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Purpose: Prolonged mechanical ventilation (MV) is a major complication following cardiac surgery. We conducted a secondary analysis of the Transfusion Requirements in Cardiac Surgery (TRICTS) III trial to describe MV duration, identify factors associated with prolonged MV, and examine associations of prolonged MV with mortality and complications., Methods: Four thousand, eight hundred and nine participants undergoing cardiac surgery at 71 hospitals worldwide were included. Prolonged MV was defined based on the Society of Thoracic Surgeons definition as MV lasting 24 hr or longer. Adjusted associations of patient and surgical factors with prolonged MV were examined using multivariable logistic regression. Associations of prolonged MV with complications were assessed using odds ratios, and adjusted associations between prolonged MV and mortality were evaluated using multinomial regression. Associations of shorter durations of MV with survival and complications were explored., Results: Prolonged MV occurred in 15% (725/4,809) of participants. Prolonged MV was associated with surgical factors indicative of complexity, such as previous cardiac surgery, cardiopulmonary bypass duration, and separation attempts; and patient factors such as critical preoperative state, left ventricular impairment, renal failure, and pulmonary hypertension. Prolonged MV was associated with perioperative but not long-term complications. After risk adjustment, prolonged MV was associated with perioperative mortality; its association with long-term mortality among survivors was weaker. Shorter durations of MV were not associated with increased risk of mortality or complications., Conclusion: In this substudy of the TRICS III trial, prolonged MV was common after cardiac surgery and was associated with patient and surgical risk factors. Although prolonged MV showed strong associations with perioperative complications and mortality, it was not associated with long-term complications and had weaker association with long-term mortality among survivors., Study Registration: www., Clinicaltrials: gov (NCT02042898); registered 23 January 2014. This is a substudy of the Transfusion Requirements in Cardiac Surgery (TRICS) III trial., (© 2022. Canadian Anesthesiologists' Society.)

This narrative review critically evaluates the evidence for risk of anemia and red blood cell (RBC) transfusion. For this purpose, it assesses large prospective randomized-controlled trials (RCTs) in medical, surgical, and critical care patient populations in which the impact of specific hemoglobin transfusion thresholds are compared. In these trials, the risks of anemia relative to those of RBC transfusion are assessed. The results of published systematic reviews and meta-analyses are also discussed. Lastly, recommendations for patient blood management and treatment of anemia are explored. The main conclusion of this review emphasizes that the decision to transfuse RBCs is complex and depends on the interaction between multiple factors including the balance between the risk of anemia and the risk of RBC transfusion, existing patient comorbidities, and medical and surgical exposures. The transfusion thresholds recommended by current guidelines vary for medical and surgical patient populations. Guidelines suggesting specific transfusion thresholds for different patient populations should be viewed as a starting point for making an informed decision about RBC transfusion. Alternatives to transfusion (i.e., patient blood management), biomarkers of anemia-induced tissue hypoxia, and transfusion alternatives should continue to be evaluated in large RCTs, with the goal of improving event-free survival in critically ill and perioperative patients.

Purpose: Post-craniotomy pain is a common clinical issue and its optimal management remains incompletely studied. Utilization of a regional scalp block has the potential advantage of reducing perioperative pain and opioid consumption, thereby facilitating optimal postoperative neurologic assessment. The purpose of this study was to assess the efficacy of regional scalp block on post-craniotomy pain and opioid consumption., Methods: We performed a prospective randomized-controlled trial in adults scheduled to undergo elective supratentorial craniotomy under general anesthesia to assess the efficacy of postoperative bilateral scalp block with 0.5% bupivacaine with 1:200,000 epinephrine compared with placebo on postoperative pain and opioid consumption. The primary outcome was the visual analogue scale (VAS) for pain at 24 hr postoperatively., Results: Eighty-nine patients were enrolled (n = 44 in block group; n = 45 in control group). There was no difference in the mean (standard deviation) VAS score at 24 hr postoperatively between the treatment group and the control group [31.2 (21.4) mm vs 23.0 (19.2) mm, respectively; mean difference, 6.6; 95% confidence interval, -2.3, 15.5; P = 0.15]. There was also no significant difference in postoperative opioid consumption. Distribution of individual VAS score and opioid consumption revealed that postoperative pain was highly variable following craniotomy. Time to hospital discharge was not different between treatment and placebo groups. No adverse events associated with scalp block were identified., Conclusion: These data show that bilateral scalp blocks using bupivacaine with epinephrine did not reduce mean postoperative VAS score or overall opioid consumption at 24 hr nor the time-to-discharge from the postanesthesia care unit or from hospital., Trial Registration: www.ClinicalTrials.gov, NCT00972790; registered 9 September, 2009.

Purpose: Iron restricted anemia is prevalent in surgical patients and is associated with an increased risk of allogeneic red blood cell (RBC) transfusion and adverse events. Treatment of anemia includes oral and intravenous iron and erythropoiesis stimulating agents (ESAs). More recent studies have focused on the use of intravenous iron as the primary approach to treating anemia. Nevertheless, the optimal treatment strategy for anemia remains to be established. Our primary objective was to evaluate the efficacy and safety of ESA and iron therapy relative to iron therapy alone in reducing RBC transfusion in surgical patients., Source: We searched the Cochrane Library, MEDLINE, EMBASE, and ClinicalTrials.gov from inception to May 2018. We included randomized-controlled trials in which adult surgical patients received an ESA and iron, vs iron alone, prior to cardiac and non-cardiac surgery. Our primary outcome was RBC transfusion rate. Secondary outcomes included hemoglobin concentration (post-treatment and postoperatively), number of RBC units transfused, mortality, stroke, myocardial infarction (MI), renal dysfunction, pulmonary embolism (PE), and deep vein thrombosis (DVT)., Principal Findings: In total, 25 studies (4,719 participants) were included. Erythropoiesis stimulating agents and iron therapy reduced RBC transfusion relative to iron therapy (relative risk [RR] 0.57; 95% confidence interval [CI], 0.46 to 0.71) without any change in mortality (RR 1.31; 95% CI, 0.80 to 2.16), stroke (RR 1.91; 95% CI, 0.63 to 5.76), MI (RR 1.12; 95% CI, 0.50 to 2.50), renal dysfunction (RR 0.96; 95% CI, 0.72 to 1.26), PE (RR 0.92; 95% CI, 0.15 to 5.83), or DVT (RR 1.48; 95% CI, 0.95 to 2.31)., Conclusion: Administration of ESA and iron therapy reduced the risk for RBC transfusion compared with iron therapy alone in patients undergoing cardiac and non-cardiac surgery. Nevertheless, publication bias and heterogeneity reduces the confidence of the finding. Although the analysis was probably under-powered for some outcomes, no difference in the incidence of serious adverse events was observed with ESA and iron compared with iron alone. Further large prospective trials are required to confirm these findings.

