High Versus Normal Blood Pressure Targets in Relation to Right Ventricular Dysfunction After Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVE: Management of right ventricular (RV) dysfunction is challenging. Current practice predominantly is based on data from experimental and small uncontrolled studies and includes augmentation of blood pressure. However, whether such intervention is effective in the clinical setting of cardiac surgery is unknown. DESIGN: Randomized controlled trial. SETTING: Single-center study in a tertiary teaching hospital. PARTICIPANTS: The study comprised 78 patients equipped with a pulmonary artery catheter (PAC), classified according to PAC-derived RV ejection fraction (RVEF); 44 patients had an RVEF of <20%, and 34 patients had an RVEF between ≥20% and <30%. INTERVENTIONS: Patients randomly were assigned to either a normal target group (mean arterial pressure 65 mmHg) or a high target group [mean arterial pressure 85 mmHg]). The primary end- point was the change in RVEF over a one-hour study period. MEASUREMENTS AND MAIN RESULTS: There was no significant between-group difference in change of RVEF <20% (-1% [-3.3 to 1.8] in the normal-target group v 0.5% [-1 to 4] in the high-target group; p = 0.159). There was no significant between-group difference in change in RVEF 20%-to-30% (-1% [-3 to 0] in the normal-target group v 1% [-1 to 3] in the high-target group; p = 0.074). These results were in line with the simultaneous observation that echocardiographic variables of RV and left ventricular function also remained unaltered over time, irrespective of either baseline RVEF or treatment protocol. CONCLUSION: In a mixed cardiac surgery population with RV dysfunction, norepinephrine-mediated high blood pressure targets did not result in an increase in PAC-derived RVEF compared with normal blood pressure targets.

The Reduction in Right Ventricular Longitudinal Contraction Parameters Is Not Accompanied by a Reduction in General Right Ventricular Performance During Aortic Valve Replacement: An Explorative Study.

OBJECTIVE: The aim of the present study was to identify whether the decrease of longitudinal parameters after cardiothoracic surgery (ie, tricuspid annular systolic plane excursion [TAPSE] and systolic excursion velocity [S']) is accompanied by a reduction in global right ventricular (RV) performance. DESIGN: Prospective, observational study. SETTING: Single-center explorative study in a tertiary teaching hospital. PARTICIPANTS: The study comprised 20 patients who underwent aortic valve replacement with or without coronary artery bypass grafting. INTERVENTIONS: During cardiac surgery, simultaneous measurements of RV function were performed with a pulmonary artery catheter and transesophageal echocardiography. MEASUREMENTS AND MAIN RESULTS: TAPSE and S' were reduced significantly directly after surgery compared with the time before surgery (TAPSE from 20.8 [16.6-23.4] mm to 9.1 [5.6-15.5] mm; p < 0.001 and S' from 8.7 [7.9-10.7] cm/s to 7.2 [5.7-8.6] cm/s; p = 0.041). However, the reduction in TAPSE and S' was not accompanied by a reduction in RV performance, as assessed with the TEE-derived myocardial performance index (MPI) and pulmonary artery catheter-derived RV ejection fraction (RVEF). Both remained statistically unaltered before and after the procedure (MPI from 0.52 [0.43-0.58] to 0.50 [0.42-0.88]; p = 0.278 and RVEF from 27% [22%-32%] to 26% [22%-28%]; p = 0.294). CONCLUSIONS: In the direct postoperative phase, the reduction of echocardiographic parameters of longitudinal RV contractility (TAPSE and S') were not accompanied by a reduction in global RV performance, expressed as MPI and RVEF. Solely relying on a single RV parameter as a marker for global RV performance may not be adequate to assess the complex adaptation of the right ventricle to aortic valve replacement.

Right Ventricular Function After Cardiac Surgery Is a Strong Independent Predictor for Long-Term Mortality.

