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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.

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.

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.

Purpose: 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)., Method: 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., Results: 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., Conclusion: It appears that mindfulness mitigates the impact of pain experiences in cancer survivors experiencing CNP post-treatment., Implications for Cancer Survivors: 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.

Objectives: To determine whether the prevalence of opioid use among patients requiring elective same-day admission (SDA) surgery is greater than the 2.5% prevalence found in the general population. Secondary objectives were to assess compliance with expert recommendations on acute pain management in opioid-tolerant patients and to examine clinical outcomes., Methods: A retrospective review of 812 systematically sampled adult SDA surgical cases between April 1, 2008 and March 31, 2009 was conducted., Results: Among 798 eligible patients, 148 (18.5% [95% CI 15.9% to 21.2%]) were prescribed opioids, with 4.4% prescribed long-acting opioids (95% CI 3.0% to 5.8%). Use of opioids was most prevalent among orthopedic and neurosurgery patients. Among the 35 patients on long-acting opioids who had a high likelihood of being tolerant, anesthesiologists correctly identified 33, but only 13 (37%) took their usual opioid preoperatively while 22 (63%) had opioids continued postoperatively. Acetaminophen, nonsteroidal anti-inflammatory drugs and pregabalin were ordered preoperatively in 18 (51%), 15 (43%) and 18 (51%) cases, respectively, while ketamine was used in 15 (43%) patients intraoperatively. Acetaminophen, nonsteroidal anti-inflammatory drugs and pregabalin were ordered postoperatively in 31 (89%), 15 (43%) and 17 (49%) of the cases, respectively. No differences in length of stay, readmissions and emergency room visits were found between opioid-tolerant and opioid-naive patients., Conclusion: Opioid use is more common in SDA surgical patients than in the general population and is most prevalent within orthopedic and neurosurgery patients. Uptake of expert opinion on the management of acute pain in the opioid tolerant patient population is lacking.

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.

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., (© 2013.)

Purpose: 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., Methods: 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., Results: 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 (P < 0.001). Decreased caregiver function at baseline was also associated with higher ZBI (linear association 0.71; P = 0.02)., Conclusions: 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: 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., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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-1990 s 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 chi-square 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.

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 < 0.001)., 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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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

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

Background: The difficulty of distinguishing solid from air emboli using transcranial Doppler has limited its use in situations where both types of emboli can occur, such as in mechanical heart valve patients. To make transcranial Doppler clinically useful, a method must be found to distinguish 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 remaining emboli would 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 (4h and 4 days after surgery). Solid embolic signals (n=31) from seven patients with bioprosthetic valves were identified with 100% oxygen within the first 4h 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 16dB 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.

Background: 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., Methods: 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., Results: 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 p < 0.01) 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)., Conclusions: Processing of shed mediastinal blood improves cardiopulmonary hemodynamics and may reduce ventilatory requirements after cardiac surgery.

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

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.

Purpose: 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. Recommendations were based on evidence from the literature and derived by consensus following recognized grading procedures., Results: 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 microg.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., Conclusions: 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 riskbenefit profile in cardiac surgery patients.

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

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 x 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 declamping 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, 2801) 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.

Objective: The application of intensity thresholds for embolus detection with transcranial Doppler (TCD) can exclude from analysis an unrecognized proportion of high-intensity transient signals (HITS))whose intensities are below the threshold. The lack of consistent threshold criteria between clinical trials may explain part of the discrepancy in the reported HITS counts. We investigated the effect of choosing different thresholds on the sensitivity and specificity of detecting HITS during cardiopulmonary bypass (CPB)., Methods: Two observers independently analyzed TCD recordings from 8 patients under CPB. Doppler signals were classified as true HITS, equivocal HITS, artifacts, and Doppler speckles according to preestablished criteria. The relative intensity of Doppler signals was measured by two different methods (TCD software vs manual). Receiver Operating Characteristic curves determined the optimal threshold for each of the two intensity methods., Results: Reviewers achieved agreement in 96% of 2190 Doppler signals (kappa = 0.90). Relative intensities calculated with the TCD-software method were 3 dB (95% CI: 3.0-3.4) higher than the manual method. The optimal threshold was found at 10 dB (sensitivity: 99%; specificity: 90.8%) with the software method and at 7 dB with the manual method (sensitivity: 96%; specificity: 83%). The use of an intensity threshold 2 dB higher than the optimal increased the rejection of true HITS by 8% and 14%, respectively., Conclusions: Using intensity thresholds higher than the optimal for embolus detection decreases HITS counts. Choosing a threshold depends on the type of method used for measuring the signal intensity. Uniform threshold criteria and comparative studies between different Doppler devices are necessary for making clinical trials more comparable.

