Conventional versus minimally invasive extra-corporeal circulation in patients undergoing cardiac surgery: A randomized controlled trial (COMICS).

INTRODUCTION: The trial hypothesized that minimally invasive extra-corporeal circulation (MiECC) reduces the risk of serious adverse events (SAEs) after cardiac surgery operations requiring extra-corporeal circulation without circulatory arrest. METHODS: This is a multicentre, international randomized controlled trial across fourteen cardiac surgery centres including patients aged ≥18 and <85 years undergoing elective or urgent isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR) surgery, or CABG + AVR surgery. Participants were randomized to MiECC or conventional extra-corporeal circulation (CECC), stratified by centre and operation. The primary outcome was a composite of 12 post-operative SAEs up to 30 days after surgery, the risk of which MiECC was hypothesized to reduce. Secondary outcomes comprised: other SAEs; all-cause mortality; transfusion of blood products; time to discharge from intensive care and hospital; health-related quality-of-life. Analyses were performed on a modified intention-to-treat basis. RESULTS: The trial terminated early due to the COVID-19 pandemic; 1071 participants (896 isolated CABG, 97 isolated AVR, 69 CABG + AVR) with median age 66 years and median EuroSCORE II 1.24 were randomized (535 to MiECC, 536 to CECC). Twenty-six participants withdrew after randomization, 22 before and four after intervention. Fifty of 517 (9.7%) randomized to MiECC and 69/522 (13.2%) randomized to CECC group experienced the primary outcome (risk ratio = 0.732, 95% confidence interval (95% CI) = 0.556 to 0.962, p = 0.025). The risk of any SAE not contributing to the primary outcome was similarly reduced (risk ratio = 0.791, 95% CI 0.530 to 1.179, p = 0.250). CONCLUSIONS: MiECC reduces the relative risk of primary outcome events by about 25%. The risk of other SAEs was similarly reduced. Because the trial terminated early without achieving the target sample size, these potential benefits of MiECC are uncertain.

Incidence, predictors and vascular sequelae of distal limb ischemia in minimally invasive cardiac surgery with femoral artery cannulation: an observational cohort study.

Literature regarding monitoring and consequences of distal limb ischemia due to femoral artery cannulation for Minimally Invasive Cardiac Surgery (MICS) remains limited. The primary objective was to determine its incidence, defined as a ≥ 15% difference in regional Oxygen Saturation (rSO2) lasting ≥ four consecutive minutes between the cannulated and non-cannulated limb. The secondary objectives included: determination of distal limb ischemia, defined as a Tissue Oxygenation Index (TOI) < 50% in the cannulated limb, identification of predictors for distal limb ischemia, determination of a possible association of NIRS-diagnosed ischemia with acute kidney injury, and the need for vascular surgery up to six months after cardiac surgery. A prospective, observational cohort study with blinded rSO2-measurements to prevent intraoperative clinical decision-making. A single-center, community-hospital, clinical study. All consecutive patients ≥ 18 years old, and scheduled for predefined MICS. Patients underwent MICS with bilateral calf muscle rSO2-measurements conducted by Near-Infrared Spectroscopy (NIRS). In total 75/280 patients (26.79%) experienced distal limb ischemia according to the primary objective, while 18/280 patients (6.42%) experienced distal limb ischemia according to the secondary objective. Multivariate logistic regression showed younger age to be an independent predictor for distal limb ischemia (p = 0.003). None of the patients who suffered intraoperative ischemia required vascular surgery within the follow-up period. The incidence of NIRS-diagnosed ischemia varied from 6.4% to 26.8% depending on the used criteria. Short and long-term vascular sequelae, however, are limited and not intraoperative ischemia related. The added value of intraoperative distal limb NIRS monitoring for vascular reasons seems limited. Future research on femoral artery cannulation in MICS should shift focus to other outcome parameters such as acute kidney injury, postoperative pain or paresthesias.

Automated Nerve Monitoring in Shoulder Arthroplasty: A Prospective Randomized Controlled Study.

