The importance of liver function assessment before cardiac surgery: A narrative review.

The demand for cardiac surgery procedures is increasing globally. Thanks to an improvement in survival driven by medical advances, patients with liver disease undergo cardiac surgery more often. Liver disease is associated with the development of heart failure, especially in patients with advanced cirrhosis. Cardiovascular risk factors can also contribute to the development of both cardiomyopathy and liver disease and heart failure itself can worsen liver function. Despite the risk that liver disease and cirrhosis represent for the perioperative management of patients who undergo cardiac surgery, liver function is often not included in common risk scores for preoperative evaluation. These patients have worse short and long-term survival when compared with other cardiac surgery populations. Preoperative evaluation of liver function, postoperative management and close postoperative follow-up are crucial for avoiding complications and improving results. In the present narrative review, we discuss the pathophysiological components related with postoperative complications and mortality in patients with liver disease who undergo cardiac surgery and provide recommendations for the perioperative management.

Evaluation of Nutritional Practices in the Critical Care patient (The ENPIC study): Does nutrition really affect ICU mortality?

BACKGROUND & AIMS: The importance of artificial nutritional therapy is underrecognized, typically being considered an adjunctive rather than a primary therapy. We aimed to evaluate the influence of nutritional therapy on mortality in critically ill patients. METHODS: This multicenter prospective observational study included adult patients needing artificial nutritional therapy for >48 h if they stayed in one of 38 participating intensive care units for ≥72 h between April and July 2018. Demographic data, comorbidities, diagnoses, nutritional status and therapy (type and details for ≤14 days), and outcomes were registered in a database. Confounders such as disease severity, patient type (e.g., medical, surgical or trauma), and type and duration of nutritional therapy were also included in a multivariate analysis, and hazard ratios (HRs) and 95% confidence intervals (95%CIs) were reported. RESULTS: We included 639 patients among whom 448 (70.1%) and 191 (29.9%) received enteral and parenteral nutrition, respectively. Mortality was 25.6%, with non-survivors having the following characteristics: older age; more comorbidities; higher Sequential Organ Failure Assessment (SOFA) scores (6.6 ± 3.3 vs 8.4 ± 3.7; P < 0.001); greater nutritional risk (Nutrition Risk in the Critically Ill [NUTRIC] score: 3.8 ± 2.1 vs 5.2 ± 1.7; P < 0.001); more vasopressor requirements (70.4% vs 83.5%; P=0.001); and more renal replacement therapy (12.2% vs 23.2%; P=0.001). Multivariate analysis showed that older age (HR: 1.023; 95% CI: 1.008-1.038; P=0.003), higher SOFA score (HR: 1.096; 95% CI: 1.036-1.160; P=0.001), higher NUTRIC score (HR: 1.136; 95% CI: 1.025-1.259; P=0.015), requiring parenteral nutrition after starting enteral nutrition (HR: 2.368; 95% CI: 1.168-4.798; P=0.017), and a higher mean Kcal/Kg/day intake (HR: 1.057; 95% CI: 1.015-1.101; P=0.008) were associated with mortality. By contrast, a higher mean protein intake protected against mortality (HR: 0.507; 95% CI: 0.263-0.977; P=0.042). CONCLUSIONS: Old age, higher organ failure scores, and greater nutritional risk appear to be associated with higher mortality. Patients who need parenteral nutrition after starting enteral nutrition may represent a high-risk subgroup for mortality due to illness severity and problems receiving appropriate nutritional therapy. Mean calorie and protein delivery also appeared to influence outcomes. TRIAL REGISTRATION: ClinicaTrials.gov NCT: 03634943.

Biomaker evaluation for major adverse cardiovascular event development in patients undergoing cardiac Surgery.

Objectives: The postoperative period of cardiac surgery (CS) is associated with the development of major adverse cardiovascular events (MACEs). However, the evaluation of MACE after CS by means of biomarkers is poorly developed. We aimed to evaluate postoperative biomarkers that could be associated with MACE. Methods: Two Hundred and ten patients who underwent CS were enrolled during the study period. The diagnosis of MACE was defined as the presence of at least one of the following complications: acute myocardial infarction, heart failure, stroke presented during intensive care unit (ICU) stay, and 30-day mortality after CS. High-sensitive troponin T (hs-TnT), C-reactive protein, procalcitonin, interleukin-6, and immature platelet fraction (IPF) were measured on ICU admission and after 24 h. The difference between both measurements (Δ) was calculated to assess their association with MACE. Early infected patients (n=13) after CS were excluded from final analysis. Results: The most frequent surgery was single-valve surgery (n=83; 38%), followed by coronary artery bypass graft (n=72; 34%). Postoperative MACE was diagnosed in 31 (14.8%) patients. Biomarker dynamics showed elevated values at 24 h compared with those at ICU admission in patients with MACE versus no-MACE. Multivariate analysis showed that ΔIPF (OR: 1.47; 95% CI: 1.110-1.960; p=0.008) and Δhs-TnT (OR: 1.001; 95% CI: 1.0002-1.001; p=0.008) were independently associated with MACE. Conclusions: These findings suggest that postoperative ΔIPF and Δhs-TnT may be useful biomarkers for the identification of patients at risk of MACE development.

