Cohort Of Cardiac Surgery Patients Research Articles

A Pilot Study of Renin-Guided Angiotensin-II Infusion to Reduce Kidney Stress After Cardiac Surgery.

Vasoplegia is common after cardiac surgery, is associated with hyperreninemia, and can lead to acute kidney stress. We aimed to conduct a pilot study to test the hypothesis that, in vasoplegic cardiac surgery patients, angiotensin-II (AT-II) may not increase kidney stress (measured by [TIMP-2]*[IGFBP7]). We randomly assigned patients with vasoplegia (cardiac index [CI] > 2.1l/min, postoperative hypotension requiring vasopressors) and Δ-renin (4-hour postoperative-preoperative value) ≥3.7 µU/mL, to AT-II or placebo targeting a mean arterial pressure ≥65 mm Hg for 12 hours. The primary end point was the incidence of kidney stress defined as the difference between baseline and 12 hours [TIMP-2]*[IGFBP7] levels. Secondary end points included serious adverse events (SAEs). We randomized 64 patients. With 1 being excluded, 31 patients received AT-II, and 32 received placebo. No significant difference was observed between AT-II and placebo groups for kidney stress (Δ-[TIMP-2]*[IGFBP7] 0.06 [ng/mL] 2 /1000 [Q1-Q3, -0.24 to 0.28] vs -0.08 [ng/mL] 2 /1000 [Q1-Q3, -0.35 to 0.14]; P = .19; Hodges-Lehmann estimation of the location shift of 0.12 [ng/mL] 2 /1000 [95% confidence interval, CI, -0.1 to 0.36]). AT-II patients received less fluid during treatment than placebo patients (2946 vs 3341 mL, P = .03), and required lower doses of norepinephrine equivalent (0.19 mg vs 4.18mg, P < .001). SAEs were reported in 38.7% of patients in the AT-II group and in 46.9% of patients in the placebo group. The infusion of AT-II for 12 hours appears feasible and did not lead to an increase in kidney stress in a high-risk cohort of cardiac surgery patients. These findings support the cautious continued investigation of AT-II as a vasopressor in hyperreninemic cardiac surgery patients.

Agitation during anaesthetic emergence: An observational study of adult cardiac surgery patients in two Australian intensive care units

BackgroundAnaesthetic emergence agitation among adult patients being recovered after open cardiac and/or thoracic aorta surgery has not been described. ObjectivesThe objective of this study was to characterise emergence agitation in terms of incidence, clinical features, and consequences in a cohort of cardiac surgery patients being recovered in the intensive care unit (ICU). MethodsA prospective, observational pilot study was implemented.Over a 5-week period, the study was conducted in two metropolitan hospitals in Victoria, Australia.The cohort comprised all patients admitted to the ICUs aged ≥18 years, who had undergone cardiac surgery via an open sternotomy with general anaesthetic, and whose emergence was directly observed.Emergence agitation was defined as a Richmond Agitation and Sedation Scale score of ≥+2. ResultsFifty patients were observed. Emergence agitation occurred in 24/50 (48%) of patients. Patients with emergence agitation experienced more clinical consequences than patients with calm emergence, including a significantly greater number of episodes of airway compromise (12/24, 50%, p < 0.001); ventilator dyssynchrony (23/24, 96%, p = 0.004); and hypertension (13/24, 54%, p = 0.004). Significant treatment interference (potentially dangerous patient movements such as pulling tubes) occurred with 23/24 patients (96%, p < 0.0001). Patients who underwent emergence agitation required significantly more interventions during anaesthetic emergence than patients who underwent a calm emergence. Interventions included extra nursing measures (16/24, 67%, p = 0.001) administration of sedative and/or opioid intravenous boluses (22/24, 92%, p = 0.001) and vasoactive agents (15/24, 63%, p = 0.05). ConclusionsIn patients recovering from cardiac surgery in the ICU, emergence agitation was clinically important. Immediate interventions were required to prevent and manage complications.

