Early sevoflurane sedation in severe COVID-19-related lung injury patients. A pilot randomized controlled trial.

BACKGROUND: This study aimed to assess a potential organ protective effect of volatile sedation in a scenario of severe inflammation with an early cytokine storm (in particular IL-6 elevation) in patients suffering from COVID-19-related lung injury with invasive mechanical ventilation and sedation. METHODS: This is a small-scale pilot multicenter randomized controlled trial from four tertiary hospitals in Switzerland, conducted between April 2020 and May 2021. 60 patients requiring mechanical ventilation due to severe COVID-19-related lung injury were included and randomized to 48-hour sedation with sevoflurane vs. continuous intravenous sedation (= control) within 24 h after intubation. The primary composite outcome was determined as mortality or persistent organ dysfunction (POD), defined as the need for mechanical ventilation, vasopressors, or renal replacement therapy at day 28. Secondary outcomes were the length of ICU and hospital stay, adverse events, routine laboratory parameters (creatinine, urea), and plasma inflammatory mediators. RESULTS: 28 patients were randomized to sevoflurane, 32 to the control arm. The intention-to-treat analysis revealed no difference in the primary endpoint with 11 (39%) sevoflurane and 13 (41%) control patients (p = 0.916) reaching the primary outcome. Five patients died within 28 days in each group (16% vs. 18%, p = 0.817). Of the 28-day survivors, 6 (26%) and 8 (30%) presented with POD (p = 0.781). There was a significant difference regarding the need for vasopressors (1 (4%) patient in the sevoflurane arm, 7 (26%) in the control one (p = 0.028)). Length of ICU stay, hospital stay, and registered adverse events within 28 days were comparable, except for acute kidney injury (AKI), with 11 (39%) sevoflurane vs. 2 (6%) control patients (p = 0.001). The blood levels of IL-6 in the first few days after the onset of the lung injury were less distinctly elevated than expected. CONCLUSIONS: No evident benefits were observed with short sevoflurane sedation on mortality and POD. Unexpectedly low blood levels of IL-6 might indicate a moderate injury with therefore limited improvement options of sevoflurane. Acute renal issues suggest caution in using sevoflurane for sedation in COVID-19. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (NCT04355962) on 2020/04/21.

Wingless-related integration site (WNT) signaling is activated during the inflammatory response upon cardiac surgery: A translational study.

Objective: Cardiac surgery and the use of cardiopulmonary bypass initiate a systemic inflammatory response. Wingless-related integration site (WNT) signaling is part of the innate immunity and has been attributed a major role in the regulation of inflammation. In preclinical research, WNT-5a may sustain an inflammatory response and cause endothelial dysfunction. Our aim was to investigate WNT signaling after cardiac surgery and its association with postoperative inflammation (Clinicaltrials.gov, NCT04058496). Methods: In this prospective, single-center, observational study, 64 consecutive patients for coronary artery bypass grafting (CABG) ± valve surgery were assigned into three groups: off-pump CABG (n = 28), on-pump CABG (n = 16) and combined valve-CABG surgery (n = 20). Blood samples were acquired before surgery, at intensive care unit (ICU) admission and 4, 8, and 48 h thereafter. Plasma concentrations of WNT-5a and its antagonists Secreted frizzled-related protein 1 (sFRP-1), Secreted frizzled-related protein 5 (sFRP-5), and WNT inhibitory factor 1 (WIF-1) were determined by enzyme-linked immunosorbent assay. In addition, plasma concentrations of six inflammatory cytokines were measured by multiplex immunoassay. Parameters were analyzed for evolution of plasma concentration over time, interactions, intergroup differences, and association with clinical outcome parameters. Results: At baseline, WNT-5a, sFRP-1, and WIF-1 were present in a minimal concentration, while sFRP-5 was elevated. A higher baseline value of WNT-5a, sFRP-5, and WIF-1 resulted in higher subsequent values of the respective parameter. At ICU admission, WNT-5a and sFRP-5 reached their maximum and minimum value, respectively. WIF-1 decreased over time and was lowest 8 h after surgery. sFRP-1 changed minimally over time. While WNT-5a returned to the baseline within 48 h, sFRP-5 and WIF-1 did not reach their baseline value at 48 h. Of the investigated WNT system components, only WIF-1 partially reflected the severity of surgery. WNT-5a and WIF-1 had an impact on postoperative fluid balance and noradrenaline requirement. Conclusion: WNT-5a, sFRP-5, and WIF-1 are part of the systemic inflammatory response after cardiac surgery. WNT-5a peaks immediately after cardiac surgery and returns to baseline within 48 h, presumably modulated by its antagonist sFRP-5. Based on this translational study, WNT-5a antagonism may be further investigated to assess potentially beneficial effects in patients with a dysregulated inflammation after cardiac surgery.

