Functional evaluation of sublingual microcirculation indicates successful weaning from VA-ECMO in cardiogenic shock.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly adopted for the treatment of cardiogenic shock (CS). However, a marker of successful weaning remains largely unknown. Our hypothesis was that successful weaning is associated with sustained microcirculatory function during ECMO flow reduction. Therefore, we sought to test the usefulness of microcirculatory imaging in the same sublingual spot, using incident dark field (IDF) imaging in assessing successful weaning from VA-ECMO and compare IDF imaging with echocardiographic parameters. METHODS: Weaning was performed by decreasing the VA-ECMO flow to 50% (F50) from the baseline. The endpoint of the study was successful VA-ECMO explantation within 48 hours after weaning. The response of sublingual microcirculation to a weaning attempt (WA) was evaluated. Microcirculation was measured in one sublingual area (single spot (ss)) using CytoCam IDF imaging during WA. Total vessel density (TVDss) and perfused vessel density (PVDss) of the sublingual area were evaluated before and during 50% flow reduction (TVDssF50, PVDssF50) after a WA and compared to conventional echocardiographic parameters as indicators of the success or failure of the WA. RESULTS: Patients (n = 13) aged 49 ± 18 years, who received VA-ECMO for the treatment of refractory CS due to pulmonary embolism (n = 5), post cardiotomy (n = 3), acute coronary syndrome (n = 2), myocarditis (n = 2) and drug intoxication (n = 1), were included. TVDssF50 (21.9 vs 12.9 mm/mm2, p = 0.001), PVDssF50 (19.7 vs 12.4 mm/mm2, p = 0.01) and aortic velocity-time integral (VTI) at 50% flow reduction (VTIF50) were higher in patients successfully weaned vs not successfully weaned. The area under the curve (AUC) was 0.99 vs 0.93 vs 0.85 for TVDssF50 (small vessels) >12.2 mm/mm2, left ventricular ejection fraction (LVEF) >15% and aortic VTI >11 cm. Likewise, the AUC was 0.91 vs 0.93 vs 0.85 for the PVDssF50 (all vessels) >14.8 mm/mm2, LVEF >15% and aortic VTI >11 cm. CONCLUSION: This study identified sublingual microcirculation as a novel potential marker for identifying successful weaning from VA-ECMO. Sustained values of TVDssF50 and PVDssF50 were found to be specific and sensitive indicators of successful weaning from VA-ECMO as compared to echocardiographic parameters.

Microcirculatory assessment of patients under VA-ECMO.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an effective technique for providing emergency mechanical circulatory support for patients with cardiogenic shock. VA-ECMO enables a rapid restoration of global systemic organ perfusion, but it has not been found to always show a parallel improvement in the microcirculation. We hypothesized in this study that the response of the microcirculation to the initiation of VA-ECMO might identify patients with increased chances of intensive care unit (ICU) survival. METHODS: Twenty-four patients were included in this study. Sublingual microcirculation measurements were performed using the CytoCam-IDF (incident dark field) imaging device. Microcirculatory measurements were performed at baseline, after VA-ECMO insertion (T1), 48-72 h after initiation of VA-ECMO (T2), 5-6 days after (T3), 9-10 days after (T4), and within 24 h of VA-ECMO removal. RESULTS: Of the 24 patients included in the study population, 15 survived and 9 died while on VA-ECMO. There was no significant difference between the systemic global hemodynamic variables at initiation of VA-ECMO between the survivors and non-survivors. There was, however, a significant difference in the microcirculatory parameters of both small and large vessels at all time points between the survivors and non-survivors. Perfused vessel density (PVD) at baseline (survivor versus non-survivor, 19.21 versus 13.78 mm/mm2, p = 0.001) was able to predict ICU survival on initiation of VA-ECMO; the area under the receiver operating characteristic curve (ROC) was 0.908 (95 % confidence interval 0.772-1.0). CONCLUSION: PVD of the sublingual microcirculation at initiation of VA-ECMO can be used to predict ICU mortality in patients with cardiogenic shock.

Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis.

INTRODUCTION: In Europe, vitamin D deficiency is highly prevalent varying between 40% and 60% in the healthy general adult population. The consequences of vitamin D deficiency for sepsis and outcome in critically ill patients remain controversial. We therefore systematically reviewed observational cohort studies on vitamin D deficiency in the intensive care unit. METHODS: Fourteen observational reports published from January 2000 to March 2014, retrieved from Pubmed and Embase, involving 9,715 critically ill patients and serum 25-hydroxyvitamin D3 (25 (OH)-D) concentrations, were meta-analysed. RESULTS: Levels of 25 (OH)-D less than 50 nmol/L were associated with increased rates of infection (risk ratio (RR) 1.49, 95% (confidence interval (CI) 1.12 to 1.99), P = 0.007), sepsis (RR 1.46, 95% (CI 1.27 to 1.68), P <0.001), 30-day mortality (RR 1.42, 95% (CI 1.00 to 2.02), P = 0.05), and in-hospital mortality (RR 1.79, 95% (CI 1.49 to 2.16), P <0.001). In a subgroup analysis of adjusted data including vitamin D deficiency as a risk factor for 30-day mortality the pooled RR was 1.76 (95% CI 1.37 to 2.26, P <0.001). CONCLUSIONS: This meta-analysis suggests that vitamin D deficiency increases susceptibility for severe infections and mortality of the critically ill.

Case Report: Early Identification of Subclinical Cardiac Tamponade in a Patient With a Left Ventricular Assist Device by the Use of Sublingual Microcirculatory Imaging: A New Diagnostic Imaging Tool?

Clinical diagnosis of cardiac tamponade can be difficult in patients with continuous flow left ventricle assist devices (cf-LVADs). This is even more so because of the lack of adequate bedside echocardiographic windows. Previous studies on monitoring sublingual microcirculation showed deterioration of end-organ perfusion in patient with cardiogenic shock. In this paper we report alterations in the sublingual microcirculation in a cf-LVAD patient prior to clinical manifestation of tamponade. Our case report suggests that such real-time monitoring of the microcirculation may provide a new diagnostic modality for early recognition of cardiac tamponade.

A novel mortality risk score predicting intensive care mortality in cardiogenic shock patients treated with veno-arterial extracorporeal membrane oxygenation.

PURPOSE: Mortality after veno-arterial extracorporeal membrane oxygenation (VA-ECMO) implantation remains a major problem in patients with cardiogenic shock. Our objective was to assess the utility of the SOFA score in combination with markers of right ventricular (RV) dysfunction in predicting mortality in the ICU. MATERIALS AND METHODS: Data were retrospectively obtained from all adult patients (n=103) who were treated with VA-ECMO between November 2004 and January 2016. The primary outcome of this study was ICU mortality after VA-ECMO implantation. Using the clinical, demographic and echocardiographic data, we developed a novel mortality risk score, the SOFA-RV score, which combine RV-function to the SOFA score at the time of VA-ECMO implantation. RESULTS: Out of 103 patients, 37 (36%) died in the ICU. The median duration of VA-ECMO support was 7 days [IQR 4-11], mean age 49 ± 16 years, and 54% were male. SOFA-RV score has an AUC of 0.70, and was significantly better than SOFA alone (AUC of 0.57) in predicting ICU mortality. In addition, SAVE and MELD scores were not able to predict ICU mortality. CONCLUSION: Adding RV-function to the existing SOFA score improves significantly the prediction of ICU mortality in patients on VA-ECMO. Dedicated evaluation of RV function in patients with VA-ECMO is therefore recommended.

Preoperative right heart hemodynamics predict postoperative acute kidney injury after heart transplantation.