Molecular mechanisms of postoperative atrial fibrillation in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) promotes atrial remodeling and fibrosis, providing a substrate for atrial fibrillation (AF). Herein, we investigate the pathophysiological mechanisms of AF in association with OSA in a cohort of cardiac surgery patients. A prospective study including patients undergoing cardiac surgery. Biomarkers reflective of AF pathophysiology (interleukin [IL-6], C-reactive protein [CRP], von Willebrand factor [vWF], N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity Troponin T [hs-TnT], and Galectin-3 [Gal-3]) was assessed by functional or immunological assays. miRNAs involved in AF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Using atrial tissue samples, fibrosis was assessed by Masson's trichrome. Connexin 40 and 43 (Cx40; Cx43) were evaluated by immunolabeling. Fifty-six patients (15 with OSA and 41 non-OSA) were included in this hypothesis-generating pilot study. OSA group had a higher incidence of postoperative AF (POAF) (46.7% vs. 19.5%; p = .042), presented an increased risk of POAF (OR 3.61, 95% CI 1.01-12.92), and had significantly higher baseline levels of NT-proBNP (p = .044), vWF (p = .049), Gal-3 (p = .009), IL-6 (p = .002), and CRP (p = .003). This group presented lower levels of miR-21 and miR-208 (both p < .05). Also, lower Cx40 levels in POAF and/or OSA patients (50.0% vs. 81.8%, p = .033) were found. The presence of interstitial fibrosis (according to myocardial collagen by Masson's trichrome) was raised in OSA patients (86.7% vs. 53.7%, p = .024). Several biomarkers and miRNAs involved in inflammation and fibrosis were dysregulated in OSA patients, which together with a higher degree of interstitial fibrosis, altered miRNA, and Cxs expression predisposes to the development of a substrate that increases the AF risk.

Association of Intraoperative Red Blood Cell Transfusions With Venous Thromboembolism and Adverse Outcomes After Cardiac Surgery.

We determined whether intraoperative packed red blood cell (PRBC) transfusion was associated with a higher incidence of hospital-acquired venous thromboembolic (HA-VTE) complications and adverse outcomes after isolated coronary artery bypass grafting (CABG) surgery. Intraoperative PRBC has been associated with increased risk for postoperative deep venous thrombosis after cardiac surgery, but validation of these findings in a large, multi-institutional, national cohort of cardiac surgery patients has been lacking. A registry-based cohort study of 751,893 patients with isolated CABG between January 1, 2015, to December 31, 2019. Using propensity score-weighted regression analysis, we analyzed the effect of intraoperative PRBC on the incidence of HA-VTE and adverse outcomes. Administration of 1, 2, 3, and ≥4 units of PRBC transfusion was associated with increased odds for HA-VTE [odds ratios (ORs): 1.27 (1.22-1.32), 1.21 (1.16-1.26), 1.93 (1.85-2.00), 1.82 (1.75-1.89)], deep venous thrombosis [ORs: 1.39 (1.33-1.46), 1.38 (1.32-1.44), 2.18 (2.09-2.28), 1.82 (1.74-1.91], operative mortality [ORs: 1.11 (1.08-1.14), 1.16 (1.13-1.19), 1.29 (1.26-1.32), 1.47 (1.43-1.50)], readmission within 30 days [ORs: 1.05 (1.04-1.06), 1.16 (1.13-1.19), 1.29 (1.26-1.32), 1.47 (1.43-1.50)], and a prolonged postoperative length of stay [mean difference in days, 0.23 (0.19-0.27), 0.34 (0.30-0.39), 0.69 (0.64-0.74), 0.77 (0.72-0.820]. The odds of pulmonary venous thromboembolism were lower for patients transfused with 1 or 2 units [ORs: 0.98 (0.91-1.06), 0.75 (0.68-0.81)] of PRBC but remained significantly elevated for those receiving 3 and ≥4 units [ORs: 1.19 (1.09-1.29), 1.35 (1.25-1.48)]. Intraoperative PRBC transfusion was associated with HA-VTE and adverse outcomes after isolated CABG surgery.

Incidence and 1-year outcome of periprocedural myocardial infarction following cardiac surgery: are the Universal Definition and Society for Cardiovascular Angiography and Intervention criteria fit for purpose?

The diagnosis and clinical implications of periprocedural myocardial infarction (PPMI) following coronary artery bypass grafting (CABG) are contentious, especially the importance of PPMI in the interpretation of trial data. Consecutive patients admitted to a cardiothoracic critical care unit over a 6-month period following open cardiac surgery had high-sensitivity cardiac troponin I assay performed on admission and every day for 48 h, regardless of whether there was a request by the supervising clinical team. Patients were categorized as PPMI using both the Universal Definition of Myocardial Infarction (UDMI) and Society of Cardiovascular Angiography and Interventions (SCAI) criteria. Multivariable Cox regression analysis was performed to assess whether any relationships between PPMI diagnoses and 1-year mortality were independent. There were 2 groups of consecutive patients: (i) after CABG (n = 245) and (ii) after non-CABG surgery (n = 243). Of the CABG patients, 20.4% met criteria for UDMI PPMI and 87.6% for SCAI PPMI. The diagnosis of UDMI PPMI was independently associated with 1-year mortality on multivariable Cox regression analysis [hazard ratio 4.16 (95% confidence interval 1.28-13.49)]. Of 243 patients who had non-CABG cardiac surgery, 11.4% met criteria for UDMI PPMI and 85.2% for SCAI PPMI but neither were associated with 1-year mortality. The incidence of SCAI PPMI in a real-world cohort of cardiac surgery patients is so high as to be of limited clinical value. In contrast, a diagnosis of UDMI PPMI post-CABG is independently associated with 1-year mortality, so may have clinical (and research) utility.