Purpose: Hemodilutional anemia is associated with acute kidney injury (AKI) and mortality in patients undergoing cardiac surgery by mechanisms that may include tissue hypoxia. Our hypothesis was to assess if changes in the potential hypoxic biomarkers, including methemoglobin and erythropoietin, correlated with a decrease in hemoglobin (Hb) concentration following hemodilution on cardiopulmonary bypass (CPB)., Methods: Arterial blood samples were taken from patients (n = 64) undergoing heart surgery and CPB at baseline, during CPB, following CPB, and in the intensive care unit (ICU). Potential hypoxic biomarkers were measured, including methemoglobin, plasma Hb, and erythropoietin. Data were analyzed by repeated measures one-way analysis of variance on ranks and linear regression., Results: Hemoglobin levels decreased following CPB and methemoglobin increased in the ICU (P < 0.001 for both). No correlation was observed between the change in Hb and methemoglobin (P = 0.23). By contrast, reduced Hb on CPB correlated with increased lactate, reduced pH, and increased erythropoietin levels following CPB (P ≤ 0.004 for all). Increased plasma Hb (P < 0.001) also correlated with plasma erythropoietin levels (P < 0.001)., Conclusion: These data support the hypothesis that erythropoietin rather than methemoglobin is a potential biomarker of anemia-induced tissue hypoxia. The observed relationships between decreased Hb during CPB and the increase in lactate, reduced pH, and increase in erythropoietin levels suggest that early changes in plasma erythropoietin may be a pragmatic early biomarker of anemia-induced renal hypoxia. Further study is required to determine if anemia-induced increases in erythropoietin may predict AKI in patients undergoing cardiac surgery., Trial Registration: www.clinicaltrials.gov (NCT01883713). Registered 21 June 2013.

Purpose: Nabilone is a synthetic cannabinoid with properties that make it an appealing candidate as a postoperative nausea and vomiting (PONV) prophylactic adjunct. Nabilone has proven clinical utility in chemotherapy-related nausea and vomiting but has not been adequately tested for PONV. The purpose of this study was to evaluate the effectiveness of a single dose of nabilone for the prevention of PONV., Methods: This was a pragmatic single-centre randomized-controlled trial comparing oral nabilone vs placebo for the prevention of PONV. Eligible patients scheduled for elective surgery under general anesthesia who had a preoperative risk of PONV greater than 60% received either nabilone 0.5 mg or placebo orally prior to surgery. As part of the pragmatic design, the study medication was given in addition to any other combination of antiemetic prophylaxis. The primary outcome was the incidence of PONV. Secondary outcomes included the effect on pain, speed of recovery, and drug side effects., Results: Of the 340 patients randomized, 172 received nabilone and 168 received placebo. There was no difference in the incidence of PONV, which occurred in 20.9% in the nabilone group and 21.4% in the placebo group (relative risk, 0.98; 95% confidence interval, 0.89 to 1.11; P = 0.99). There were also no differences in pain scores, opioid consumption, or reported drug side effects., Conclusion: Oral nabilone 0.5 mg given as a single dose prior to surgery is ineffective in reducing PONV. This trial was registered at ClinicalTrials.gov, identifier: NCT02115529.

Purpose: Tranexamic acid (TXA) therapy can reduce red blood cell (RBC) transfusion; however, this therapy remains underutilized in many surgical patient populations. We assessed whether implementation of a protocol to facilitate universal administration of TXA in patients undergoing total hip or knee arthroplasty would reduce the incidence of RBC transfusion without increasing adverse clinical outcomes., Methods: We implemented a quality of care policy to provide universal administration of intravenous TXA at a dose of 20 mg·kg(-1) iv to all eligible patients undergoing total hip or knee arthroplasty from October 21, 2013 to April 30, 2014. We compared data from an equal number of patients before and after protocol implementation (n = 422 per group). The primary outcome was RBC transfusion with secondary outcomes including postoperative hemoglobin concentration (Hb) and length of hospital stay. Adverse events were identified from the electronic medical records. Data were analyzed by a Chi square test and adjusted logistic and linear regression analysis., Results: Implementation of the protocol resulted in an increase in TXA utilization from 45.8% to 95.3% [change 49.5%; 95% confidence interval (CI), 44.1 to 54.5; P < 0.001]. This change was associated with a reduction in the rate of RBC transfusion from 8.8% to 5.2%, (change -3.6%; 95% CI, -0.1 to -7.0; P = 0.043). Pre- and post-protocol mean [standard deviation (SD)] Hb values were similar, including the nadir Hb prior to RBC transfusion [72 (8) g·L(-1) vs 70 (8) g·L(-1), respectively; mean difference -1 g·L(-1); 95% CI, -3 to 5; P = 0.569]. Length of stay was not altered, and no increase in adverse events was observed., Conclusions: Implementation of a perioperative TXA protocol was associated with both an increase in TXA use and a reduction in RBC transfusion following hip or knee arthroplasty. Adverse events and length of hospital stay were not influenced by the protocol.