OBJECTIVE: To establish the all-cause mortality of right ventricular dysfunction after cardiac surgery in a heterogeneous group of cardiac surgery patients. DESIGN: Retrospective analysis of a heterogeneous group of 1,109 cardiac surgery patients in a 4-year period. SETTING: Single-center study in a tertiary teaching hospital. PARTICIPANTS: One thousand one hundred nine cardiac surgery patients. By protocol, patients were monitored with a pulmonary artery catheter, enabling continuous right ventricular ejection fraction (RVEF) measurements. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements were performed once per minute for the first 24 postoperative hours and expressed as average over the complete period. Primary outcome was 2-year all-cause mortality. RVEF was categorized into 3 subgroups: <20%, 20-30%, and >30%. Median follow-up time was 739 days. Two-year mortality was significantly different across groups: 4.1% for patients with RVEF >30%, 8.2% in the group with RVEF 20-30%, and 16.7% for patients with RVEF <20%, p < 0.001. Additional risk factors for a poor RVEF were age, body weight, New York Heart Association class, chronic obstructive pulmonary disease, poor left ventricular function, and higher risk scores (Acute Physiology and Chronic Health Evaluation and European System for Cardiac Operative Risk Evaluation). In a multivariate analysis, RVEF as a continuous variable was associated independently with the primary outcome (odds ratio 0.95 confidence interval 0.91-0.99, p = 0.011.) Odds ratios for RVEF <20% were 1.88 (confidence interval 1.18-3.00, p = 0.008). CONCLUSIONS: Right ventricular function is associated independently with 2-year all-cause mortality in a heterogenic cardiac surgery population.

Impaired microcirculatory perfusion in a rat model of cardiopulmonary bypass: the role of hemodilution.

Although hemodilution is attributed as the main cause of microcirculatory impairment during cardiopulmonary bypass (CPB), this relationship has never been investigated. We investigated the distinct effects of hemodilution with or without CPB on microvascular perfusion and subsequent renal tissue injury in a rat model. Male Wistar rats (375-425 g) were anesthetized, prepared for cremaster muscle intravital microscopy, and subjected to CPB (n = 9), hemodilution alone (n = 9), or a sham procedure (n = 6). Microcirculatory recordings were performed at multiple time points and analyzed for perfusion characteristics. Kidney and lung tissue were investigated for mRNA expression for genes regulating inflammation and endothelial adhesion molecule expression. Renal injury was assessed with immunohistochemistry. Hematocrit levels dropped to 0.24 ± 0.03 l/l and 0.22 ± 0.02 l/l after onset of hemodilution with or without CPB. Microcirculatory perfusion remained unaltered in sham rats. Hemodilution alone induced a 13% decrease in perfused capillaries, after which recovery was observed. Onset of CPB reduced the perfused capillaries by 40% (9.2 ± 0.9 to 5.5 ± 1.5 perfused capillaries per microscope field; P < 0.001), and this reduction persisted throughout the experiment. Endothelial and inflammatory activation and renal histological injury were increased after CPB compared with hemodilution or sham procedure. Hemodilution leads to minor and transient disturbances in microcirculatory perfusion, which cannot fully explain impaired microcirculation following cardiopulmonary bypass. CPB led to increased renal injury and endothelial adhesion molecule expression in the kidney and lung compared with hemodilution. Our findings suggest that microcirculatory impairment during CPB may play a role in the development of kidney injury.

Intraoperative High-Dose Dexamethasone and Severe AKI after Cardiac Surgery.

Administration of prophylactic glucocorticoids has been suggested as a strategy to reduce postoperative AKI and other adverse events after cardiac surgery requiring cardiopulmonary bypass. In this post hoc analysis of a large placebo-controlled randomized trial of dexamethasone in 4465 adult patients undergoing cardiac surgery, we examined severe AKI, defined as use of RRT, as a primary outcome. Secondary outcomes were doubling of serum creatinine level or AKI-RRT, as well as AKI-RRT or in-hospital mortality (RRT/death). The primary outcome occurred in ten patients (0.4%) in the dexamethasone group and in 23 patients (1.0%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.19 to 0.96). In stratified analyses, the strongest signal for potential benefit of dexamethasone was in patients with an eGFR<15 ml/min per 1.73 m(2). In conclusion, compared with placebo, intraoperative dexamethasone appeared to reduce the incidence of severe AKI after cardiac surgery in those with advanced CKD.

'Sepsis-related anemia' is absent at hospital presentation; a retrospective cohort analysis.

