Fewer transfusions are still more-red blood cell transfusions affect long-term mortality in cardiac surgery.

OBJECTIVES: Previous studies indicated higher long-term mortality after the transfusion of allogeneic red blood cells (RBC); newer recommendations emphasize lower transfusion rates. The consequences of the transfusion of RBCs in cardiac surgery are unclear because later studies focused on transfusion triggers and short-term outcomes. Reports on long-term complications after cardiac surgery are few. MATERIAL AND METHODS: The mandatory Western Denmark Heart Registry was used to identify all adult cardiac operations performed in 4 centres from 2000 to 2019. Patients with multiple entries or previous cardiac operations, special/complex procedures, dying within 30 days and not eligible for follow-up were excluded. RESULTS: A total of 32,581 adult cardiac operations performed in 4 centres from 2000 to 2019 were included. The Kaplan-Meier survival plot for low-risk patients undergoing simple cardiac operations showed a significantly lower 15-year survival (0.384 vs 0.661) of patients who received perioperative RBC transfusions [odds ratio 2.43 (confidence level 2.23-2.66)]. The risk decreased with increasing comorbidity or age. No difference was found in high-risk patients. The adjusted risk ratio after an RBC transfusion, including age, sex, comorbidity and surgery, was 1.62 (1.48-1.77). CONCLUSIONS: Despite reduced transfusion rates, long-term follow-up on especially low-risk patients undergoing comparable cardiac operations still demonstrates substantially more deaths of patients receiving perioperative RBC transfusions. Even transfusion of 1-2 units is associated with increased long-term mortality.

Selection of patients for mechanical circulatory support for refractory out-of-hospital cardiac arrest.

OBJECTIVE: To describe characteristics of patients admitted with refractory cardiac arrest for possible extracorporeal cardiopulmonary resuscitation (ECPR) and gain insight into the reasons for refraining from treatment in some. METHODS: Nationwide retrospective cohort study involving all tertiary centres providing ECPR in Denmark. Consecutive patients admitted with ongoing chest compression for evaluation for ECPR treatment were enrolled. Presenting characteristics, duration of no-flow and low-flow time, end-tidal carbon dioxide (ETCO2), lactate and pH, and recording of reasons for refraining from ECPR documented by the treating team were recorded. Outcomes were survival to intensive care unit admission and survival to hospital discharge. RESULTS: Of 579 patients admitted with refractory cardiac arrest for possible ECPR, 221 patients (38%) proceeded to ECPR and 358 patients (62%) were not considered candidates. Median prehospital low-flow time was 70 min (IQR 56 to 85) in ECPR patients and 62 min (48 to 81) in no-ECPR patients, p<0.001. Intra-arrest transport was more than 50 km in 92 (42%) ECPR patients and 135 in no-ECPR patients (38%), p=0.25. The leading causes for not initiating ECPR stated by the treating team were duration of low-flow time in 39%, severe metabolic derangement in 35%, and in 31% low ETCO2. The prevailing combination of contributing factors were non-shockable rhythm, low ETCO2, and metabolic derangement or prehospital low-flow time combined with low ETCO2. Survival to discharge was only achieved in six patients (1.7%) in the no-ECPR group. CONCLUSIONS: In this large nationwide study of patients admitted for possible ECPR, two-thirds of patients were not treated with ECPR. The most frequent reasons to abstain from ECPR were long duration of prehospital low-flow time, metabolic derangement and low ETCO2.

Extracorporeal cardiopulmonary resuscitation: a national study on the association between favourable neurological status and biomarkers of hypoperfusion, inflammation, and organ injury.

