centers (58%), no specific processing steps were utilized exclusive of the integrated cardiotomy reservoir filter. Of the remaining centers, two (6%) reported using lipid/leukocyte filtration and 15 (42%) reported washing their cardiotomy blood. Three centers (8%) reported using MUF at the end of CPB. Conclusions: Despite growing concern about the potential detrimental effects of cardiotomy blood, few centers in Canada routinely manage this blood with additional filtration and/or centrifugal processing prior to reinfusion. Similarly, MUF, demonstrated to be effective in the pediatric population, has not seen popular application in adult cardiac surgical practice.

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.

Purpose. The authors investigated whether ultrasonic characteristics of embolic signals could be used to differentiate embolic composition. Materials and Methods. The authors analyzed high-intensity transient signals (HITS) from 3 patients with patent foramen ovale during the bubble contrast test and during total joint replacement surgery. In 3 anesthetized dogs, latex microspheres, fat particles, and air bubbles were injected into the internal carotid artery and HITS were identified in the cerebral circulation. The area under the receiver operating characteristic curve quantified the usefulness of each measure to distinguish embolic composition. Results. In humans, HITS intensity (area: 0.80) and frequency (area: 0.73) but not duration (area: 0.32) were useful to distinguish air bubbles from presumed solid emboli. In animals, intensity distinguished micro-spheres from air (area: 0.94) and microspheres from fat (area: 0.94) but was less useful for fat and air (area: 0.64). The duration (area: 0.54–0.76) and frequency (area: 0.54–0.63) were poor discriminators. Conclusion. The HITS intensity best distinguished embolic composition. Particle size should be taken into account in future research.

OBJECTIVES: We report a potential limitation of transcranial Doppler for assessing cerebral circulation during suspected brain death in children. DESIGN: Review of two case series identified during our clinical practice. PATIENTS: Eight children with suspected brain death and seven with intact-brain and cardiovascular anomalies. MEASUREMENTS AND MAIN RESULTS: Brain-death criteria included lack of cerebral-brainstem reactivity, electrocortical silence and absent blood flow by brain scintigraphy ((99m)Tc-hexamethylpropylenamine oxime). Five intracranial Doppler patterns were found in eight cases of suspected brain death: A) orthograde continuous flow; B) reduced systolic flow velocity with absence of diastolic flow; C) reduced systolic flow velocity with retrograde diastolic flow, sometimes with antegrade late diastolic flow; D) systolic spikes of very low flow velocity; and E) absence of Doppler signals. Only patterns "C," "D," and "E" were associated with the absence of supra- and infratentorial brain perfusion. The most common Doppler alterations in patients with intact-brain and cardiovascular anomalies were the absence of diastolic flow (pattern "B") or the presence of retrograde flow during diastole (pattern "C"). CONCLUSION: Transcranial Doppler monitoring of pediatric patients may have value in identifying patients who have severe cerebral compromise, who may progress to brain death. However, key Doppler alterations, such as absent or retrograde flow during diastole, are not uniquely associated with the diagnosis of brain death, particularly in the setting of congential heart disease. The use of conventional methodology for the diagnosis of brain death in infants and children remains the "gold standard."

Background The Cardiac Anesthesia Risk Evaluation (CARE) score is a simple risk classification for cardiac surgical patients. It is based on clinical judgment and three clinical variables: comorbid conditions categorized as controlled or uncontrolled, surgical complexity, and urgency of the procedure. This study compared the CARE score with the Parsonnet, Tuman, and Tu multifactorial risk indexes for prediction of mortality and morbidity after cardiac surgery. Methods In this prospective study, 3,548 cardiac surgical patients from one institution were risk stratified by two investigators using the CARE score and the three tested multifactorial risk indexes. All patients were also given a CARE score by their attending cardiac anesthesiologist. The first 2,000 patients served as a reference group to determine discrimination of each classification with receiver operating characteristic curves. The following 1,548 patients were used to evaluate calibration using the Pearson chi-square goodness-of-fit test. Results The areas under the receiver operating characteristic curves for mortality and morbidity were 0.801 and 0.721, respectively, with the CARE score rating by the investigators; 0.786 and 0.710, respectively, with the CARE score rating by the attending anesthesiologists (n = 8); 0.808 and 0.726, respectively, with the Parsonnet index; 0.782 and 0.697, respectively, with the Tuman index; 0.770 and 0.724 with the Tu index, respectively. All risk models had acceptable calibration in predicting mortality and morbidity, except for the Parsonnet classification, which failed calibration for morbidity (P = 0.026). Conclusions The CARE score performs as well as multifactorial risk indexes for outcome prediction in cardiac surgery. Cardiac anesthesiologists can integrate this score in their practice and predict patient outcome with acceptable accuracy.