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.

Background: Traditional harvesting of the internal thoracic artery (ITA) for use as a conduit in coronary bypass surgery involves the dissection of a rim of tissue surrounding the artery on either side. Recent studies, primarily observational, have suggested that skeletonization of the ITA can improve conduit flow, increase length, and reduce the risk of deep sternal infection in high risk patients. Furthermore, skeletonization of the ITA can potentially preserve intercostal nerves and reduce post-operative pain and dysesthesias associated with ITA harvesting. In order to assess the effects of ITA skeletonization, we report a prospective, randomized, within-patient study design that shares many features of a cross-over study., Methods: Patients undergoing bilateral internal thoracic artery harvest will be randomized to having one side skeletonized and the other harvested in a non-skeletonized manner. Outcome measures include ITA flow and length measured intra-operatively, post-operative pain and dysesthesia, evaluated at discharge, four weeks, and three months post-operatively, and sternal perfusion assessed using single photon emission computed tomography. Harvest times as well as safety endpoints of ITA injury will be recorded., Discussion: This study design, using within-patient comparisons and paired analyses, minimizes the variability of the outcome measures, which is seldom possible in the evaluation of surgical techniques, with minimal chance of carryover effects that can hamper the interpretation of traditional cross-over studies. This study will provide a valid evaluation of clinically relevant effects of internal thoracic artery skeletonization in improving outcomes following coronary artery bypass surgery.

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.

Objective: To determine the association between high-intensity transient signals (HITS) and perfusionist interventions, purging techniques, pump flows and venous reservoir blood volume levels during cardiopulmonary bypass., Methods: Transcranial Doppler was used to detect HITS in the middle cerebral artery during the period of aortic crossclamping in patients undergoing coronary artery bypass grafting. Perfusionist-related interventions were recorded and included blood sampling (including the number of times that the oxygenator sampling manifold was purged), drug bolus injections and infusions (vasopressors, crystalloid and mannitol). Pump flows and venous reservoir volume levels were also documented., Results: There were 534 interventions in 90 patients [median number of interventions per patient: 6 (quartiles: 4, 8)]. The median total HITS count from all interventions was 17 (5, 37). This represented 38% of the total HITS counts during aortic crossclamping. Factors contributing to differences in the HITS count included type of intervention (p <0.0001) and perfusionist (p =0.0012). Blood sampling (p<0.001) and drug bolus injections (p=0.06) had higher HITS counts per patient than infusions. Repetitive purging significantly increased HITS counts (r=0.74; p <0.001). Purging perfusionists (purging: 1-10 times) had higher HITS counts per patient [5 HITS (1, 15) than nonpurgers [0 HITS (0, 1) p <0.0001]. HITS counts were significantly correlated with reservoir volumes (r= -0.20, p=0.017) and pump flow rates (r=0.21, p =0.008). Reservoir volume levels < or =800 mL were associated with higher HITS counts per intervention [11 HITS (2, 27)] during blood sampling compared with higher volume levels [3 HITS (1, 10), p =0.001]., Conclusions: Cerebral emboli associated with perfusionist interventions can be minimized by not purging the sampling manifold, using continuous infusions rather than bolus injections, and maintaining high blood-volume levels (>800mL) in the venous reservoir.

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 (N=98) undergoing primary CABG were randomized to receive naproxen (500 mg q12hX5 doses via suppository started 1h after operation, followed by oral 250 mg q8hX6 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 47+/-17% on average before chest physiotherapy (P=0.034), and 44+/-13% after chest physiotherapy (P=0.0092). Patients who received naproxen also had better preservation of SVC over the first 4 postoperative days (mean loss of SVC from baseline: 2.1+/-0.1 vs. 2.5+/-0.1l, naproxen vs. placebo, P=0.0032). This was concomitant with a lower white blood cell count observed in naproxen patients (9.2+/-0.3 vs. 12.7+/-1.5x10(9)/l, naproxen vs. placebo, P=0.03). Patients who received naproxen had more chest tube drainage after 4h 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.

