Timing of Chest Tube Removal Following Adult Cardiac Surgery: A Cluster Randomized Controlled Trial.

OBJECTIVES: Early chest tube removal following cardiac surgery may be associated with an increased risk of pleural or pericardial effusions following cardiac surgery. This study compares the effects of two fast-track chest tube removal protocols regarding the risk of pleural or pericardial effusions, requirement of opioids, respiratory function, and postoperative complications. DESIGN: Prospective non-blinded cluster-randomized study with alternating chest tube removal protocol in adult patients undergoing elective cardiac surgery. Monthly changing allocation to scheduled chest tube removal on the day of surgery (Day 0) versus removal on the 1st postoperative day (Day 1) provided no air leakage and output < 200 mL within the last four hours. RESULTS: A total of 527 patients were included in the study from September 1st 2020 until October 29th 2021 and randomly allocated to chest tube removal at day 0 (n = 255), and day 1 (n = 272). More than every fourth patient required drainage for pleural effusion with no significant difference between the groups. Earlier removal of chest tubes did not reduce requirement of analgesics, improve early respiratory function, or reduce postoperative complications. The study was halted for futility after halfway interim analysis showed insufficient promise of any treatment benefit. CONCLUSION: Fast-track protocols with chest tube removal within the first 24 h after cardiac surgery may be associated a high rate of pleural effusions.

The use of prone position ventilation in Danish patients with COVID-19-induced severe acute respiratory distress syndrome treated with veno-venous extracorporeal membrane oxygenation: A nationwide cohort study with focus on pulmonary effects.

BACKGROUND: Prone position ventilation (PPV) is recommended for patients with COVID-19 induced severe Adult Respiratory Distress Syndrome (ARDS) and is used for patients supported with V-V ECMO as well. The purpose of this study was to describe the use of PPV in these patients focusing on physiological effects with the hypothesis that PPV could reduce oxygen need and improve dynamic compliance. METHODS: This study was a nationwide retrospective analysis of all COVID-19 patients in Denmark from March 2020 - December 2021 with severe ARDS and need of V-V ECMO support. Data on the number of patients treated with PPV, number of PPV sessions, timing, the time spent in prone position, pulmonary physiological response types with analysis of variables affecting the response are reported. RESULTS: Out of 68 patients 44 were treated with 220 PPV sessions and a positive clinical response was observed in 80% of patients but only in 45% of sessions. On a single session level, increased compliance was observed in 38% and increased oxygenation in only 15% of 220 sessions, with within-patient heterogeneity. Higher dynamic compliance at the beginning of a PPV session was associated with a lower delta change in dynamic compliance during PPV. The response to a PPV session could not be predicted by the response in the prior session. Dynamic compliance did not change during the ECMO course. CONCLUSION: Eighty percent of patients responded positively during a PPV session, but this was not associated with overall pulmonary improvement. On a single patient level, responses were heterogenous and only 45% of sessions resulted in clinical improvement. Response in dynamic compliance was associated with starting values of compliance.

Use of prone position ventilation in patients with COVID-19 induced severe ARDS supported with V-V ECMO: A danish cohort study with focus on adverse events.

INTRODUCTION: Prone position ventilation (PPV) of patients with adult respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO) may improve oxygenation and alveolar recruitment and is recommended when extensive dorsal consolidations are present, but only few data regarding adverse events (AE) related to PPV in this group of patients have been published. METHODS: Nationwide retrospective analysis of 68 COVID-19 patients admitted from March 2020 - December 2021 with severe ARDS and need of V-V ECMO support. The number of patients treated with PPV, number of PPV-events, timing, the time spent in prone position, number and causes of AE are reported. Causes to stop the PPV regimen and risk factors for AE were explored. RESULTS: 44 out of 68 patients were treated with PPV, and 220 PPV events are evaluated. AE were identified in 99 out of 220 (45%) PPV events and occurred among 31 patients (71%). 1 fatal PPV related AE was registered. Acute supination occurred in 19 events (9%). Causes to stop the PPV regimen were almost equally distributed between effect (weaned from ECMO), no effect, death (of other reasons) and AE. Frequent causes of AE were pressures sores and ulcers, hypoxia, airway related and ECMO circuit related. Most AE occurred during patients first or second PPV event. CONCLUSIONS: PPV treatment was found to carry a high incidence of PPV related AE in these patients. Causes and preventive measures to reduce occurrence of PPV related AE during V-V ECMO support need further exploration.