Reference interval for immature platelet fraction on Sysmex XN haematology analyser in adult population.

INTRODUCTION: The Sysmex XN-series haematology analyser has newly adopted a fluorescent channel to measure immature platelet fraction (IPF). To promote the clinical utility of this promising parameter, establishing a reliable reference interval is mandatory. According to previous studies, IPF values may be affected by the employed analyser and the ethnic background of the individual, but no differences seem to be found between individuals' genders. Therefore, this study aimed to define the reference interval for IPF in a Spanish population following Clinical and Laboratory Standard Institute (CLSI) guidelines. MATERIALS AND METHODS: A total of 153 healthy Caucasian adults from Spain met the inclusion criteria. IPF measurement was performed by means of a Sysmex XN-2000 haematology analyser. A non-parametric percentile method was used to calculate the reference intervals in accordance with CLSI guidelines. RESULTS: The obtained reference interval for IPF on the Sysmex XN-2000 was 1.6-9.6% (90% confidence intervals (CIs) were 1.5-1.8 and 9.3-11.5, respectively). No significant gender difference in IPF reference intervals was observed (P = 0.101). CONCLUSIONS: This study provides, for the first time, a reference interval for IPF using a Sysmex XN-2000 in a Spanish population, ranging from 1.6 to 9.6%. These data are needed to evaluate platelet production in several conditions such as thrombocytopenia, inflammatory states and cardiovascular diseases, as well as for future research.

Factors Associated with the Development of Tertiary Peritonitis in Critically Ill Patients.

BACKGROUND: Critically ill surgical patients remain at a high risk of adverse outcomes as a result of secondary peritonitis (SP). The risk is even higher if tertiary peritonitis (TP) develops. Factors related to the development of TP, however, are scarce in the literature. The main aim of our study was to identify factors associated with the development of TP in patients with SP in the intensive care unit (ICU), and also to report differences in microbiologic patterns and antibiotic therapy in patients with the two conditions. PATIENTS AND METHODS: A prospective, observational study was conducted at our institution from 2010 to 2014. Baseline characteristics on admission, outcomes, microbiologic results, and antibiotic therapy were recorded for analysis. RESULTS: We included 343 patients with SP, of whom TP developed in 185 (53.9%). Almost two-thirds (64.4%) were male; mean age was 63.7 ± 14.3 years, and mean APACHE was 19.4 ± 7.8. In-hospital death was 42.6% (146). Multivariable analysis showed that longer ICU stay (odds ratio [OR]: 1.019; 95% confidence interval [CI]: 1.004-1.034; p = 0.010), urgent operation on hospital admission (OR: 3.247; 95% CI: 1.392-7.575; p = 0.006), total parenteral nutrition (TPN) (OR: 3.079; 95% CI: 1.535-6.177; p = 0.002) and stomach-duodenum as primary infection site (OR: 4.818; 95% CI: 1.429-16.247; p = 0.011) were factors associated with the development of TP, whereas patients with localized peritonitis were less prone to have TP develop (OR: 0.308; 95% CI: 0.152-0.624; p = 0.001). Higher incidences of Candida spp. (OR: 1.275; 95% CI: 1.096-1.789; p = 0.016), Enterococcus faecium (OR: 1.085; 95% CI: 1.018-1.400; p = 0.002), and Enterococcus spp. (OR: 1.370; 95% CI: 1.139-1.989; p = 0.047) were found in TP, and higher rates of cephalosporin use in SP (OR: 3.51; 95% CI: 1.139-10.817; p = 0.035). CONCLUSIONS: Complicated peritonitis remains a cause of a high numbers of deaths in the ICU. The need for TPN, urgent operation on hospital admission, and particularly surgical procedures in the proximal gastrointestinal tract were factors associated with development of TP and may potentially help to identify patients with SP at risk for development of TP. Physicians should be aware concerning multi-drug-resistant germs when treating these patients.