Incidence and one year outcome of periprocedural myocardial infarction following cardiac surgery: are the universal definition and SCAI criteria fit for purpose?

Abstract Introduction The diagnosis and clinical implication of periprocedural myocardial infarction (PPMI) following coronary artery bypass grafting (CABG) is contentious, especially given its importance in the interpretation of trial data. Two accepted definitions of PPMI yield discrepant results. Little is known about the association between the diagnosis of PPMI, using high sensitivity troponin (hs-cTn), and medium term mortality in patients who undergo CABG, either alone or in conjunction with another procedure. In addition, there are currently no criteria for the diagnosis of PPMI following non-CABG surgery. Method Consecutive patients admitted to a cardiothoracic critical care unit (CCCU) over a six month period following open cardiac surgery had hs-cTnI assay performed on admission and every day for forty-eight hours, regardless of whether there was a clinical indication. Patients were categorised as PPMI using both the Universal Definition of MI (UDMI) and Society of Cardiovascular Angiography and Interventions (SCAI) criteria. Comorbidity data, surgical details and clinical progress in CCCU were recorded. One year mortality data were obtained from NHS Digital. Results There were 245 CABG patients, of whom 20.4% met criteria for UDMI PPMI and 87.6% for SCAI UDMI (figure 1). The diagnosis of UDMI PPMI was independently associated with one year mortality (hazard ratio 4.175 (95% confidence interval 1.281 – 13.608)), whereas there was no association between SCAI PPMI and one year mortality (figure 2). Of the 243 patients who had non CABG cardiac surgery, 11.4% met criteria for UDMI PPMI and 85.2% for SCAI PPMI (figure1) but neither was associated with one year mortality. Conclusions The incidence of SCAI PPMI in a real world cohort of cardiac surgery patients is so high as to be of limited clinical value. By contrast, a diagnosis of UDMI PPMI post CABG is independently associated with one year mortality, so may have clinical utility. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Beckman Coulter - supplied the assays used in the study but had no role in the study Figure 1. Frequency of PPMIFigure 2. Kaplan Meier curves

DNA methylation patterns from peripheral blood separate coronary artery disease patients with and without heart failure.

AimsNatriuretic peptides are useful for diagnosis and prognostication of heart failure of any cause. Now, research aims to discover novel biomarkers that will more specifically define the heart failure phenotype. DNA methylation plays a critical role in the development of cardiovascular disease with the potential to predict fundamental pathogenic processes. There is a lack of data relating DNA methylation in heart failure that specifically focuses on patients with severe multi‐vessel coronary artery disease. To begin to address this, we conducted a pilot study uniquely exploring the utility of powerful whole‐genome methyl‐binding domain‐capture sequencing in a cohort of cardiac surgery patients, matched for the severity of their coronary artery disease, aiming to identify candidate peripheral blood DNA methylation markers of ischaemic cardiomyopathy and heart failure.Methods and resultsWe recruited a cohort of 20 male patients presenting for coronary artery bypass graft surgery with phenotypic extremes of heart failure but who otherwise share a similar coronary ischaemic burden, age, sex, and ethnicity. Methylation profiling in patient blood samples was performed using methyl‐binding domain‐capture sequencing. Differentially methylated regions were validated using targeted bisulfite sequencing. Gene set enrichment analysis was performed to identify differences in methylation at or near gene promoters in certain known Reactome pathways. We detected 567 188 methylation peaks of which our general linear model identified 68 significantly differentially methylated regions in heart failure with a false discovery rate <0.05. Of these regions, 48 occurred within gene bodies and 25 were located near enhancer elements, some within coding genes and some in non‐coding genes. Gene set enrichment analyses identified 103 significantly enriched gene sets (false discovery rate <0.05) in heart failure. Validation analysis of regions with the strongest differential methylation data was performed for two genes: HDAC9 and the uncharacterized miRNA gene MIR3675. Genes of particular interest as novel candidate markers of the heart failure phenotype with reduced methylation were HDAC9, JARID2, and GREM1 and with increased methylation PDSS2.ConclusionsWe demonstrate the utility of methyl‐binding domain‐capture sequencing to evaluate peripheral blood DNA methylation markers in a cohort of cardiac surgical patients with severe multi‐vessel coronary artery disease and phenotypic extremes of heart failure. The differential methylation status of specific coding genes identified are candidates for larger longitudinal studies. We have further demonstrated the value and feasibility of examining DNA methylation during the perioperative period to highlight biological pathways and processes contributing to complex phenotypes.