A Descriptive Study of Perioperative Hemodynamics in Open Cardiac Surgery Patients.

OBJECTIVES: The purpose of the present study was to describe how the perioperative hemodynamic profile before and after cardiopulmonary bypass during cardiac surgery is influenced by age and to describe the association between postoperative hemodynamics and one-year mortality. DESIGN: A retrospective registry-based study. SETTING: University Hospital of Aarhus, Denmark. PARTICIPANTS: The study comprised 6,595 patients undergoing elective on-pump cardiac surgery from 2006 to 2016. MEASUREMENTS AND MAIN RESULTS: Perioperative hemodynamic values were derived from computerized anesthesia and intensive care reports, including mean arterial pressure, cardiac index, and oxygenation saturation from mixed venous blood in the pulmonary artery, during the perioperative period. Perioperative hemodynamic values were stratified according to age. Logistic regression was applied to predict the crude probability of death within one year from surgery according to hemodynamic values at six hours after surgery, stratified by age and use of inotropic agents, respectively. Lower values for cardiac index and mixed venous blood in the pulmonary artery with increasing age, across all points in time in the perioperative course, were observed. Higher probability of death was associated with lower hemodynamic values in the postoperative phase, and the probability of death was modified by age and the need for inotropic agents. DISCUSSION: This is a large registry based study describing the perioperative hemodynamic profile of patients undergoing cardiac surgery and the results enhance our understanding of age-differentiated values of CI and SvO2 in this specific population.

Outcome of hybrid compared to conventional revascularization in multivessel coronary artery disease.

OBJECTIVES: Evaluation of 3-year clinical outcome of hybrid myocardial revascularization (HMR) compared to conventional revascularization strategies in patients with multivessel coronary artery disease involving the proximal left anterior descending artery. Design. Retrospective matched cohort study based on a prospective feasibility study including 103 elective patients undergoing staged HMR from October 2010 until February 2012. The Western Denmark Heart Registry was used to identify patients who underwent coronary artery bypass grafting (CABG) and multivessel percutaneous coronary intervention (PCI) by matching on number of diseased vessels, age and comorbidity score. Primary endpoint was the composite rate of major adverse cardiovascular and cerebrovascular events (MACCE) at 3-year follow-up. Secondary endpoints included individual MACCE components, acute kidney injury, and cardiovascular readmissions. Results. There was no difference between MACCE in the three groups (HMR 31.1%; CABG 20.4%; PCI 20.4%, p = .11). Estimates of repeat revascularization were significantly increased with HMR versus CABG. In the CABG group, fewest patients required cardiovascular readmissions though with the highest incidence of acute kidney injury. Conclusions. HMR was not superior with respect to MACCE compared with CABG and PCI. It may, however, represent a safe alternative to conventional revascularization treatment considering the specific procedure-associated morbidity.

Intraoperative milrinone versus dobutamine in cardiac surgery patients: a retrospective cohort study on mortality.