BACKGROUND: Anemia is a common feature during sepsis that occurs due to iatrogenic blood loss, depression of serum iron levels and erythropoietin production, and a decreased lifespan of erythrocytes. However, these mechanisms are unlikely to play a role in anemia at the start of sepsis. Moreover, sequestration of fluids, renal failure and increase of intravascular space may additionally influence the change in hemoglobin concentration during intravenous fluid administration in the acute phase of sepsis. METHODS: In this retrospective study, patients who were admitted acutely to the Intensive Care Unit (ICU) were included. Patients who fulfilled the international criteria for severe sepsis or septic shock were included in the sepsis group (S-group). The remaining patients were allocated to the control group (C-group). Laboratory data from blood samples taken at first presentation to the hospital and at admission to the ICU, the amount of intravenous fluid administration and length of stay in the emergency department were collected and tested for significant differences between groups. RESULTS: The difference in hemoglobin concentration between the S-group (n = 296) and C-group (n = 320) at first presentation in hospital was not significant (8.8 ± 1.2 versus 8.9 ± 1.2 mmol/l, respectively, p = 0.07). The reduction in hemoglobin concentration from the first presentation at the emergency department to ICU admission was significantly greater in the S-group compared to the C-group (1 [0.5-1.7] versus 0.5 [0.1-1.1] mmol/l, (p < 0.001)). Spearman rho correlation coefficients between the reduction in hemoglobin concentration and the amount of intravenous fluids administered or the creatinine level in the emergency department were significant (0.3 and 0.4, respectively, p < 0.001). In a multivariate regression analysis, creatinine, the amount of fluid administration and the presence of sepsis remained independently associated. CONCLUSIONS: Prior to in-hospital intravenous fluid administration, there is no significant difference in hemoglobin concentration between acute septic patients and acutely ill controls. Within several hours after hospital admission, there is a significant reduction in hemoglobin concentration, not only associated with the amount of intravenous fluids administered and the creatinine level, but also independently with sepsis itself.

Identifying risk factors for perioperative decline in right ventricular performance in cardiac surgery patients: a prospective observational study in a tertiary care hospital.

OBJECTIVES: Impaired right ventricular (RV) function after cardiac surgery is associated with morbidity and long-term mortality. The purpose of this study was to identify factors that play a role in the development of RV dysfunction in the perioperative cardiac surgery setting. DESIGN: We performed a prospective, observational, single centre study. Over a 2-year period, baseline and perioperative characteristics were recorded. For analysis, subjects were divided into three groups: patients with a ≥3% absolute increase in postoperative RV ejection fraction (RVEF) in comparison to baseline (RVEF+), patients with a ≥3% absolute decrease in RVEF (RVEF-) and patients with a <3% absolute change in RVEF (RVEF=). SETTING: Tertiary care hospital in the Netherlands. PARTICIPANTS: We included all cardiac surgery patients ≥18 years of age equipped with a pulmonary artery catheter and admitted to the ICU in 2015-2016. There were no exclusion criteria. A total number of 267 patients were included (65.5% men). OUTCOME MEASURES: Risk factors for a perioperative decline in RV function. RESULTS: A reduction in RVEF was observed in 40% of patients. In multivariate analysis, patients with RVEF- were compared with patients with RVEF= (first-mentioned OR) and RVEF+ (second-mentioned OR). Preoperative use of calcium channel blocker (CCB) (OR 3.06, 95% CI 1.24 to 7.54/OR 2.73, 95% CI 1.21 to 6.16 (both p=0.015)), intraoperative fluid balance (FB) (OR 1.45, 95% CI 1.02 to 2.06 (p=0.039)/OR 1.09, 95% CI 0.80 to 1.49 (p=0.575)) and baseline RVEF (OR 1.22; 95% CI 1.14 to 1.30/OR 1.27, 95% CI 1.19 to 1.35 (both p<0.001)) were identified as independent risk factors for a decline in RVEF during surgery. CONCLUSION: Apart from the impact of the perioperative FB, preoperative use of a CCB as a risk factor for perioperative reduction in RVEF is the most prominent new finding of this study.

Hemodynamic Characteristics of Mechanically Ventilated COVID-19 Patients: A Cohort Analysis.