Mortality prediction by SOFA score in ICU-patients after cardiac surgery; comparison with traditional prognostic\u2013models

BackgroundThere are many prognostic models and scoring systems in use to predict mortality in ICU patients. The only general ICU scoring system developed and validated for patients after cardiac surgery is the APACHE-IV model. This is, however, a labor-intensive scoring system requiring a lot of data and could therefore be prone to error. The SOFA score on the other hand is a simpler system, has been widely used in ICUs and could be a good alternative.The goal of the study was to compare the SOFA score with the APACHE-IV and other ICU prediction models.MethodsWe investigated, in a large cohort of cardiac surgery patients admitted to Dutch ICUs, how well the SOFA score from the first 24 h after admission, predict hospital and ICU mortality in comparison with other recalibrated general ICU scoring systems. Measures of discrimination, accuracy, and calibration (area under the receiver operating characteristic curve (AUC), Brier score, R2, and Ĉ-statistic) were calculated using bootstrapping. The cohort consisted of 36,632 Patients from the Dutch National Intensive Care Evaluation (NICE) registry having had a cardiac surgery procedure for which ICU admission was necessary between January 1st, 2006 and June 31st, 2018.ResultsDiscrimination of the SOFA-, APACHE-IV-, APACHE-II-, SAPS-II-, MPM24-II - models to predict hospital mortality was good with an AUC of respectively: 0.809, 0.851, 0.830, 0.850, 0.801. Discrimination of the SOFA-, APACHE-IV-, APACHE-II-, SAPS-II-, MPM24-II - models to predict ICU mortality was slightly better with AUCs of respectively: 0.809, 0.906, 0.892, 0.919, 0.862. Calibration of the models was generally poor.ConclusionAlthough the SOFA score had a good discriminatory power for hospital- and ICU mortality the discriminatory power of the APACHE-IV and SAPS-II was better. The SOFA score should not be preferred as mortality prediction model above traditional prognostic ICU-models.

Case-mix affects calibration of cardiosurgical severity scores.

Prognostic models are often used to assess the quality of healthcare. Several scores were developed to predict mortality after cardiac surgery, but none has reached optimal performance in subsequent validations. We validate the most used scores (EUROSCORE I and II, STS, and ACEF) on a cohort of cardiac-surgery patients, assessing their robustness against case-mix changes. The scores were validated on 14,559 patients admitted to 16 Italian cardiosurgical ICUs participating to Margherita-Prosafe project in 2014 and 2015. Calibration was assessed through Hosmer-Lemeshow Test, standardized mortality ratio, and GiViTI calibration test and belt. Discrimination was measured by the area under the ROC curve. The study included 10,317 patients who were eligible to the calculation of the STS Score (4156 isolated valve, 4681 isolated CABG and 1480 single valve and CABG) which calibrated well in these subgroups. The ACEF Score and EUROSCORE I and II were available for 14,139, and 14,071 patients, respectively. EUROSCORE I significantly overestimated mortality; EUROSCORE II calibrated well overall, but underestimated mortality of patients undergoing complex surgery and non-elective ones. The ACEF Score calibrated poorly in elective and non-elective patients. Discrimination was acceptable for all models (AUC>0.70), but not for the ACEF Score. Cardiac surgery scores calibrate poorly when the case-mix of validation and development samples differs. To grant reliability for benchmarking, they should be validated in the clinical settings on which they are applied and updated periodically. Advanced statistical tools are essential for the correct interpretation and application of severity scores.

La tasa de filtrado glomerular estimada es un biomarcador precoz de la insuficiencia renal aguda asociada a la cirugía cardíaca

Backgroundand objective Acute kidney injury (AKI) diagnosis is still based on serum creatinine and diuresis. However, increases in creatinine are typically delayed 48h or longer after injury. Our aim was to determine the utility of routine postoperative renal function blood tests, to predict AKI one or 2days in advance in a cohort of cardiac surgery patients. Patients and methodsUsing a prospective database, we selected a sample of patients who had undergone major cardiac surgery between January 2002 and December 2013. The ability of the parameters to predict AKI was based on Acute Kidney Injury Network serum creatinine criteria. A cohort of 3,962 cases was divided into 2groups of similar size, one being exploratory and the other a validation sample. The exploratory group was used to show primary objectives and the validation group to confirm results. The ability to predict AKI of several kidney function parameters measured in routine postoperative blood tests, was measured with time-dependent ROC curves. The primary endpoint was time from measurement to AKI diagnosis. ResultsAKI developed in 610 (30.8%) and 623 (31.4%) patients in the exploratory and validation samples, respectively. Estimated glomerular filtration rate using the MDRD-4 equation showed the best AKI prediction capacity, with values for the AUC ROC curves between 0.700 and 0.946. We obtained different cut-off values for estimated glomerular filtration rate depending on the degree of AKI severity and on the time elapsed between surgery and parameter measurement. Results were confirmed in the validation sample. ConclusionsPostoperative estimated glomerular filtration rate using the MDRD-4 equation showed good ability to predict AKI following cardiac surgery one or 2days in advance.