BACKGROUND: Several choices of inotropic therapy are available and used in relation to cardiac surgery. Comparisons are necessary to select optimal therapy. In Denmark, dobutamine and milrinone are the two inotropic agents most commonly used to treat post-bypass low cardiac output syndrome. This study compares all-cause mortality with these drugs. METHODS: In a retrospective observational study we investigated 10,700 consecutive patients undergoing cardiac surgery from 1 April 2006 to 31 December 2013 at Aarhus and Aalborg University Hospitals in the Central and Northern Denmark Region. Prospectively entered data in the Western Danish Heart Registry on intraoperative use of inotropes were used to identify 952 patients treated with milrinone, 418 patients treated with dobutamine, and 82 patients receiving a combination of the two inotropes. All-cause mortality among patients receiving dobutamine was compared to all-cause mortality among milrinone receivers. Multiple logistic regression analyses including preoperative and intraoperative variables along with g-formula analyses were used to model 30-day and 1-year mortality risks. Reported were standardized mortality risk differences between the treatment groups. RESULTS: Among patients receiving intraoperative dobutamine, 18 (4.3%) died within 30 days and 49 (11.7%) within 1 year. Corresponding 30-day and 1-year mortality for milrinone receivers were 81 (8.5%) and 170 (17.9%). Risk of death within 30 days and 1 year was increased for intraoperative milrinone compared to dobutamine with a standardized risk difference of 4.06% (confidence interval (CI) 1.23; 6.89, p = 0.005) and 4.77% (CI 0.39; 9.15, p = 0.033), respectively. Sensitivity analyses including adjustment for milrinone preference, hemodynamic instability prior to cardiopulmonary bypass, and separate analyses on hospital level all confirmed a sign toward increased mortality among milrinone receivers. CONCLUSIONS: Intraoperative use of milrinone in cardiac surgery may be associated with an increase in all-cause mortality compared to use of dobutamine.

Outcome of inotropic therapy: is less always more?

PURPOSE OF REVIEW: Positive inotropic agents are widely used in the management of the critical ill patient presenting with low cardiac output state. Different inotropic agents are available, and different effects on hemodynamic endpoints may be recognized, but data on relevant clinical endpoints are scarce. A growing body of literature suggests that overuse of inotropes may have detrimental effects on cardiomyocytes, resulting in an increased risk of morbidity and mortality. The present review will summarize recent literature, focusing on outcome studies among adult patients related to use of inotropes in different clinical settings. RECENT FINDINGS: Use of inotropic therapy shows a manifold variation between hospitals and individual providers even after risk standardization. No recent studies have shown inotropic therapy to provide short-term and long-term improvement of morbidity and mortality in patients with advanced nonsurgical heart failure or septic shock or as part of goal-directed treatment in high-risk noncardiac surgery. Levosimendan may show beneficial effect on mortality in cardiac surgery. CONCLUSION: A 'less is more' approach may show to be appropriate when relating to routine use of inotropes. Inotropic therapy should be restricted to patients with heart failure and clinical signs of end-organ hypoperfusion.

Health outcomes with and without use of inotropic therapy in cardiac surgery: results of a propensity score-matched analysis.

BACKGROUND: Inotropes used to obtain short-term hemodynamic benefits in cardiac surgery may carry a risk of increased myocardial ischemia and adverse outcomes. This study investigated the association between intra- and postoperative use of inotropes and mortality and postoperative complications. METHODS: A historic cohort study using prospective data from the Western Denmark Heart Registry on 6,005 consecutive cardiac surgery cases from three university hospitals. Propensity matching on pre- and intraoperative variables was used to identify a subgroup of patients receiving inotropic therapy (n = 1,170) versus comparable nonreceivers (n = 1,170) for outcome analysis. RESULTS: Two thousand ninety-seven patients (35%) received inotropic therapy; 3,908 (65%) did not receive any inotropic or vasopressor support perioperatively. Among propensity-matched cohort including 2,340 patients 30-day mortality was 3.2% and 1-yr mortality was 7.6%. In the matched cohort, patients exposed to inotropes had a higher 30-day mortality (adjusted hazards ratio, 3.7; 95% CI, 2.1 to 6.5) as well as a higher 1-yr mortality rate (adjusted hazards ratio, 2.5; 95% CI, 1.8 to 3.5) compared with nonreceivers. Among propensity-matched, the following absolute events rates were observed: myocardial infarction 2.4%, stroke 2.8%, arrhythmia 35%, and renal replacement therapy 23.9%. Inotropic therapy was independently associated with postoperative myocardial infarction (adjusted odds ratio, 2.1; 95% CI, 1.4 to 3.0), stroke (adjusted odds ratio, 2.4; 95% CI, 1.4 to 4.3), and renal replacement therapy (adjusted odds ratio, 7.9; 95% CI, 3.8 to 16.4). CONCLUSION: Use of intra- and postoperative inotropes was associated with increased mortality and major postoperative morbidity.