Purpose: Acute kidney injury (AKI) is a potentially serious complication of cardiac surgery. Anemia and red blood cell (RBC) transfusion have individually been identified as potentially modifiable risk factors, but their interrelationship with AKI has not been clearly defined. The purpose of this study was to explore the interrelationship of preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery with AKI in cardiac surgery., Methods: This historical cohort study included 16 hospitals, each contributing data on approximately 100 consecutive patients who underwent cardiac surgery with cardiopulmonary bypass. Acute kidney injury was defined as a > 50% increase in creatinine levels during the first postoperative week. Multivariable regression was used to identify the interrelationship between preoperative anemia (hemoglobin < 130 g·L(-1) in males and < 120 g·L(-1) in females), intraoperative anemia (hemoglobin < 80 g·L(-1) during cardiopulmonary bypass), RBC transfusion on the day of surgery, and their interaction terms, after adjusting for site and baseline AKI risk., Results: Of the 1,444 patients included in the study, 541 (37%) had preoperative anemia, 501 (35%) developed intraoperative anemia, 619 (43%) received RBC transfusions, and 238 (16%) developed AKI. After risk-adjustment, an individual with the combination of these three risk factors had a 2.6-fold (95% confidence interval 2.0 to 3.3) increase in the relative risk of AKI over an individual with none of these risk factors., Conclusions: Preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery are interrelated risk factors for AKI after cardiac surgery. Targeting these risk factors may reduce the burden of AKI.

Purpose: Recombinant activated factor VII (rFVIIa) is a pro-hemostatic drug that is approved for treatment of bleeding in hemophilia patients, but it is frequently used off-label in non-hemophiliacs. The purpose of this study was to determine if the off-label use of rFVIIa is expanding and whether this poses a net harm to patients., Methods: For this historical cohort study, data were collected on all non-hemophilia patients who received rFVIIa from 2007 to 2010 at 16 Canadian centres, and the pattern of use was examined. Logistic regression was used to determine the prognostic importance of severity of bleeding and the presence of an rFVIIa dose-effect relationship with major adverse events., Results: One thousand three hundred seventy-eight patients received rFVIIa off-label, and 987 (72%) of these patients underwent cardiac surgery. The median [interquartile range] dose was 57 [36-85] µg·kg(-1). Usage increased from 2007 to 2008 (n = 341 and 380, respectively) but decreased in 2009 and 2010 (n = 350 and 307, respectively). Dose of rFVIIa and bleeding severity were associated with measured adverse events (P < 0.05). After adjusting for bleeding severity, dose was not associated with any of the adverse events., Conclusions: The off-label use of rFVIIa in Canada remains stable. Since severity of bleeding is prognostically important, the benefits of rapidly gaining control of bleeding that is non-responsive to conventional therapies may at times warrant the use of potent hemostatic drugs with established risk profiles, such as rFVIIa.

Purpose: Platelet transfusion in cardiac surgery is often empiric as no established point-of-care tests are available for clear guidance of blood product administration, and there are many variables that can potentially increase the risk of bleeding during cardiopulmonary bypass. The objectives of this study were to determine the factors that influenced physicians' decisions to transfuse platelets perioperatively and to determine whether these factors coincide with characteristics using chart abstraction., Methods: This study was conducted at three university affiliated hospitals using focused physician questionnaires to assess factors influencing decisions to transfuse platelets and data abstraction to determine characteristics of patients receiving platelet transfusion during cardiac surgery., Results: Seventy-six physicians participated in the questionnaire; 41% identified bleeding and 22% identified both bleeding and the platelet count as the most significant factors influencing their decision to transfuse platelets. Of the 629 patients included in the study, 24.5% received a platelet transfusion intraoperatively and 4.5% received the transfusion postoperatively. The following factors were identified with the highest odds of receiving a platelet transfusion intraoperatively: combined bypass and valvular surgery (odds ratio [OR] 3.94; 95% confidence interval [CI] 1.94 to 8.00) and the presence of liver disease (OR 6.43; 95% CI 1.17 to 35.37)., Conclusion: The use of focused physician questionnaires identified relevant aspects of patient care not apparent in the chart review that influenced the decision to transfuse platelets. The identification of bleeding, thrombocytopenia, more complex surgery, and the presence of liver disease highlights the requirement for standardized measures to assess the need for platelet transfusions in bleeding patients.

Purpose: This study was designed to show the relationship between tricuspid annular plane systolic excursion (TAPSE) and stroke volume (SV) by thermodilution using three different methods and also to assess whether TAPSE can track hemodynamic changes associated with volume loading and ephedrine administration., Methods: This was an observational study in 61 elective patients with a pulmonary artery catheter who were undergoing coronary artery bypass graft surgery in a cardiac surgical centre. We measured TAPSE by three methods using transesophageal echocardiography: M mode, speckle tracking at the lateral wall, and tissue tracking at the inferior wall. There were two interventions: leg raising (volume recruitment) or administration of ephedrine 5 mg iv. Echo and hemodynamic measurements were performed before and after each intervention., Results: Eleven patients were excluded due to poor imaging. There were 26 patients in the leg raising group and 24 patients in the ephedrine group. The correlation coefficient between stroke volume (SV) and TAPSE by M mode, speckle tracking, and tissue tracking was 0.48, 0.44, and 0.09, respectively. There was a significant increase in SV following each intervention; however, the changes in TAPSE by any method and velocity were not large enough to reach statistical significance., Conclusion: Tricuspid annular plane systolic excursion by M mode and by speckle tracking correlates modestly with SV. There was no correlation between TAPSE and SV by tissue tracking at the inferior wall of the right ventricle. Tricuspid annular plane systolic excursion by M mode and by speckle tracking does not track changes in SV following either volume loading or ephedrine administration.