Five-year mortality in cardiac surgery patients with low cardiac output syndrome treated with levosimendan: prognostic evaluation of NT-proBNP and C-reactive protein.

BACKGROUND: To determine the clinical risk factors predictive of the 5-year mortality in patients with low cardiac output syndrome (LCOS) after cardiac surgery. In addition, to assess the influence of inflammation and myocardial dysfunction severity, as measured by C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, on outcome. METHODS: We studied 30 patients who underwent cardiac surgery and developed postoperative LCOS requiring inotropic support for longer than 48 hours after intensive care unit (ICU) admission. All patients received a 24-hour infusion of levosimendan after study enrolment. We measured the following at baseline, 24 h, 48 h and 7 days: clinical data, serum NT-proBNP and serum CRP levels. Patients were followed-up at 5 years for death by any cause. A risk-adjusted Cox proportional hazards regression model was used for statistical analysis. Hazard ratios and their 95% confidence intervals (CI) are presented. RESULTS: The 5-year mortality was 36.6% (n.=11). The predictors of 5-year mortality were the presence of dilated cardiomyopathy (HR=36.909; 95% CI: 1.901-716.747; P=0.017), a higher central venous pressure (CVP) at 48 hours (HR=2.686; 95% CI: 1.383-5.214; P=0.004), and lower CRP levels on day 7 (HR=0.963; 95% CI: 0.933-0.994; P=0.021). NT-proBNP levels showed a trend to higher initial levels in survivors without statistical significance, but were not associated with 5-year mortality. CONCLUSIONS: The presence of dilated cardiomyopathy, elevated CVP at 48 h and reduced CRP levels on day 7 predicted 5-year mortality in patients who developed postoperative LCOS after cardiac surgery. NT-proBNP levels in the first postoperative week were not predictors of long-term outcomes.

Outcomes of abdominal surgery in patients with liver cirrhosis.

Patients suffering from liver cirrhosis (LC) frequently require non-hepatic abdominal surgery, even before liver transplantation. LC is an important risk factor itself for surgery, due to the higher than average associated morbidity and mortality. This high surgical risk occurs because of the pathophysiology of liver disease itself and to the presence of contributing factors, such as coagulopathy, poor nutritional status, adaptive immune dysfunction, cirrhotic cardiomyopathy, and renal and pulmonary dysfunction, which all lead to poor outcomes. Careful evaluation of these factors and the degree of liver disease can help to reduce the development of complications both during and after abdominal surgery. In the emergency setting, with the presence of decompensated LC, alcoholic hepatitis, severe/advanced LC, and significant extrahepatic organ dysfunction conservative management is preferred. A multidisciplinary, individualized, and specialized approach can improve outcomes; preoperative optimization after risk stratification and careful management are mandatory before surgery. Laparoscopic techniques can also improve outcomes. We review the impact of LC on surgical outcome in non-hepatic abdominal surgeries required in this cirrhotic population before, during, and after surgery.

Evaluation of Serial Arterial Lactate Levels as a Predictor of Hospital and Long-Term Mortality in Patients After Cardiac Surgery.

OBJECTIVES: Although hyperlactatemia is common after cardiac surgery, its value as a prognostic marker is unclear. The aim of the present study was to determine whether postoperative serial arterial lactate (AL) measurements after cardiac surgery could predict outcome. DESIGN: Prospective, observational study. SETTING: Surgical intensive care unit in a tertiary-level university hospital. PARTICIPANTS: Participants included 2,935 consecutive patients. INTERVENTIONS: AL was measured on admission to the intensive care unit and 6, 12, and 24 hours after surgery, and evaluated together with clinical data and outcomes including in-hospital and long-term mortality. MEASUREMENTS AND MAIN RESULTS: In-hospital and long-term mortality (mean follow-up 6.3±1.7 years) were 5.9% and 8.7%, respectively. Compared with survivors, nonsurvivors showed higher mean AL values in all measurements (p<0.001). Hyperlactatemia (AL>3.0 mmol/L) was a predictor for in-hospital mortality (odds ratio = 1.468; 95% confidence interval = 1.239-1.739; p<0.001) and long-term mortality (hazard ratio = 1.511; 95% confidence interval = 1.251-1.825; p<0.001). Recent myocardial infarction and longer cardiopulmonary bypass time were predictors of hyperlactatemia. The pattern of AL dynamics was similar in both groups, but nonsurvivors showed higher AL values, as confirmed by repeated measures analysis of variance (p<0.001). The area under the curve also showed higher levels of AL in nonsurvivors (80.9±68.2 v 49.71±25.8 mmol/L/h; p = 0.038). Patients with hyperlactatemia were divided according to their timing of peak AL, with higher mortality and worse survival in patients in whom AL peaked at 24 hours compared with other groups (79.1% v 86.7%-89.2%; p = 0.03). CONCLUSIONS: The dynamics of the postoperative AL curve in patients undergoing cardiac surgery suggests a similar mechanism of hyperlactatemia in survivors and nonsurvivors, albeit with a higher production or lower clearance of AL in nonsurvivors. The presence of a peak of hyperlactatemia at 24 hours is associated with higher in-hospital and long-term mortality.