Predictors associated with mortality of extracorporeal life support therapy for acute heart failure: single-center experience with 679 patients.

Background: Extracorporeal life support (ECLS) therapy is increasingly used for cardiac and respiratory support postcardiotomy, refractory cardiogenic shock and cardiopulmonary resuscitation. This study aims to describe in-hospital mortality of patients requiring ECLS, identify independent predictors associated with mortality and analyze changes of mortality over time. Methods: This retrospective study includes all adult ECLS cases at the University Hospital Zurich, a designated ECLS center in Switzerland, in the period 2007 to 2019. Results: ECLS therapy was required in 679 patients (median age 60 years, 27.5% female). In-hospital mortality was 55.5%. Cubic spline interpolation did not detect evidence for a change in mortality over the whole period of 13 years. In-hospital mortality significantly varied between ECLS indications: 70.7% (152/215) for postcardiotomy, 67.9% (108/159) for cardiopulmonary resuscitation, 47.0% (110/234) for refractory cardiogenic shock, and 9.9% (7/71) for lung transplantation and expansive thoracic surgery (P<0.001). Logistic regression modelling showed excellent discrimination in the receiver operating characteristic (ROC) area under the curve (AUC) of 0.89 [95% confidence interval (CI): 0.87-0.92] and identified significant mortality predictors: age, simplified acute physiology score (SAPS) II, as well as new liver failure and each allogenic blood transfusion unit given per day. ECLS after cardiopulmonary resuscitation was associated with significantly higher mortality compared to ECLS for refractory cardiogenic shock. Conclusions: In-hospital mortality of patients treated with ECLS therapy is high. Outcomes have not changed significantly in the observed period. We identified age, SAPS II, new liver failure and each allogenic blood transfusion unit given per day as independent mortality predictors. Knowledge of predictors strongly associated with in-hospital mortality may affect future decisions about ECLS indications and the respective management to use this elaborate therapy more effectively.

Cerebral desaturation during neonatal congenital heart surgery is associated with perioperative brain structure alterations but not with neurodevelopmental outcome at 1 year.

OBJECTIVES: The significance of intraoperative cerebral desaturation (CD) measured by near-infrared spectroscopy (NIRS) to predict neurological outcome after congenital heart surgery is uncertain. The goal of this study was to compare brain structure changes and neurodevelopmental outcome in patients with severe congenital heart disease with and without intraoperative CD. METHODS: Neonates requiring congenital heart surgery were enrolled in a cohort study. NIRS data from their first cardiac operation were collected. Pre- and postoperative brain magnetic resonance imaging results and Bayley-III scores at 1 year were compared between patients with and without CD, defined by 2 NIRS thresholds: regional cerebral oxygen saturation (rSO2) of 45% (45%rSO2) and rSO2 below 20% of baseline value (20%BLrSO2). RESULTS: Thirty-two patients (72% male) with d-transposition of the great arteries (n = 24, 75%) and other complex types of congenital heart diseases (n = 8, 25%) were analysed. Perioperative relative lateral ventricle volume change was increased in patients with versus without intraoperative CD (P = 0.003 for 45%rSO2, P = 0.008 for 20%BLrSO2). For 45%rSO2, the effect of CD remained significant after adjusting for age at postoperative scan, time between scans and cardiac diagnosis (P = 0.019). New intracranial lesions occurred predominantly in CD groups (6/6 patients for 45%rSO2, 5/6 patients for 20%BLrSO2). Neurodevelopmental outcome at 1 year was not associated with intraoperative CD. CONCLUSIONS: This study demonstrates the clinical relevance of NIRS monitoring during congenital heart surgery. The occurrence of intraoperative CD is associated with perioperative lateral ventricle volume change and new intracranial lesions.