Estimated glomerular filtration rate is an early biomarker of cardiac surgery-associated acute kidney injury

BackgroundAcute kidney injury (AKI) diagnosis is still based on serum creatinine and diuresis. However, increases in creatinine are typically delayed 48h or longer after injury. Our aim was to determine the utility of routine postoperative renal function blood tests, to predict AKI one or 2days in advance in a cohort of cardiac surgery patients. Patients and methodsUsing a prospective database, we selected a sample of patients who had undergone major cardiac surgery between January 2002 and December 2013. The ability of the parameters to predict AKI was based on Acute Kidney Injury Network serum creatinine criteria. A cohort of 3962 cases was divided into 2 groups of similar size, one being exploratory and the other a validation sample. The exploratory group was used to show primary objectives and the validation group to confirm results. The ability to predict AKI of several kidney function parameters measured in routine postoperative blood tests, was measured with time-dependent ROC curves. The primary endpoint was time from measurement to AKI diagnosis. ResultsAKI developed in 610 (30.8%) and 623 (31.4%) patients in the exploratory and validation samples, respectively. Estimated glomerular filtration rate using the MDRD-4 equation showed the best AKI prediction capacity, with values for the AUC ROC curves between 0.700 and 0.946. We obtained different cut-off values for estimated glomerular filtration rate depending on the degree of AKI severity and on the time elapsed between surgery and parameter measurement. Results were confirmed in the validation sample. ConclusionsPostoperative estimated glomerular filtration rate using the MDRD-4 equation showed good ability to predict AKI following cardiac surgery one or 2days in advance.

Right Ventricular Systolic Performance Determined by 2D Speckle-Tracking Echocardiography and Acute Kidney Injury After Cardiac Surgery

An association between central venous pressure and acute kidney injury (AKI) has been observed following cardiac surgery, but it is unknown whether this reflects intravascular volume status or impaired right ventricular (RV) myocardial performance. This study was performed to test the hypothesis that decreased RV peak longitudinal strain (PLSS), as measured by 2-dimensional speckle-tracking echocardiography, is associated with AKI following cardiac surgery. Retrospective observational cohort study. Cardiovascular intensive care unit in a 576-bed referral hospital. Adult patients having undergone cardiac surgery in whom a transthoracic echocardiogram (TTE) was performed within 48hours after chest closure. This was a retrospective study. Urine output and serum creatinine values were recorded at baseline and for 48hours after surgery. Statistical analysis was performed to identify differences in baseline demographic and echo-derived values between patients with and without postoperative AKI criteria. One hundred ninety-nine subjects had postprocessing of TTE performed. AKI was observed in 87% of patients (173 of 199). Age, body mass index, and preoperative serum creatinine were higher in the AKI group. The mean PLSS was -17.2% ± 4.3% versus -17.1% ± 3.7% in patients with AKI versus those without (p = 0.95). The calculated RV systolic pressure was elevated in the AKI group compared to the non-AKI group (38.9 ± 9.9 v 34.6 ± 7.9 mmHg, p = 0.02). In this cohort of cardiac surgery patients, speckle-tracking analysis of RV myocardial performance was feasible. Elevated RV systolic pressure associated with AKI, while speckle tracking-derived echocardiography measurements did not.

Motion at the Sternal Edges During Upper Limb and Trunk Tasks In-Vivo as Measured by Real-Time Ultrasound Following Cardiac Surgery: A Three-Month Prospective, Observational Study