Purpose: Transfusion of allogeneic red blood cells (RBCs) is one of the main treatments of acute anemia secondary to blood loss and fluid resuscitation within the operating room. Decisions to transfuse blood are based largely on intermediate biological markers (hemoglobin, arterial oxygen saturation, blood pressure, heart rate) which may not accurately reflect inadequacy of tissue oxygen delivery. Based on experimental studies, we hypothesized that anemia-induced tissue hypoxia activates adaptive mechanisms which promote local vascular nitric oxide (NO) production to improve tissue perfusion and survival during acute anemia. Hemoglobin (Hb) oxidation to methemoglobin (MetHb) may be a byproduct of such local NO production. Therefore, we tested the hypothesis that MetHb is a biomarker of hypoxic-anemic stress during acute hemodilution associated with cardiopulmonary bypass., Methods: With institutional ethics approval, routine laboratory arterial blood gas and co-oximetry values were obtained from 295 patients undergoing heart surgery during February 1 to September 30, 2010, and the values were assessed retrospectively. All samples with an arterial oxygen saturation value ≥ 90% were included (n = 1,421). The maximal change in Hb associated with hemodilution on cardiopulmonary bypass was determined within 48 hr of surgery (n = 180). A chart review was performed to determine the incidence of RBC transfusion and exogenous nitrate administration. All anonymous data were analyzed by linear regression to determine the relationship between Hb and MetHb. A Wilcoxon Signed Rank Test and Student's t test were used to determine changes in Hb, MetHb, and carboxyhemoglobin (CarboxHb) levels. All data are presented as mean and significance was assigned at P < 0.05., Results: A significant decrease in Hb [118 (20) g x L(-1) vs 94 (18) g x L(-1)] was associated with an increase in MetHb [0.88 (0.22)% vs 0.95 (0.24)%] (P < 0.001 for both), but not CarboxHb [1.08 (0.47)% vs 1.08 (0.49)%]. Regression analysis revealed a significant relationship between the change in Hb and MetHb (F = 40.3; P < 0.001) but not between the change in Hb and CarboxyHb (F = 0.2; P = 0.694). This correlation was not influenced by RBC transfusion or exogenous nitrate use., Conclusions: A negative correlation was observed between the change in Hb and MetHb in patients undergoing cardiac surgery and cardiopulmonary bypass. These data support the previously unreported hypothesis that MetHb may be a marker of anemic stress associated with reduced tissue perfusion during acute hemodilution in humans. Further prospective studies are needed to determine if these changes in MetHb are linked to adverse outcomes in patients undergoing cardiac surgery.

Purpose: Clinical studies demonstrate that anemia increases the risk of morbidity and mortality. Tissue hypoxia is an attractive but incompletely characterized candidate mechanism of anemia-induced organ injury. Physiological responses that optimize tissue oxygen delivery (nitric oxide synthase-NOS) and promote cellular adaptation to tissue hypoxia (hypoxia inducible factor-HIF) may reduce the risk of hypoxic organ injury and thereby improve survival during anemia. The presence of vascular diseases would likely impair the efficacy of these physiological mechanisms, increasing the risk of anemia-induced organ injury. In all cases, biological signals that indicate the activation of these adaptive mechanisms could provide an early and treatable warning signal of impending anemia-induced organ injury. Thus, we review the evidence for tissue hypoxia during acute hemodilutional anemia and also explore the novel hypothesis that methemoglobin, a measurable byproduct of increased NOS-derived nitric oxide (NO), may serve as a biomarker for "anemic stress"., Source: Published peer-reviewed studies provided the main source of information. Data from experimental studies were reassessed to derive the relationship between hemodilution (reduced hemoglobin concentration) and increased methemoglobin levels., Principal Findings: Active physiological mechanisms (sympathetic nervous system) are required to maintain optimal tissue oxygen delivery during hemodilutional anemia. Despite these responses, tissue hypoxia occurs during acute hemodilution, as demonstrated by a decrease in tissue PO(2) and an increase in hypoxic cellular responses (NOS, HIF). Optimal tissue oxygen delivery may be compromised further when cardiovascular responses are impaired. The positive correlation between decreased hemoglobin concentration (Hb) and an increase in methemoglobin levels in acutely anemic animals supports the hypothesis that anemia-induced increases in tissue NOS activity could promote methemoglobin formation. Methemoglobin may be a measurable byproduct of NO-mediated Hb oxidation., Conclusions: Evidence continues to demonstrate that anemia increases morbidity and mortality, possibly via hypoxic mechanisms. A potential strategy for assessing "anemic stress" was derived from experimental data based on a readily measurable biomarker, methemoglobin. New methods for measuring real-time hemoglobin and methemoglobin levels in patients may provide the basis to translate this idea into clinical practice. Further mechanistic studies are required to determine if the impact of reduced tissue oxygen delivery and activation of hypoxic cellular mechanism can be linked to measurable changes in biomarkers and clinical outcomes in acutely anemic patients.

Purpose: Hemodilution in perioperative patients has been associated with neurological morbidity and increased mortality by undefined mechanisms. This study assesses whether hemodilutional anemia up-regulated inflammatory cerebral gene expression (microarray) to help define the mechanism., Methods: Hemodilution was performed in anesthetized rats by exchanging 50% of the estimated blood volume (30 mL kg(-1)) with pentastarch. Two groups of control animals were utilized, i.e., a non-anesthetized control (Normal Control) and an anesthetized control group (Anesthesia Control). Blood pressure, hemoglobin concentration, and arterial blood gas analysis were performed before and after hemodilution. Cerebral cortex was harvested from isoflurane-anesthetized rats (n = 6) after 6 and 24 hr of recovery and was used to perform complimentary DNA (cDNA) microarray analyses. Pro-inflammatory chemokine and cytokine protein levels were also measured., Results: Microarray analysis demonstrated up-regulation of 72 and 27 genes (6 and 24 hr, respectively) in anemic cerebral cortex. These genes were involved in a number of biological functions, including (1) inflammatory responses; (2) angiogenesis; (3) vascular homeostasis; (4) cellular biology; and (5) apoptosis. Chemokine ribonucleic acid (RNA) expression (CXCL-1, -10, and -11) was highest in anemic brain tissue (P < 0.0125 for each). Protein measurements demonstrated a significant increase in interleukin-6, tumor necrosis factor alpha, and monocyte chemoattractant protein-1 (P < 0.05 for each)., Conclusion: This study utilizes microarray technology to elucidate changes in cerebral cortical gene expression in response to acute hemodilution. These findings demonstrate an increase in pro-inflammatory chemokines (RNA, protein) and cytokines (protein). An improved understanding of the inflammatory response to anemia may help to minimize associated morbidity and mortality.

