Protocol for a multicentre, randomised, parallel-control, superiority trial comparing administration of clotting factor concentrates with a standard massive haemorrhage protocol in severely bleeding trauma patients: the FiiRST 2 trial (a 2020 EAST multicentre trial).

INTRODUCTION: Acute traumatic coagulopathy (ATC) in bleeding trauma patients increase in-hospital mortality. Fibrinogen concentrate (FC) and prothrombin complex concentrate (PCC) are two purified concentrates of clotting factors that have been used to treat ATC. However, there is a knowledge gap on their use compared with the standard of care, the transfusion of plasma. METHODS AND ANALYSIS: The factors in the initial resuscitation of severe trauma 2 trial is a multicentre, randomised, parallel-control, single-blinded, phase IV superiority trial. The study aims to address efficacy and safety of the early use of FC and PCC compared with a plasma-based resuscitation. Adult trauma patients requiring massive haemorrhage protocol activation on hospital arrival will receive FC 4 g and PCC 2000 IU or plasma 4 U, based on random allocation. The primary outcome is a composite of the cumulative number of all units of red cells, plasma and platelets transfused within 24 hours following admission. Secondary outcomes include measures of efficacy and safety of the intervention. Enrolment of 350 patients will provide an initial power >80% to demonstrate superiority for the primary outcome. After enrolment of 120 patients, a preplanned adaptive interim analysis will be conducted to reassess assumptions, check for early superiority demonstration or reassess the sample size for remainder of the study. ETHICS AND DISSEMINATION: The study has been approved by local and provincial research ethics boards and will be conducted according to the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. As per the Tri-Council Policy Statement, patient consent will be deferred due to the emergency nature of the interventions. If superiority is established, results will have a major impact on clinical practice by reducing exposure to non-virally inactivated blood products, shortening the time for administration of clotting factors, correct coagulopathy more efficaciously and reduce the reliance on AB plasma. TRIAL REGISTRATION NUMBER: NCT04534751, pre results.

Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery: A Randomized Pilot Trial.

Importance: Approximately 15% of patients undergoing cardiac surgery receive frozen plasma (FP) for bleeding. Four-factor prothrombin complex concentrates (PCCs) have logistical and safety advantages over FP and may be a suitable alternative. Objectives: To determine the proportion of patients who received PCC and then required FP, explore hemostatic effects and safety, and assess the feasibility of study procedures. Design, Setting, and Participants: Parallel-group randomized pilot study conducted at 2 Canadian hospitals. Adult patients requiring coagulation factor replacement for bleeding during cardiac surgery (from September 23, 2019, to June 19, 2020; final 28-day follow-up visit, July 17, 2020). Data analysis was initiated on September 15, 2020. Interventions: Prothrombin complex concentrate (1500 IU for patients weighing ≤60 kg and 2000 IU for patients weighing >60 kg) or FP (3 U for patients weighing ≤60 kg and 4 U for patients weighing >60 kg), repeated once as needed within 24 hours (FP used for any subsequent doses in both groups). Patients and outcome assessors were blinded to treatment allocation. Main Outcomes and Measures: Hemostatic effectiveness (whether patients received any hemostatic therapies from 60 minutes to 4 and 24 hours after initiation of the intervention, amount of allogeneic blood components administered within 24 hours after start of surgery, and avoidance of red cell transfusions within 24 hours after start of surgery), protocol adherence, and adverse events. The analysis set comprised all randomized patients who had undergone cardiac surgery, received at least 1 dose of either treatment, and provided informed consent after surgery. Results: Of 169 screened patients, 131 were randomized, and 101 were treated (54 with PCC and 47 with FP), provided consent, and were included in the analysis (median age, 64 years; interquartile range [IQR], 54-73 years; 28 [28%] were female; 82 [81%] underwent complex operations). The PCC group received a median 24.9 IU/kg (IQR, 21.8-27.0 IU/kg) of PCC (2 patients [3.7%; 95% CI, 0.4%-12.7%] required FP). The FP group received a median 12.5 mL/kg (IQR, 10.0-15.0 mL/kg) of FP (4 patients [8.5%; 95% CI, 2.4%-20.4%] required >2 doses of FP). Hemostatic therapy was not required at the 4-hour time point for 43 patients (80%) in the PCC group and for 32 patients (68%) in the FP group (P = .25) nor at the 24-hour time point for 41 patients (76%) in the PCC group and for 31 patients (66%) patients in the FP group (P = .28). The median numbers of units for 24-hour cumulative allogeneic transfusions (red blood cells, platelets, and FP) were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 14.0 U (IQR, 8.0-20.0 U) in the FP group (ratio, 0.58; 95% CI, 0.45-0.77; P < .001). After exclusion of FP administered as part of the investigational medicinal product, the median numbers of units were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 10.0 U (IQR, 6.0-16.0 U) in the FP group (ratio, 0.80; 95% CI, 0.59-1.08; P = .15). For red blood cells alone, the median numbers were 1.5 U (IQR, 0.0-4.0 U) in the PCC group and 3.0 U (IQR, 1.0-5.0 U) in the FP group (ratio, 0.69; 95% CI, 0.47-0.99; P = .05). During the first 24 hours after start of surgery, 15 patients in the PCC group (28%) and 8 patients in the FP group (17%) received no red blood cells (P = .24). Adverse event profiles were similar. Conclusions and Relevance: This randomized clinical trial found that the study protocols were feasible. Adequately powered randomized clinical trials are warranted to determine whether PCC is a suitable substitute for FP for mitigation of bleeding in cardiac surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT04114643.

Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery: The FIBRES Randomized Clinical Trial.

IMPORTANCE: Excessive bleeding is a common complication of cardiac surgery. An important cause of bleeding is acquired hypofibrinogenemia (fibrinogen level <1.5-2.0 g/L), for which guidelines recommend fibrinogen replacement with cryoprecipitate or fibrinogen concentrate. The 2 products have important differences, but comparative clinical data are lacking. OBJECTIVE: To determine if fibrinogen concentrate is noninferior to cryoprecipitate for treatment of bleeding related to hypofibrinogenemia after cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial at 11 Canadian hospitals enrolling adult patients experiencing clinically significant bleeding and hypofibrinogenemia after cardiac surgery (from February 10, 2017, to November 1, 2018). Final 28-day follow-up visit was completed on November 28, 2018. INTERVENTIONS: Fibrinogen concentrate (4 g; n = 415) or cryoprecipitate (10 units; n = 412) for each ordered dose within 24 hours after cardiopulmonary bypass. MAIN OUTCOMES AND MEASURES: Primary outcome was blood components (red blood cells, platelets, plasma) administered during 24 hours post bypass. A 2-sample, 1-sided test for the ratio of the mean number of units was conducted to evaluate noninferiority (threshold for noninferiority ratio, <1.2). RESULTS: Of 827 randomized patients, 735 (372 fibrinogen concentrate, 363 cryoprecipitate) were treated and included in the primary analysis (median age, 64 [interquartile range, 53-72] years; 30% women; 72% underwent complex operations; 95% moderate to severe bleeding; and pretreatment fibrinogen level, 1.6 [interquartile range, 1.3-1.9] g/L). The trial met the a priori stopping criterion for noninferiority at the interim analysis after 827 of planned 1200 patients were randomized. Mean 24-hour postbypass allogeneic transfusions were 16.3 (95% CI, 14.9 to 17.8) units in the fibrinogen concentrate group and 17.0 (95% CI, 15.6 to 18.6) units in the cryoprecipitate group (ratio, 0.96 [1-sided 97.5% CI, -∞ to 1.09; P < .001 for noninferiority] [2-sided 95% CI, 0.84 to 1.09; P = .50 for superiority]). Thromboembolic events occurred in 26 patients (7.0%) in the fibrinogen concentrate group and 35 patients (9.6%) in the cryoprecipitate group. CONCLUSIONS AND RELEVANCE: In patients undergoing cardiac surgery who develop clinically significant bleeding and hypofibrinogenemia after cardiopulmonary bypass, fibrinogen concentrate is noninferior to cryoprecipitate with regard to number of blood components transfused in a 24-hour period post bypass. Use of fibrinogen concentrate may be considered for management of bleeding in patients with acquired hypofibrinogenemia in cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03037424.

Selective serotonin re-uptake inhibitors: risk of blood product transfusion and inotrope requirements in patients undergoing cardiac surgery.

