Six-Month Outcomes after Restrictive or Liberal Transfusion for Cardiac Surgery.

BACKGROUND: We reported previously that, in patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive transfusion strategy was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or 28 days after surgery, whichever came first. We now report the clinical outcomes at 6 months after surgery. METHODS: We randomly assigned 5243 adults undergoing cardiac surgery to a restrictive red-cell transfusion strategy (transfusion if the hemoglobin concentration was <7.5 g per deciliter intraoperatively or postoperatively) or a liberal red-cell transfusion strategy (transfusion if the hemoglobin concentration was <9.5 g per deciliter intraoperatively or postoperatively when the patient was in the intensive care unit [ICU] or was <8.5 g per deciliter when the patient was in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis occurring within 6 months after the initial surgery. An expanded secondary composite outcome included all the components of the primary outcome as well as emergency department visit, hospital readmission, or coronary revascularization occurring within 6 months after the index surgery. The secondary outcomes included the individual components of the two composite outcomes. RESULTS: At 6 months after surgery, the primary composite outcome had occurred in 402 of 2317 patients (17.4%) in the restrictive-threshold group and in 402 of 2347 patients (17.1%) in the liberal-threshold group (absolute risk difference before rounding, 0.22 percentage points; 95% confidence interval [CI], -1.95 to 2.39; odds ratio, 1.02; 95% CI, 0.87 to 1.18; P=0.006 for noninferiority). Mortality was 6.2% in the restrictive-threshold group and 6.4% in the liberal-threshold group (odds ratio, 0.95; 95% CI, 0.75 to 1.21). There were no significant between-group differences in the secondary outcomes. CONCLUSIONS: In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy for red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis at 6 months after surgery. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .).

Anaesthetic depth and complications after major surgery: an international, randomised controlled trial.

BACKGROUND: An association between increasing anaesthetic depth and decreased postoperative survival has been shown in observational studies; however, evidence from randomised controlled trials is lacking. Our aim was to compare all-cause 1-year mortality in older patients having major surgery and randomly assigned to light or deep general anaesthesia. METHODS: In an international trial, we recruited patients from 73 centres in seven countries who were aged 60 years and older, with significant comorbidity, having surgery with expected duration of more than 2 h, and an anticipated hospital stay of at least 2 days. We randomly assigned patients who had increased risk of complications after major surgery to receive light general anaesthesia (bispectral index [BIS] target 50) or deep general anaesthesia (BIS target 35). Anaesthetists also nominated an appropriate range for mean arterial pressure for each patient during surgery. Patients were randomly assigned in permuted blocks by region immediately before surgery, with the patient and assessors masked to group allocation. The primary outcome was 1-year all-cause mortality. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000632897, and is closed to accrual. FINDINGS: Patients were enrolled between Dec 19, 2012, and Dec 12, 2017. Of the 18 026 patients screened as eligible, 6644 were enrolled, randomly assigned to treatment or control, and formed the intention-to-treat population (3316 in the BIS 50 group and 3328 in the BIS 35 group). The median BIS was 47·2 (IQR 43·7 to 50·5) in the BIS 50 group and 38·8 (36·3 to 42·4) in the BIS 35 group. Mean arterial pressure was 3·5 mm Hg (4%) higher (median 84·5 [IQR 78·0 to 91·3] and 81·0 [75·4 to 87·6], respectively) and volatile anaesthetic use was 0·26 minimum alveolar concentration (30%) lower (0·62 [0·52 to 0·73] and 0·88 [0·74 to 1·04], respectively) in the BIS 50 than the BIS 35 group. 1-year mortality was 6·5% (212 patients) in the BIS 50 group and 7·2% (238 patients) in the BIS 35 group (hazard ratio 0·88, 95% CI 0·73 to 1·07, absolute risk reduction 0·8%, 95% CI -0·5 to 2·0). Grade 3 adverse events occurred in 954 (29%) patients in the BIS 50 group and 909 (27%) patients in the BIS 35 group; and grade 4 adverse events in 265 (8%) and 259 (8%) patients, respectively. The most commonly reported adverse events were infections, vascular disorders, cardiac disorders, and neoplasms. INTERPRETATION: Among patients at increased risk of complications after major surgery, light general anaesthesia was not associated with lower 1-year mortality than deep general anaesthesia. Our trial defines a broad range of anaesthetic depth over which anaesthesia may be safely delivered when titrating volatile anaesthetic concentrations using a processed electroencephalographic monitor. FUNDING: Health Research Council of New Zealand; National Health and Medical Research Council, Australia; Research Grant Council of Hong Kong; National Institute for Health and Research, UK; and National Institutes of Health, USA.

Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.

BACKGROUND: Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes. Furthermore, there are concerns that tranexamic acid may have prothrombotic and proconvulsant effects. METHODS: In a trial with a 2-by-2 factorial design, we randomly assigned patients who were scheduled to undergo coronary-artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. RESULTS: Of the 4662 patients who were enrolled and provided consent, 4631 underwent surgery and had available outcomes data; 2311 were assigned to the tranexamic acid group and 2320 to the placebo group. A primary outcome event occurred in 386 patients (16.7%) in the tranexamic acid group and in 420 patients (18.1%) in the placebo group (relative risk, 0.92; 95% confidence interval, 0.81 to 1.05; P=0.22). The total number of units of blood products that were transfused during hospitalization was 4331 in the tranexamic acid group and 7994 in the placebo group (P<0.001). Major hemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the tranexamic acid group and in 2.8% of the patients in the placebo group (P=0.001), and seizures occurred in 0.7% and 0.1%, respectively (P=0.002 by Fisher's exact test). CONCLUSIONS: Among patients undergoing coronary-artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Tranexamic acid was associated with a higher risk of postoperative seizures. (Funded by the Australian National Health and Medical Research Council and others; ATACAS Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639 .).

Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery.

BACKGROUND: The effect of a restrictive versus liberal red-cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. METHODS: In this multicenter, open-label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red-cell transfusion threshold (transfuse if hemoglobin level was <7.5 g per deciliter, starting from induction of anesthesia) or a liberal red-cell transfusion threshold (transfuse if hemoglobin level was <9.5 g per deciliter in the operating room or intensive care unit [ICU] or was <8.5 g per deciliter in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first. Secondary outcomes included red-cell transfusion and other clinical outcomes. RESULTS: The primary outcome occurred in 11.4% of the patients in the restrictive-threshold group, as compared with 12.5% of those in the liberal-threshold group (absolute risk difference, -1.11 percentage points; 95% confidence interval [CI], -2.93 to 0.72; odds ratio, 0.90; 95% CI, 0.76 to 1.07; P<0.001 for noninferiority). Mortality was 3.0% in the restrictive-threshold group and 3.6% in the liberal-threshold group (odds ratio, 0.85; 95% CI, 0.62 to 1.16). Red-cell transfusion occurred in 52.3% of the patients in the restrictive-threshold group, as compared with 72.6% of those in the liberal-threshold group (odds ratio, 0.41; 95% CI, 0.37 to 0.47). There were no significant between-group differences with regard to the other secondary outcomes. CONCLUSIONS: In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy regarding red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis, with less blood transfused. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .).

Quality of Recovery After Breast Surgery: A Multicenter Randomized Clinical Trial Comparing Pectoral Nerves Interfascial Plane (Pectoral Nerves II) Block With Surgical Infiltration.

BACKGROUND: Pectoral nerves (PECS II) block is a popular regional analgesia technique for breast surgery. PECS II block or local infiltration by surgeon may improve outcomes including quality of recovery (QoR). METHODS: In this multicenter randomized clinical trial, 104 female patients undergoing breast surgery received: (1) PECS II block with local anesthetic and surgical infiltration with 0.9% saline (PECS group) or (2) PECS II block with 0.9% saline and surgical infiltration with local anesthetic (infiltration group). Patients, anesthetists, surgeons, nursing staff, and research assistants were blinded to group allocation. Patients received standardized general anesthesia and multimodal analgesia. The primary outcome was the global score (maximum score, 150; good recovery, 118) of the multidimensional (pain, comfort, independence, psychological, emotional) QoR-15 questionnaire measured 24 hours postoperatively. Secondary outcomes were pain, and its functional interference measured 24 hours and 3 months postoperatively using the Brief Pain Inventory (BPI) short form (0, optimal; 120, worst possible). Randomly assigned groups were compared on outcomes using the Wilcoxon rank-sum test, and the results were reported as median difference with 95% confidence interval. RESULTS: One hundred eight patients were recruited from August 17, 2016 to June 8, 2018, and 4 patients were withdrawn. Twelve patients from 104 had mastectomy, with the remainder having less invasive surgery. Baseline QoR-15 global scores reported as median [quartiles] were 135 [129, 143] in the PECS group and 139 [127, 143] in the infiltration group. The 24-hour QoR-15 global score reported as median [quartiles] was 131 [116, 140] in the PECS group and 123 [117, 143] in the infiltration group (P = .60), with median difference (95% confidence interval) of -2 (-9 to 5). The median difference reported as infiltration minus PECS for QoR-15 domains was pain 0 (-2 to 1), physical comfort -1 (-3 to 2), physical independence 0 (-2 to 1), psychological support 0 (0-0), and emotions 0 (-1 to 2) (P > .28). The BPI pain subscale at 24 hours (0-40, lower score indicates less pain), reported as median [quartiles], was 7 [2, 13] in the PECS group and 10 [5, 17] in the infiltration group (P = .15). The BPI global score at 24 hours, reported as median [quartiles], was 20 [7, 36] in the PECS group and 23 [10, 43] in the infiltration group (P = .34) and at 3 months was 0 [0, 14] and 0 [0, 11] (P = .85). CONCLUSIONS: After mostly minor surgery for breast cancer, PECS II block was not superior to local infiltration by the surgeon.

