Julika Schön

A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery

BACKGROUND Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. METHODS We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. RESULTS A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed. CONCLUSIONS Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.).

Preoperative Cerebral Oxygen Saturation and Clinical Outcomes in Cardiac Surgery

Background: The current study was designed to determine the relation between preoperative cerebral oxygen saturation (Sco2), variables of cardiopulmonary function, mortality, and morbidity in a heterogeneous cohort of cardiac surgery patients. Methods: In this study, 1,178 consecutive patients scheduled for on-pump surgery were prospectively studied. Preoperative Sco2, demographics, N-terminal pro-B-type natriuretic peptide, high-sensitive troponin T, clinical outcomes, and 30-day and 1-yr mortality were recorded. Results: Median additive EuroSCORE was 5 (range: 0–19). Thirty-day and 1-yr mortality and major morbidity (at least two major complications and/or a high-dependency unit stay of at least 10 days) were 3.5%, 7.7%, and 13.3%, respectively. Median minimal preoperative oxygen supplemented Sco2 (Sco2min-ox) was 64% (range: 15–92%). Sco2min-ox was correlated (all: P value <0.0001) with N-terminal pro-B-type natriuretic peptide (&rgr;: −0.35), high-sensitive troponin T (&rgr;: −0.28), hematocrit (&rgr;: 0.34), glomerular filtration rate (&rgr;: 0.19), EuroSCORE (&tgr;: 0.20), and left ventricular ejection fraction class (&tgr;: 0.12). Thirty-day nonsurvivors had a lower Sco2min-ox than survivors (median 58% [95% CI, 50.7–62%] vs. 64% [95% CI, 64–65%]; P < 0.0001). Receiver-operating curve analysis of Sco2min-ox and 30-day mortality revealed an area-under-the-curve of 0.71 (95% CI, 0.68–0.73%; P < 0.0001) in the total cohort and an area-under-the-curve of 0.77 (95% CI, 0.69–0.86%; P < 0.0001) in patients with a EuroSCORE more than 10. Logistic regression based on different EuroSCORE categories (0–2; 3–5, 6–10, >10), Sco2min-ox, and duration of cardiopulmonary bypass showed that a Sco2min-ox equal or less than 50% is an independent risk factor for 30-day and 1-yr mortality. Conclusions: Preoperative Sco2 levels are reflective of the severity of cardiopulmonary dysfunction, associated with short- and long-term mortality and morbidity, and may add to preoperative risk stratification in patients undergoing cardiac surgery.

Variations in arterial blood pressure are associated with parallel changes in FlowTrac/Vigileo-derived cardiac output measurements: a prospective comparison study.

IntroductionThe reliability of autocalibrated pressure waveform analysis by the FloTrac-Vigileo® (FTV) system for the determination of cardiac output in comparison with intermittent pulmonary arterial thermodilution (IPATD) is controversial. The present prospective comparison study was designed to determine the effects of variations in arterial blood pressure on the reliability of the FTV system in patients undergoing coronary artery bypass grafting (CABG).MethodsComparative measurements of cardiac output by FTV (derived from a femoral arterial line; software version 1.14) and IPATD were performed in 16 patients undergoing elective CABG in the period before institution of cardiopulmonary bypass. Measurements were performed after induction of anesthesia, after sternotomy, and during five time points during graft preparation. During graft preparation, arterial blood pressure was increased stepwise in intervals of 10 to 15 minutes by infusion of noradrenaline and lowered thereafter to baseline levels.ResultsMean arterial blood pressure was varied between 85 mmHg and 115 mmHg. IPATD cardiac output did not show significant changes during periods with increased arterial pressure either during sternotomy or after pharmacological manipulation. In contrast, FTV cardiac output paralleled changes in arterial blood pressure; i.e. increased significantly if blood pressure was raised and decreased upon return to baseline levels. Mean arterial blood pressure (MAP) and FTV cardiac output were closely correlated (r = 0.63 (95% confidence interval [CI]: 0.49 - 0.74), P < 0.0001) while no correlation between MAP and IPATD cardiac output was observed. Bland-Altman analyses for FTV versus IPATD cardiac output measurements revealed a bias of 0.4 l/min (8.5%) and limits of agreement from 2.1 to -1.3 l/min (42.2 to -25.3%).ConclusionsAcute variations in arterial blood pressure alter the reliability of the FlowTrac/Vigileo® device with the second-generation software. This finding may help to explain the variable results of studies comparing the FTV system with other cardiac output monitoring techniques, questions the usefulness of this device for hemodynamic monitoring of patients undergoing rapid changes in arterial blood pressure, and should be kept in mind when using vasopressors during FTV-guided hemodynamic optimization.