Despite a paucity of evidence, patients following cardiac surgery via median sternotomy are routinely prescribed sternal precautions that restrict upper limb and trunk movements, with the rationale of reducing postoperative sternal complications such as sternal wound dehiscence, instability, infection and/or pain. The primary aim of this study was to measure motion at the sternal edges during dynamic upper limb and trunk tasks to better inform future sternal precautions and optimise postoperative recovery. Motion at the sternal edges was measured using ultrasound, which has been demonstrated to be a clinically valid and reliable measure in patients following cardiac surgery. Seventy-five (75) patients following cardiac surgery via median sternotomy with conventional stainless steel wire closure were recruited. Motion at the sternal edges in the lateral (coronal plane) and anterior-posterior (sagittal plane) directions was measured at the level of the fourth intercostal space (mid-sternum) using ultrasound. Ultrasound measures were taken at rest and during five dynamic upper limb and trunk tasks (deep inspiration, cough, unilateral and bilateral upper limb elevation and sit to stand), over the first 3 postoperative months (3 to 7 days, 6 weeks and 3 months postoperatively). Sternal pain, functional status and sternal healing were also observed over the same postoperative period. The magnitude of overlap of the sternal edges in the lateral direction, and separation of the sternal edges in the anterior-posterior direction, both significantly decreased by 0.01cm, over the first 3 postoperative months (p<0.01). Coughing, however, produced a significant increase in separation of the sternal edges in the lateral direction (0.01-0.02cm) and pain (12-63%), compared to rest and all other tasks, at each postoperative time point (p<0.01). Additionally, there was a significant decrease in sternal pain (81%) and increase in postoperative function (79%) over the same postoperative period (p<0.01). At 3 months postoperatively, five (7%) participants demonstrated radiological sternal union and one (1%) participant was diagnosed with clinical sternal instability. A small magnitude of multi-planar motion at the sternal edges, at the mid-sternum, was demonstrated during dynamic upper limb and trunk tasks in a cohort of cardiac surgery patients post-sternotomy, over the first 3 postoperative months. Future research investigating motion at different levels of the sternum, with varying methods of sternal closure, and over a longer postoperative period is warranted to better inform sternal precautions and optimise postoperative recovery.

Remote Ischemic Preconditioning Does Not Affect the Release of Humoral Factors in Propofol-Anesthetized Cardiac Surgery Patients: A Secondary Analysis of the RIPHeart Study

In contrast to several smaller studies, which demonstrate that remote ischemic preconditioning (RIPC) reduces myocardial injury in patients that undergo cardiovascular surgery, the RIPHeart study failed to demonstrate beneficial effects of troponin release and clinical outcome in propofol-anesthetized cardiac surgery patients. Therefore, we addressed the potential biochemical mechanisms triggered by RIPC. This is a predefined prospective sub-analysis of the randomized and controlled RIPHeart study in cardiac surgery patients (n = 40) that was recently published. Blood samples were drawn from patients prior to surgery, after RIPC of four cycles of 5 min arm ischemia/5 min reperfusion (n = 19) and the sham (n = 21) procedure, after connection to cardiopulmonary bypass (CPB), at the end of surgery, 24 h postoperatively, and 48 h postoperatively for the measurement of troponin T, macrophage migration inhibitory factor (MIF), stromal cell-derived factor 1 (CXCL12), IL-6, CXCL8, and IL-10. After RIPC, right atrial tissue samples were taken for the measurement of extracellular-signal regulated kinase (ERK1/2), protein kinase B (AKT), Glycogen synthase kinase 3 (GSK-3β), protein kinase C (PKCε), and MIF content. RIPC did not significantly reduce the troponin release when compared with the sham procedure. MIF serum levels intraoperatively increased, peaking at intensive care unit (ICU) admission (with an increase of 48.04%, p = 0.164 in RIPC; and 69.64%, p = 0.023 over the baseline in the sham procedure), and decreased back to the baseline 24 h after surgery, with no differences between the groups. In the right atrial tissue, MIF content decreased after RIPC (1.040 ± 1.032 Arbitrary units [au] in RIPC vs. 2.028 ± 1.631 [au] in the sham procedure, p < 0.05). CXCL12 serum levels increased significantly over the baseline at the end of surgery, with no differences between the groups. ERK1/2, AKT, GSK-3β, and PKCɛ phosphorylation in the right atrial samples were no different between the groups. No difference was found in IL-6, CXCL8, and IL10 serum levels between the groups. In this cohort of cardiac surgery patients that received propofol anesthesia, we could not show a release of potential mediators of signaling, nor an effect on the inflammatory response, nor an activation of well-established protein kinases after RIPC. Based on these data, we cannot exclude that confounding factors, such as propofol, may have interfered with RIPC.