A pilot randomized-controlled trial evaluating the erector spinae plane block in thoracic and breast surgery.

PURPOSE: This pilot study evaluated the feasibility of investigating the effect of the erector spinae plane (ESP) block on the patient-centred outcomes of quality of recovery-15 (QoR-15), and brief pain inventory (BPI) in thoracic and breast surgery patients. METHODS: In this randomized-controlled pilot trial, 82 patients undergoing video-assisted thoracoscopic surgery (n = 77) and mastectomy (n = 5) received either continuous ESP block with ropivacaine (ropivacaine group) or the same procedure with 0.9% saline (saline group). All patients received surgical intercostal block (thoracic surgery) or local anesthetic infiltration (breast surgery). Feasibility as the primary outcome was evaluated on recruitment (three patients per week), catheter retention (above 90% at 24 hr), and patient attrition (less than 10%). Secondary outcomes comprised of QoR-15, BPI, and opioid consumption. RESULTS: Recruitment rate was 1.8 patients per week. Catheters were retained in 77 patients (94%) at 24 hr. At three months, five patients were lost to follow-up (6%). At 24 hr compared with baseline, the ropivacaine group had a smaller decline in QoR-15 score (median difference, 14; 95% confidence interval [CI], 2 to 26; P = 0.02) and a smaller increase in BPI global score (median difference, 14; 95% CI, 0 to 24; P = 0.048). There was no difference in opioid consumption (P = 0.08). CONCLUSIONS: In this pilot study, the target recruitment rate was not met, but catheter retention and patient attrition rates were both satisfactory. A definitive trial with QoR-15 as the primary outcome would require 300 study participants. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ID12618000701224); registered 30 April 2018.

RéSUMé: OBJECTIF: Cette étude pilote a évalué la faisabilité d'explorer l'effet d'un bloc du plan des muscles érecteurs du rachis sur des résultats centrés sur le patient, soit la qualité de récupération (QoR-15) et le Questionnaire concis de la douleur (QCD ou BPI 'Brief Pain Inventory'), chez les patients de chirurgie thoracique et mammaire. MéTHODE: Dans cette étude pilote randomisée contrôlée, 82 patients subissant une chirurgie thoracoscopique (n = 77) ou une mastectomie (n = 5) ont reçu soit un bloc continu du plan des muscles érecteurs du rachis avec de la ropivacaïne (groupe ropivacaïne), ou la même intervention avec une solution saline à 0,9 % (groupe salin). Tous les patients ont reçu un bloc intercostal chirurgical (chirurgie thoracique) ou une infiltration d'anesthésique local (chirurgie mammaire). La faisabilité a été évaluée par les critères de recrutement (trois patients par semaine), de la rétention du cathéter (plus de 90 % à 24 h), et du taux d'attrition des patients (moins de 10 %). Les critères d'évaluation secondaires comportaient la QoR-15, le QCD et la consommation d'opioïdes. RéSULTATS: Le taux de recrutement était de 1,8 patients par semaine. Les cathéters sont restés en place chez 77 patients (94 %) à 24 h. À trois mois, cinq patients ont été perdus au suivi (6 %). Après 24 h, par rapport aux valeurs de base, le groupe ropivacaïne présentait un déclin plus léger du score de QoR-15 (différence médiane, 14; intervalle de confiance [IC] 95 %, 2 à 26; P = 0,02) ainsi qu'une augmentation moindre du score global de QCD (différence médiane, 14; IC 95 %, 0 à 24; P = 0,048). Aucune différence n'a été observée en matière de consommation d'opioïdes (P = 0,08). CONCLUSION: Dans cette étude pilote, le taux de recrutement cible n'a pas été atteint, mais les taux de rétention des cathéters et d'attrition des patients étaient tous deux satisfaisants. Une étude définitive de la QoR-15 en tant que critère d'évaluation principal nécessiterait le recrutement de 300 participants. ENREGISTREMENT DE L'éTUDE: Australian New Zealand Clinical Trials Registry (ID12618000701224); enregistrée le 30 avril 2018.