High thoracic epidural analgesia in cardiac surgery. Part 1--high thoracic epidural analgesia improves cardiac performance in cardiac surgery patients.

OBJECTIVE: The purpose of this study was to evaluate the perioperative cardioprotective effect of high thoracic epidural analgesia (HTEA), primarily expressed as an effect on cardiac performance and hemodynamics in patients undergoing cardiac surgery. DESIGN: A randomized, prospective study. PARTICIPANTS: Sixty low-to-moderate risk patients between the ages of 65 and 80 years scheduled for elective coronary artery bypass graft surgery with or without aortic valve replacement. SETTING: A university hospital. INTERVENTION: Patients randomized to receive HTEA as a supplement to general anesthesia. MEASUREMENTS AND MAIN RESULTS: Perioperative hemodynamic measurements, perioperative fluid balance, and postoperative release of cardiac enzymes were collected. The end-diastolic volume index (EDVI), the stroke volume index (overall 38 v 32 mL), the cardiac index (overall 2.35 v. 2.18 L/minute/m(2)), the central venous pressure, and central venous oxygenation were higher in the HTEA group. The mean arterial blood pressure was marginally lower in the HTEA group, whereas no difference was noted in the heart rate or peripheral saturation between the groups. No differences were found in the postoperative levels of troponin T and CK-MB between groups. NT-proBNP changed over time (p < 0.001) and was lower in the HTEA group (p = 0.013), with maximal values of 291 ± 265 versus 326 ± 274. CONCLUSIONS: The findings of a higher stroke volume index and central venous oxygenation without an increase in heart rate or mean arterial pressure suggest that HTEA improves cardiac performance in elderly cardiac surgery patients.

High thoracic epidural analgesia in cardiac surgery. Part 2--high thoracic epidural analgesia does not reduce time in or improve quality of recovery in the intensive care unit.

OBJECTIVE: To evaluate the postoperative effect of high thoracic epidural analgesia on the time in the intensive care unit (ICU) and the quality of cardiac recovery in patients undergoing cardiac surgery. DESIGN: A randomized prospective study. PARTICIPANTS: Sixty low-risk patients 65 to 80 years of age scheduled for elective coronary artery bypass graft surgery with or without aortic valve replacement. SETTING: A university hospital. INTERVENTIONS: Patients randomized to receive high thoracic epidural analgesia (HTEA) as a supplement to general anesthesia. MEASUREMENTS AND MAIN RESULTS: The eligible time to discharge from the ICU and the quality of recovery were evaluated by an objective ICU scoring system. The time to eligible discharge from the ICU, the ventilation time, and the actual time in the ICU were not shorter in the HTEA group compared with patients receiving conventional general anesthesia. Patients receiving HTEA in addition to general anesthesia received less morphine postoperatively but with no consequent beneficial effect on respiration, nausea, sedation, or motor function. CONCLUSIONS: HTEA does not reduce the time in the ICU or improve the quality of recovery in the ICU.

Impact of perioperative course during cardiac surgery on outcomes in patients 80 years and older.

OBJECTIVE: To describe the associations among preoperative characteristics, intraoperative and postoperative factors, and mortality and morbidity after open-heart surgery in patients age ≥80 years. METHODS: This retrospective multicenter register study was based on prospectively collected data of all patients age ≥80 years undergoing open-heart surgery in western Denmark between 1999 and 2016. Logistic regression was used to estimate the associations among preoperative characteristics, intraoperative and postoperative factors, and morbidity and mortality. Bonferroni correction was used for multiple comparisons. RESULTS: The study population included 2342 patients age ≥80 years undergoing open-heart surgery. We observed an association between severely impaired preoperative renal function and death within 1-year postsurgery (odds ratio [OR], 4.6; 95% confidence interval [CI], 2.7-7.2). Furthermore, renal clearance <40 mL/min and prolonged cardiopulmonary bypass time of >180 minutes were associated with a >50% probability of death within 1 year. The adjusted OR for death within 1 year was increased significantly with a postoperative length of stay in intensive care of ≥3 days (OR, 5.9; 95% CI, 4.1-8.6) and a duration of postoperative mechanical ventilation ≥2 days (OR, 7.5; 95% CI, 4.1-13.9). Various preoperative and intraoperative characteristics were associated with in-hospital dialysis, in particular cardiopulmonary bypass time >180 minutes (OR, 11.6; 95% CI, 4.7-28.5). CONCLUSIONS: Our findings emphasize the importance of careful referral regarding the procedural burden for very elderly patients and may provide support for informed patient discussions about prognosis and recovery.