Surgical site infection in critically ill patients with secondary and tertiary peritonitis: epidemiology, microbiology and influence in outcomes.

BACKGROUND: Surgical site infection (SSI) remains a significant problem in the postoperative period that can negatively affect clinical outcomes. Microbiology findings are typically similar to other nosocomial infections, with differences dependent on microbiology selection due to antibiotic pressure or the resident flora. However, this is poorly understood in the critical care setting. We therefore aimed to assess the incidence, epidemiology and microbiology of SSI and its association with outcomes in patients with severe peritonitis in the intensive care unit (ICU). METHODS: We prospectively studied 305 consecutive patients admitted to our surgical ICU from 2010 to 2014 with a diagnosis of secondary or tertiary peritonitis. We collected the following data: SSI diagnosis, demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II score, type of surgery, microbiology, antibiotic treatment and outcomes. Microbiological sampling was done by means of swabs. RESULTS: We identified 269 episodes of SSI in 162 patients (53.1%) aged 64.4 ± 14.3 years, of which 200 episodes occurred in men (64.6%). The mean APACHE II and SAPS II scores were 19.7 ± 7.8 and 36.5 ± 16.1 respectively. The mean ICU and hospital stays were 19.8 ± 24.8 and 21.7 ± 30 days respectively. Pseudomonas spp. (n = 52, 19.3%), Escherichia coli (n = 55, 20.4%) and Candida spp. (n = 46, 17.1%) were the most frequently isolated microorganisms, but gram-positive cocci (n = 80, 29.7%) were also frequent. Microorganisms isolated from SSIs were associated with a higher incidence of antibiotic resistance (64.9%) in ICU patients, but not with higher in-hospital mortality. However, patients who suffered from SSI had longer ICU admissions (odds ratio = 1.024, 95% confidence interval 1.010-1.039, P = 0.001). CONCLUSIONS: The incidence of SSI in secondary or tertiary peritonitis requiring ICU admission is very high. Physicians may consider antibiotic-resistant pathogens, gram-positive cocci and fungi when choosing empiric antibiotic treatment for SSI, although more studies are needed to confirm our results due to the inherent limitations of the microbiological sampling with swabs performed in our research. The presence of SSI may be associated with prolonged ICU stays, but without any influence on overall mortality.

The inflammatory response in cardiac surgery: an overview of the pathophysiology and clinical implications.

During cardiac surgery different factors, such as the aortic clamp, the extracorporeal circulation and the surgical injury itself, produce complex inflammatory responses which can lead to varying degrees of ischemia-reperfusion injury and/or systemic inflammatory response. This may have clinical implications due to hemodynamic changes related with an enlarged vasodilatory response. Thus, maintaining adequate levels of blood pressure during and after cardiac surgery represents a challenge for physicians when inflammatory response appears. The use of noradrenaline to raise arterial pressure is the most current pharmacological approach in the operating room and ICU. However, it is not always effective and other drugs, such as methylene blue, have to be used among others in specific cases as rescue therapy. The aim of our research is to review briefly the pathophysiology and clinical implications in the treatment of the inflammatory response in cardiac surgery, together with the mechanisms involved in those treatments.

Influence of cirrhosis in cardiac surgery outcomes.

Liver cirrhosis has evolved an important risk factor for cardiac surgery due to the higher morbidity and mortality that these patients may suffer compared with general cardiac surgery population. The presence of contributing factors for a poor outcome, such as coagulopathy, a poor nutritional status, an adaptive immune dysfunction, a degree of cirrhotic cardiomyopathy, and a degree of renal and pulmonary dysfunction, have to be taken into account for surgical evaluation when cardiac surgery is needed, together with the degree of liver disease and its primary complications. The associated pathophysiological characteristics that liver cirrhosis represents have a great influence in the development of complications during cardiac surgery and the postoperative course. Despite the population of cirrhotic patients who are referred for cardiac surgery is small and recommendations come from small series, since liver cirrhotic patients have increased their chance of survival in the last 20 years due to the advances in their medical care, which includes liver transplantation, they have been increasingly considered for cardiac surgery. Indeed, there is an expected rise of cirrhotic patients within the cardiac surgical population due to the increasing rates of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, especially in western countries. In consequence, a more specific approach is needed in the assessment of care of these patients if we want to improve their management. In this article, we review the pathophysiology and outcome prediction of cirrhotic patients who underwent cardiac surgery.