Prior intake of new oral anticoagulants adversely affects outcome following surgery for acute type A aortic dissection.

OBJECTIVES: Oral anticoagulation prior to emergency surgery is associated with an increased risk of perioperative bleeding, especially when this therapy cannot be discontinued or reversed in time. The goal of this study was to analyse the impact of different oral anticoagulants on the outcome of patients who underwent emergency surgery for acute type A aortic dissection (ATAAD). METHODS: This was a single-centre retrospective study of patients treated with oral anticoagulation at the time of surgery for ATAAD. Outcomes of patients on new oral anticoagulant (NOAC) therapy were compared to respective outcomes of patients on Coumadin. Additionally, a survival analysis was performed comparing these 2 groups with patients who were operated on with no prior anticoagulation. RESULTS: Between January 2013 and April 2020, a total of 437 patients (63.8 ± 11.8 years, 68.4% male) received emergency surgery for ATAAD; 35 (8%) were taking oral anticoagulation at the time of hospital admission: 20 received phenprocoumon; 14, rivaroxaban; and 1, dabigatran. Compared to Coumadin, NOAC was associated with a greater need for blood-product transfusions and haemodynamic compromise. Operative mortality was 53% in the NOAC group and 30% in the Coumadin group. A 5-year survival analysis showed no significant difference between the NOAC and the Coumadin group (P = 0.059). Compared to 402 patients treated during the study period without anticoagulation, patients taking NOAC had significantly worse survival (P = 0.001), whereas that effect was not observed in patients undergoing surgery who were taking Coumadin (P = 0.99). CONCLUSIONS: Emergency surgery for ATAAD in patients taking NOAC is associated with high morbidity and mortality. NOAC are a major risk factor for uncontrollable bleeding and haemodynamic compromise. New treatment strategies must be defined to improve surgical outcomes in these high-risk patients.

Outcome, demography and resource utilization in ICU Patients with delirium and malignancy.

Delirium in the general intensive care unit (ICU) population is common, associated with adverse outcomes and well studied. However, knowledge on delirium in the increasing number of ICU patients with malignancy is scarce. The aim was to assess the frequency of delirium and its impact on resource utilizations and outcomes in ICU patients with malignancy. This retrospective, single-center longitudinal cohort study included all patients with malignancy admitted to ICUs of a University Hospital during one year. Delirium was diagnosed by an Intensive Care Delirium Screening Checklist (ICDSC) score ≥ 4. Of 488 ICU patients with malignancy, 176/488 (36%) developed delirium. Delirious patients were older (66 [55-72] vs. 61 [51-69] years, p = 0.001), had higher SAPS II (41 [27-68] vs. 24 [17-32], p < 0.001) and more frequently sepsis (26/176 [15%] vs. 6/312 [1.9%], p < 0.001) and/or shock (30/176 [6.1%] vs. 6/312 [1.9%], p < 0.001). In multivariate analysis, delirium was independently associated with lower discharge home (OR [95% CI] 0.37 [0.24-0.57], p < 0.001), longer ICU (HR [95% CI] 0.30 [0.23-0.37], p < 0.001) and hospital length of stay (HR [95% CI] 0.62 [0.50-0.77], p < 0.001), longer mechanical ventilation (HR [95% CI] 0.40 [0.28-0.57], p < 0.001), higher ICU nursing workload (B [95% CI] 1.92 [1.67-2.21], p < 0.001) and ICU (B [95% CI] 2.08 [1.81-2.38], p < 0.001) and total costs (B [95% CI] 1.44 [1.30-1.60], p < 0.001). However, delirium was not independently associated with in-hospital mortality (OR [95% CI] 2.26 [0.93-5.54], p = 0.074). In conclusion, delirium was a frequent complication in ICU patients with malignancy independently associated with high resource utilizations, however, it was not independently associated with in-hospital mortality.

The effect of hemoadsorption on rivaroxaban blood plasma concentration in emergency cardiac surgery.