PURPOSE: Acute kidney injury (AKI) frequently occurs after heart transplantation (HTx), but its relation to preoperative right heart hemodynamic (RHH) parameters remains unknown. Therefore, we aimed to determine their predictive properties for postoperative AKI severity within 30 days after HTx. METHODS: From 1984 to 2016, all consecutive HTx recipients (n = 595) in our tertiary referral center were included and analyzed for the occurrence of postoperative AKI staged by the kidney disease improving global outcome criteria. The effects of preoperative RHH parameters on postoperative AKI were calculated using logistic regression, and predictive accuracy was assessed using integrated discrimination improvement (IDI), net reclassification improvement (NRI), and area under the receiver operating characteristic curves (AUC). RESULTS: Postoperative AKI occurred in 430 (72%) patients including 278 (47%) stage 1, 66 (11%) stage 2, and 86 (14%) stage 3 cases. Renal replacement therapy (RRT) was administered in 41 (7%) patients. Patients with higher AKI stages had also higher baseline right atrial pressure (RAP; median 7, 7, 8, and in RRT 11 mmHg, p trend = 0.021), RAP-to-pulmonary capillary wedge pressure ratio (median 0.37, 0.36, 0.40, 0.47, p trend = 0.009), and lower pulmonary artery pulsatility index (PAPi) values (median 2.83, 3.17, 2.54, 2.31, p trend = 0.012). Higher RAP and lower PAPi values independently predicted AKI severity [adjusted odds ratio (OR) per doubling of RAP 1.16 (1.02-1.32), p = 0.029; of PAPi 0.85 (0.75-0.96), p = 0.008]. Based on IDI, NRI, and delta AUC, inclusion of these parameters improved the models' predictive accuracy. CONCLUSIONS: Preoperative PAPi and RAP strongly predict the development of AKI early after HTx and can be used as early AKI predictors.

Ventilation according to the open lung concept attenuates pulmonary inflammatory response in cardiac surgery.

OBJECTIVE: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response, which is correlated with outcome. We hypothesized that ventilation according to the open lung concept (OLC) attenuates cytokine release. METHODS: A prospective, single center randomized controlled clinical study containing 62 patients scheduled for elective coronary artery bypass graft and/or valve surgery with cardiopulmonary bypass. Before surgery, patients were randomly assigned to three groups: (1) conventional mechanical ventilation (CV), (2) OLC started after arrival on the ICU (late open lung, LOL), and (3) OLC started directly after intubation (early open lung, EOL). In both OLC groups, recruitment maneuvers were applied until PaO(2)/FiO(2)>50. The CV group received no recruitment maneuvers. Interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma were measured preoperatively, immediately after cessation of CPB, and 3h, 5h, 24h, 2, and 3 days after cessation of CPB. RESULTS: CPB caused a significant increase of IL-6, IL-8, and IL-10 in all groups. Thereafter, IL-8 decreased significantly more rapidly in both OLC groups compared to CV. IL-10 decreased significantly more rapidly after CPB only in the EOL group, compared with CV. Three hours after cessation of the CPB, IL-10 was already comparable with preoperative levels in the EOL group, but not in the LOL or CV group. IL-6, TNF-alpha, and IFN-gamma did not differ significantly between groups. CONCLUSIONS: OLC ventilation leads to an attenuated inflammatory response, presumably by reducing additional lung injury after cardiac surgery. Studies on cytokines after cardiac surgery should take these findings into account.

Adrenal insufficiency presenting as bilateral rigid auricles: a case report.

INTRODUCTION: Stiff ears appear to be a warning sign for adrenal insufficiency. This remarkable and rare sign has not been described to present in adrenal insufficiency in the setting of critical care. CASE PRESENTATION: We present the case of a 68-year-old Caucasian male who underwent a thymoma resection and suffered from preoperative weight loss and lack of strength. The perioperative phase was characterised by hypotension and sputum stasis due to muscle weakness, which caused two readmissions to the intensive care unit. His physical examination showed two fully rigid auricles. In retrospect, our patient suffered from secondary adrenal insufficiency and hypogonadism. CONCLUSIONS: The bilateral rigid auricles appeared to be a warning sign for adrenal insufficiency. This remarkable sign is easily checked, and should prompt a higher index of suspicion towards adrenal insufficiency and other hormonal deficiencies.