BACKGROUND: Evoked potential monitoring is believed to prevent neurologic injury in various surgical settings; however, its clinical effect has not been scrutinized. It was hypothesized that an automated nerve monitor can minimize intraoperative nerve injury and thereby improve clinical outcomes in patients undergoing shoulder arthroplasty. METHODS: A prospective, blinded, parallel group, superiority design, single-center, randomized controlled study was conducted. Study participants were equally randomized into either the automated nerve-monitored or the blinded monitored groups. The primary outcome was intraoperative nerve injury burden as assessed by the cumulative duration of nerve alerts. Secondary outcomes were neurologic deficits and functional scores of the operative arm, and the quality of life index (Euro Quality of life-5 domain-5 level score) at postoperative weeks 2, 6, and 12. RESULTS: From September 2018 to July 2019, 213 patients were screened, of whom 200 were randomized. There was no statistically significant difference in the duration of nerve alerts between the automated nerve-monitored and control groups (median [25th, 75th interquartile range]: 1 [0, 18] and 5 [0, 26.5]; Hodges-Lehman difference [95% CI]: 0 [0 to 1] min; P = 0.526). There were no statistically significant differences in secondary outcomes between groups. However, in the ancillary analysis, there were reductions in neurologic deficits and improvements in quality of life index occurring in both groups over the course of the study period. CONCLUSIONS: Protection from nerve injury is a shared responsibility between surgeons and anesthesiologists. Although a progressive improvement of clinical outcomes were observed over the course of the study in both groups as a consequence of the real-time feedback provided by the automated nerve monitor, this trial did not demonstrate that automated nerve monitoring by itself changes important clinical outcomes compared with no monitoring.

Perioperative Peripheral Nerve Injury After General Anesthesia: A Qualitative Systematic Review.

Perioperative peripheral nerve injury (PNI) is a well-recognized complication of general anesthesia that continues to result in patient disability and malpractice claims. However, the multifactorial etiology of PNI is often not appreciated in malpractice claims given that most PNI is alleged to be due to errors in patient positioning. New advances in monitoring may aid anesthesiologists in the early detection of PNI. This article reviews recent studies of perioperative PNI after general anesthesia and discusses the epidemiology and potential mechanisms of injury and preventive measures. We performed a systematic literature search, reviewed the available evidence, and identified areas for further investigation. We also reviewed perioperative PNI in the Anesthesia Closed Claims Project database for adverse events from 1990 to 2013. The incidence of perioperative PNI after general anesthesia varies considerably depending on the type of surgical procedure, the age and risk factors of the patient population, and whether the detection was made retrospectively or prospectively. Taken together, studies suggest that the incidence in a general population of surgical patients undergoing all types of procedures is <1%, with higher incidence in cardiac, neurosurgery, and some orthopedic procedures. PNI represent 12% of general anesthesia malpractice claims since 1990, with injuries to the brachial plexus and ulnar nerves representing two-thirds of PNI claims. The causes of perioperative PNI after general anesthesia are likely multifactorial, resulting in a "difficult to predict and prevent" phenomenon. Nearly half of the PNI closed claims did not have an obvious etiology, and most (91%) were associated with appropriate anesthetic care. Future studies should focus on the interaction between different mechanisms of insult, severity and duration of injury, and underlying neuronal reserves. Recent automated detection technology in neuromonitoring with somatosensory evoked potentials may increase the ability to identify at-risk patients and individualize patient management.

A Novel Automated Somatosensory Evoked Potential (SSEP) Monitoring Device for Detection of Intraoperative Peripheral Nerve Injury in Cardiac Surgery: A Clinical Feasibility Study.

OBJECTIVE: Peripheral nerve injury (PNI) is a common and potentially devastating complication in cardiac surgery. Somatosensory evoked potential (SSEP) monitoring is one of the modalities for PNI; however, its application is limited by complicated logistics. This study aimed to assess the feasibility of using a novel, automated SSEP device (EPAD; SafeOp Surgical, Hunt Valley, MD) for detection of intraoperative PNI during cardiac surgery. DESIGN: Prospective, observational study. SETTING: Single university hospital. PARTICIPANTS: Cardiac surgical patients. INTERVENTIONS: After Ethics Board approval and written consent, study participants were monitored using the EPAD automated SSEP device during cardiac surgery. All patients with prolonged and abnormal SSEP changes were evaluated postoperatively, and if they were symptomatic, they were referred for further nerve conduction and electromyographic assessment. MEASUREMENTS AND MAIN RESULTS: Of the 43 patients who consented to study inclusion, 33 were monitored successfully. With increasing clinical experience the authors encountered minimal technical issues, and satisfactory signals were obtained in most patients. Abnormal SSEP signal changes, which were encountered in 5 (15.2%) patients, were interpreted as impending PNI; 3 patients experienced prolonged signal changes (>1 h), and 2 (6.1%) of these developed symptomatic peripheral neuropathy that was confirmed with nerve conduction studies. CONCLUSIONS: The EPAD automated SSEP device is a viable option for detecting PNI during cardiac surgery. A high incidence of intraoperative peripheral nerve compromise and a 6.1% incidence of postoperative peripheral neuropathy were observed. This study reports the clinical feasibility of using the EPAD automated SSEP device; additional studies are required to evaluate the diagnostic test accuracy and the outcome benefit of routine SSEP monitoring in cardiac surgical patients.