Superb Microvascular Imaging Improves Detection of Vascularity in Indeterminate Renal Masses.

OBJECTIVES: Vascular assessment of indeterminate renal masses (iRMs) remains a crucial element of diagnostic imaging, as the presence of blood flow within renal lesions suggests malignancy. We compared the utility of Superb Microvascular Imaging (SMI; Canon Medical Systems, Tustin, CA), a novel Doppler technique, to standard color Doppler imaging (CDI) and power Doppler imaging (PDI) for the detection of vascularity within iRMs. METHODS: Patients undergoing contrast-enhanced ultrasound (CEUS) evaluations for iRMs first underwent a renal ultrasound examination with the following modes: CDI, PDI, color Superb Microvascular Imaging (cSMI), and monochrome Superb Microvascular Imaging (mSMI), using an Aplio i800 scanner with an i8CX1 transducer (Canon Medical Systems). After image randomization, each mode was assessed for iRM vascularity by 4 blinded readers on a diagnostic confidence scale of 1 to 5 (5 = most confident). The results were compared to CEUS as the reference standard. RESULTS: Forty-one patients with 50 lesions met inclusion criteria. Relative to the other 3 modalities, mSMI had the highest sensitivity (63.3%), whereas cSMI had the highest specificity (62.1%). Both cSMI and mSMI also had the highest diagnostic accuracy (0.678 and 0.680, respectively; both P < 0.001) compared to CDI (0.568) and PDI (0.555). Although the reader-reported confidence interval of mSMI (mean ± SD, 3.6 ± 1.1) was significantly lower than CDI (4.1 ± 1.0) and PDI (4.0 ± 1.0; P < 0.001), the confidence level of cSMI (4.1 ± 0.9) was not (P > 0.173). CONCLUSIONS: Preliminary data suggest that SMI is a potentially useful modality in detecting microvasculature in iRMs compared to standard Doppler techniques. Future studies should aim to compare the efficacy of both SMI and CEUS and to assess the ability of SMI to characterize malignancy in iRMs.

Transient cholinergic enhancement does not significantly affect either the magnitude or selectivity of perceptual learning of visual texture discrimination.

Perceptual learning (PL), often characterized by improvements in perceptual performance with training that are specific to the stimulus conditions used during training, exemplifies experience-dependent cortical plasticity. An improved understanding of how neuromodulatory systems shape PL promises to provide new insights into the mechanisms of plasticity, and by extension how PL can be generated and applied most efficiently. Previous studies have reported enhanced PL in human subjects following administration of drugs that increase signaling through acetylcholine (ACh) receptors, and physiological evidence indicates that ACh sharpens neuronal selectivity, suggesting that this neuromodulator supports PL and its stimulus specificity. Here we explored the effects of enhancing endogenous cholinergic signaling during PL of a visual texture discrimination task. We found that training on this task in the lower visual field yielded significant behavioral improvement at the trained location. However, a single dose of the cholinesterase inhibitor donepezil, administered before training, did not significantly impact either the magnitude or the location specificity of texture discrimination learning compared with placebo. We discuss potential explanations for discrepant findings in the literature regarding the role of ACh in visual PL, including possible differences in plasticity mechanisms in the dorsal and ventral cortical processing streams.

History of Cardiac Anesthesia in New Zealand.

New Zealand has a long and proud history of innovation in cardiac surgery and anesthesia. There have been a number of prominent men and women who have contributed to the development of cardiac anesthesia in New Zealand. There are numerous ongoing challenges in providing cardiac anesthetic services to the population of New Zealand.

Lower Prefrontal and Hippocampal Volume and Diffusion Tensor Imaging Differences Reflect Structural and Functional Abnormalities in Abstinent Individuals with Alcohol Use Disorder.