BACKGROUND: Solid data on cardiovascular derangements in critically ill COVID-19 patients remain scarce. The aim of this study is to describe hemodynamic characteristics in a cohort of COVID-19-related critically ill patients. METHODS: A retrospective observational cohort study in twenty-eight consecutive mechanically ventilated COVID-19 patients. Pulse contour analysis-derived data were obtained from all patients, using the PiCCO® system. RESULTS: The mean arterial pressure increased from 77 ± 10 mmHg on day 1 to 84 ± 9 mmHg on day 21 (p=0.04), in combination with the rapid tapering and cessation of norepinephrine and the gradual use of antihypertensive drugs in the vast majority of patients. The cardiac index increased significantly from 2.8 ± 0.7 L/min/m2 on day 1 to 4.0 ± 0.8 L/min/m2 on day 21 (p < 0.001). Dobutamine was administered in only two patients. Mean markers of left ventricular contractility and peripheral perfusion, as well as lactate levels, remained within the normal range. Despite a constant fluid balance, extravascular lung water index decreased significantly from 17 ± 7 mL/kg on day 1 to 11 ± 4 mL/kg on day 21 (p < 0.001). Simultaneously, intrapulmonary right-to-left shunt fraction (Q s/Q t) decreased significantly from 27 ± 10% in week 1 to 15 ± 9% in week 3 (p=0.007). PaO2/FiO2 ratio improved from 159 ± 53 mmHg to 319 ± 53 mmHg (p < 0.001), but static lung compliance remained unchanged. CONCLUSIONS: In general, this cohort of patients with COVID-19 respiratory failure showed a marked rise in blood pressure over time, not accompanied by distinctive markers of circulatory failure. Characteristically, increased extravascular lung water, vascular permeability, and intrapulmonary shunt diminished over time, concomitant with an improvement in gas exchange.

Right Ventricular Function and Long-Term Outcome in Sepsis: A Retrospective Cohort Study.

BACKGROUND: Sepsis-related myocardial dysfunction is associated with impaired outcome. Traditionally, in this setting the main focus has been on left ventricular performance. Currently, specific knowledge on the prognostic importance of right ventricular dysfunction is scarce. The aim of this study was to determine whether right ventricular ejection fraction (RVEF) is predictive of long-term mortality in sepsis. METHODS: Single-centre retrospective cohort study in adult patients admitted to the ICU with severe sepsis and septic shock, and equipped with a pulmonary artery catheter within the first day after admission. RVEF was recorded as an average over the first 24 h (sample rate of 1 per min). Patients were separated a priori into subgroups according to their RVEF: RVEF less than 20% (A), RVEF 20% to 30% (B), and RVEF more than 30% (C). The primary endpoint was 1-year all-cause mortality. RESULTS: In a 7-year period, 101 patients fulfilled all entry criteria and 98 were included in the study. One-year all-cause mortality was significantly different between groups: 57% in group A (n = 21), 18% in group B (n = 55), and 23% in group C (n = 22); P = 0.003. Kaplan-Meier survival analysis revealed a clear separation between groups A and B/C (X = 14.00, P = 0.001). In a multivariate logistic regression analysis RVEF, both as a categorical variable (RVEF <20%) and as a continuous variable remained independently associated with the primary endpoint (odds ratio [OR] 4.1; 95% confidence interval [CI], 1.3-13.4; P = 0.018 and OR 0.92; 95% CI, 0.85-0.99; P = 0.018, respectively). CONCLUSIONS: RVEF was independently associated with 1-year all-cause mortality in a highly selected group of patients with severe sepsis and septic shock.

Unilateral intracarotid injection of holmium microspheres to induce bilateral MRI-validated cerebral embolization in rats.

BACKGROUND: Cerebral embolization models have been hindered by the fact that delivery is predominantly one-sided and cannot be quantified easily. We have developed a model for bilateral cerebral micro-embolization. By using holmium microspheres, it is possible to quantify intracerebral delivery using MRI. METHODS: To validate the quantification of holmium microspheres a phantom study was performed in which concentration of microspheres in solution was compared with the number of holmium-induced artifacts on MRI. After that identical microspheres were administered by unilateral injection in the carotid artery, while the opposite carotid artery was clamped. On post-injection MRI scans, intracerebral delivery and right/left distribution of the microspheres was determined. RESULTS: In the phantom study it was shown that quantification by MRI is possible and that MRI artifacts represent single microspheres. In the rat brain, about one-third of the injected dose was consistently located on the contralateral side. The administration was reproducible regarding distribution and number of microspheres. CONCLUSIONS: The use of holmium microspheres enables quantification of delivered dose as single microspheres induce artifacts on MRI. By clamping the contralateral carotid artery, one-third of the dose is diverted to the contralateral hemisphere.