Background: Hypothermia in the perioperative period is associated with adverse effects, particularly bleeding. Before termination of cardiopulmonary bypass, rewarming times and perfusion temperatures are often increased to avoid post-cardiopulmonary bypass hypothermia and the presumed complications. This practice may, however, also have adverse effects, particularly cerebral hyperthermia. We present safety outcomes from a trial in which patients undergoing coronary artery surgery were randomly assigned to normothermia or hypothermia for the entire surgical procedure., Methods: Consenting patients over the age of 60 years presenting for a first, elective coronary artery surgery with cardiopulmonary bypass were randomly assigned to having their nasopharyngeal temperature maintained at either 37 degrees C (group N; 73 patients) or 34 degrees C (group H; 71 patients) throughout the intraoperative period, with no rewarming before arrival in the intensive care unit. All received tranexamic acid., Results: There was no clinically important difference in intraoperative blood product or inotrope use. Temperatures on arrival in the intensive care unit were 36.7 degrees C +/- 0.38 degrees C and 34.3 degrees C +/- 0.38 degrees C in groups N and H, respectively. Blood loss during the first 12 postoperative hours was 596 +/- 356 mL in group N and 666 +/- 405 mL in group H (mean difference +/- 95% confidence interval, 70 +/- 126 mL; P =.28). There was no significant difference in blood product utilization, intubation time, time in the hospital, myocardial infarction, or mortality. The mean time in the intensive care unit was 8.4 hours less in the hypothermic group (P =.02)., Conclusions: Our data support the safety of perioperative mild hypothermia in patients undergoing elective nonreoperative coronary artery surgery with cardiopulmonary bypass. These findings suggest that complete rewarming after hypothermic cardiopulmonary bypass is not necessary in all cases.

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 microspheres 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.

Background: Neuropsychological deficits occur in 30% to 80% of patients undergoing heart surgery and are due in part to ischemic cerebral injury during cardiopulmonary bypass. We tested whether mild hypothermia, the most efficacious neuroprotective strategy found in laboratory studies, improved cognitive outcome in patients undergoing coronary artery surgery., Methods and Results: Patients 60 years or older scheduled for coronary artery surgery were enrolled. During cardiopulmonary bypass, patients were initially cooled to 32 degrees C then randomly assigned to rewarming to 37 degrees C (control) or 34 degrees C (hypothermic), with no further intraoperative warming. Testing was scheduled preoperatively and 1 week and 3 months postoperatively. Eleven tests were combined into 3 cognitive domains: memory, attention, and psychomotor speed and dexterity. A patient was classified as having a cognitive deficit if a decrease of >/=0.50 SD was realized in 1 or more domains. The incidence of cognitive deficits 1 week after surgery, which was the primary outcome, was 62% () in the control group and 48% () in the hypothermic group (relative risk 0.77, P=0.048). In the hypothermic group, the magnitude of deterioration in attention and in speed and dexterity was reduced by 55.6% (P=0.038) and 41.3% (P=0.042), respectively. At 3 months, the hypothermic group still performed better on one test of speed and dexterity (grooved pegboard). There was no difference in morbidity or mortality., Conclusions: Our findings support a neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery and should encourage physicians and perfusionists to pay careful attention to brain temperature during cardiopulmonary bypass.

Background: To decrease the complications associated with cardiopulmonary bypass, novel biomaterials have been introduced that may be less thrombogenic than standard synthetic surfaces., Methods: 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)., Results: 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 (p<0.005). 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., Conclusions: 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.