Comparison of isoflurane and sevoflurane in cardiac surgery: a randomized non-inferiority comparative effectiveness trial.

PURPOSE: Volatile anesthetics possess cardioprotective properties, but it is unknown if the cardioprotective effects extend equally to all members of the class. Although sevoflurane is a relatively newer anesthetic than isoflurane, its introduction into practice was not preceded by a head-to-head comparison with isoflurane in a trial focusing on clinically important outcomes. Our objective was to determine whether sevoflurane was non-inferior to isoflurane on a clinically important primary outcome in a heterogeneous group of adults undergoing cardiac surgery. METHODS: This was a pragmatic randomized non-inferiority comparative effectiveness clinical trial in 464 adults having coronary artery bypass graft and/or single valve surgery during November 2011 to March 2014. The intervention was maintenance of anesthesia with sevoflurane (n = 231) or isoflurane (n = 233) administered at a dose of 0.5-2.0 MAC throughout the entire operation. All caregivers were blinded except for the anesthesiologist and perfusionist. The primary outcome was a composite of intensive care unit (ICU) length of stay ≥ 48 hr and all-cause 30-day mortality. We hypothesized that sevoflurane would be non-inferior to isoflurane (non-inferiority margin < 10% based on an expected event rate of 25%). Secondary outcomes included prolonged ICU stay, 30- and 365-day all-cause mortality, inotrope or vasopressor usage, new-onset hemodialysis or atrial fibrillation, stroke, and readmission to the ICU. RESULTS: No losses to follow-up occurred. The primary outcome occurred in 25% of sevoflurane patients and 30% of isoflurane patients (absolute difference, -5.4%; one-sided 95% confidence interval, 1.4), thus non-inferiority was declared. Sevoflurane was not superior to isoflurane for the primary outcome (P = 0.21) or for any secondary outcomes. CONCLUSION: Sevoflurane is non-inferior to isoflurane on a composite outcome of prolonged ICU stay and all-cause 30-day mortality. Sevoflurane is not superior to isoflurane on any other of the clinically important outcomes. This trial was registered at clinicaltrials.gov; NCT01477151.

RéSUMé: OBJECTIF: Les agents anesthésiques volatils possèdent des propriétés cardioprotectrices, mais nous ne savons pas si ces effets cardioprotecteurs sont équivalents pour tous les agents de cette classe. Bien que le sévoflurane soit un anesthésique plus récent que l'isoflurane, son introduction dans notre pratique n'a pas été précédée par une comparaison directe à l'isoflurane dans une étude s'intéressant à d'importants critères d'évaluation cliniques. Notre objectif était de déterminer si le sévoflurane était non inférieur à l'isoflurane en relation à un critère d'évaluation principal important d'un point de vue clinique dans un groupe hétérogène d'adultes subissant une chirurgie cardiaque. MéTHODE: Nous avons réalisé une étude clinique randomisée et pragmatique d'efficacité comparative et de non-infériorité auprès de 464 adultes subissant des pontages coronariens et/ou une chirurgie valvulaire unique entre novembre 2011 et mars 2014. L'intervention consistait en le maintien de l'anesthésie à l'aide de sévoflurane (n = 231) ou d'isoflurane (n = 233) administré à une dose de 0,5-2,0 MAC tout au long de l'opération. Aucun intervenant ne connaissait l'agent utilisé, à l'exception de l'anesthésiologiste et du perfusionniste. Le critère d'évaluation principal était une composée de la durée de séjour à l'unité de soins intensifs (USI) ≥ 48 h et de la mortalité, toutes causes confondues, à 30 jours. Nous avons émis l'hypothèse que le sévoflurane ne serait pas inférieur à l'isoflurane (marge de non-infériorité < 10 % sur la base d'un taux de complications attendu de 25 %). Les critères d'évaluation secondaires comprenaient un séjour prolongé à l'USI, la mortalité toutes causes confondues à 30 et à 365 jours, l'utilisation d'inotropes ou de vasopresseurs, une hémodialyse ou une fibrillation auriculaire nouvelles, un accident vasculaire cérébral et une réadmission à l'USI. RéSULTATS: Nous n'avons perdu aucun patient au suivi. Le critère d'évaluation principal est survenu chez 25 % des patients ayant reçu du sévoflurane et 30 % des patients ayant reçu de l'isoflurane (différence absolue, −5,4 %; intervalle de confiance unilatéral 95 %, 1,4): la non-infériorité a donc été déclarée. Le sévoflurane n'était pas supérieur à l'isoflurane en ce qui touchait au critère d'évaluation principal (P = 0,21) ou aux critères d'évaluation secondaires. CONCLUSION: Le sévoflurane n'est pas inférieur à l'isoflurane selon un critère d'évaluation composé d'une durée de séjour prolongée à l'USI et de la mortalité toutes causes confondues à 30 jours. Le sévoflurane n'est pas supérieur à l'isoflurane en ce qui touche à n'importe quel autre critère clinique important. Cette étude a été enregistrée au ClinicalTrials.gov, numéro NCT01477151.