AIMS: In refractory out-of-hospital cardiac arrest (OHCA) with prolonged whole-body ischaemia, global tissue injury proceeds even after establishment of circulation with extracorporeal cardiopulmonary resuscitation (ECPR). We aimed to investigate the role of biomarkers reflecting hypoperfusion, inflammation, and organ injury in prognostication of patients with refractory OHCA managed with ECPR. METHODS AND RESULTS: This nationwide retrospective study included 226 adults with refractory OHCA managed with ECPR in Denmark (2011-2020). Biomarkers the first days after ECPR-initiation were assessed. Odds ratio of favourable neurological status (Cerebral Performance Category 1-2) at hospital discharge was estimated by logistic regression analyses. Cut-off values were calculated using the Youden's index. Fifty-six patients (25%) survived to hospital discharge, 51 (91%) with a favourable neurological status. Factors independently associated with favourable neurological status were low flow time <81 min, admission leukocytes ≥12.8 × 109/L, admission lactate <13.2 mmol/L, alkaline phosphatase (ALP) < 56 (day1) or <55 U/L (day2), and day 1 creatine kinase MB (CK-MB) < 500 ng/mL. Selected biomarkers (leukocytes, C-reactive protein, and lactate) were significantly better predictors of favourable neurological status than classic OHCA-variables (sex, age, low-flow time, witnessed arrest, shockable rhythm) alone (P = 0.001) after hospital admission. CONCLUSION: Biomarkers of hypoperfusion (lactate), inflammation (leucocytes), and organ injury (ALP and CK-MB) were independently associated with neurological status at hospital discharge. Biomarkers of hypoperfusion and inflammation (at hospital admission) and organ injury (days 1 and 2 after ECPR) may aid in the clinical decision of when to prolong or terminate ECPR in cases of refractory OHCA.

ICU Nurses-An Impact Factor on Patient Turnover in Cardiac Surgery in Western Denmark?

OBJECTIVE: The aim of this study was to describe changes in performance indicators such as length of stay [LOS] in the intensive care unit [ICU] and ventilation time, during the last six years in an attempt to identify associations between patient and systemic performance indicators, including the impact of nurse turnover. DESIGN: A retrospective study of prospectively registered data (2013-2018). Propensity- score matching was performed to establish comparable groups. SETTING: Three Danish university hospitals. PARTICIPANTS: The study included a total of 12,404 adult cardiac surgical patients registered in the Western Denmark Heart Registry. The cohort was divided into an "early" group (2013-2016) and a "late" group (2017-2018). INTERVENTIONS: An analysis of dynamics in patient indicators and systemic performance indicators, including the impact from selected performance parameters and nurse turnover. MEASUREMENTS AND MAIN RESULTS: Comorbidity, calculated from the European System for Cardiac Operative Risk Evaluation, and the mean age were stable in the study period. Strong predictors of long LOS in the ICU included postoperative use of inotropes, re-exploration surgery, high postoperative drainage, and the "late" time group. Time parameters (relative risks) were all significantly longer in the "late" time group": ventilation time 1.21 (1.05-1.39), length of stay ICU 1.28 (1.11-1.48), and in-hospital time 1.36 (1.19-1.57). ICU nurse turnover increased from four (2013-2014) to 52 (2017-2018). CONCLUSION: No single patient factor, such as age or comorbidity, could explain the decrease in patient turnover in the ICU. In the same period, the turnover of ICU nurses increased. Patient turnover is complex and affected by a mix of patient and systemic performance factors.

Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study.

BACKGROUND: Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome. METHODS: This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan-Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality. RESULTS: A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow-Pittsburgh Cerebral Performance Categories 1-2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow < 100 min, pH > 6.8 and lactate < 15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified asystole (RR 1.36, 95% CI 1.18-1.57), pulseless electrical activity (RR 1.20, 95% CI 1.03-1.41), initial pH < 6.8 (RR 1.28, 95% CI 1.12-1.46) and lactate levels > 15 mmol/L (RR 1.16, 95% CI 1.16-1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52-0.76). CONCLUSIONS: A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.

The association between a three-day ticagrelor discontinuation and perioperative bleeding complications.