Purpose: To illustrate the multiple causes of hypoxemia to be considered following cardiopulmonary bypass and how therapy given to improve oxygen delivery may have contributed to a decrease in arterial oxygen saturation to life-threatening levels., Clinical Features: A 61 yr old man with severe mitral regurgitation and chronic obstructive lung disease underwent surgery for mitral valve repair. A pulmonary artery catheter with the capacity to measure cardiac output and mixed venous oxygen saturation (SvO2) continuously was used. Two unsuccessful attempts were made to repair the valve which was finally replaced, requiring cardiopulmonary bypass of 317 min. Dobutamine 5 micrograms.kg-1.min-1 and sodium nitroprusside 1 microgram.kg-1.min-1 were used to increase cardiac output. Soon after, the SvO2 decreased progressively from 55 to 39%. The patient became cyanotic with a PaO2 of 39 mmHg. Sodium nitroprusside was stopped and amrinone 100 mg bolus followed by 10 micrograms.kg-1.min-1 was given in addition to adding PEEP to the ventilation. With these measures PaO2 could be maintained of safe levels but PEEP and high inspired oxygen concentrations were needed postoperatively until the trachea could be extubated on the third postoperative day., Conclusion: The profound hypoxemia in this case was likely due to a combination of intra- and extrapulmonary shunt, both augmented by sodium nitroprusside. The desaturation of mixed venous blood amplified the effect of these shunts in decreasing arterial oxygen saturation. The interaction of these factors are analyzed in this report.

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.

During hypothermic cardiopulmonary bypass (CPB) patients are cooled, usually to between 30-32 degrees C, and, after myocardial blood flow is restored, they are rewarmed with blood heated in the pump-oxygenator. We audited our local practice by recording tympanic and nasopharyngeal temperatures in 11 patients undergoing hypothermic CPB. We found that, during rewarming, nasopharyngeal and tympanic temperatures commonly exceeded 38 degrees C although temperature measured in the bladder was < 37 degrees C. A survey of cardiac surgery centres in Canada suggested that most centres induce hyperthermia in highly perfused tissues during rewarming, sometimes inadvertently. This may be of some importance because it has become widely appreciated by neuroscientists that mild degrees of brain cooling (2-5 degrees C) are capable of conferring dramatic protection from ischaemic brain injury and, conversely, mild temperature elevation may be markedly deleterious. If control of brain temperature is considered desirable then we would suggest that nasopharyngeal temperature be monitored during rewarming on CPB.

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.

This randomized double-blind study compared the hemodynamic and metabolic effects of pancuronium and vecuronium during treatment of shivering after cardiac surgery with hypothermic cardiopulmonary bypass. Thirty sedated and pain-free patients who shivered after cardiac surgery were treated with pancuronium (n = 15) or vecuronium (n = 15) 0.08 mg/kg. Baseline values of heart rate (HR), mean arterial pressure, arterial and venous blood gases, total body oxygen consumption indexed to body surface area (VO2-I), and pressure work index (PWI, an estimate of myocardial oxygen consumption) were measured on arrival in the intensive care unit, at onset of shivering, and repeatedly for 2 h after treatment. Continuous ST segment analysis of leads II and V5 were used for detection of myocardial ischemia. Treatment of shivering with pancuronium decreased VO2-I by 32% (P = 0.0001). This was accompanied by a 14% increase in HR (P = 0.001) and a 10% increase in PWI (P = 0.03). Vecuronium decreased VO2-I by 36% (P = 0.003) with a 4% decrease in HR (P = 0.04) and a 6% decrease in PWI (P = 0.06). Myocardial ischemia (n = 3) and ventricular arrhythmias (n = 3) occurred in five patients treated with pancuronium. Only one patient treated with vecuronium had ventricular arrhythmia (P = 0.08). Seven patients treated with pancuronium and eight treated with vecuronium were taking beta-adrenergic blockers preoperatively which was associated with lower HR (96 +/- 16 vs 109 +/- 15 bpm; P = 0.025) and lower PWI (8.8 +/- 1.2 vs 10.7 +/- 1.92 mL.min-1 x 100 g-1; P = 0.003) at onset of shivering. However, beta-adrenergic blockers did not attenuate the relative HR increase induced by pancuronium. No relationship was found between hypercapnia and tachycardia or hypertension. These results suggest that, when compared to pancuronium for treatment of postoperative shivering, vecuronium may be advantageous because it does not increase myocardial work. The disproportionate relationship between VO2-I and PWI after treatment with muscle relaxants indicates that increased VO2-I does not contribute significantly to the hemodynamic disturbances associated with shivering. These disturbances are more likely the results of increased adrenergic activity related to pain and recovery from anesthesia. Shivering and its associated hemodynamic disturbances appear to be concomitant but independent signs of awakening.