Tissue microcirculation measured by vascular occlusion test during anesthesia induction.

Tissue microcirculation measured by vascular occlusion test is impaired during septic shock. However, it has not been investigated extensively during anesthesia induction. The aim of the study is to evaluate tissue microcirculation during anesthesia induction. We hypothesized that during anesthesia induction, tissue microcirculation measured by vascular occlusion test might be enhanced with peripheral vasodilation during anesthesia induction. We conducted a prospective observational study of 50 adult patients undergoing cardiac surgery. During anesthesia induction, we measured and analyzed tissue oxygen saturation, vascular occlusion test, cerebral oximetry, forearm-minus-fingertip skin temperature gradients and hemodynamic data in order to evaluate microcirculation as related to alterations in peripheral vasodilation as reflected by increased Tforearm-finger thermal gradients. During anesthesia induction, recovery slope during vascular occlusion test and cerebral oxygen saturation increased from 4.0 (1.5) to 4.7 (1.3) % s(-1) (p = 0.02) and 64.0 (10.2) to 74.2 (9.2) % (p < 0.001), respectively. Forearm-minus-fingertip skin temperature gradients decreased from 1.9 (2.9) to -1.4 (2.2) °C (p < 0.001). There was an inverse correlation between changes in the skin temperature gradients and changes in cerebral oximetry (r = 0.33; p = 0.02). During anesthesia induction, blood pressure and forearm-minus-fingertip skin temperature gradients decrease while cerebral oximetry and vascular occlusion test recovery slope increase. These findings suggest that anesthesia induction increases tissue microcirculation with peripheral vasodilation.

Microvascular reactivity and clinical outcomes in cardiac surgery.

INTRODUCTION: Microvascular reactivity is decreased in patients with septic shock; this is associated with worse clinical outcomes. The objectives of the present study were to investigate microvascular reactivity in cardiac surgery patients and to assess any association with clinical outcomes. METHODS: We retrospectively analyzed a prospectively collected registry. In total, 254 consecutive adult patients undergoing cardiac and thoracic aortic surgeries from January 2013 through May 2014 were analyzed. We performed a vascular occlusion test (VOT) by using near-infrared spectroscopy to measure microvascular reactivity. VOT was performed three times per patient: prior to the induction of anesthesia, at the end of surgery, and on postoperative day 1. The primary endpoint was a composite of major adverse complications, including death, myocardial infarction, acute kidney injury, acute respiratory distress syndrome, and persistent cardiogenic shock. RESULTS: VOT recovery slope decreased during the surgery. VOT recovery slope on postoperative day 1 was significantly lower in patients with composite complications than those without (3.1 ± 1.6 versus 4.0 ± 1.5%/s, P = 0.001), although conventional hemodynamic values, such as cardiac output and blood pressure, did not differ between the groups. On multivariable regression and linear analyses, low VOT recovery slope on postoperative day 1 was associated with increases of composite complications (odds ratio 0.742; 95% confidence interval (CI) 0.584 to 0.943; P = 0.015) and hospital length of stay (regression coefficient (B) -1.276; 95% CI -2.440 to -0.112; P = 0.032). CONCLUSION: Microvascular reactivity largely recovered on postoperative day 1 in the patients without composite complications, but this restoration was attenuated in patients with composite complications. TRIAL REGISTRATION: ClinicalTrials.gov NCT01713192. Registered 22 October 2012.