BACKGROUND: Alcohol use disorder (AUD) is known to have adverse effects on brain structure and function. Multimodal assessments investigating volumetric, diffusion, and cognitive characteristics may facilitate understanding of the consequences of long-term alcohol use on brain circuitry, their structural impairment patterns, and their impact on cognitive function in AUD. METHODS: Voxel- and surface-based volumetric estimations, diffusion tensor imaging (DTI), and neuropsychological tests were performed on 60 individuals: 30 abstinent individuals with AUD (DSM-IV) and 30 healthy controls. Group differences in the volumes of cortical and subcortical regions, fractional anisotropy (FA), axial and radial diffusivities (AD and RD, respectively), and performance on neuropsychological tests were analyzed, and the relationship among significantly different measures was assessed using canonical correlation. RESULTS: AUD participants had significantly smaller volumes in left pars orbitalis, right medial orbitofrontal, right caudal middle frontal, and bilateral hippocampal regions, lower FA in 9 white matter (WM) regions, and higher FA in left thalamus, compared to controls. In AUD, lower FA in 6 of 9 WM regions was due to higher RD and due to lower AD in the left external capsule. AUD participants scored lower on problem-solving ability, visuospatial memory span, and working memory. Positive correlations of prefrontal cortical, left hippocampal volumes, and FA in 4 WM regions with visuospatial memory performance and negative correlation with lower problem-solving ability were observed. Significant positive correlation between age and FA was observed in bilateral putamen. CONCLUSIONS: Findings showed specific structural brain abnormalities to be associated with visuospatial memory and problem-solving ability-related impairments observed in AUD. Higher RD in 6 WM regions suggests demyelination, and lower AD in left external capsule suggests axonal loss in AUD. The positive correlation between FA and age in bilateral putamen may reflect accumulation of iron depositions with increasing age.

Transfusion Requirements in Cardiac Surgery III (TRICS III): Study Design of a Randomized Controlled Trial.

OBJECTIVES: To determine if a restrictive transfusion threshold is noninferior to a higher threshold as measured by a composite outcome of mortality and serious morbidity. DESIGN: Transfusion Requirements in Cardiac Surgery (TRICS) III was a multicenter, international, open-label randomized controlled trial of two commonly used transfusion strategies in patients having cardiac surgery using a noninferiority trial design (ClinicalTrials.gov number, NCT02042898). SETTING: Eligible patients were randomized prior to surgery in a 1:1 ratio. PARTICIPANTS: Potential participants were 18 years or older undergoing planned cardiac surgery using cardiopulmonary bypass (CPB) with a preoperative European System for Cardiac Operative Risk Evaluation (EuroSCORE I) of 6 or more. INTERVENTIONS: Five thousand patients; those allocated to a restrictive transfusion group received a red blood cell (RBC) transfusion if the hemoglobin concentration (Hb) was less than 7.5 g/dL intraoperatively and/or postoperatively. Patients allocated to a liberal transfusion strategy received RBC transfusion if the Hb was less than 9.5 g/dL intraoperatively or postoperatively in the intensive care unit or less than 8.5 g/dL on the ward. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of all-cause mortality, myocardial infarction, stroke, or new onset renal dysfunction requiring dialysis at hospital discharge or day 28, whichever comes first. The primary outcome was analyzed as a per-protocol analysis. The trial monitored adherence closely as adherence to the transfusion triggers is important in ensuring that measured outcomes reflect the transfusion strategy. CONCLUSION: By randomizing prior to surgery, the TRICS III trial captured the most acute reduction in hemoglobin during cardiopulmonary bypass.

Managing Postoperative Analgesic Failure: Tramadol Versus Morphine for Refractory Pain in the Post-Operative Recovery Unit.

Objective: This study aimed to discover whether co-analgesia with tramadol or additional morphine was more effective for patients who still had severe pain despite being given 10 mg intravenous morphine in the post-anesthesia care unit (PACU). Methods: All eligible patients were consented and recruited to the trial pre-operatively, but only a small subgroup ­ whose pain was not successfully controlled (pain score 6/10 or more) after receiving 10 mg of morphine in the PACU­were then randomized to enter the trial and receive, in a double blinded fashion, the analgesic study drug; which consisted of either a further 10 mg of morphine, or 100 mg of tramadol, titrated intravenously to control their pain. The groups were compared as to: the time to readiness for discharge, the patient's pain scores over time, and the presence of side effects. Results: There was no statistically significant difference in any of the outcomes measured. The time to readiness for discharge from PACU was 119 minutes in the morphine group and 120 minutes in the tramadol group. However in approximately half the cases who entered the trial (i.e., where pain had not been controlled with the pre-enrollment baseline 10 mg of morphine in PACU) neither a further 10 mg of morphine nor 100 mg of tramadol effectively relieved the patient's pain. Conclusions: We found no difference between additional morphine and co-analgesia with tramadol in this study. Patients who don't respond to reasonable doses of opioids in PACU are very likely to be unresponsive to further opioids, and other non-opioid analgesic techniques (such as regional anesthesia) should be considered early in this group of patients.