Hemoadsorption was used in a 59-year-old patient with an acute type A aortic dissection, who was on rivaroxaban and dual antiplatelet therapy with clopidogrel and acetylsalicylic acid. Our aim was to expeditiously remove rivaroxaban preoperatively. After 8 h of hemoadsorption, the rivaroxaban blood plasma concentration (RBPC) did not decrease below 42.1 µg/l. Intraoperatively, hemoadsorption was repeated during extracorporeal circulation. Sixteen hours after surgery and a total of 13 h of hemoadsorption, the RBPC was 40.1 µg/l. Thereafter, the RBPC spontaneously decreased to 24.7 µg/l within 14 h. In our patient, hemoadsorption may have enhanced rivaroxaban removal at higher RBPC (cutoff value 40-50 µg/l). At lower RBPC, the removal of rivaroxaban may depend solely on the natural drug elimination process. The evolution of the RBPC under hemoadsorption in vivo warrants a thorough investigation. Further clinical studies are required to assess the effectiveness and limitations of hemoadsorption to preclude a fatal bleeding event in patients with rivaroxaban in need of major emergency surgery.

Extracorporeal life support as bridge to recovery in yew poisoning: case reports and literature review.

AIMS: This short communication aims to review the treatment of cardiogenic shock in patients with yew poisoning based on two case reports from our institution, focusing on the use of extracorporeal life support (ECLS). METHODS AND RESULTS: We report two cases of Taxus baccata poisoning treated with ECLS at our institution and review the literature based on a search in PubMed and Google Scholar on the topic of yew poisoning and ECLS. All cases were combined for analysis of demographics, ECLS therapy, and outcome. Case 1: A 35-year-old woman developed polymorphic ventricular tachycardia followed by cardiovascular arrest 5 h after orally ingesting a handful of yew needles. Successful resuscitation required ECLS for 72 h due to ongoing cardiac arrhythmias and cardiogenic shock. The patient left the hospital without neurological sequelae after 10 days. Case 2: A 30-year-old woman developed refractory cardiac arrhythmias and circulatory arrest. Resuscitation included ECLS for 71 h. T. baccata needles found by gastroscopy confirmed the diagnosis. The patient had no neurologic deficits and was transferred to psychiatry after 11 days. REVIEW OF THE LITERATURE: Nine case reports were found and analysed along with our two cases. Five out of the 11 (45%) patients were female. Median (range) age was 28 (19-46) years. T. baccata needles were ingested with a suicidal intention in all patients. Median (range) duration of ECLS was 70 h (24-120 h). Eight (73%) patients had full neurological recovery. CONCLUSIONS: Yew poisoning is a differential diagnosis in young psychiatric patients presenting with polymorphic ventricular tachycardia and cardiogenic shock. A characteristic cardiac contraction pattern in echocardiography may present a diagnostic clue. The early use of ECLS is a valuable bridge to recovery in most of these patients.

Cardiovascular Safety of Clonidine and Dexmedetomidine in Critically Ill Patients after Cardiac Surgery.

PURPOSE: The aim of this retrospective study was to assess the haemodynamic adverse effects of clonidine and dexmedetomidine in critically ill patients after cardiac surgery. METHODS: 2769 patients were screened during the 30-month study period. Heart rate (HR), mean arterial pressure (MAP), and norepinephrine requirements were assessed 3-hourly during the first 12 hours of the continuous drug infusion. Results are given as median (interquartile range) or numbers (percentages). RESULTS: Patients receiving clonidine (n = 193) were younger (66 (57-73) vs 70 (63-77) years, p=0.003) and had a lower SAPS II (35 (27-48) vs 41 (31-54), p=0.008) compared with patients receiving dexmedetomidine (n = 141). At the start of the drug infusion, HR (90 (75-100) vs 90 (80-105) bpm, p=0.028), MAP (70 (65-80) vs 70 (65-75) mmHg, p=0.093), and norepinephrine (0.05 (0.00-0.11) vs 0.12 (0.03-0.19) mcg/kg/min, p < 0.001) were recorded in patients with clonidine and dexmedetomidine. Bradycardia (HR < 60 bpm) developed in 7.8% with clonidine and 5.7% with dexmedetomidine (p=0.51). Between baseline and 12 hours, norepinephrine remained stable in the clonidine group (0.00 (-0.04-0.02) mcg/kg/min) and decreased in the dexmedetomidine group (-0.03 (-0.10-0.02) mcg/kg/min, p=0.007). CONCLUSIONS: Dexmedetomidine and the low-cost drug clonidine can both be used safely in selected patients after cardiac surgery.