The metabolic and renal effects of adrenaline and milrinone in patients with myocardial dysfunction after coronary artery bypass grafting

IntroductionMyocardial dysfunction necessitating inotropic support is a typical complication after on-pump cardiac surgery. This prospective, randomized pilot study analyzes the metabolic and renal effects of the inotropes adrenaline and milrinone in patients needing inotropic support after coronary artery bypass grafting (CABG).MethodsDuring an 18-month period, 251 patients were screened for low cardiac output upon intensive care unit (ICU) admission after elective, isolated CABG surgery. Patients presenting with a cardiac index (CI) of less than 2.2 liters/minute per square meter upon ICU admission – despite adequate mean arterial (titrated with noradrenaline or sodium nitroprusside) and filling pressures – were randomly assigned to 14-hour treatment with adrenaline (n = 7) or milrinone (n = 11) to achieve a CI of greater than 3.0 liters/minute per square meter. Twenty patients not needing inotropes served as controls. Hemodynamics, plasma lactate, pyruvate, glucose, acid-base status, insulin requirements, the urinary excretion of alpha-1-microglobuline, and creatinine clearance were determined during the treatment period, and cystatin-C levels were determined up to 48 hours after surgery (follow-up period).ResultsAfter two to four hours after ICU admission, the target CI was achieved in both intervention groups and maintained during the observation period. Plasma lactate, pyruvate, the lactate/pyruvate ratio, plasma glucose, and insulin doses were higher (p < 0.05) in the adrenaline-treated patients than during milrinone or control conditions. The urinary excretion of alpha-1-microglobuline was higher in the adrenaline than in the control group 6 to 14 hours after admission (p < 0.05). No between-group differences were observed in creatinine clearance, whereas plasma cystatin-C levels were significantly higher in the adrenaline than in the milrinone or the control group after 48 hours (p < 0.05).ConclusionThis suggests that the use of adrenaline for the treatment of postoperative myocardial dysfunction – in contrast to treatment with the PDE-III inhibitor milrinone – is associated with unwarranted metabolic and renal effects.Clinical trials registration: ClinicalTrials.gov NCT00446017.

Lack of agreement between pulmonary arterial thermodilution cardiac output and the pressure recording analytical method in postoperative cardiac surgery patients

BACKGROUND Pulse-contour analysis method (PCM) cardiac output (CO) monitors are increasingly used for CO monitoring during anaesthesia and in the critically ill. Very recently, several systems have been introduced that do not need calibration; among them the pressure recording analytical method (PRAM). Sparse data comparing the accuracy of the PRAM-CO with conventional thermodilution CO (ThD-CO) in cardiac surgery patients are available. METHODS In this prospective comparison study, paired CO measurements with a pulmonary artery catheter and a PRAM monitoring set were obtained 20-30 min apart (t1, t2) in 23 extubated patients on the first postoperative day after cardiac surgery. Data were analysed by the Bland-Altman method. RESULTS A total of 46 paired CO measurements (23 for each interval) were collected. The Bland-Altman analysis showed a mean difference (bias) of 0.0 litre min(-1) and limits of agreement (1.96 sd) of 4.53 to -4.54 litre min(-1) [upper 95% confidence interval (CI), 3.26-5.80; lower 95% CI, -5.8 to -3.27]. The percentage error (1.96 sd/mean of the reference method) was 87%. CONCLUSIONS These results question the reliability of the PRAM technology for the determination of CO in postoperative cardiac surgery patients.

Growth differentiation factor 15: a novel risk marker adjunct to the EuroSCORE for risk stratification in cardiac surgery patients.