Objective: To investigate the cardioprotective effect of both the amino terminal of bovine parathyroid hormone (bPTH-[1-34]) and human parathyroid hormone (hPTH-[1-84]) following coronary artery occlusion., Design: Animals were randomly assigned to one of three treatment groups following circumflex coronary artery occlusion., Animals: Experiments were performed using 19 mongrel dogs of either sex. As four animals died during experimentation, data are shown for 15 dogs (n = 5 for each treatment group)., Interventions: Animals received saline, bPTH-(1-34) or hPTH-(1-84) following occlusion of the circumflex coronary artery. Peptides were given at 0.008 nmol/kg/min. All treatments were infused directly into the coronary circulation. Infusion rate was 1 mL/min for 10 mins at 30 min intervals until the end of the experiment (480 mins after onset of occlusion). Hemodynamic variables were monitored throughout the experiment. Radioactive microspheres were injected 10 mins before, and 30, 240 and 480 mins following, occlusion of the coronary vessel to determine regional myocardial blood-flows. At the end of the experiment, area at risk and infarct size were measured by simultaneous infusion of Evans blue dye and triphenyl tetrazolium chloride stain., Main Results: Neither bPTH-(1-34) nor hPTH-(1-84) significantly reduced area of risk or infarct size as a percentage of area at risk compared with controls. These results were corroborated by regional blood-flows measured using radioactive microspheres. There was no significant difference in hemodynamic variables among the groups except that left atrial pressure was consistently lower following treatment with hPTH-(1-84)., Conclusions: No evidence was found that either bPTH-(1-34) or hPTH-(1-84) salvaged ischemic myocardium in a canine model of myocardial infarction. Treatment with hPTH-(1-84) was associated with a reduction in left atrial pressure. This latter phenomenon may constitute a beneficial effect of this peptide on diastolic myocardial function.

We compared the effects of isoflurane, enflurane, and halothane on myocardial blood flow, function, and metabolism in normally perfused and ischemic regions of the swine heart. A model of single vessel incomplete occlusion was used so that the capacity of these anesthetics to cause transmural coronary steal could be tested. After median sternotomy, the left anterior descending coronary artery (LAD) was cannulated and autoperfused from the carotid artery. Systolic segment shortening was measured in the regions of the heart perfused by the LAD and left circumflex arteries. Regional myocardial blood flow was measured with radioactive microspheres. Blood was obtained from the anterior cardiac vein for measurement of lactate. Measurements were made during imposition of a stenosis on the perfusion circuit sufficient to decrease resting flow by 25%. The same stenosis was imposed during three treatment periods in a randomized and balanced cross-over design. In one group of 12 swine, treatments were two doses of intracoronary adenosine and a control period. A second group of 12 were given 1.5% isoflurane, 2.18% enflurane, and 0.98% halothane. Heart rate, mean aortic pressure, and left atrial pressure were matched during the three treatments in each animal. Adenosine caused transmural steal resulting in diminished systolic segment shortening in the ischemic LAD region. During isoflurane, compared to halothane, the first derivative of left ventricular pressure with respect to time was greater by 28%, and systolic segment shortening in the normal left circumflex artery and ischemic LAD regions was greater by 27% and 31%, respectively. Subepicardial flow in the ischemic region was greater with isoflurane but subendocardial flow was unchanged. Lactate production during isoflurane was 52% and 76% greater than during halothane and enflurane, respectively. Our results indicate that isoflurane is not a sufficiently potent arteriolar vasodilator in swine to cause transmural steal. Although myocardial performance was superior with isoflurane in both ischemic and normally perfused regions, lactate production also increased, suggesting worsened ischemic metabolism. It is likely that the myocardial oxygen supply/demand ratio worsened with isoflurane because it caused less myocardial depression than the other anesthetics.

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 (MAP < 70 mmHg) and hypertension (MAP > 100 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 CI > or = 2.4 L/min/m2 and a mean arterial pressure > or = 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 rate > 130/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.

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.