BACKGROUND: Patients undergoing cardiac surgery exhibit a high prevalence of concomitant depression. The first-line pharmacological treatment modality for depression includes selective serotonin re-uptake inhibitors (SSRIs). Despite their efficacy, SSRIs are not without their own side-effects. METHODS: We conducted a retrospective observational study to determine if preoperative SSRI therapy was associated with higher rates of perioperative blood product transfusion, and higher incidence of inotropic requirements in patients undergoing elective cardiac surgery. A total of 2,943 patients were included in the study. Patients undergoing emergency surgery or surgery without cardiopulmonary bypass (CPB) were excluded. Based on preoperative SSRI status patients were classed into either SSRI group (n=95), or non-SSRI group (n=2,848). Data was acquired from the Toronto Anesthesia Perioperative Outcomes Database. RESULTS: Baseline preoperative variables included age, sex, body surface area, smoking history, past medical history, preoperative medications, baseline hemoglobin, creatinine, and planned surgical procedures. Perioperative transfusion of blood products and inotropic utilization were collected. Univariate analysis showed that patients in SSRI group were more likely to be female, have history of congestive heart failure, preoperative anemia, and likelihood of having more complex surgery, received more inotropes and fresh frozen plasma, and were more likely to have chest reopening for bleeding. There was no difference in postoperative morbidity and mortality between the SSRI and non-SSRI groups. Separate statistical models were constructed to determine association between transfusion of red blood cells, fresh frozen plasma, platelets, composite inotrope use, and SSRI therapy. SSRI variable was not significant in any of the multivariate models, indicating the lack of evidence of association between the SSRIs and either blood product transfusion, or inotrope requirements. Significant predictors of blood product transfusion included smaller body surface area, female gender, older age, low baseline hemoglobin levels, elevated creatinine, increased CPB, presence of deep hypothermic circulatory arrest, complex cardiac surgery, history diabetes mellitus, and congestive heart failure. Predictors of inotrope use included older age, elevated creatinine, increased CPB time, history of diabetes mellitus, and congestive heart failure. CONCLUSIONS: The current study suggests that modifying preoperative therapy pertinent to SSRI treatment in patients undergoing elective cardiac surgery is not warranted.

Postoperative Pain Management Strategies and Delirium After Transapical Aortic Valve Replacement: A Randomized Controlled Trial.

OBJECTIVE(S): This study was designed to compare 2 different perioperative analgesia strategies with respect to the incidence of postoperative delirium after a transapical approach for transcatheter aortic valve replacement (TAVR). The authors hypothesized that perioperative thoracic paravertebral analgesia with a local anesthetic would decrease opioid consumption and in turn reduce the incidence of postoperative delirium when compared with systemic opioid-based analgesia after a transapical TAVR procedure. DESIGN: Prospective, randomized controlled clinical trial. SETTING: Tertiary referral center, university hospital. PARTICIPANTS: The study comprised 44 patients undergoing a transapical TAVR procedure. Patients with a history of serious mental illness, delirium, and severe dementia and/or patients with contraindications to regional anesthesia were excluded. INTERVENTIONS: Patients were randomly assigned to either the paravertebral group (perioperative continuous thoracic paravertebral block with local anesthetic) or the patient-controlled analgesia group (systemically administered opioids) using a computer-generated randomization code in blocks of four patients. MEASUREMENTS AND MAIN RESULTS: Assessment of postoperative delirium was performed by trained research staff using the confusion assessment method for intensive care unit preoperatively and postoperatively every 12 hours or more often if needed according to the patient's condition during the first 7 postoperative days or until discharge. Pain was assessed with a 10 cm Visual Analog Scale pain score system during the 48 hours postoperatively. The sedation level was assessed using the Sedation Agitation Scale during the same period. Overall postoperative delirium was detected in 12/44 (27%) patients, with 7/22 (32%) in the patient-controlled analgesia and 5/22 (23%) in the paravertebral groups, respectively (p = 0.73). Both groups were similar with respect to demographic data, preoperative medications, and comorbidities. Paravertebral analgesia was associated with an opioid-sparing effect during surgery and during the 48-hour postoperative period. Sedation and pain scores were similar between the 2 groups. In addition, paravertebral analgesia was associated with earlier extubation times; however, the overall morbidity and mortality were similar between the 2 groups. CONCLUSIONS: Paravertebral analgesia in patients undergoing transapical TAVR procedures appears to have an opioid-sparing effect. However, it did not translate into a statistically significant decrease in the rate of postoperative delirium.