Intraoperative Cerebral Autoregulation Assessment Using Ultrasound-Tagged Near-Infrared-Based Cerebral Blood Flow in Comparison to Transcranial Doppler Cerebral Flow Velocity: A Pilot Study.

OBJECTIVE: This was a pilot study comparing the ability of a new ultrasound-tagged near-infrared (UT-NIR) device to detect cerebral autoregulation (CA) in comparison to transcranial Doppler (TCD). DESIGN: An unblinded, prospective, clinical feasibility study. SETTING: Tertiary-care university hospital cardiac surgical operating rooms. PARTICIPANTS: Twenty adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: There were no clinical interventions based on study monitoring devices, but a continuous correlation analysis of digital data from transcranial Doppler (TCD) velocity was compared with a novel UT-NIR device and correlation analysis of change signals versus mean arterial pressure was performed in order to detect presence or absence of intact CA and for determination of the lower limit of cerebral autoregulation during CPB. MEASUREMENTS AND MAIN RESULTS: Similar and highly significant concordance (κ = 1.00; p<0.001) was demonstrated between the 2 methodologies for determination of CA, indicating good correlation between the 2 methodologies. Intact CA was absent in 2 patients during CPB, and both devices were able to detect this. CONCLUSIONS: To the authors' knowledge this is the first clinical report of a UT-NIR device that shows promise as a clinically useful modality for detection of CA and the lower limit of cerebral autoregulation. The utility of UT-NIR was demonstrated further during times at which extensive usage of electrocautery or functional absence of the transcranial window rendered TCD uninterpretable.

Use of near infrared spectroscopy to detect impaired tissue oxygen saturation in patients with complex regional pain syndrome type 1.

PURPOSE: Deep tissue hypoxia has been hypothesized in the pathogenesis of complex regional pain syndrome type 1 (CRPS 1) for some patients. The purpose of this study was to determine if near-infrared spectroscopy (NIRS) could detect differences in deep tissue oxygen saturation (StO2) and microcirculatory function in the hands of patients with CRPS 1. METHODS: Tissue oxygen saturation was evaluated at baseline and during an ischemia reperfusion challenge using vascular occlusion testing (VOT) in affected vs unaffected hands of patients with unilateral upper limb CRPS 1. A non-randomized experimental study design was used with baseline StO2 as the primary outcome measure. Secondary outcome measures were occlusion and reperfusion slopes from VOT. Values were compared with the unaffected, contralateral hand and with the dominant and non-dominant hands of sex and age-matched volunteers. Correlations between values derived from NIRS and measures of pain and function from the Brief Pain Inventory (BPI) and the Disability of the Arm, Shoulder and Hand (DASH) questionnaires were explored. RESULTS: Independent of handedness, the baseline StO2 of the affected hands of ten CRPS 1 patients was significantly lower than that of their unaffected hands (-5.8%; 95% confidence interval [CI] -10.6 to -1.0; P = 0.02). The baseline StO2 of affected CRPS 1 hands was also significantly lower than the non-dominant hands of ten volunteers (-7.3%; 95% CI -12.4 to -2.3; P = 0.007). Differences in VOT occlusion and reperfusion slopes did not reveal changes that could be uniquely attributed to CRPS 1. No significant correlations were detected between values derived from VOT and values for pain and function obtained from BPI and DASH questionnaires for patients with CRPS 1. CONCLUSIONS: Hands of patients affected by CRPS 1 of the upper limb showed significantly lower StO2 compared with their unaffected contralateral hand as well as the hands of control subjects. This trial was registered at: ClinicalTrials.gov: NCT01586377.

A novel assessment of peripheral tissue microcirculatory vasoreactivity using vascular occlusion testing during cardiopulmonary bypass.