Purpose: In this prospective observational cohort study, we investigated whether tricuspid annular velocities (TAV) are altered after induction of anesthesia in patients undergoing coronary artery bypass graft (CABG) surgery., Methods: Twenty-four elective CABG patients were assessed before and after induction of anesthesia, and a convenience sample of nine healthy volunteers was used for comparison of TAV only. Measurements included mean arterial pressure (MAP), heart rate (HR), pulmonary artery pressure (PAP), and cardiac index (CI) as assessed post-induction. Tricuspid annular plane systolic excursion (TAPSE) was measured in anatomical M-mode. The S (systolic) wave velocity and isovolemic acceleration (IVA) were measured from colour tissue Doppler (TD). Paired and unpaired Student's t tests were used to compare all variables pre-and post-induction., Results: In response to anesthetic induction, MAP decreased from 105 +/- 14 to 79 +/- 9 mmHg, but HR was unchanged (67 +/- 13 beats x min(-1) pre-induction compared with 67 +/- 9 beats x min(-1) post-induction). The mean PAP and CI post-induction were 20 +/- 6 mmHg and 2.3 +/- 0.4 L x min(-1) x m(-2), respectively. While there was no change post-induction in either S velocity (8.80 +/- 1.23 vs 9.0 +/- 1.92 cm x sec(-1)) or IVA (1.63 +/- 0.61 vs 1.84 +/- 0.83 m x sec(-2)), TAPSE decreased from 23 +/- 4 to 21 +/- 4 mm (P = 0.039). All pre-induction echocardiographic variables were lower in the CABG group compared with the normal group (IVA: 2.34 +/- 0.34 m x sec(-2), S wave: 11.14 +/- 2.78 cm x sec(-1), TAPSE 2D: 26 +/- 4 mm), respectively., Conclusions: Induction of anesthesia for CABG surgery does not alter velocity-based parameters of RV function. There was a small decrease in TAPSE. The TD parameters were lower in CABG patients compared with the normal group.

Purpose: Acute anemia increases the cerebral expression of hypoxic molecules including neuronal nitric oxide synthase (nNOS) and hypoxia inducible factor-1alpha (HIF-1alpha). This study assessed the effects of acute hemodilution on inducible NOS (iNOS) and systemic inflammatory cytokines., Methods: Anesthetized rats (n = 5-7 per group) underwent 50% hemodilution with pentastarch, whole blood exchange or no fluid exchange. Cerebral cortical nNOS and iNOS protein levels were characterized using Western blot analysis and immunostaining (1 and 18 h). Plasma cytokine levels were assessed by enzyme-linked immunosorbent assay (1, 4, and 18 h). Data were analyzed by two-way analysis of variance to determine significance (P < 0.05, mean +/- SD)., Results: No differences in mean arterial blood pressure or arterial blood gases were observed between groups after hemodilution. A comparable hemoglobin target (approximately 70 g . L(-1)) was achieved in all groups following hemodilution. Cerebral cortical iNOS protein levels were increased in anemic rats, relative to controls. The nNOS protein levels increased to a greater degree (P < 0.05 for both). Immunostaining demonstrated that iNOS localized to endothelium, glial fibrillary acidic protein (GFAP) positive (astrocytes) and GFAP negative cells within the brain. Plasma cytokine levels (tumour necrosis factor alpha, interleukin (IL)-1beta and IL-6) increased transiently, to the same levels, in both control and hemodiluted rats., Conclusions: Cerebral cortical iNOS and nNOS protein levels were both increased in anemic rats. The nNOS response was predominant. This suggests that NOS-derived NO may be an important signalling pathway which is activated in the brain during anemia. These cellular responses could maintain cerebral homeostasis, or contribute to neuronal injury, during acute hemodilutional anemia.

Purpose: Hospital variation in transfusion practices has been described previously but the proportion of variation attributable to the hospital has not. The objective of this report was to quantify hospital variation in red cell transfusion decisions perioperatively for patients undergoing coronary artery bypass surgery (CABG)., Methods: We used a cross-sectional study design using pretested self-administered mailed questionnaires sent to all anesthesiologists and cardiac surgeons involved in CABG in Canada., Results: Responses were received from anesthesiologists from all 32 hospital sites and from cardiac surgeons from 30/32 sites (94%). There was variation attributable to the hospital in transfusion triggers selected (P<0.0001). For patients who had uncomplicated CABG surgery, the range of transfusion triggers among hospitals for the intraoperative and postoperative case scenarios were 61 to 80 gxL(-1) and 64 to 80 gxL(-1), respectively. The hospital accounted for 20% of the variation in the transfusion practice intraoperatively and postoperatively. The remainder of the variation was attributable to the individual physician. Academic affiliation and the number of surgical cases performed at the hospital were not significant factors impacting on the transfusion triggers selected, Conclusion: This is the first study to quantify the variation in red cell transfusion practices according to individual physicians and the hospital. The variation attributed to the hospital is significant. The explanation for the variation in transfusion decisions that relate to the hospital needs to be explored further in order to help optimize transfusion practice.