The effect of limited rewarming and postoperative hypothermia on cognitive function in a rat cardiopulmonary bypass model.

BACKGROUND: Clinical studies have failed to demonstrate significant benefits of hypothermia for the prevention of postoperative cognitive dysfunction (POCD) after cardiopulmonary bypass (CPB). One explanation for this might be that potentially injurious cerebral hyperthermia occurs during rewarming at the end of CPB, off-setting the protective benefits of hypothermia. In this study, we investigated the relative influence of CPB temperature, rewarming strategies, and postoperative temperature in a rat CPB model. METHODS: Four groups of male Sprague-Dawley rats were surgically prepared and subjected to 90 min of CPB. Group A was normothermic (37.5 degrees C) during and after CPB. Group B underwent hypothermic (32 degrees C) CPB, followed by rewarming to 37.5 degrees C at the end of bypass. Group C had hypothermic (32 degrees C) CPB, followed by limited rewarming to 35 degrees C. Group D had normothermic CPB with hypothermia (35 degrees C) induced only postoperatively. Groups were compared for POCD determined by the performance in the Morris water maze on postoperative days 3-9. Histologic analysis of the brains (CA1 and CA3 hippocampal regions) was also performed. RESULTS: Hypothermia induced only during (group B versus group A) or after CPB (group D versus group A) conferred no significant POCD benefit. Hypothermia when induced during CPB and continued into the postoperative period resulted in a significant improvement in water maze performance versus all other temperature regimens (group C versus group A, P = 0.044; group C versus group B, P = 0.011; group C versus group D, P = 0.012). No histological differences among groups were demonstrated. CONCLUSIONS: The combination of hypothermic (32 degrees C) CPB coupled with limited rewarming and prolonged postoperative hypothermia (35 degrees C) decreased POCD after CPB in rats.

Perfluorocarbon administration during cardiopulmonary bypass in rats: an inflammatory link to adverse outcome?

BACKGROUND: Perfluorocarbon (PFC) emulsions are artificial oxygen carriers that have been shown to attenuate the effects of air embolism. Cerebral air embolism, known to occur during cardiopulmonary bypass (CPB), may contribute to adverse cerebral outcomes after cardiac surgery. We designed this study to evaluate the effect of a 60% PFC emulsion (perfluoro-tert-butylcyclohexane; PTBCH) on the inflammatory response and neurocognitive outcome of rats after CPB. METHODS: Twenty-eight Sprague Dawley rats subjected to 60 min of CPB were randomly divided into two groups: PTBCH CPB animals receiving 3 mL/kg of PTBCH into the venous reservoir and control CPB animals receiving 3 mL/kg of 0.9% saline. At several time points, the cytokines interleukin (IL)-1beta, IL-6, IL-10, and tumor necrosis factor (TNF)-alpha were measured. Neurocognitive testing was planned postoperatively using the Morris water maze. Histologic samples were obtained in a separate series of experiments. RESULTS: Physiologic variables were comparable between groups, but the PTBCH CPB animals required more phenylephrine compared with the controls. Cytokine levels in the PTBCH CPB group were significantly higher than in the control group at 2 and 4 h after CPB (P < 0.05). Neurocognitive outcome could not be evaluated as none of the animals in the PTBCH CPB group survived. Myocardial histological analysis revealed increased areas of contraction band necrosis in the PTBCH CPB animals (P = 0.034). CONCLUSIONS: Administration of PTBCH during CPB was associated with an excessive release of cytokines. This enhanced inflammatory response with subsequent hypotension may have contributed to mortality in rats receiving PTBCH. The observed patterns of myocardial injury indicate global hypoperfusion and catecholamine excess.

Impaired right ventricular ejection fraction after cardiac surgery is associated with a complicated ICU stay.