Evaluation of the PaO2/FiO2 ratio after cardiac surgery as a predictor of outcome during hospital stay.

BACKGROUND: The arterial partial pressure of O2 and the fraction of inspired oxygen (PaO2/FiO2) ratio is widely used in ICUs as an indicator of oxygenation status. Although cardiac surgery and ICU scores can predict mortality, during the first hours after cardiac surgery few instruments are available to assess outcome. The aim of this study was to evaluate the usefulness of PaO2/FIO2 ratio to predict mortality in patients immediately after cardiac surgery. METHODS: We prospectively studied 2725 consecutive cardiac surgery patients between 2004 and 2009. PaO2/FiO2 ratio was measured on admission and at 3 h, 6 h, 12 h and 24 h after ICU admission, together with clinical data and outcomes. RESULTS: All PaO2/FIO2 ratio measurements differed between survivors and non-survivors (p < 0.001). The PaO2/FIO2 at 3 h after ICU admission was the best predictor of mortality based on area under the curve (p < 0.001) and the optimum threshold estimation gave an optimal cut-off of 222 (95% Confidence interval (CI): 202-242), yielding three groups of patients: Group 1, with PaO2/FIO2 > 242; Group 2, with PaO2/FIO2 from 202 to 242; and Group 3, with PaO2/FIO2 < 202. Group 3 showed higher in-ICU mortality and ICU length of stay and Groups 2 and 3 also showed higher respiratory complication rates. The presence of a PaO2/FIO2 ratio < 202 at 3 h after admission was shown to be a predictor of in-ICU mortality (OR:1.364; 95% CI:1.212-1.625, p < 0.001) and of worse long-term survival (88.8% vs. 95.8%; Log rank p = 0.002. Adjusted Hazard ratio: 1.48; 95% CI:1.293-1.786; p = 0.004). CONCLUSIONS: A simple determination of PaO2/FIO2 at 3 h after ICU admission may be useful to identify patients at risk immediately after cardiac surgery.

Influence of acute kidney injury on short- and long-term outcomes in patients undergoing cardiac surgery: risk factors and prognostic value of a modified RIFLE classification.

INTRODUCTION: The development of acute kidney injury (AKI) is associated with poor outcome. The modified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification for AKI, which classifies patients with renal replacement therapy needs according to RIFLE failure class, improves the predictive value of AKI in patients undergoing cardiac surgery. Our aim was to assess risk factors for post-operative AKI and the impact of renal function on short- and long-term survival among all AKI subgroups using the modified RIFLE classification. METHODS: We prospectively studied 2,940 consecutive cardiosurgical patients between January 2004 and July 2009. AKI was defined according to the modified RIFLE system. Pre-operative, operative and post-operative variables usually measured on and during admission, which included main outcomes, were recorded together with cardiac surgery scores and ICU scores. These data were evaluated for association with AKI and staging in the different RIFLE groups by means of multivariable analyses. Survival was analyzed via Kaplan-Meier and a risk-adjusted Cox proportional hazards regression model. A complete follow-up (mean 6.9 ± 4.3 years) was performed in 2,840 patients up to April 2013. RESULTS: Of those patients studied, 14% (n = 409) were diagnosed with AKI. We identified one intra-operative (higher cardiopulmonary bypass time) and two post-operative (a longer need for vasoactive drugs and higher arterial lactate 24 hours after admission) predictors of AKI. The worst outcomes, including in-hospital mortality, were associated with the worst RIFLE class. Kaplan-Meier analysis showed survival of 74.9% in the RIFLE risk group, 42.9% in the RIFLE injury group and 22.3% in the RIFLE failure group (P <0.001). Classification at RIFLE injury (Hazard ratio (HR) = 2.347, 95% confidence interval (CI) 1.122 to 4.907, P = 0.023) and RIFLE failure (HR = 3.093, 95% CI 1.460 to 6.550, P = 0.003) were independent predictors for long-term patient mortality. CONCLUSIONS: AKI development after cardiac surgery is associated mainly with post-operative variables, which ultimately could lead to a worst RIFLE class. Staging at the RIFLE injury and RIFLE failure class is associated with higher short- and long-term mortality in our population.