Protocol for the electroencephalography guidance of anesthesia to alleviate geriatric syndromes (ENGAGES-Canada) study: A pragmatic, randomized clinical trial.

Background:  There is some evidence that electroencephalography guidance of general anesthesia can decrease postoperative delirium after non-cardiac surgery.  There is limited evidence in this regard for cardiac surgery.  A suppressed electroencephalogram pattern, occurring with deep anesthesia, is associated with increased incidence of postoperative delirium (POD) and death.  However, it is not yet clear whether this electroencephalographic pattern reflects an underlying vulnerability associated with increased incidence of delirium and mortality, or whether it is a modifiable risk factor for these adverse outcomes. Methods:  The Electroe ncephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes ( ENGAGES-Canada) is an ongoing pragmatic 1200 patient trial at four Canadian sites.  The study compares the effect of two anesthetic management approaches on the incidence of POD after cardiac surgery.  One approach is based on current standard anesthetic practice and the other on electroencephalography guidance to reduce POD. In the guided arm, clinicians are encouraged to decrease anesthetic administration, primarily if there is electroencephalogram suppression and secondarily if the EEG index is lower than the manufacturers recommended value (bispectral index (BIS) or WAVcns below 40 or Patient State Index below 25).  The aim in the guided group is to administer the minimum concentration of anesthetic considered safe for individual patients.  The primary outcome of the study is the incidence of POD, detected using the confusion assessment method or the confusion assessment method for the intensive care unit; coupled with structured delirium chart review.  Secondary outcomes include unexpected intraoperative movement, awareness, length of intensive care unit and hospital stay, delirium severity and duration, quality of life, falls, and predictors and outcomes of perioperative distress and dissociation. Discussion:  The ENGAGES-Canada trial will help to clarify whether or not using the electroencephalogram to guide anesthetic administration during cardiac surgery decreases the incidence, severity, and duration of POD. Registration: ClinicalTrials.gov ( NCT02692300) 26/02/2016.

Dexmedetomidine versus Propofol Sedation Reduces Delirium after Cardiac Surgery: A Randomized Controlled Trial.

BACKGROUND: Postoperative delirium (POD) is a serious complication after cardiac surgery. Use of dexmedetomidine to prevent delirium is controversial. The authors hypothesized that dexmedetomidine sedation after cardiac surgery would reduce the incidence of POD. METHODS: After institutional ethics review board approval, and informed consent, a single-blinded, prospective, randomized controlled trial was conducted in patients 60 yr or older undergoing cardiac surgery. Patients with a history of serious mental illness, delirium, and severe dementia were excluded. Upon admission to intensive care unit (ICU), patients received either dexmedetomidine (0.4 µg/kg bolus followed by 0.2 to 0.7 µg kg h infusion) or propofol (25 to 50 µg kg min infusion) according to a computer-generated randomization code in blocks of four. Assessment of delirium was performed with confusion assessment method for ICU or confusion assessment method after discharge from ICU at 12-h intervals during the 5 postoperative days. Primary outcome was the incidence of POD. RESULTS: POD was present in 16 of 91 (17.5%) and 29 of 92 (31.5%) patients in dexmedetomidine and propofol groups, respectively (odds ratio, 0.46; 95% CI, 0.23 to 0.92; P = 0.028). Median onset of POD was on postoperative day 2 (1 to 4 days) versus 1 (1 to 4 days), P = 0.027, and duration of POD 2 days (1 to 4 days) versus 3 days (1 to 5 days), P = 0.04, in dexmedetomidine and propofol groups, respectively. CONCLUSIONS: When compared with propofol, dexmedetomidine sedation reduced incidence, delayed onset, and shortened duration of POD in elderly patients after cardiac surgery. The absolute risk reduction for POD was 14%, with a number needed to treat of 7.1.

Type of anesthesia and postoperative delirium after vascular surgery.