Establishing a pre-clinical growing animal model to test a tissue engineered valved pulmonary conduit.

BACKGROUND: Many valvular pathologies of the heart may be only sufficiently treated by replacement of the valve if a reconstruction is not feasible. However, structural deterioration, thrombosis with thromboembolic events and infective endocarditis are commonly encountered complications over time and often demand a re-operation. In congenital heart disease the lack of small diameter valves with the potential to grow poses additional challenges and limits treatment options to homo- or xenograft implants. METHODS: In this study, a chronic sheep model (24 months follow-up), a self-constructed valved conduit was created out of a tissue engineered (TE) patch (CorMatrix® Cardiovascular, Inc, USA) and implanted in orthotopic right ventricular (RV)-pulmonary artery (PA) position. Thereafter, the sheep were regularly monitored by clinical, laboratory and echocardiographic examinations to evaluate cardiac function and the implanted RV-PA-conduit. DISCUSSION: Here, we summarize the study protocol and our experiences during the perioperative phase and the follow up period and explain how we constructed a valved conduit out of a commercially available TE patch. TRIAL REGISTRATION: License number: ZH 284/14.

Comparison of Levosimendan and Milrinone for ECLS Weaning in Patients After Cardiac Surgery-A Retrospective Before-and-After Study.

OBJECTIVES: Pharmacodynamics suggests that levosimendan might be a valuable inotrope for weaning from extracorporeal life support (ECLS). As there is a paucity of evidence regarding the effectiveness and safety of such an approach, the aim was to report the authors' experiences in ECLS weaning before and after the implementation of levosimendan in clinical practice. DESIGN: Retrospective before-and-after study. SETTING: Cardiac intensive care unit of a university hospital. PARTICIPANTS: A total of 64 patients under ECLS for postcardiotomy cardiac failure, who underwent an ECLS weaning trial. INTERVENTION: Group comparisons between patients treated with levosimendan and patients treated with milrinone were made with the Mann-Whitney U test or the Pearson chi-squared test. Results are given as median (interquartile range) or numbers (percentages). MEASUREMENTS AND MAIN RESULTS: Of 64 patients, 26 (41%) received levosimendan. Successful ECLS weaning was achieved in 24 (92%) and 30 patients (79%) in the levosimendan and milrinone group, respectively (p = 0.18). In the levosimendan group, fewer patients had an intra-aortic balloon pump for weaning (2 [7.7%] v 15 [40%], p = 0.008). The support with norepinephrine was similar in the levosimendan and milrinone groups at the time of ECLS removal (0.06 [0.01-0.11] v 0.07 [0.01-0.16] µg/kg/min, p = 0.64) and 24 hours later (0.06 [0.04-0.09] v 0.04 [0.00-0.09] µg/kg/min, p = 0.15). Twenty-eight days (9/26 (35%) v 14/35 (40%), p = 0.28) and 180 days (13/26 [50%] v 15/34 [44%], p = 0.80) mortalities after ECLS removal were similar in the levosimendan and the milrinone groups. CONCLUSION: Levosimendan enabled ECLS weaning without increasing norepinephrine requirements when compared to a control group receiving milrinone.

Investigating the Usability and Acute Effects of a Bedside Video Console to Prefrontal Cortical Activity Alterations: A Preclinical Study in Healthy Elderly.