OBJECTIVES This study sought to determine the usefulness of plasma growth differentiation factor 15 (GDF-15) for risk stratification in patients undergoing cardiac surgery in comparison with the additive European System of Cardiac Operative Risk Evaluation (EuroSCORE), N-terminal pro-B-type natriuretic peptide (NTproBNP), and high-sensitive troponin T (hsTNT). BACKGROUND GDF-15 is emerging as a humoral marker for risk stratification in cardiovascular disease. No data are available if this marker may also be used for risk stratification in cardiac surgery. METHODS In total, 1,458 consecutive patients were prospectively studied. Pre-operative plasma GDF-15, NTproBNP, hsTNT, clinical outcomes, and 30-day and 1-year mortality were recorded. GDF-15 was determined with a pre-commercial electrochemiluminescence immunoassay. RESULTS Median additive EuroSCORE (addES) was 5 (interquartile range: 3 to 8); 30-day and 1-year mortality were 3.4% and 7.6%, respectively. Median GDF-15 levels were 1.04 ng/ml (95% confidence interval [CI]: 1.0 to 1.07 ng/ml) in 30-day survivors and 2.62 ng/ml (95% CI: 1.88 to 3.88) in 30-day nonsurvivors (p < 0.0001). C-statistics showed that the area under the curve of a combined model of GDF-15 and addES for 30-day mortality was significantly greater (0.85 vs. 0.81; p = 0.0091) than of the addES alone. For the EuroSCORE categories (0 to 2, 3 to 5, 6 to 10, >10) the presence of GDF-15 ≥1.8 ng/ml resulted in a significant 41.4% (95% CI: 19.2 to 63.7%; p < 0.001) net reclassification improvement and an integrated discrimination improvement of 0.038 (95% CI: 0.022 to 0.0547; p < 0.0001) compared to the model including only the addES, whereas the presence of NTproBNP (cutoff ≥2,000 pg/ml) or hsTNT (cutoff 14 pg/ml) did not result in significant reclassification. CONCLUSIONS The pre-operative plasma GDF-15 level is an independent predictor of post-operative mortality and morbidity in cardiac surgery patients, can further stratify beyond established risk scores and cardiovascular markers, and thus adds important additional information for risk stratification in these patients. (The Usefulness of Growth Differentiation Factor 15 [GDF-15] for Risk Stratification in Cardiac Surgery; NCT01166360).

A perioperative infusion of sodium bicarbonate does not improve renal function in cardiac surgery patients: a prospective observational cohort study

IntroductionCardiac-surgery-associated-acute-kidney-injury (CSA-AKI) is associated with increased morbidity and mortality. Recent data from patients undergoing on-pump coronary artery bypass grafting suggest that a perioperative infusion of sodium-bicarbonate may decrease the incidence of CSA-AKI. The present study aims to analyze the renoprotective effects of a 24h infusion of sodium-bicarbonate in a large, heterogeneous group of cardiac surgical patientsMethodsStarting in 4/2009, all patients undergoing cardiac surgery at our institution were enrolled in a prospective trial analyzing the relationship between preoperative cerebral oxygen saturation and postoperative organ dysfunction. We used this prospectively sampled data set to perform a cohort analysis of the renoprotective efficiency of a 24h continuous perioperative infusion of sodium-bicarbonate on the incidence of CSA-AKI that was routinely introduced in 7/2009. After exclusion of patients with endstage chronic kidney disease, off-pump procedures, and emergency cases, perioperative changes in renal function were assessed in 280 patients treated with a perioperative infusion of 4 mmol sodium-bicarbonate / kg body weight in comparison with a control cohort of 304 patients enrolled from April to June in this prospective cohort study.Postoperative changes in urine flow, plasma creatinine, estimated creatinine clearance, and the need for renal replacement therapy were determined according to AKI injury network criteria. Concomitantly, hemodynamics, treatments, complications, and clinical outcomes were recorded. Univariate statistical analyses were performed para- and nonparametrically, as appropriate.ResultsWith the exception of a lower prevalence of a history of myocardial infarction and a lower preoperative use of intravenous heparin in the bicarbonate-group, no significant between group differences in patient demographics, surgical risk, type, and duration of surgery were observed. Patients in the bicarbonate group had a lower mean arterial blood pressure after induction of anesthesia, needed more fluids, more vasopressors, and a longer treatment time in the high dependency unit. Despite a higher postoperative diuresis, no differences in the incidence of AKI grade 1 to 3 and the need for renal replacement were observed.ConclusionsRoutine perioperative administration of sodium bicarbonate failed to improve postoperative renal function in a large population of cardiac surgical patients.

The association of non-invasive cerebral and mixed venous oxygen saturation during cardiopulmonary resuscitation

Mixed venous oxygen saturation (SvO(2)) is an accepted surrogate parameter for the ratio between oxygen delivery and demand and may thus be used to determine the adequacy of the function of the cardiopulmonary system. Cerebral oxygen saturation monitoring by near infrared spectroscopy is a non-invasive method for the determination of the cerebral oxygen delivery to demand ratio that is applicable outside the operating room or the intensive care unit and does not require calibration. The present case highlights the agreement of non-invasive cerebral and SvO(2) in an 87-year-old female cardiac surgery patient with severe aortic stenosis scheduled for transapical aortic valve replacement during prolonged cardiopulmonary resuscitation.