OBJECTIVES: Dual antiplatelet therapy at the time of cardiac surgery is associated with excessive perioperative bleeding. International guidelines, therefore, recommended discontinuing oral adenosine diphosphate receptor antagonists prior to non-emergency surgery. In this study, we analysed whether a 3-day ticagrelor discontinuation was sufficient to avoid major bleeding complications. METHODS: This study is a retrospective cohort analysis of 3377 patients undergoing coronary artery bypass or single-valve surgery from January 2013 to September 2017. Patients exposed to ticagrelor prior to surgery were compared with control patients exposed to aspirin only. Outcome measures included transfusion requirements, bleeding volumes, the need for re-exploration and the composite outcome major bleeding complication. Data were retrieved from the the Western Denmark Heart Registry. RESULTS: During the study period, 101 patients were preoperatively exposed to ticagrelor, whereas 3276 patients were exposed to aspirin only. Propensity-score matching resulted in 90 pairs of patients. Overall, ticagrelor exposure was associated with a greater risk of major bleeding complications compared with control patients [31 vs 12%, relative risk 2.6, 95% confidence interval (CI) 1.4-4.8]. While ticagrelor exposure within 0-72 h before surgery (n = 42) was associated with a substantially increased risk of major bleeding complications (48 vs 10%, relative risk 5.0, 95% CI 1.9-13.4), ticagrelor exposure 72-120 h before surgery (n = 48) showed no statistically significant association (17 vs 15%, relative risk 1.1, 95% CI 0.4-2.9). CONCLUSIONS: In our historical cohort, ticagrelor exposure 0-72 h prior to cardiac surgery was associated with an increased risk of major bleeding complications. On the other hand, ticagrelor exposure 72-120 h prior to surgery was not associated with a clinically relevant increase in major bleeding complications.

Cerebral blood flow measured by positron emission tomography during normothermic cardiopulmonary bypass: an experimental porcine study.

BACKGROUND: Mean arterial blood pressure (MAP) and/or pump flow during normothermic cardiopulmonary bypass (CPB) are the most important factors of cerebral perfusion. The aim of this study was to explore the influence of CPB blood flow on cerebral blood flow (CBF) measured by dynamic positron emission tomography (PET) using 15O-labelled water with no pharmacological interventions to maintain the MAP. METHODS: Eight pigs (69-71 kg) were connected to normothermic CPB. After 60 minutes (min) with a CPB pump flow of 60 mL/kg/min, the pigs were changed to either 35 mL/kg/min or 47.5 mL/kg/min for 60 min and, thereafter, all the pigs returned to 60 mL/kg/min for another 60 min. The MAP was measured continuously and the CBF was measured by positron emission tomography (PET) during spontaneous circulation and at each CPB pump flow after 30 min of steady state. RESULTS: Two pigs were excluded due to complications. CBF increased from spontaneous circulation to a CPB pump flow of 60 mL/kg/min. A reduction in CPB pump flow to 47.5 mL/kg/min (n=3) resulted in only minor changes in CBF while a reduction to 35 mL/kg/min (n=3) caused a pronounced change (correlation coefficient (R2) 0.56). A return of CPB pump flow to 60 mL/kg/min was followed by an increase in CBF, except in the one pig with the lowest CBF during low flow (R2=0.44). CBF and MAP were not correlated (R2=0.20). CONCLUSION: In this experimental porcine study, a relationship was observed between pump flow and CBF under normothermic low-flow CPB. The effect of low pump flow on MAP showed substantial variations, with no correlation between CBF and MAP.

Keep Ventilating the Lungs While the Heart is Still Ejecting on Femoro-femoral Cardiopulmonary Bypass.

Femoro-femoral cardiopulmonary bypass (CPB) followed by deep hypothermic circulatory arrest is one of the modalities used for ascending aortic pseudoaneurysm repair to achieve cardiac unloading and to avoid severe hemorrhage due to the risk of rupture during the sternal entry. However, due to the limited size of the cannulas, it can be challenging to achieve total cardiopulmonary support. Therefore, despite the achievement of total cardiopulmonary support, the heart may still be able to eject antegrade blood flow that meets the retrograde blood flow from the arterial side of the CPB. The point where the blood flow meets in the aorta is called the watershed area. If the antegrade blood flow is large due to a left ventricular ejection, the watershed area will be located in the descending aorta. Therefore, if ventilation is stopped, deoxygenated blood will be ejected to the cerebral circulation. Cerebral near-infrared spectroscopy (NIRS) may be used as a noninvasive and continuous measurement of regional brain oxygen saturation (rSO2). This case demonstrates that cerebral desaturation due to discontinued mechanical ventilation, when the heart was still ejecting during the initial phase of femoro-femoral CPB, immediately was detected by a pronounced drop bilaterally: In the left frontal lobe, rSO2 fell from 56% to 21%, and in the right frontal lobe it fell from 47% to 25%. The authors recommend monitoring cerebral saturation using NIRS in the case of femoro-femoral CPB.