OBJECTIVE: The purpose of this study was to investigate the association between general (GA), regional (RA), and local (LA) anesthetic techniques with respect to the development of delirium after vascular surgery. The authors hypothesized that patients undergoing GA for vascular surgery would have a higher incidence of postoperative delirium. The role of LA with respect to postoperative delirium in vascular surgery patients previously has not been reported. DESIGN: Retrospective review. SETTING: Tertiary referral center, university hospital. PARTICIPANTS: 500 patients undergoing vascular surgical procedures. INTERVENTIONS: Based on the chosen anesthetic technique, all patients were divided into GA, RA, and LA groups, respectively. Exclusion criteria were patients with preoperative dementia or abnormal level of consciousness, patients undergoing open abdominal aneurysm repair surgery, and patients undergoing carotid endarterectomy. All anesthetic techniques were conducted according to routine institutional practices. Patients in both the RA and LA groups received intravenous sedation. MEASUREMENTS AND MAIN RESULTS: Three hundred ninety-six (79%) patients received GA, 73 (15%) RA, and 31 (6%) LA. The overall incidence of delirium was 19.4% and rates were similar among the 3 groups, with 73 (18.4%) patients in the GA group, 17 (23.2%) in the RA group, and 7 (22.5%) in the LA group (p = 0.56). Patients in the LA group were more likely to have emergency surgery and also had a higher incidence of previous cerebrovascular accidents or transient ischemic attacks. There was no significant difference with respect to either onset or duration of delirium among the 3 groups. Median length of hospital stay and in-hospital mortality were similar among the 3 groups. CONCLUSIONS: Delirium rates after vascular surgery were similar with local, regional, or general anesthesia techniques. The presence of risk factors for the development of postoperative delirium should not influence the type of anesthesia provided.

The Revised Cardiac Risk Index in the new millennium: a single-centre prospective cohort re-evaluation of the original variables in 9,519 consecutive elective surgical patients.

PURPOSE: Cardiac complications following non-cardiac surgery are major causes of morbidity and mortality. The Revised Cardiac Risk Index (RCRI) has become a standard for predicting post-surgical cardiac complications. This study re-examined the original six risk factors to confirm their validity in a large modern prospective database. METHODS: Using the definitions in the original risk index, this study included 9,519 patients aged ≥ 50 undergoing elective non-cardiac surgery with an expected length of stay ≥ two days at two major tertiary-care teaching hospitals. The validity of the original predictors was tested in this population using binomial logistic regression modelling, area under the receiver operator curve (ROC) analysis, and the net reclassification index. RESULTS: Rates of major cardiac complications with 0, 1, 2, ≥ 3 of the predictors were 0.5%, 2.6%, 7.2%, and 14.4%, respectively, in our patient cohort compared with 0.4%, 1.1%, 4.6%, and 9.7%, respectively, in the original cohort. Similar to the original report, binary logistic regression analysis showed that both preoperative treatment with insulin (odds ratio [OR] 1.4; 95% confidence interval [CI] 0.7 to 2.6) and preoperative creatinine > 176.8 mmol·L(-1) (OR 1.7; 95% CI 0.8 to 3.6) did not improve the predictive ability of the index. Analysis of the remaining four factors resulted in an area under the curve (AUC) identical to that seen for the reconstructed six-factor RCRI (AUC = 0.79). We found that a glomerular filtration rate (GFR) < 30 mL·min(-1) was a better predictor of major cardiac complications (OR 2.2; 95% CI 1.2 to 4.3) than creatinine > 176.8 mmol·L(-1). The receiver operating characteristic analysis of this resultant 5-Factor model resulted in an AUC of 0.79, with 0, 1, 2, ≥ 3 of the predictors representing 0.5%, 2.9%, 7.4%, and 17.0% risk, respectively, among our patient cohort. CONCLUSION: Compared with the RCRI, a simplified 5-Factor model using a high-risk type of surgery, a history of ischemic heart disease, congestive heart failure, cerebrovascular disease, and a preoperative GFR < 30 mL·min(-1) results in superior prediction of major cardiac complications following elective non-cardiac surgery.

Endovascular versus open approach to aortic aneurysm repair surgery: rates of postoperative delirium.