Postoperative intubation time is associated with acute kidney injury in cardiac surgical patients

IntroductionAcute kidney injury (AKI) is a frequent complication after cardiac surgery and is associated with a poor prognosis. Mechanical ventilation is an important risk factor for developing AKI in critically ill patients. Ventilation with high tidal volumes has been associated with postoperative organ dysfunction in cardiac surgical patients. No data are available about the effects of the duration of postoperative respiratory support in the immediate postoperative period on the incidence of AKI in patients after cardiac surgery.MethodWe performed a secondary analysis of 584 elective cardiac surgical patients enrolled in an observational trial on the association between preoperative cerebral oxygen saturation and postoperative organ dysfunction and analyzed the incidence of AKI in patients with different times to extubation. The latter variable was graded in 4 h intervals (if below 16 h) or equal to or greater than 16 h. AKI was staged according to the AKI Network criteria.ResultsOverall, 165 (28.3%) patients developed AKI (any stage), 43 (7.4%) patients needed renal replacement therapy. Patients developing AKI had a significantly (P <0.001) lower renal perfusion pressure (RPP) in the first 8 hours after surgery (57.4 mmHg (95% CI: 56.0 to 59.0 mmHg)) than patients with a postoperatively preserved renal function (60.5 mmHg ((95% CI: 59.9 to 61.4 mmHg). The rate of AKI increased from 17.0% in patients extubated within 4 h postoperatively to 62.3% in patients ventilated for more than 16 h (P <0.001). Multivariate logistic regression analysis of variables significantly associated with AKI in the univariate analysis revealed that the time to the first extubation (OR: 1.024/hour, 95% CI: 1.011 to 1.044/hour; P <0.001) and RPP (OR: 0.963/mmHg; 95% CI: 0.934 to 0.992; P <0.001) were independently associated with AKI.ConclusionWithout taking into account potentially unmeasured confounders, these findings are suggestive that the duration of postoperative positive pressure ventilation is an important and previously unrecognized risk factor for AKI in cardiac surgical patients, independent from low RPP as an established AKI trigger, and that even a moderate delay of extubation increases AKI risk. If replicated independently, these findings may have relevant implications for clinical care and for further studies aiming at the prevention of cardiac surgery associated AKI.

Effect of Xenon Anesthesia Compared to Sevoflurane and Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery on Postoperative Cardiac Troponin Release: An International, Multicenter, Phase 3, Single-blinded, Randomized Noninferiority Trial

Background: Ischemic myocardial damage accompanying coronary artery bypass graft surgery remains a clinical challenge. We investigated whether xenon anesthesia could limit myocardial damage in coronary artery bypass graft surgery patients, as has been reported for animal ischemia models. Methods: In 17 university hospitals in France, Germany, Italy, and The Netherlands, low-risk elective, on-pump coronary artery bypass graft surgery patients were randomized to receive xenon, sevoflurane, or propofol-based total intravenous anesthesia for anesthesia maintenance. The primary outcome was the cardiac troponin I concentration in the blood 24 h postsurgery. The noninferiority margin for the mean difference in cardiac troponin I release between the xenon and sevoflurane groups was less than 0.15 ng/ml. Secondary outcomes were the safety and feasibility of xenon anesthesia. Results: The first patient included at each center received xenon anesthesia for practical reasons. For all other patients, anesthesia maintenance was randomized (intention-to-treat: n = 492; per-protocol/without major protocol deviation: n = 446). Median 24-h postoperative cardiac troponin I concentrations (ng/ml [interquartile range]) were 1.14 [0.76 to 2.10] with xenon, 1.30 [0.78 to 2.67] with sevoflurane, and 1.48 [0.94 to 2.78] with total intravenous anesthesia [per-protocol]). The mean difference in cardiac troponin I release between xenon and sevoflurane was −0.09 ng/ml (95% CI, −0.30 to 0.11; per-protocol: P = 0.02). Postoperative cardiac troponin I release was significantly less with xenon than with total intravenous anesthesia (intention-to-treat: P = 0.05; per-protocol: P = 0.02). Perioperative variables and postoperative outcomes were comparable across all groups, with no safety concerns. Conclusions: In postoperative cardiac troponin I release, xenon was noninferior to sevoflurane in low-risk, on-pump coronary artery bypass graft surgery patients. Only with xenon was cardiac troponin I release less than with total intravenous anesthesia. Xenon anesthesia appeared safe and feasible.