[Extracorporeal membrane oxygenation therapy of acute respiratory distress syndrome in adults in Denmark].

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is an established treatment option in critically ill patients with acute respiratory distress syndrome (ARDS). The overall mortality in patients with ARDS has fallen over the past 30 years. VV-ECMO for selected patients has contributed to this. In Denmark, VV-ECMO is centralised to Aarhus University Hospital and Rigshospitalet, as it is a complex multidisciplinary therapy. The treatment involves many specialities and personnel groups, all with special training and experience. This review presents the current literature in the ARDS and ECMO treatment.

The absorption of aspirin is reduced after coronary artery bypass grafting.

BACKGROUND: Despite treatment with the antiplatelet drug aspirin, some patients who undergo coronary artery bypass grafting (CABG) experience a thromboembolic event in the early postoperative period. The etiology of a reduced aspirin effect after CABG is still unsolved. Hence, we investigated whether patients who undergo CABG have a reduced absorption of aspirin after surgery, measured as levels of plasma salicylic acid (SA). METHODS: In total, 53 patients were included between October 2015 and May 2018. Blood samples where obtained at the day before surgery, and at the first (day 1) and second (day 2) postoperative day. A subgroup of 10 patients had additional blood samples obtained on day 1. Plasma SA was measured using liquid chromatography-electrospray-ionization tandem-mass spectrometry. Multiplate Analyzer (Roche, Roche Diagnostics, Mannheim, Germany) and VerifyNow Aspirin Test (Accumetrics, San Diego, Calif) were used to assess platelet aggregation as a measurement of the antiplatelet effect of aspirin. RESULTS: A comparison of the difference in change of SA concentration between the day before surgery with day 1 and day 2 showed a significantly reduced increase in SA plasma levels after intake of aspirin at day 1 and day 2 after surgery (P < .0001), including a significantly reduced SA increase in the subgroup at 2, 3, and 4 hours after intake of aspirin. Corresponding with a reduced effect of aspirin, neither Multiplate Analyzer arachidonic acid, nor VerifyNow Aspirin Test showed a significant reduction in platelet aggregation 1 hour after intake of aspirin at day 1 (P < .0001). This also accounted for the subgroup 2, 3, and 4 hours after aspirin intake on day 1. At day 2 the same pattern as preoperatively was detected. CONCLUSIONS: After CABG, the SA level and the effect of aspirin were reduced in the immediate postoperative period.

Results from more than 20 years of surgical pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension in Denmark.

OBJECTIVES: Chronic thromboembolic pulmonary hypertension is a fatal disease if left untreated, and pulmonary endarterectomy (PEA) is the potentially curable treatment of choice. We aimed to estimate the current in-hospital mortality rate, complication rate and long-term survival for patients with chronic thromboembolic pulmonary hypertension undergoing PEA in Denmark. METHODS: All chronic thromboembolic pulmonary hypertension patients who underwent PEA in the period 1994 till 2016 were consecutively enrolled in our single-centre study. All patients were followed from PEA until death or end of study. Kaplan-Meier survival analysis was used to estimate the 3-, 5- and 10-year survival rates with 95% confidence interval (CI). RESULTS: In total, 239 patients were operated in the study period. A significant reduction in mean pulmonary arterial pressure from 48 mmHg to 33 mmHg, and pulmonary vascular resistance from 800 dynes s cm-5 to 289 dynes s cm-5, was observed during the first postoperative day after PEA. Overall, in-hospital mortality rate was 8.4%. A significantly lower mortality rate in the late decade (2005-2016) compared with the early decade (1994-2004) was observed (4.3% vs 22.6%, P < 0.001). In-hospital mortality during the last 5 years (n = 80) was 2.5%. Three-, 5- and 10-year survival rates were 84% (CI: 77.8-88), 77% (CI: 70.7-82.7) and 62% (CI: 53-69.1), respectively. The majority of patients improved in World Health Organization functional class from III/IV to I/II and significantly increased their 6-min walking distance. CONCLUSIONS: PEA in Denmark is associated with a low in-hospital mortality rate and significant improvements in both haemodynamics and exercise capacity. Long-term survival is excellent and similar to high-volume international centres.