Purpose: This study assessed the effect of oxygen affinity and molecular weight (MW) of o-raffinose cross-linked hemoglobin based oxygen carriers (HBOCs) on cerebral oxygen delivery and mean arterial blood pressure (MAP) following hemorrhage and resuscitation in rats., Methods: Isoflurane anesthetized rats (n = 6-7 per group) underwent 30% hemorrhage and resuscitation with an equivalent volume of one of three different HBOCs: 1) High P50 Poly o-raffinose hemoglobin (Poly OR-Hb, P50 = 70 mmHg); 2) High P50 > 128 Poly OR-Hb (MW > 128 kDa, P50 = 70 mmHg) and 3) Low P50 > 128 Poly OR-Hb (MW >128 kDa, P50 = 11 mmHg). Hippocampal cerebral tissue oxygen tension, regional cerebral blood flow (rCBF), MAP, total hemoglobin concentration and arterial blood gases were measured. Data analysis by two-way ANOVA and post hoc Tukey tests determined significance (P < 0.05, mean +/- SD)., Results: Hippocampal tissue oxygen tension increased in all HBOC groups following resuscitation. The rCBF remained unchanged after HBOC resuscitation in all groups. Following resuscitation, the peak MAP was higher in the High P50 Poly OR-Hb group (152 +/- 13 mmHg) when compared to either the Low or High P50 large MW, (> 128 kDa) HBOC group (119 +/- 15 mmHg or 127 +/- 18 respectively, P < 0.05 for both)., Conclusions: O-raffinose polymerized HBOC, with or without lower MW components, maintained cerebral tissue oxygen delivery following hemorrhage and resuscitation in rats. The higher MW HBOCs showed a decrease in peak MAP, which did not alter oxygen delivery. No significant effect of oxygen affinity on cerebral tissue oxygen tension or blood flow was observed.

Purpose: Labetalol is an effective antihypertensive medication frequently used to treat systemic hypertension in acute care settings, including the management of hypertension associated with a subarachnoid hemorrhage. We present a case of profound hypotension, refractory to inotropic and vasopressor therapy following an iv infusion of labetalol., Clinical Features: Initiation of an iv labetalol infusion resulted in good blood pressure control in a patient suffering from a Fisher grade 3 subarachnoid hemorrhage with an initial Glascow coma scale of 14/15 and mild hydrocephalus. Progressive deterioration of neurological symptoms and evidence of worsening hydrocephalus preceded the sudden development of profound hypotension (60/35 mmHg) and bradycardia with a minimum heart rate of 40 beats.min(-1). Initial resuscitative efforts included administration of intravascular fluid, hypertonic saline, atropine, adrenalin (more than 10 mg in divided doses) and noradrenalin. These measures restored the blood pressure to 80/45 with a HR of 98 beats.min(-1). Intraoperative placement of an intraventricular drain released cerebrospinal fluid under pressure with an initial intracranial pressure of 15 cm H(2)O. A combination of adrenalin, noradrenalin, dopamine and vasopressin infusions were required to restore the blood pressure to 130/65 mmHg after an additional two hours. All inotropic and vasopressor support was weaned off after the 14th hr (about two drug half-lives). The patient was awake and responsive the following day, with no obvious neurological consequences. No evidence of neurological injury, drug administration error or myocardial dysfunction was documented., Conclusion: The episode of profound hypotension which occurred after initiating a labetolol infusion required maximal combined vasopressor therapy to restore the blood pressure suggesting that this patient demonstrated an extreme sensitivity to labetalol. Combination therapy with adrenergic and nonadrenergic agonists may be required for optimal treatment of profound hypotension associated with labetalol-induced vasoplegia.

Purpose: To test the hypotheses that deliberate elevation of PaCO(2) increases cerebral tissue oxygen tension (PBrO(2)) by augmenting PaO(2) and regional cerebral blood flow (rCBF)., Methods: Anesthetized rats were exposed to increasing levels of inspired oxygen (O(2)) or carbon dioxide (CO(2); 5%, 10% and 15%, n = 6). Mean arterial blood pressure (MAP), PBrO(2) and rCBF were measured continuously. Blood gas analysis and hemoglobin concentrations were determined for each change in inspired gas concentration. Data are presented as mean +/- standard deviation with P < 0.05 taken to be significant., Results: The PBrO(2) increased in proportion to arterial oxygenation (PaO(2)) when the percentage of inspired O(2) was increased. Proportional increases in PaCO(2) (48.7 +/- 4.9, 72.3 +/- 6.0 and 95.3 +/- 15.4 mmHg), PaO(2) (172.2 +/- 33.1, 191.7 +/- 42.5 and 216.0 +/- 41.8 mmHg), and PBrO(2) (29.1 +/- 9.2, 49.4 +/- 19.5 and 60.5 +/- 23.0 mmHg) were observed when inspired CO(2) concentrations were increased from 0% to 5%, 10% and 15%, respectively, while arterial pH decreased (P < 0.05 for each). Exposure to CO(2) increased rCBF from 1.04 +/- 0.67 to a peak value of 1.49 +/- 0.45 (P < 0.05). Following removal of exogenous CO(2), arterial blood gas values returned to baseline while rCBF and PBrO(2) remained elevated for over 30 min. The hypercapnia induced increase in PBrO(2) was threefold higher than that resulting from a comparable increase in PaO(2) achieved by increasing the inspired O(2) concentration (34.9 +/- 14.5 vs 11.4 +/- 5.0 mmHg, P < 0.05)., Conclusion: These data support the hypothesis that the combined effect of increased CBF, PaO(2) and reduced pH collectively contribute to augmenting cerebral PBrO(2) during hypercapnia.

Purpose: To describe a case of persistent and excessive bleeding following an aortic valve and ascending aorta replacement that was successfully managed with recombinant factor VIIa (rFVIIa). The postulated mechanisms for rFVIIa are discussed., Clinical Features: A 75-yr-old female with no preoperative coagulopathy underwent a tissue aortic valve replacement and supracoronary ascending aorta replacement for severe aortic stenosis and an ascending aortic aneurysm. Following surgery, she bled in excess of 200 mL x hr(-1) despite a nearly normal platelet count and nearly normal coagulation parameters. The patient was surgically re-explored twice in seven hours, and despite the presence of near normal in vitro coagulation parameters, the patient continued to bleed. Multiple units of fresh frozen plasma, platelets and cryoprecipitate were administered empirically. We then administered a single 6-mg (107 microg x kg(-1)) iv dose of rFVIIa. Following the administration of rFVIIa, blood loss decreased to a total of 440 mL over the next 12 hr., Conclusions: This case describes the use of rFVIIa for intractable bleeding postcardiovascular surgery in the presence of nearly normal laboratory markers of coagulation. Further controlled laboratory and clinical studies are required to define the role of rFVIIa in patients undergoing cardiovascular surgery.