OBJECTIVE: Cardiac surgery and cardiopulmonary bypass are associated with release of inflammatory mediators and microcirculatory alterations that result in organ dysfunction. Near-infrared spectroscopic measurement of tissue oxygen saturation (StO2) and the vascular occlusion test (VOT) were utilized in a study of elective cardiac surgical patients as a novel, noninvasive method of assessing microcirculatory vasoreactivity during nonpulsatile cardiopulmonary bypass (CPB). The objective of this pilot study was to determine whether differences in microcirculatory function and vasoreactivity could be measured in cardiac surgery using StO2 and VOT. DESIGN: A prospective, observational trial. SETTING: Tertiary care teaching hospital. PARTICIPANTS: Thirteen patients undergoing elective cardiac surgery using tepid, nonpulsatile cardiopulmonary bypass. INTERVENTIONS: Patients had continuous regional oxygen saturation monitoring using near-infrared spectroscopy and vascular occlusion tests performed in the perioperative period before, during, and after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Occlusion slope and hyperemic area did not vary significantly. Mean reperfusion slope was significantly lower during cardiopulmonary bypass (2.4%/second) compared to before and after bypass (4.1 and 3.5%/second, respectively). Reperfusion slope decreased as a function of CPB duration. CONCLUSIONS: This pilot study demonstrates a significant difference in reperfusion slopes during cardiopulmonary bypass when compared to prebypass and postbypass, suggesting impaired peripheral microvascular reactivity. Reperfusion slopes also exhibited a successive decline with duration of CPB, implying worsening microcirculatory dysfunction that returned to baseline values in all patients within 1 hour of separation from CPB. This noninvasive technique has potential to optimize circulatory parameters during cardiopulmonary bypass.

A prospective observational study of seizures after cardiac surgery using continuous EEG monitoring.

INTRODUCTION: Recently, there have been several retrospective reports suggesting an increased frequency in seizures after cardiopulmonary bypass, associated with increased patient morbidity. We sought to prospectively investigate the incidence of electrographic seizures without clear convulsive clinical correlates and subsequent neurologic injury following cardiac surgery. METHODS: This single-center, prospective, observational study used continuous subhairline electroencephalographic (cEEG) monitoring in the intensive care unit following routine cardiac surgery, ranging from coronary bypass surgery to complex aortic arch reconstruction. The primary outcome was the proportion of patients developing postoperative seizures, as confirmed on cEEG monitoring. Secondary outcomes included neurologic injury, post-operative complications, mortality, and ICU and hospital lengths of stay. RESULTS: 101 consenting patients were included and 3 patients had seizures (2 focal and convulsive, 1 generalized and electrographic). All three patients with seizures were ≥65 years old, had "open-chamber" procedures, and had cardiopulmonary bypass times >120 min. One of the 3 patients with seizures was exposed to higher doses of tranexamic acid. None of the patients with seizures had permanent neurologic sequelae and all were doing well at 1-year follow-up. There was no increased morbidity or mortality in patients with seizures. CONCLUSIONS: Electrographic seizures occur infrequently after cardiac surgery and are generally associated with a good prognosis. Prophylactic cEEG monitoring is unlikely to be cost-effective in this population. (ClinicalTrials.gov Identifier: NCT01291992).

Assessing changes in regional cerebral hemodynamics in adults with a high-density full-head coverage time-resolved near-infrared spectroscopy device.

Significance: Cerebral oximeters have the potential to detect abnormal cerebral blood oxygenation to allow for early intervention. However, current commercial systems have two major limitations: (1) spatial coverage of only the frontal region, assuming that surgery-related hemodynamic effects are global and (2) susceptibility to extracerebral signal contamination inherent to continuous-wave near-infrared spectroscopy (NIRS). Aim: This work aimed to assess the feasibility of a high-density, time-resolved (tr) NIRS device (Kernel Flow) to monitor regional oxygenation changes across the cerebral cortex during surgery. Approach: The Flow system was assessed using two protocols. First, digital carotid compression was applied to healthy volunteers to cause a rapid oxygenation decrease across the ipsilateral hemisphere without affecting the contralateral side. Next, the system was used on patients undergoing shoulder surgery to provide continuous monitoring of cerebral oxygenation. In both protocols, the improved depth sensitivity of trNIRS was investigated by applying moment analysis. A dynamic wavelet filtering approach was also developed to remove observed temperature-induced signal drifts. Results: In the first protocol (28±5 years; five females, five males), hair significantly impacted regional sensitivity; however, the enhanced depth sensitivity of trNIRS was able to separate brain and scalp responses in the frontal region. Regional sensitivity was improved in the clinical study given the age-related reduction in hair density of the patients (65±15 years; 14 females, 13 males). In five patients who received phenylephrine to treat hypotension, different scalp and brain oxygenation responses were apparent, although no regional differences were observed. Conclusions: The Kernel Flow has promise as an intraoperative neuromonitoring device. Although regional sensitivity was affected by hair color and density, enhanced depth sensitivity of trNIRS was able to resolve differences in scalp and brain oxygenation responses in both protocols.

Effect of cardiopulmonary bypass on thrombin generation and protein C pathway.