Objective: Blood contact with synthetic surfaces during cardiopulmonary bypass (CPB), inevitably results in the activation of a variety of interrelated pathways of inflammation and coagulation that may contribute to postoperative complications in cardiac surgery patients. The objective of this trial was to evaluate clinical events and complement activation related to the use of a novel biomaterial, into which a surface modifying additive had been incorporated into the polymer used to prepare the bypass circuit. Methods: A prospective, doubleblind trial was carried out with 34 patients randomized to surgery, with either a standard circuit or a circuit treated (‘tip to tip’) with the surface modifying additive. Variables recorded included perioperative haemodynamics, volume replacement, a-agonist and inotrope use. Terminal complement complex (SC5b-9) was measured using an ELISA. Results: Upon initiation of bypass, there was a decrease in mean arterial pressure (MAP) in the control group, not seen in the test group ( P = 0.0005, ANOVA). There was a decrease in the total volume of replacement fluid given intraoperatively in the test group as compared with the control group (total plus prime; control 5.3 ∠ 1.2 L, test 4.4 ∠ 1.9 L, P = 0.03, Mann‐Whitney test). There was a trend to decreased need for inotrope infusion in the test group after CPB (test 1/17, control 6/17, Fisher exact test; P = 0.085). No difference was seen in the generation of terminal complement complex between the groups either during or after CPB. Conclusions: The decrease in blood pressure in the control group, upon the initiation of CPB, did not occur in patients undergoing CPB with the circuit prepared with the surface modifying additive. The decrease in blood pressure was likely associated with the increase in total administered fluids intraoperatively (approximately 1 l/patient) and perhaps the trend towards higher use of inotropes in the control patients as opposed to the test patients. These haemodynamic changes did not appear to be related to complement activation early in CPB. © 1999 Elsevier Science B.V. All rights reserved.

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).

Background. Right ventricular blood flow may be adversely affected during left ventricular assist device (LVAD) use leading to right ventricular (RV) ischemia and RV dysfunction. This study characterized normal RV blood flow responses to LVAD operation. Methods. Seven Yorkshire pigs weighing 74.4 ± 3.4 kg underwent right coronary artery blood flow measurements with an ultrasonic flow probe and injection of radiolabeled microspheres. A Thoratec LVAD was used in either synchronous or asynchronous modes and RV loading was increased using a pulmonary artery snare. Results. The RV blood flow was compared between three regions that differed in proximity to the right coronary artery: proximal segment, mid-RV, and distal. The right ventricular distal flows was 0.93 ± 0.07 mL · min −1 · g −1 compared with 0.74 ± 0.06 mL · min −1 · g −1 at right ventricular proximal flow during control measurements ( p = 0.0001). This difference was maintained during LVAD operation in either synchronous or asynchronous modes and also during pulmonary artery constriction. Conclusions. Global RV flow is not adversely affected by LVAD use. A flow gradient occurs along the right coronary artery with the distal vascular bed having relatively less reserve, which may be more susceptible to ischemia in patients with preexisting coronary disease or RV distention during LVAD use.

In animals mild hypothermia (32-35 degrees C) reduces ischaemic brain injury, but this has not been investigated in humans. During hypothermic cardiopulmonary bypass (CPB) patients are made hypothermic (usually to 30-32 degrees C) but are then rewarmed at a time when they are still at risk of ischaemic brain injury. We investigated the feasibility and safety of maintaining mild hypothermia throughout the CPB period. Thirty adult cardiac surgical patients were randomized to either rewarming to 36-37 degrees C or to maintaining temperature at 34 degrees C without rewarming. On arrival in the recovery room, patients in the hypothermic group had a mean bladder temperature of 33.8 +/- 0.45 degrees C compared with 35.4 +/- 0.58 degrees C (mean +/- SD, P < 0.05) in the rewarmed patients. There were no differences between groups in intra- or postoperative blood loss or blood use, inotrope use, dysrhythmias, or myocardial infarction. The hypothermic group received more muscle relaxant for the treatment of shivering postoperatively. Our results suggest that mild hypothermia following CPB did not increase morbidity although larger studies are needed for confirmation.