Purpose: Many types of tracheal tubes (TT) including silicone, polyvinylchloride (PVC) and armoured have been used for blind tracheal intubation (TI) via the intubating laryngeal mask airway (ILMA) and may cause trauma to the airway. We examined the maximal in vitro forces and pressures exerted by the tip of various TT as it exits the ILMA., Methods: Silicone, PVC and armoured TT were studied. A #5 ILMA was secured on a wooden platform. With the use of a Harvard pump, force was applied to push the TT through the ILMA at 0.34 cm*sec(-1). Forces exerted to push the TT and forces exerted by the TT tips on distal objects were calculated using proximal and distal pressure manometres. The areas of contact between the distal TT tips and the distal objects were measured by planimetry of an imprint. The final pressures exerted by the TT tips on a fixed distal object were calculated by dividing the forces exerted by the areas of contact., Results: When compared to silicone and armoured TT, PVC TT exerted seven to ten times higher forces and pressures on distal objects. (P < 0.05). Heating PVC TT and inserting PVC TT with reverse curvature to the ILMA did not decrease the forces and pressures exerted by the distal tip., Conclusion: The high forces and pressures exerted by PVC TT may theoretically contribute to increased morbidity to patients' airway and esophagus. Caution should be exercised before attempting blind TI via the ILMA with a PVC TT.

Purpose: Transesophageal echocardiography (TEE) is a useful diagnostic and monitoring tool in the operating room. In the United States, an increasing number of centres are training anesthesiologists to preform intraoperative TEE. In Canada, TEE has been slow to gain acceptance as an intraoperative monitor and little information is available on its use by the anesthesiologists across the country., Methods: We surveyed all members of the cardiovascular section of the Canadian Anesthesiologists' Society, to find out how many perform TEE, how they acquired their skills and how they use TEE in their practice., Results: The response rate was 48.4%. Most respondents were Canadian-trained cardiac anesthesiologists working in university centres. 91% of respondents stated that their centres offer intraoperative TEE services. Of those services, 35.1% were provided by anesthesiologists only, 13% by cardiologists only, and 51.9% by both. 53.8% of respondents have certification in intraoperative TEE (NBE/SCA, ASE or Provincial College). 90% of respondents use equipment that is less than five years old and multiplane probes are used by almost everyone. There was strong support for Canadian-based continuing medical education events in perioperative TEE., Conclusion: TEE appears to be available in most cardiac centres in Canada and anesthesiologists are actively involved in providing intraoperative TEE services, using state-of-the-art equipment. Many anesthesiologists have formal training in TEE.

Purpose: To determine whether a group of experienced clinicians can predict intensive care unit (ICU) length of stay (LOS) following cardiac surgery., Methods: A cohort of 265 adult patients undergoing cardiac surgery at St. Michael's Hospital, Toronto, Ontario, between January 2, 1992, and June 26, 1992, were seen preoperatively by the clinicians participating in the study and ICU length of stay was predicted based on the clinicians' preoperative assessment and/or information recorded in the patient's chart., Results: Five hundred and ten ICU length of stay predictions were obtained from a group of eight experienced clinicians (anaesthetists/intensivists, cardiologists, nurses). The clinicians predicted the exact ICU length of stay (in days) correctly 51.2% of the time and were within +/- 1 day 84.5% of the time. The clinicians correctly predicted short ICU stays (< or = 2 days) for 87.6% of the patients who had short ICU stays but only predicted long ICU stays (> 2 days) in 39.4% of the patients who had long ICU stays., Conclusions: Experienced clinicians can predict preoperatively with a considerable degree of accuracy patients who will have short ICU lengths of stay following cardiac surgery. However, many patients who had long ICU stays were not correctly identified preoperatively. Unidentified preoperative risk factors or unanticipated intraoperative/postoperative events may be causing these patients to have longer than expected ICU stays.

Purpose: To describe the serum concentrations of ketamine following a clinically relevant dosing schedule during cardiopulmonary bypass (CPB)., Design: Prospective case series., Setting: Tertiary care teaching hospital., Patients: Six patients undergoing coronary artery bypass grafting and over age 60 yr., Intervention: Following induction of anaesthesia each patient received a bolus of ketamine 2 mg.kg-1 followed by an infusion of 50 micrograms.kg-1.min-1 which ran continuously until two hours after bypass., Main Outcome Measures: Ketamine serum concentrations were measured at five minutes after bolus, immediately following aortic cannulation, 10 and 20 min on CPB, termination of CPB, termination of the drug infusion and three and six hours after infusion termination., Results: At the time of aortic cannulation, ketamine concentrations were 3.11 +/- 0.81 micrograms.ml-1, these levels decreased by one third with the initiation of CPB. By the end of CPB the concentrations had returned to levels roughly equivalent to those observed at the time of aortic cannulation. Following cessation of the infusion, ketamine concentration declined in a log-linear fashion with a half-life averaging 2.12 hr. (range 1.38-3.09 hr)., Conclusion: This dosage regimen maintained general anaesthetic concentrations of ketamine throughout the operative period. These levels should result in brain tissue concentrations in excess of those previously shown to be neuroprotective in animals. Thus we conclude that this infusion regimen would be reasonable to be use in order to assess the potential neuroprotective effects of ketamine in humans undergoing CPB.