Latent variable modeling improves AKI risk factor identification and AKI prediction compared to traditional methods

BackgroundAcute kidney injury (AKI) is diagnosed based on postoperative serum creatinine change, but AKI models have not consistently performed well, in part due to the omission of clinically important but practically unmeasurable variables that affect creatinine. We hypothesized that a latent variable mixture model of postoperative serum creatinine change would partially account for these unmeasured factors and therefore increase power to identify risk factors of AKI and improve predictive accuracy.MethodsWe constructed a two-component latent variable mixture model and a linear model using data from a prospective, 653-subject randomized clinical trial of AKI following cardiac surgery (NCT00791648) and included established AKI risk factors and covariates known to affect serum creatinine. We compared model fit, discrimination, power to detect AKI risk factors, and ability to predict AKI between the latent variable mixture model and the linear model.ResultsThe latent variable mixture model demonstrated superior fit (likelihood ratio of 6.68 × 1071) and enhanced discrimination (permutation test of Spearman’s correlation coefficients, p < 0.001) compared to the linear model. The latent variable mixture model was 94% (−13 to 1132%) more powerful (median [range]) at identifying risk factors than the linear model, and demonstrated increased ability to predict change in serum creatinine (relative mean square error reduction of 6.8%).ConclusionsA latent variable mixture model better fit a clinical cohort of cardiac surgery patients than a linear model, thus providing better assessment of the associations between risk factors of AKI and serum creatinine change and more accurate prediction of AKI. Incorporation of latent variable mixture modeling into AKI research will allow clinicians and investigators to account for clinically meaningful patient heterogeneity resulting from unmeasured variables, and therefore provide improved ability to examine risk factors, measure mechanisms and mediators of kidney injury, and more accurately predict AKI in clinical cohorts.

Procalcitonin and white blood cells, combined predictors of infection in cardiac surgery patients

BackgroundSepsis is strongly associated with an increased risk of postoperative mortality, longer length of hospital stay, and elevated health care costs. Early clinical symptoms overlap with those of systemic inflammatory response syndrome, a response that commonly occurs after cardiac surgery with cardiopulmonary bypass. Since a combination of biomarkers has been demonstrated to improve the prediction of postoperative infection, the objective of the present study was to test whether the combination of C-reactive protein (CRP), white blood cells (WBC), and procalcitonin (PCT) is able to predict postoperative infection in a large cohort of cardiac surgery patients. Material and methodsCase-control study involving 423 patients who underwent cardiac surgery with cardiopulmonary bypass. Patients were retrospectively classified into two groups based on whether they developed severe sepsis or septic shock during the postoperative period. Blood samples for biological measurements (PCT, CRP, and WBC) were drawn on the first day in the intensive care unit, then once daily in the morning until the 10th postoperative day. ResultsCRP median values were similar in both groups. WBC and PCT median values were significantly higher in patients with infection than without during the first 10 postoperative days. With elevation cutoffs ≤3 times (OR: 4.058; 95% CI: 2.206-7.463; P = 0.001) and ≥4 times (OR: 10.274, 95% CI: 3.690-28.604; P < 0.001), the median value for PCT (1.7 ng/mL) and/or WBC (13,000 cells/mm3) on the second postoperative day was significantly associated with the development of infection. ConclusionsThe goal of this study was to use a large cohort of cardiac surgery patients to ensure that the results were representative of this population. The combination of PCT and WBC levels over the first three postoperative days was able to predict postoperative infection within the 30 d following cardiac surgery.

Use of lidocaine in endotracheal intubation. Blood and urine concentrations in patients and deceased after unsuccessful resuscitation

In toxicological analysis of postmortem samples the local anesthetic lidocaine is often identified. In most cases, lidocaine levels result from its use as aid in endotracheal intubation. The range of the drug's concentration in blood and urine was studied under controlled conditions from a cohort of cardiac surgery patients (n=35).Plasma concentrations 1h after exposure to lidocaine in the range of the recommended 81mg coating the endotracheal tube were less than 0.2mg/l, its metabolite monoethylglycinxylidide (MEGX) less than 0.05mg/l (median ratio 0.18, range 0.03–1.23). Also the concentrations of lidocaine and MEGX in urine samples were low (less than 1.2 and 0.1mg/l, respectively) with MEGX/lidocaine ratios of 0.11 (median, range up to 1.2). These data were compared with results obtained by analyzing postmortem blood and urine samples of 18 deceased with a documented cardiopulmonary resuscitation attempt prior to death. Blood concentrations were in the same range (lidocaine median 0.07, range 0.02–1.07mg/l; MEGX median 0.01, range <0.001–0.044mg/l); besides low lidocaine concentrations in urine. MEGX was detected only in 2 out of 9 urine samples.The results of the present study confirm that lidocaine is absorbed in the trachea from the endotracheal tube coated with lidocaine containing gel. Postmortem quantitative results can be explained on the basis of the data obtained in the controlled study.