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.

Perioperative cardiac complications are associated with a high mortality rate. During the preoperative assessment the anaesthetist must determine if the patient is at risk so that appropriate interventions can be made to ensure the best possible outcome. Over the past three decades several indices have been proposed to identify the surgical patient at risk of cardiac morbidity or mortality. These indices can be thought of as diagnostic tests which determine the likelihood of perioperative cardiac complication. In this article the authors review the epidemiological basis of diagnostic tests and apply this theory to three currently available indices of perioperative risk: the American Society of Anesthesiologists physical status classification, the Goldman multifactorial cardiac, risk index and a modified version devised by Detsky. A case history describing a surgical patient with unstable angina is first presented to show how different indices can lead to different predictions. These indices are then analysed as if they were diagnostic tests to predict cardiac complications after surgery. The characteristics of diagnostic tests such as sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic curves are described and applied to the indices. Basic principles such as odds ratio, likelihood ratio and their relation to prevalence and post-test probability are also presented. This overview will help the anaesthetist to understand the limitations of risk indices as predictors of adverse cardiac outcome and to apply these scales more effectively to individual patients at different institutions.

Summary Myocardial ischemia results from a decline in the oxygen supply-and-demand ratio. The consequences of ischemia range from metabolic disturbances, detectable only by research techniques, to sudden death. The heart is unique in that it must generate pressure for its own perfusion. This results in complex interrelationships between the factors determining myocardial oxygen supply and demand. In the presence of a coronary stenosis, the effects of hemodynamic changes become even more difficult to predict. An understanding of the physiology of the normal and diseased coronary circulation helps the anesthesiologist protect the patient with coronary artery disease from cardiac morbidity.

Background:The difficulty of distinguishing solid from air emboliusing transcranial Dopplerhas limitedits use in situations where both types of embolicanoccur,suchasinmechanicalheartvalvepatients.TomaketranscranialDopplerclinicallyuseful,amethodmustbefoundtodistinguish benign air bubbles from the more damaging solid particulates. Since inhalation of 100% oxygen reduces the amount of air bubbles in mechanical heart valve patients, the ultrasonic features of the remainingemboliwould be characteristic of solid particulates. Objective:We determined the accuracy of the signal relative intensity measured with transcranial Doppler to distinguish between gaseous and non-gaseous emboli in mechanical heart valve patients examined during room air and 100% oxygen. Embolic signals detected in patients with bioprosthetic valves examined during 100% oxygen comprised the source of solid particulates. Methods: Embolic signals were detected during room air (n = 141) and 100% oxygen (n = 45) from 17 mechanical valve patients at two Doppler examinations (4 h and 4 days after surgery). Solid embolic signals (n = 31) from seven patients with bioprosthetic valves were identified with 100% oxygen within the first 4 h after surgery. Frequency plots and receiver operating characteristic curves assessed signal intensity differences between mechanical and bioprosthetic valve groups during 100% oxygen and the efficacy of the relative intensity for differentiating gaseous from solid emboli. Results: Administration of 100% oxygen during transcranial Doppler examination in mechanical heart valve patients decreased the count of embolic signals compared with room air (p = 0.006). The embolic signals of mechanical heart valve patients breathing 100% oxygen showed lower relative intensities compared with those during room air. The distribution of the signal relative intensity between mechanical and bioprosthetic valve groups during 100% oxygen was similar. A 16 dB cut-off threshold achieved the best accuracy for differentiating non-gaseous from gaseous emboli (sensitivity: 60%; specificity: 82%; area: 0.721; p < 0.0001). Conclusions: The use of a signal intensity cut-off offers adequate discrimination of the embolic composition in mechanical heart valve patients. Future studies evaluating prophylactic treatments of thrombosis in these patients should assess the predictive value of this intensity threshold and their potential association with outcome indicators and procoagulant markers. # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.