PURPOSE: Our objective was to compare open and endovascular aortic aneurysm repair with respect to postoperative delirium. METHODS: After Institutional Ethics Review Board approval, we conducted a retrospective review of all patients who underwent abdominal and thoraco-abdominal aortic aneurysm repair surgery at Toronto General Hospital during June 2006 to December 2007. Patients were classed into either the OPEN or the endovascular (EVAR) group based on the type of surgery and were assessed for the presence of delirium after surgery. The NEECHAM Confusion Scale and the validated chart review instrument were used for diagnosis of delirium. Patients with dementia and/or abnormal levels of consciousness preoperatively were excluded. RESULTS: There were 256 patients included in the study, 149 (58%) in the OPEN group and 107 (42%) in the EVAR group. Patients in the EVAR group were considerably older, 74 (10) yr vs 68 (9) yr, and they had shorter duration of surgery, 150 [119, 180] min vs 200 [165, 260] min, respectively, P < 0.0001. Postoperative delirium was present in 43 (29%) patients in the OPEN group and 14 (13%) patients in the EVAR group (95% confidence interval [CI], 22 to 36 vs 95% CI, 7 to 19, respectively; P = 0.003). Hospital length of stay was 8.3 [6.6, 13.4] days in the OPEN group and 4.5 [3.1, 6.4] days in the EVAR group, P < 0.0001. CONCLUSIONS: Perioperative management of patients undergoing endovascular aortic aneurysm repair was associated with lower rates of delirium after surgery than that of patients undergoing open aortic aneurysm repair.

Early benefit of preserved cognitive function is not sustained at one-year after cardiac surgery: a longitudinal follow-up of the randomized controlled trial.

PURPOSE: Recently, we showed that processing of shed blood with a continuous-flow cell saver during cardiopulmonary bypass resulted in a clinically significant reduction in postoperative cognitive decline (POCD) six weeks after coronary artery bypass graft (CABG) surgery. The current study examined if the early benefit of reduced POCD was sustained in the same patient population at one-year follow-up. METHODS: One hundred seventy patients (cell saver group, n = 84; controls, n = 86) underwent neuropsychological testing at baseline and one year after surgery. The raw scores for each test were converted to Z-scores, and a combined Z-score of ten main variables was then calculated for each study group. RESULTS: Postoperative cognitive decline was present in 16 of 84 (19%) patients in the cell saver group (95% confidence interval [CI], 10.8 to 27.2) vs 15 of 86 (17.4%) patients in the control group (95% CI, 9.6 to 25.2) (P = 0.786). Six of the 15 patients in the control group with POCD at six weeks had the impairment at one year and five did not; four were lost to follow-up. Three of the six cell saver patients with POCD at six weeks still had impairment at one year, two did not, and one was not tested. Thirteen (15.4%) and nine (10.5%) patients in the cell saver and control groups, respectively, developed new POCD which was not evident at the six-week follow-up. CONCLUSIONS: The short-term preservation of cognitive function in elderly patients using the cell saver management strategy did not translate into a long-term benefit one year after CABG surgery. The presence of progressing cerebrovascular disease may be responsible for the long-term cognitive decline.

Gender differences in mortality following non-cardiovascular surgery: an observational study.

PURPOSE: Although inequality between males and females in cardiovascular surgery is well recognized, few studies have examined the influence of sex on mortality following non-cardiovascular surgery. The objective of the study was to determine whether there are differences in mortality between males and females following non-cardiovascular surgery and to ascertain to what extent preoperative risk factors explain these differences. METHODS: This was an observational study of 39,433 consecutive non-cardiovascular inpatient surgical cases from non-sex-biased surgical services from 2003 to 2009. Data on the surgical procedure, patient risk factors, and outcomes was retrieved from the institutional Electronic Data Warehouse. The primary outcome was in-hospital mortality within 30 days of surgery. Multivariate analysis using logistic regression was conducted to determine the role of risk factors for mortality. RESULTS: The 30-day mortality was 2.76% for males and 1.89% for females (odds ratio, 1.47; 95% confidence interval [CI], 1.29 to 1.69). Logistic regression showed that age, number of Charlson comorbidities, American Society of Anesthesiologists (ASA) classification, and emergent/urgent status were independent predictors of mortality (receiver operating characteristic area, 0.90). After adjustment for these factors, the odds ratio for male mortality was reduced to 1.31 (95% CI, 1.14 to 1.52). CONCLUSION: Males present for non-cardiovascular surgery with a higher ASA classification, with more comorbidities, and more often emergently than females, providing a partial explanation of the observed difference in mortality.