Elderly people at risk of developing cognitive decline; e.g., following surgery, may benefit from structured, challenging, and repetitive cognitive video training. This study assessed usability and acute effects of a newly developed bedside console (COPHYCON). Fifteen healthy elderly individuals performed a one-time 80-min intervention, including cognitive video games aimed at improving awareness and selective attention. Perceived usefulness and perceived ease of use (Technology Acceptance Model) were assessed together with measures of the achieved game level, reaction times, (in-) correct responses during ALERT and SELECT game play. Further, prefrontal cortical involvement of the regional cerebral hemoglobin saturation (rS02%) assessed with functional near infrared spectroscopy (fNIRS) (n = 5) and EEG power (n = 10) was analyzed. All participants completed the study without any adverse events. Perceived usefulness and perceived ease of use (TAM scores range 1-7) of the system varied between 3.9 and 6.3. The game levels reached for awareness varied between 9 and 11 (initial score 8-10), for reaction speed between 439 and 469 ms, and for correct responses between 74.1 and 78.8%. The highest level for the selective attention games was 2 (initial score 1), where reaction speed varied between 439 and 469 ms, correct responses between 96.2 and 98.5%, respectively. The decrease of rS02% in the right prefrontal cortex during gameplay was significantly (p < 0.001) lower, compared to the left prefrontal cortex. Four participants yielded significant lower rS02% measures after exergaming with the ALERT games (p < 0.000), but not with the SELECT games. EEG recordings of theta power significantly decreased in the averaged ~0.25-0.75 time interval for the left prefrontal cortex sensor across the cognitive game levels between the ALERT 1 and SELECT 1, as well as between SELECT 1 and 2 games. Participants rated the usability of the COPHYCON training positively. Further results indicate that video gaming may be an effective measure to affect prefrontal cortical functioning in elderly. The results warrant a clinical explorative study investigating the feasibility of the COPHYCON in a clinical setting.

Dexmedetomidine-Associated Hyperthermia: A Series of 9 Cases and a Review of the Literature.

Dexmedetomidine, an α2-adrenergic agonist, can be used to perform mild to moderate sedation in critically ill patients. In this case series, 9 cardiovascular intensive care unit patients with hyperthermia during dexmedetomidine administration, suggestive of drug fever, are presented. Hyperthermia (>38.5°C) occurred 6 (4-10) hours (median [interquartile range]) after dexmedetomidine initiation at a dose of 1.0 (0.8-1.3) µg/kg/h and was resolved 3 (1-8) hours after discontinuation of dexmedetomidine. All patients were screened for infectious and noninfectious causes of hyperthermia, and the findings were analyzed by 2 adverse drug reaction (ADR) assessment methods-the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) Causality Assessment and the Naranjo ADR scale. This resulted in a "probable" ADR in all 9 patients (WHO) and a "probable" and "possible" ADR in 1 and 8 patients (Naranjo), respectively. This case series supports published case reports, suggesting that dexmedetomidine administration may be associated with the occurrence of clinically relevant hyperthermia. The underlying mechanisms and risk factors are uncertain and require further research.

Intra-operative events during cardiac surgery are risk factors for the development of delirium in the ICU.

BACKGROUND: Risk factors for delirium following cardiac surgery are incompletely understood. The aim of this study was to investigate whether intra-operative pathophysiological alterations and therapeutic interventions influence the risk of post-operative delirium. METHODS: This retrospective cohort study was performed in a 12-bed cardiosurgical intensive care unit (ICU) of a university hospital and included patients consecutively admitted after cardiac surgery during a 2-month period. The diagnosis of delirium was made clinically using validated scores. Comparisons between patients with and without delirium were performed with non-parametric tests. Logistic regression was applied to identify independent risk factors. Results are given as number (percent) or median (range). RESULTS: Of the 194 consecutive post-cardiac surgery patients, 50 (26 %) developed delirium during their ICU stay. Univariate analysis revealed that significant differences between patients with and without delirium occurred in the following intra-operative variables: duration of cardiopulmonary bypass (184 [72-299] vs 113 (37-717) minutes, p < 0.001), lowest mean arterial pressure (50 [30-70] vs 55 [30-75] mmHg, p = 0.004), lowest haemoglobin level (85 [56-133] vs 98 [53-150] g/L, p = 0.005), lowest body temperature (34.5 [24.4-37.2] vs 35.1 [23.9-37.2] °C, p = 0.035), highest noradrenaline support (0.11 [0.00-0.69] vs 0.07 [0.00-0.42] µg/kg/minute, p = 0.001), and frequency of red blood cell transfusions (18 [36 %] vs 26 [18 %], p = 0.018) and platelet transfusions (23 [46 %] vs 24 [17 %], p < 0.001). Only platelet transfusions remained an independent risk factor in the multivariate analysis (p < 0.001). CONCLUSIONS: In patients undergoing cardiac surgery, various intra-operative events, such as transfusion of platelets, were risk factors for the development of a post-operative delirium in the ICU. Further research is needed to unravel the underlying mechanisms.