The Risk of Acute Kidney Injury With Co-Occurrence of Anemia and Hypotension During Cardiopulmonary Bypass Relative to Anemia Alone

Postoperative acute kidney injury (AKI) is a common serious consequence of cardiac surgery. One recent study found higher AKI rates when anemia and hypotension occurred during cardiopulmonary bypass (CPB) relative to anemia alone. To revalidate this post hoc observation we analyzed detailed data from a large cardiac surgery cohort. Patient, procedural, and outcome data were collected for nonemergent aortocoronary bypass and valve surgeries between July 2001 and September 2012. The occurrence of AKI (as defined by the Acute Kidney Injury Network criteria) was analyzed relative to known renal risk factors, and CPB hematocrit and blood pressure determinations in univariate and multivariable linear regression analyses. In our 3,963-patient cohort, we did not observe different AKI rates with the co-occurrence of anemia and hypotension relative to anemia alone (41.6% versus 44.3%; p = 0.39). Secondary analyses using linear definitions for AKI, CPB anemia, and hypotensive burden, and assessing for coincident timing also did not demonstrate significant association of anemia and hypotension with AKI risk relative to anemia alone. In a large cohort of cardiac surgery patients, we did not confirm any association of cardiac surgery-related AKI risk with the co-occurrence of hypotension and anemia during CPB relative to anemia alone. More detailed analyses also failed to support an anemia-hypotension interaction. Additional studies are required to better understand the relationship among anemia, hypotension during CPB, and postoperative AKI, but existing evidence is insufficient to support changes in clinical practice.

Blood transfusion in cardiac surgery does increase the risk of 5‐year mortality: results from a contemporary series of 1714 propensity‐matched patients

Studies have found that cardiac surgery patients receiving blood transfusions are at risk for increased mortality during the first year after surgery, but risk appears to decrease after the first year. This study compared 5-year mortality in a propensity-matched cohort of cardiac surgery patients. Between July 1, 2004, and June 30, 2011, 3516 patients had cardiac surgery with 1920 (54.6%) requiring blood transfusion. Propensity matching based on 22 baseline characteristics yielded two balanced groups (blood transfusion group [BTG] and nontransfused control group [NCG]) of 857 patients (1714 in total). The type and number of blood products were compared in the BTG. Operative mortality was higher in BTG versus NCG (2.3% vs. 0.4%; p < 0.0001). Kaplan-Meier analysis of 5-year survival demonstrated no difference between groups in the first 2 years (BTG 96.3% and 93.0% vs. NCG 96.4% and 93.9%, respectively). There was a significant divergence during Years 3 to 5 (BTG 82.0% vs. NCG 89.3% at 5 years; p < 0.007). Five-year survival was significantly lower in patients who received at least 2 units of blood (79.6% vs. 88.0%; p < 0.0001). In multivariate Cox regression analyses, transfusion was independently associated with increased risk for 5-year mortality. Patients receiving cryoprecipitate products had a twofold mortality risk increase (adjusted hazard ratio, 2.106; p = 0.002). Blood transfusion, specifically cryoprecipitates, was independently associated with increased 5-year mortality. Transfusion during cardiac surgery should be limited to patients who are in critical need of blood products.

Complex Assessment of the Incidence and Risk Factors of Delirium in a Large Cohort of Cardiac Surgery Patients: A Single-Center 6-Year Experience

Background. Previous reports provided inconsistent data on the occurrence of postoperative delirium and emphasized its considerable impact on outcome. This study sought to evaluate the incidence and predictors of delirium, together with its relation to cerebral ischemia in a large cohort of cardiac surgery patients in a tertiary high-volume center. Methods and Results. Consecutive patients (n = 8792) were prospectively enrolled from 2003 to 2008. Exclusion criteria were history of psychiatric disorders, use of psychoactive drugs, alcohol abuse, and data incompleteness. Finally, 5781 patients were analyzed in terms of 100 perioperative patient-specific and treatment variables. The incidence of postoperative delirium (DSM IV criteria) was 4.1% and it coexisted with cerebral ischemia in 1.1% of patients. In bivariate analysis, 49 variables were significantly linked to postoperative delirium. Multivariate analysis confirmed that delirium was independently associated with postoperative stroke (logistic odds ratio (logOR) = 2.862, P = 0.004), any blood transfusions (logOR = 4.178, P < 0.0001), age > 65 years (logOR = 2.417, P = 0.002), carotid artery stenosis (logOR = 2.15, P = 0.01), urgent/emergent surgery (logOR = 1.982, P = 0.02), fasting glucose level, intraoperative oxygen partial pressure fluctuations, and hematocrit. Area under ROC curve for the model was 0.8933. Conclusions. Early identification of nonpsychiatric perioperative determinants of delirium facilitates its diagnosis and might help develop preventive strategies to improve long-term outcome after cardiac surgery procedures.