The effect of nasogastric tube application during cardiac surgery on postoperative nausea and vomiting--a randomized trial.

OBJECTIVE: Postoperative nausea and vomiting (PONV) are significant morbidities following cardiac surgery. The purpose of this study was to determine if application of a nasogastric (NG) tube during cardiac surgery can reduce the prevalence of postoperative PONV. DESIGN: This study was a prospective randomized controlled trial. SETTING: University tertiary referral center. PARTICIPANTS: Two hundred two patients undergoing elective cardiac procedures. INTERVENTIONS: Patients were prospectively enrolled and randomized to either receive or not receive an NG tube after induction of anesthesia. Standard anesthetic technique and postoperative care were employed in all patients. Preoperative demographic data, pain score, nausea score and incidence of vomiting were recorded early (0-8 hours) and late (8-16 hours) following extubation. Antiemetic and analgesic medications were compared between the 2 groups. MEASUREMENTS AND MAIN RESULTS: One hundred three patients were randomized to no an NG tube (controls) and 99 received an NG tube as part of their perioperative management. Demographic data and surgical characteristics were similar between the 2 groups. However, the control group had more smokers. Incidence and severity of nausea, pain scores, and analgesic requirements were similar between the 2 groups. Prevalence of vomiting was more frequent in the control group (24%) than in the NG tube group (10%, p = 0.007), and was more frequent in patients who underwent valve and redo procedures. CONCLUSIONS: Use of an NG tube during cardiac surgery may reduce the incidence of postoperative vomiting.

N-acetylcysteine is associated with increased blood loss and blood product utilization during cardiac surgery.

OBJECTIVE: When used to prevent perioperative inflammation and ischemia-reperfusion injury, N-acetylcysteine may inadvertently impair hemostasis. We, therefore, performed a post hoc analysis of a recent randomized controlled trial in cardiac surgery to determine whether N-acetylcysteine was associated with increased blood loss and blood product transfusion. DESIGN: Blinded (patients, caregivers, outcome assessors) placebo-controlled parallel group randomized trial (www.ClinicalTrials.gov ID NCT00188630). SETTING: Tertiary care hospital in Toronto, Ontario, Canada (September 2003 to October 2005). PATIENTS: A total of 177 patients with preexisting moderate renal insufficiency (estimated glomerular filtration rate or=5 units of red blood cells within 24 hours of surgery was significantly higher with N-acetylcysteine (relative risk 1.85, 95% CI 1.06-3.21, p = 0.03; adjusted relative risk 2.09, 95% CI 1.24-3.83, p = 0.005). CONCLUSIONS: In patients who have preexisting moderate renal insufficiency and are undergoing cardiac surgery, N-acetylcysteine was associated with important effects on blood loss and blood product transfusion. Clinicians and researchers should, therefore, consider the potential for impaired hemostasis when using N-acetylcysteine in the perioperative setting. Further research is needed to elucidate mechanisms by which N-acetylcysteine may impair hemostasis, and the risk-benefit profile of N-acetylcysteine for perioperative organ protection.

The clinical utility of an index of global oxygenation for guiding red blood cell transfusion in cardiac surgery.

BACKGROUND: This observational study explored the potential utility of oxygen extraction ratio (O2ER) as an adjunct to the hemoglobin (Hb) concentration for guiding red blood cell (RBC) transfusion decisions after cardiac surgery with cardiopulmonary bypass (CPB). STUDY DESIGN AND METHODS: Hb and O2ER measures were obtained before as well as 15 and 120 minutes after RBC transfusion episodes (defined as 1-2 RBC units given in succession after CPB, within 24 hr. of surgery). Changes related to RBC transfusions among patients with normal (30%) and elevated(>30%) pretransfusion O2ERs were analyzed. RESULTS: Of the 176 patients enrolled, 74 received RBC transfusions. Of these, 50 had data available for 62 transfusion episodes. Pretransfusion episode O2ER values were elevated in 27 cases and normal in 35(56%) cases. Among those who received transfusion for low Hb concentration, 43 percent (27/62) had normal pretransfusion O2ER values. While the posttransfusion O2ER values did not change in patients with normal pretransfusion O2ER values, they did decrease inpatients with elevated pretransfusion O2ER values (% change [+/-SD] at 15 and 120 min after transfusion was -5.2 +/- 7.8 and -3.8 +/- 8.0%, respectively; p < 0.05). CONCLUSION: If a normal O2ER in anemic patients with no evidence of organ dysfunction indicates adequate tissue oxygen delivery, then our findings suggest that incorporating O2ER into the transfusion decision will substantially reduce post-cardiac surgery RBC transfusions by allowing us to safely avoid transfusing this group of patients. Future studies are needed to assess the validity of this conclusion.