Haemodynamic changes during bilateral cemented arthroplasty (BCA) were compared in dogs anaesthetized with isoflurane/N2O (ISOF) or diazepam/fentanyl (100 microg x kg(-1))N2O(FENT). Eight animals were anaesthetized with each regimen. After establishing monitoring and recording baseline values, BCA was performed. Haemodynamic measurements included aortic blood pressure (ABP), pulmonary artery pressure (PAP), right and left atrial pressures, and cardiac output. These were recorded at 30, 60, 180 and 300 sec after BCA. Lungs were removed and examined postmortem using quantitative morphometry. Groups demonstrated similar increases in PAP (ISOF 15 +/- 2 to 32 +/- 7, FENT 19 +/- 4 to 38 +/- 13; P> 0.05 between groups, P< 0.05 vs baseline). The proportion of lung vasculature occluded by fat was not different between groups (ISOF 9.63 +/- 3.38%, FENT 8.85 +/- 2.20%). Stroke volume decreased similarly in both groups (P> 0,05 between groups, P< 0.05 vs baseline). However, ABP decreased within one minute of BCA in ISOF (111 +/- 17 to 55 +/- mmHg, P< 0.05 and two of eight dogs died. All FENT dogs survived and hypotension (118 +/- 20 to 102 +/- 24 mmHg) was transient and less severe (P< 0.05 vs ISOF). Increased heart rate (HR) was noted in FENT following BCA (73 +/- 8 to 108 +/- 25 beats x min(-1); P< 0.05). Baseline HR was higher in ISOF (P< 0.05) and no increase in HR was noted. Systemic vascular resistance decreased in ISOF (P< 0.05), but not FENT (P> 0.05 vs baseline, P< 0.05 vs ISOF). To assess the role of slower baseline HR in FENT (73 +/-8) versus ISOF (131 +/- 5), six FENT dogs were paced (130 beats x min(-1)) with epicardial leads and an AV sequential pulse generator to simulate the ISOF group's baseline HR. Haemodynamic stability was maintained in this group in spite of a more rapid baseline HR. The choice of anaesthetic regimen strongly influenced acute haemodynamic changes in response to BCA.

The popularity of the Residents' Competition at the annual meeting of the Canadian Anaesthetists' Society inspired this 25 yr review of the competitors and their presentations. Data were collected from a questionnaire survey of all participants and all current Anaesthesia programme directors, review of the Canadian Anaesthetists' Society records, and a Medline data-base search. Over the 25 yr review period, 226 presentations have been given by 211 different participants, with the annual number of participants ranging from 6 to 13. The majority of participants have been male (85.3% vs 14.2% female, P < 0.001), and the majority of presentations have been clinical in nature (74% vs 26% laboratory, P < 0.01). Over half of all the presentations (53.1%) subsequently were published as scientific papers, and 71.7% of all participants practised anaesthesia in an academic environment at some point in their career. The Residents' Competition appears to have been successful in encouraging scientific excellence in physician's training in anaesthesia in Canada.

The intravenous administration of propofol is associated with a considerable decrease in arterial blood pressure. The present study was undertaken to test the hypothesis that myocardial function is not affected by propofol and therefore does not contribute to the hypotensive effect of this anaesthetic agent. Propofol was administered in anaesthetized, open-chest dogs by direct arterial infusion into the left anterior descending coronary artery (LAD). Mean arterial blood pressure, heart rate, left ventricular pressure, dP/dt, regional lactate and oxygen extraction, as well as coronary blood flow were measured. Diastolic function was determined by calculation of the time constant of isovolumetric relaxation from the left ventricular pressure measurement and dP/dt. Contractility was evaluated by measuring regional systolic shortening in an area of the myocardium supplied by the LAD. This was compared with systolic shortening in the distribution of the circumflex (CIRC) artery and with the effects obtained with the intracoronary administration of thiopentone. Intracoronary infusions of propofol and thiopentone did not produce any change in systemic arterial blood pressure, heart rate, or left ventricular end diastolic pressure. Propofol, at a concentration of 5 or 10 micrograms.ml-1 did not decrease systolic shortening in the area perfused by the LAD while thiopentone (40 micrograms.ml-1) reduced systolic shortening by 33% (P < or = 0.05). Neither drug had an effect on systolic shortening in the CIRC area, LAD blood flow or diastolic function. The results of this study suggest that propofol does not have an effect on myocardial contractility. The hypotension associated with the intravascular administration of propofol is more likely due to either a direct vascular or a central effect.

Conclusion: Perioperative myocardial ischaemia is common in patients who have or are at risk of coronary artery disease, occurring frequently in the pre-, intra- and postoperative periods. The majority of perioperative ischaemic episodes are silent, being unaccompanied by any symptoms of angina. The use of appropriate preoperative laboratory investigations may help in the diagnosis of CAD and the prediction of risk of adverse cardiac outcome. A properly placed and properly calibrated ECG is the best overall monitor of ischaemia. Maintenance of haemodynamic stability is important to reduce the incidence of myocardial ischemia, but ischaemia may occur in the absence of adverse haemodynamic changes. Although our efforts have largely been devoted to the prevention and treatment of intraoperative ischaemia, it is hoped that similar efforts outside the operating room in the postoperative period will further improve patient care and outcome.

The decision to withhold cardiopulmonary resuscitation from a patient within an intensive care unit (ICU) may be a difficult but appropriate one for which there are few guidelines. We describe the formulation of a Do Not Resuscitate (DNR) policy in our multidisciplinary ICU. To evaluate the effect of implementation of the DNR policy on physician practice and on communication among physicians, nurses, patients and their families, we interviewed physicians and nurses caring for patients designated DNR before (n = 8) and after (n = 17) implementation of the DNR policy. We found that DNR orders in the ICU were not infrequent (2-3 per week). All patients designated DNR were either irreversibly ill or not responsive to maximal therapy, and 22 of 25 were not competent. The DNR order was not accompanied by withdrawal of other therapy in 50% of cases and one patient recovered and was discharged from hospital. The implementation of the DNR policy encouraged greater physician consultation with other physicians, patients and their families. Although there were differences in perception of communication between physicians and nurses, we believe that the DNR policy influenced physician practice and enhanced overall communication in the ICU.