Is single-dose prophylactic gentamicin associated with acute kidney injury in patients undergoing cardiac surgery? A matched-pair analysis.

OBJECTIVE: Although aminoglycoside treatment has been associated with nephrotoxic effects, single-dose gentamicin has been considered safe in surgery. However, the effect of a single-dose prophylactic aminoglycoside on the risk of acute kidney injury among patients undergoing cardiac surgery remains uncertain. METHODS: A population-based cohort study with matched-pair analysis of 2892 consecutive patients undergoing cardiac surgery at Aarhus University Hospital, Denmark, was performed. Two different prophylactic antibiotic regimens were used during the study period. The patients exposed to a single dose of prophylactic gentamicin were compared with those had not received gentamicin. Statistical analysis for matched data was performed. The data were retrieved from the Western Denmark Heart Registry. RESULTS: Matching resulted in 668 patient pairs. Patients receiving gentamicin had higher maximum serum creatinine during the first postoperative 72 hours (median, 96 vs 90 mmol/L; P=.0002). Also, a greater fraction of patients receiving gentamicin developed acute kidney injury according to the Acute Kidney Injury Network criteria (22% vs 17%; P=.02). The hospital length of stay was shorter in the control group (5.0 vs 5.6 days; P<.0001). No difference was found in the incidence of patients requiring postoperative dialysis, 30-day and 1-year mortality, or the incidence of sternal infection between the 2 groups. CONCLUSIONS: A single-dose prophylactic aminoglycoside in adult cardiac surgery patients was associated with an increased risk of acute kidney injury but not with a greater frequency of postoperative dialysis or mortality. No differences in the incidence of sternal infections between groups were observed.

Perioperative aminoglycoside treatment is associated with a higher incidence of postoperative dialysis in adult cardiac surgery patients.

BACKGROUND: Aminoglycoside treatment has been associated with nephrotoxic effects. However, the effect of perioperative aminoglycoside treatment on the risk of acute kidney injury requiring dialysis among patients undergoing cardiac surgery remains uncertain. METHODS: We performed a register study based on prospectively collected data from population-based health care databases of 3625 consecutive patients undergoing cardiac surgery at the Aarhus University Hospital, Skejby, Denmark. Patients requiring preoperative dialysis were excluded, leaving a total of 3587 patients (99% of original patient cohort), of whom 89 received perioperative aminoglycosides. RESULTS: The cumulative risk of in-hospital dialysis-dependent acute kidney injury was 3.2% (n = 115). Perioperative use of aminoglycosides was associated with an increased risk of postoperative dialysis (adjusted odds ratio [OR], 4.41; 95% confidence interval [CI], 1.83-10.59). Other predictors included reoperation because of bleeding (adjusted OR, 2.80; 95% CI, 1.63-4.80), use of inotropic support during anesthesia (adjusted OR, 2.10; 95% confidence interval, 1.49-2.95), and cardiopulmonary bypass lasting longer than 120 minutes (adjusted OR, 1.95; 95% CI, 1.19-3.20) along with EuroSCORE variables. Postoperative dialysis was associated with higher 30-day mortality (10.9% vs 2.5%, P < .0001, χ(2) test), but use of aminoglycosides was not independently associated with mortality. CONCLUSIONS: Perioperative use of aminoglycosides in adults undergoing cardiac surgery was associated with increased risk of postoperative dialysis.