BACKGROUND: Right ventricular (RV) dysfunction is a known risk factor for increased mortality in cardiac surgery. However, the association between RV performance and ICU morbidity is largely unknown. METHODS: We performed a single-centre, retrospective study including cardiac surgery patients equipped with a pulmonary artery catheter, enabling continuous right ventricular ejection fraction (RVEF) measurements. Primary endpoint of our study was ICU morbidity (as determined by ICU length of stay, duration of mechanical ventilation, usage of inotropic drugs and fluids, and kidney dysfunction) in relation to RVEF. Patients were divided into three groups according to their RVEF; < 20%, 20-30%, and > 30%. RESULTS: We included 1109 patients. Patients with a RVEF < 20% had a significantly longer stay in ICU, a longer duration of mechanical ventilation, higher fluid balance, a higher incidence of inotropic drug usage, and more increase in postoperative creatinine levels in comparison to the other subgroups. In a multivariate analysis, RVEF was independently associated with increased ICU length of stay (OR 0.934 CI 0.908-0.961, p < 0.001), prolonged duration of mechanical ventilation (OR 0.969, CI 0.942-0.998, p = 0.033), usage of inotropic drugs (OR 0.944, CI 0.917-0.971, p < 0.001), and increase in creatinine (OR 0.962, CI 0.934-0.991, p = 0.011). CONCLUSIONS: A decreased RVEF is independently associated with a complicated ICU stay.

Cardiopulmonary bypass and long-term neurocognitive dysfunction in the rat.

Neurologic and neurocognitive complications after cardiac surgery with cardiopulmonary bypass (CPB) have been reported repeatedly. To better understand its etiology and design protective strategies, an appropriate animal model may prove useful. Although impaired short-term neurocognitive function has been recently demonstrated after CPB in rats, the demonstration of persistent long-term neurocognitive changes would be more relevant from a clinical perspective. We hypothesized that CPB results in long-term impairment of neurocognitive performance in rats. Male rats were exposed to either 60 min of normothermic non-pulsatile CPB, using a roller-pump and a neonatal membrane oxygenator, or to cannulation only (sham animals). Long-term neurocognitive function was assessed at 4 to 7 weeks after CPB (Can test), and again after 12 weeks (Morris water maze) in both operated groups and in a non-operated control group, followed by histologic evaluation of the hippocampus. In separate groups of CPB and sham animals, we also measured TNF-alpha and IL-6 in plasma. There were no significant differences in long-term neurocognitive performance or histological outcome between the three groups. Cytokine patterns were also similar in both operated groups. We conclude that CPB did not appear to cause long-term neurocognitive dysfunction in this model of CPB in young healthy rats. The lack of long-term deficits may be due to the absence of clinically important etiologic factors such as atheromatous and gaseous embolization in this model. Similar cytokine patterns in both operated groups suggest that surgical trauma rather than exposure of blood to extra-corporeal circuit was probably responsible for the inflammatory response.

Reduction in air bubble size using perfluorocarbons during cardiopulmonary bypass in the rat.

BACKGROUND: Perfluorocarbon (PFC) emulsions are artificial oxygen-carrying compounds with a high solubility for gases that have experimentally been shown to ameliorate cerebral air embolism. Cerebral air embolism has been associated with adverse cerebral outcomes after cardiac surgery using cardiopulmonary bypass (CPB). We designed this study to test whether PFC emulsions could reduce the volume of bubbles within the CPB circuit. METHODS: Male Sprague-Dawley rats undergoing 60 min of normothermic nonpulsatile CPB were randomized to one of the three groups. The PFC group (n = 10) received 60% O(2)/36% N(2)/4% CO(2) via the membrane oxygenator and 2.7 g/kg (4.5 mL/kg) of PFC into the venous reservoir; the control group (n = 10) received the same gas mixture and 4.5 mL/kg of saline; the N(2)O group (n = 6) was exposed to 36% N(2)O/60% O(2)/4% CO(2) and received 4.5 mL/kg of saline. After 10 min and 35 min of CPB, 400 microL of air was injected into a bubble chamber in the CPB circuit. After 20 min, the bubble was removed for volumetric analysis. RESULTS: Compared with baseline, the bubble decreased 13% +/- 5% in size in the PFC group and increased 46% +/- 9% in the nitrous oxide group, both of these changes significantly different from the control group (P < 0.0001). CONCLUSION: The results suggest that PFC administration may be useful in reducing the volume of gaseous bubbles present during CPB.