Surgical technique: establishing a pre-clinical large animal model to test aortic valve leaflet substitute.

To overcome current limitations of valve substitutes and tissue substitutes the technology of tissue engineering (TE) continues to offer new perspectives in congenital cardiac surgery. We report our experiences and results implanting a decellularized TE patch in nine sheep in orthotropic position as aortic valve leaflet substitute. Establishing the animal model, feasibility, cardiopulmonary bypass issues and operative technique are highlighted.

Shock Management for Cardio-surgical Intensive Care Unit Patient: The Silver Days.

Shock in cardio-surgical intensive care unit (ICU) patients requires prompt identification of the underlying condition and timely therapeutic interventions. Management during the first 6 hours, also referred to as "the golden hours", is of paramount importance to reverse the shock state and improve the patient's outcome. The authors have previously described a state-of-the-art diagnostic work-up and discussed how to optimise preload, vascular tone, contractility, heart rate and oxygen delivery during this phase. Ideally, shock can be reversed during this initial period. However, some patients might have developed multiple organ dysfunction, which persists beyond the first 6 hours despite the early haemodynamic treatment goals having been accomplished. This period, also referred to as "the silver days", is the focus of this review. The authors discuss how to reduce vasopressor load and how to minimise adrenergic stress by using alternative inotropes, extracorporeal life-support and short acting beta-blockers. The review incorporates data on fluid weaning, safe ventilation, daily interruption of sedation, delirium management and early rehabilitation. It includes practical recommendations in areas where the evidence is scarce or controversial. Although the focus is on cardio-surgery ICU patients, most of the considerations apply to critical ill patients in general.

Comparison of conventional ROTEM® cups and pins to the ROTEM® cup and pin mini measuring cells (MiniCup).

BACKGROUND: Thromboelastometry (ROTEM®) is a well-established measurement to guide perioperative coagulation management. Recently, an enhancement for low volume specimens using cup and pin mini measuring cells (MiniCup) was invented for scientific non-clinical use. The MiniCup measuring cells allow testing with half of the blood volume required to run a test as compared to the conventional ROTEM® cup and pin (150 µL vs. 300 µL per assay). OBJECTIVES: The aim of this prospective study was to compare ROTEM® results using conventional cups and pins to the results of the MiniCup measuring cells. METHODS: Blood samples drawn during major pediatric surgery were analyzed using the conventional ROTEM® and the MiniCup system to compare parameters from the EXTEM, INTEM and FIBTEM assays. RESULTS: Citrated blood samples (n = 120) from 70 pediatric patients were analyzed. Results of the MiniCup cells were considerably different than the conventional ROTEM® cups and pins measurements. The MiniCup results show less clot firmness and demonstrate higher variability in the parameters reflecting the kinetics of clot building. CONCLUSION: The MiniCup measuring cells may offer advantages in pediatric care or research facilities, but specific reference ranges need to be established first, and adequate reproducibility must be determined by further studies before clinical use can be recommended.

Shock Management for Cardio-surgical ICU Patients - The Golden Hours.

Postoperative shock following cardiac surgery is a serious condition with a high morbidity and mortality. There are four types of shock: cardiogenic, hypovolemic, obstructive and distributive and these can occur alone or in combination. Early identification of the underlying diseases and understanding of the mechanisms at play are key for successful management of shock. Prompt resuscitation measures are necessary to reverse the shock state and avoid permanent organ dysfunction or death. In this review, the authors focus on the management during the first 6 hours of shock (the 'golden hours'). They discuss how to optimise preload, vascular tone, contractility, heart rate and oxygen delivery. The review incorporates the findings of recent trials on early goal-directed therapy and includes practical recommendations in areas in which the evidence is scare or controversial. While the review focuses on cardio-surgical patients, the suggested treatment algorithms might be usefully expanded to other critically ill patients with shock arising from other causes.