Preoperative use of statins is associated with reduced early delirium rates after cardiac surgery.

BACKGROUND: Delirium is an acute deterioration of brain function characterized by fluctuating consciousness and an inability to maintain attention. Use of statins has been shown to decrease morbidity and mortality after major surgical procedures. The objective of this study was to determine an association between preoperative administration of statins and postoperative delirium in a large prospective cohort of patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: After Institutional Review Board approval, data were prospectively collected on consecutive patients undergoing cardiac surgery with cardiopulmonary bypass from April 2005 to June 2006 in an academic hospital. All patients were screened for delirium during their hospitalization using the Confusion Assessment Method in the intensive care unit. Multivariable logistic regression analysis was used to identify independent perioperative predictors of delirium after cardiac surgery. Statins were tested for a potential protective effect. RESULTS: Of the 1,059 patients analyzed, 122 patients (11.5%) had delirium at any time during their cardiovascular intensive care unit stay. Administration of statins had a protective effect, reducing the odds of delirium by 46%. Independent predictors of postoperative delirium included older age, preoperative depression, preoperative renal dysfunction, complex cardiac surgery, perioperative intraaortic balloon pump support, and massive blood transfusion. The model was reliable (Hosmer-Lemeshow test, P = 0.3) and discriminative (area under receiver operating characteristic curve = 0.77). CONCLUSIONS: Preoperative administration of statins is associated with the reduced risk of postoperative delirium after cardiac surgery with cardiopulmonary bypass.

Dealing with death: first encounters for first-year nursing students.

End-of-life care, particularly for older people, is often sub-optimal in England, and the Government has introduced several initiatives to improve this care. The authors believe the twin frameworks of emotional labour and ethics of non-abandonment underpin the provision of high-quality care. This article discusses a research project that investigated first-year nursing students' encounters with patient deaths. The research found that, to the student, every death in clinical practice is a learning experience and potentially a source of emotional distress; some students reported experiencing flashbacks afterwards and were developing avoidance behaviours. Students sometimes felt unsupported by mentors and also felt that sometimes dying patients and families were inadequately cared for. The theme of abandonment was evident in the students' stories. The authors conclude that there is still room for improvement in end-of-life care. Good role modelling and pastoral care by mentors is vital to student development. Link lecturers and mentors need to be alert to student distress.

Prevalence of claustrophobia and magnetic resonance imaging after coronary artery bypass graft surgery.

BACKGROUND: The purpose of this study was to determine the prevalence of claustrophobia in patients undergoing magnetic resonance imaging (MRI) after coronary artery bypass graft (CABG) surgery. METHODS: After IRB approval, we conducted a substudy of a prospective randomized controlled clinical trial of 311 patients evaluating administration of tranexamic acid and early saphenous vein graft patency with MRI after conventional CABG surgery. Chest tube drainage was measured at 6, 12, and 24 hours after surgery. The rate of transfusion and the amount of red blood cells (RBC), fresh frozen plasma (FFP), and platelets transfused were recorded. RESULTS: A total of 237(76%) patients underwent MRI after surgery. 39 (14%, [95% CI, 10.2 to 18.0]) patients experienced severe anxiety caused by a fear of enclosed space in the MRI coil necessitating termination of the procedure. Patients with claustrophobia were on average 5 years younger. They were more likely to have diabetes mellitus and hypertension. Patients with claustrophobia had increased chest tube drainage during the postoperative period. The rate of blood product transfusion was similar between the two groups but patients with claustrophobia who were transfused received significantly more RBC and FFP than patients without claustrophobia. CONCLUSIONS: Postoperative claustrophobia and anxiety, leading to inability to undergo MRI, may be more common than previously described.