Effect of high or low protamine dosing on postoperative bleeding following heparin anticoagulation in cardiac surgery. A randomised clinical trial.

While experimental data state that protamine exerts intrinsic anticoagulation effects, protamine is still frequently overdosed for heparin neutralisation during cardiac surgery with cardiopulmonary bypass (CPB). Since comparative studies are lacking, we assessed the influence of two protamine-to-heparin dosing ratios on perioperative haemostasis and bleeding, and hypothesised that protamine overdosing impairs the coagulation status following cardiac surgery. In this open-label, multicentre, single-blinded, randomised controlled trial, patients undergoing on-pump coronary artery bypass graft surgery were assigned to a low (0.8; n=49) or high (1.3; n=47) protamine-to-heparin dosing group. The primary outcome was 24-hour blood loss. Patient haemostasis was monitored using rotational thromboelastometry and a thrombin generation assay. The low protamine-to-heparin dosing ratio group received less protamine (329 ± 95 vs 539 ± 117 mg; p<0.001), while post-protamine activated clotting times were similar among groups. The high dosing group revealed increased intrinsic clotting times (236 ± 74 vs 196 ± 64 s; p=0.006) and the maximum post-protamine thrombin generation was less suppressed in the low dosing group (38 ± 40 % vs 6 ± 9 %; p=0.001). Postoperative blood loss was increased in the high dosing ratio group (615 ml; 95 % CI 500-830 ml vs 470 ml; 95 % CI 420-530 ml; p=0.021) when compared to the low dosing group, respectively. More patients in the high dosing group received fresh frozen plasma (11 % vs 0 %; p=0.02) and platelet concentrate (21 % vs 6 %; p=0.04) compared to the low dosing group. Our study confirms in vitro data that abundant protamine dosing is associated with increased postoperative blood loss and higher transfusion rates in cardiac surgery.

Intraoperative High-Dose Dexamethasone in Cardiac Surgery and the Risk of Rethoracotomy.

BACKGROUND: Cardiac surgery with the use of cardiopulmonary bypass is associated with a systemic inflammatory response. Intraoperative corticosteroids are administered to attenuate this inflammatory response. The recent Dexamethasone for Cardiac Surgery (DECS) trial could not demonstrate a beneficial effect of dexamethasone on major adverse events in cardiac surgical patients. Previous studies suggest that corticosteroids may affect postoperative coagulation and blood loss, and therefore could influence the risk of surgical reinterventions. We investigated the effects of prophylactic intraoperative dexamethasone treatment on the rate of rethoracotomy after cardiac surgery. METHODS: We performed a post-hoc additional data collection and analysis in the DECS trial. A total of 4,494 adult patients undergoing cardiac surgery with cardiopulmonary bypass were randomly assigned to intravenous dexamethasone (1.0 mg/kg) or placebo. The primary endpoint for the present study was the incidence of any rethoracotomy within the first 30 postoperative days. Secondary endpoints included the reason for rethoracotomy and the incidence of perioperative transfusion of blood products. RESULTS: In the dexamethasone group, 217 patients (9.7%) underwent a rethoracotomy, and in the placebo group, 165 patients did (7.3%; relative risk 1.32, 95% confidence interval: 1.09 to 1.61, p = 0.005). The most common reason for rethoracotomy was tamponade in both groups: 3.9% versus 2.1%, respectively (relative risk 1.84, 95% confidence interval: 1.30 to 2.61, p < 0.001). CONCLUSIONS: Intraoperative high-dose dexamethasone administration in cardiac surgery was associated with an increased rethoracotomy risk.

A new miniature fiber oxygenator for small animal cardiopulmonary bypass.

Neurocognitive decline following cardiac surgery is an increasing problem, particularly affecting older patients. The use of cardiopulmonary bypass is a suspected cause. Research into pathophysiology and possible preventive measures requires the use of an animal model. Commercial oxygenators are too large and expensive for use in small animals. We describe a fiber oxygenator scaled for use in the rat. In vitro and in vivo testing show that it is able to support full gas exchange in this size of animal, and causes no allergic or toxic reactions.