OBJECTIVE: The purpose of this study was to evaluate the mechanisms of cardiopulmonary bypass (CPB)-induced dysregulation between thrombin and its regulatory anticoagulant activated protein C (APC). DESIGN: A prospective observational cohort study. SETTING: A tertiary care university hospital and associated research laboratory. PATIENTS: Twenty patients undergoing elective coronary artery bypass surgery with (n = 10) or without CPB (n = 10). INTERVENTIONS: Blood samples were collected at 7 time points: preinduction; after heparin; 1 hour after the institution of CPB (or the completion of distal anastomoses in off-CPB group); after protamine; and at 0, 4, and 18 hours in the Intensive care unit (ICU). Samples were analyzed for prothrombin fragments (F1+2), thrombin-antithrombin complexes, protein C (PC), APC, soluble thrombomodulin (sTM), and soluble endothelial protein C receptor (sEPCR). MEASUREMENTS AND MAIN RESULTS: F1+2 levels increased significantly 1 hour after the initiation of CPB in comparison with baseline (2.7 ± 0.5 v 0.5 ± 0.2 nmol/L, p < 0.001) (mean ± standard deviation) and remained elevated until 4 hours after ICU admission (p < 0.001). In contrast, APC levels did not show any significant changes over time in either group. sEPCR, sTM, and PC levels did not change during CPB although sEPCR decreased significantly after the termination of CPB compared with baseline in the CPB group. CONCLUSIONS: Exposure to CPB is associated with a distinct thrombin surge that continues postoperatively for 4 hours. The impaired ability to generate APC reflects a complex process that is not associated with increased levels of sEPCR and thrombomodulin during CPB. Further studies are required to evaluate the regulation of the host APC response in cardiac surgery.

Assessing the Sensitivity of Multi-Distance Hyperspectral NIRS to Changes in the Oxidation State of Cytochrome C Oxidase in the Brain.

Near-infrared spectroscopy (NIRS) measurements of tissue oxygen saturation (StO2) are frequently used during vascular and cardiac surgeries as a non-invasive means of assessing brain health; however, signal contamination from extracerebral tissues remains a concern. As an alternative, hyperspectral (hs)NIRS can be used to measure changes in the oxidation state of cytochrome c oxidase (ΔoxCCO), which provides greater sensitivity to the brain given its higher mitochondrial concentration versus the scalp. The purpose of this study was to evaluate the depth sensitivity of the oxCCO signal to changes occurring in the brain and extracerebral tissue components. The oxCCO assessment was conducted using multi-distance hsNIRS (source-detector separations = 1 and 3 cm), and metabolic changes were compared to changes in StO2. Ten participants were monitored using an in-house system combining hsNIRS and diffuse correlation spectroscopy (DCS). Data were acquired during carotid compression (CC) to reduce blood flow and hypercapnia to increase flow. Reducing blood flow by CC resulted in a significant decrease in oxCCO measured at rSD = 3 cm but not at 1 cm. In contrast, significant changes in StO2 were found at both distances. Hypercapnia caused significant increases in StO2 and oxCCO at rSD = 3 cm, but not at 1 cm. Extracerebral contamination resulted in elevated StO2 but not oxCCO after hypercapnia, which was significantly reduced by applying regression analysis. This study demonstrated that oxCCO was less sensitive to extracerebral signals than StO2.

A comparison of aprotinin and lysine analogues in high-risk cardiac surgery.

BACKGROUND: Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding and to reduce exposure to blood products. We sought to determine whether aprotinin was superior to either tranexamic acid or aminocaproic acid in decreasing massive postoperative bleeding and other clinically important consequences. METHODS: In this multicenter, blinded trial, we randomly assigned 2331 high-risk cardiac surgical patients to one of three groups: 781 received aprotinin, 770 received tranexamic acid, and 780 received aminocaproic acid. The primary outcome was massive postoperative bleeding. Secondary outcomes included death from any cause at 30 days. RESULTS: The trial was terminated early because of a higher rate of death in patients receiving aprotinin. A total of 74 patients (9.5%) in the aprotinin group had massive bleeding, as compared with 93 (12.1%) in the tranexamic acid group and 94 (12.1%) in the aminocaproic acid group (relative risk in the aprotinin group for both comparisons, 0.79; 95% confidence interval [CI], 0.59 to 1.05). At 30 days, the rate of death from any cause was 6.0% in the aprotinin group, as compared with 3.9% in the tranexamic acid group (relative risk, 1.55; 95% CI, 0.99 to 2.42) and 4.0% in the aminocaproic acid group (relative risk, 1.52; 95% CI, 0.98 to 2.36). The relative risk of death in the aprotinin group, as compared with that in both groups receiving lysine analogues, was 1.53 (95% CI, 1.06 to 2.22). CONCLUSIONS: Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative mortality trend associated with aprotinin, as compared with the lysine analogues, precludes its use in high-risk cardiac surgery. (Current Controlled Trials number, ISRCTN15166455 [controlled-trials.com].).