Muscle Tissue Saturation Compared With Muscle Tissue Perfusion During Low Blood Flows: An Experimental Study.

OBJECTIVE: To investigate whether changes in muscle tissue perfusion measured with positron emission tomography would be reflected by parallel changes in muscle tissue oxygen saturation (StO2) measured using near-infrared spectroscopy during high and low blood flow levels achieved using cardiopulmonary bypass (CPB) in an animal model. DESIGN: A prospective, randomized study. SETTING: Research laboratory, single institution. PARTICIPANTS: Eight pigs (69-71 kg). INTERVENTIONS: In anesthetized pigs, normothermic CPB was established with a blood flow of 60 mL/kg/min for 1 hour. Thereafter, a low blood flow of either 47.5 or 35 mL/kg/min was applied for 1 hour followed by a blood flow of 60 mL/kg/min for an additional hour. Regional StO2 was measured continuously by placing a near-infrared spectroscopy electrode on the skin above the gracilis muscle of the noncannulated back leg. Muscle tissue perfusion was measured using positron emission tomography with 15O-labeled water during spontaneous circulation and the different CPB blood flows. Systemic oxygen consumption was estimated by measurement of venous saturation and lactate levels. MEASUREMENTS AND MAIN RESULTS: The results showed profound systemic ischemia during low CPB blood flow. StO2 remained high until muscle tissue perfusion decreased to about 50%, after which StO2 paralleled the linear decrease in muscle tissue perfusion. CONCLUSION: In an experimental CPB animal model, StO2 was stable until muscle tissue perfusion was reduced by about 50%, and at lower blood flow levels, there was almost a linear relationship between StO2 and muscle tissue perfusion.

Regional muscle tissue saturation is an indicator of global inadequate circulation during cardiopulmonary bypass: a randomized porcine study using muscle, intestinal and brain tissue metabolomics.

BACKGROUND: Muscle tissue saturation (StO2) measured with near-infrared spectroscopy has generally been considered a measurement of the tissue microcirculatory condition. However, we hypothesized that StO2 could be more regarded as a fast and reliable measure of global than of regional circulatory adequacy and tested this with muscle, intestinal and brain metabolomics at normal and two levels of low cardiopulmonary bypass blood flow rates in a porcine model. METHODS: Twelve 80 kg pigs were connected to normothermic cardiopulmonary bypass with a blood flow of 60 mL/kg/min for one hour, reduced randomly to 47.5 mL/kg/min (Group I) or 35 mL/kg/min (Group II) for one hour followed by one hour of 60 mL/kg/min in both groups. Regional StO2 was measured continuously above the musculus gracilis (non-cannulated leg). Metabolomics were obtained by brain tissue oxygen monitoring system (Licox) measurements of the brain and microdialysis perfusate from the muscle, intestinal mucosa and brain. A non-parametric statistical method was used. RESULTS: The systemic parameters showed profound systemic ischaemia during low CPB blood flow. StO2 did not change markedly in Group I, but in Group II, StO2 decreased immediately when blood flow was reduced and, furthermore, was not restored despite blood flow being normalized. Changes in the metabolomics from the muscle, colon and brain followed the changes in StO2. CONCLUSION: We found, in this experimental cardiopulmonary bypass model, that StO2 reacted rapidly when the systemic circulation became inadequate and, furthermore, reliably indicate insufficient global tissue perfusion even when the systemic circulation was restored after a period of systemic hypoperfusion.