Comparison of MAX-ACT and K-ACT values when using bivalirudin anticoagulation during minimally invasive hybrid off-pump coronary artery bypass graft surgery.

OBJECTIVE: To compare the kaolin-activated coagulation time (K-ACT) to the MAX-ACT for monitoring anticoagulation with bivalirudin in patients undergoing hybrid off-pump coronary artery revascularization procedures. DESIGN: A prospective, observational study. SETTING: A cardiac surgical operating room of a university-affiliated hospital. PARTICIPANTS: Twelve patients undergoing off-pump coronary artery bypass graft surgery and percutaneous coronary intervention during the same procedure anticoagulated with bivalirudin to a target K-ACT of >300 seconds. INTERVENTION: At baseline and at frequent intervals during anticoagulation, K-ACT and MAX-ACT assays were run contemporaneously, and the pairs of results were analyzed with descriptive statistics, by correlation analysis, and with Bland-Altman analysis. MEASUREMENTS AND MAIN RESULTS: The MAX-ACT and K-ACT assays were highly correlated, but the MAX-ACT assay consistently reported significantly lower ACT values compared with the K-ACT. The mean bias (K-ACT minus MAX-ACT) was 94 seconds (limits of agreement, 51-138 seconds). CONCLUSION: To maximize patient safety, centers using bivalirudin for anticoagulation during cardiac surgical procedures need to be aware of the different performance characteristics of ACT assay subtypes.

Monitoring brain oxygen saturation during coronary bypass surgery improves outcomes in diabetic patients: a post hoc analysis.

BACKGROUND: Having previously demonstrated in a prospective study of 200 coronary artery bypass (CAB) patients that by using the brain as an index organ, interventions to improve cerebral oxygenation would have systemic outcome benefits, we undertook a post hoc analysis of the diabetic subset (n = 57) of the overall study group to determine whether the outcomes of these patients were similarly improved. METHODS: Case-report forms for the 200 CAB patients study patients with a preoperative diagnosis of diabetes mellitus were stratified to intraoperative cerebral regional oxygen saturation (rSO2) monitoring with active display and a treatment intervention protocol (intervention group, n = 28) or to blinded rSO2 monitoring (control group, n = 29) and analyzed. RESULTS: There were no significant differences between the 2 groups in overall risk factors, although there were trends toward a higher body mass index, a worse angina score, a worse grade of ventricle, and greater use of off-pump coronary revascularization in the control group of patients. The 2 groups were similar with respect to overall insulin dosage and perioperative blood glucose concentrations. Significantly more diabetic patients in the control group demonstrated profound cerebral desaturation, with an area under the curve of <50%/min (P = .043; d = 0.55), longer intensive care unit (ICU) stays (P = .045; d = 0.58), and longer overall postoperative hospital stays (P = .036; d = 0.47), compared with patients in the intervention group. Compared with the intervention group, the control group had a significantly higher incidence of sternal wound infection (P = .028; φ = 0.31) and a significantly greater number of diabetic patients with >2 postoperative complications (P = .006; φ = 0.37). An analysis after removing the patients who underwent off-pump surgery revealed that the control group had significantly more patients with sternal wound infections (5 versus 0; P = .047) and ≥2 postoperative complications (6 versus 0; P = .008) than the intervention group, as well as a trend toward longer ICU and postoperative hospitalization stays in the control group. CONCLUSION: Monitoring and management of cerebral rSO2 in diabetic CAB patients avoid profound cerebral desaturation and are associated with significantly lower incidences of complications and shorter postoperative lengths of stay. IMPLICATION STATEMENT: A post hoc analysis of the diabetic cohort of a prospective, randomized, and blinded study of CAB patients revealed that those in whom cerebral oxygen saturation was actively monitored and maintained demonstrated significantly lower incidences of complications, resulting in shorter ICU and postoperative hospital stays compared with an unmonitored control group.