Conventional hemodynamic resuscitation may fail to optimize tissue perfusion: an observational study on the effects of dobutamine, enoximone, and norepinephrine in patients with acute myocardial infarction complicated by cardiogenic shock.

AIM: To investigate the effects of inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock. METHODS AND RESULTS: Thirty patients with cardiogenic shock were included. Patients received dobutamine, enoximone, or norepinephrine. We performed hemodynamic measurements at baseline and after titration of the inotropic agent until cardiac index (CI) ≥ 2.5 L.min-1.m(-2) or mixed-venous oxygen saturation (SvO2) ≥ 70% (dobutamine or enoximone), and mean arterial pressure (MAP) ≥ 70 mmHg (norepinephrine). As parameters of tissue perfusion, we measured central-peripheral temperature gradient (delta-T) and sublingual perfused capillary density (PCD). All patients reached predefined therapeutic targets. The inotropes did not significantly change delta-T. Dobutamine did not change PCD. Enoximone increased PCD (9.1 [8.9-10.2] vs. 11.4 [8.4-13.9] mm.mm(-2); p<0.05), and norepinephrine tended to decrease PCD (9.8 [8.5-11.9] vs. 8.8 [8.2-9.6] mm.mm-2, p = 0.08). Fifteen patients (50%) died within 30 days after admission. Patients who had low final PCD (≤ 10.3 mm.mm-2; 64%) were more likely to die than patients who had preserved PCD (>10.3 mm.mm(-2); mortality 72% vs. 17%, p = 0.003). CONCLUSION: This study demonstrates the effects of commonly used inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock. Despite hemodynamic optimization, tissue perfusion was not sufficiently restored in most patients. In these patients, mortality was high. Interventions directed at improving microcirculation may eventually help bridging the gap between improved hemodynamics and dismal patient outcome in cardiogenic shock.

Open lung ventilation does not increase right ventricular outflow impedance: An echo-Doppler study.

OBJECTIVE: Ventilation according to the open lung concept (OLC) consists of recruitment maneuvers, followed by low tidal volume and elevated positive end-expiratory pressure (PEEP). Elevated PEEP is associated with an increased right ventricular afterload. We investigated the effect of OLC ventilation on right ventricular outflow impedance during inspiration and expiration in patients after cardiac surgery using transesophageal echo-Doppler. DESIGN: A prospective, single-center, crossover, randomized, controlled clinical study. SETTING: Cardiothoracic intensive care unit of a university hospital. PATIENTS: Twenty-eight patients scheduled for elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: In the intensive care unit, each patient was ventilated for approximately 30 mins according to both OLC and conventional ventilation. During OLC ventilation, recruitment maneuvers were applied until PaO2/FiO2 was >375 torr (50 kPa); during conventional ventilation no recruitment maneuvers were performed. MEASUREMENTS AND MAIN RESULTS: Transesophageal echo-Doppler measurements were performed at end-inspiration and end-expiration in a steady-state condition, 20 mins after initiation of a ventilation strategy. Mean acceleration of flow was determined in the long axis of the pulmonary artery in a transverse axis view. During OLC ventilation, a total PEEP of 14 +/- 4 cm H2O was applied vs. 5 cm H2O during conventional ventilation. Mean acceleration during expiration was comparable between groups. During inspiration, OLC ventilation did not cause a decrease of mean acceleration compared with expiration, whereas this did occur during conventional ventilation. CONCLUSIONS: Despite the use of elevated PEEP levels, ventilation according to OLC does not change right ventricular outflow impedance during expiration and decreases right ventricular outflow impedance during inspiration.

Open lung ventilation improves functional residual capacity after extubation in cardiac surgery.

OBJECTIVE: After cardiac surgery, functional residual capacity (FRC) after extubation is reduced significantly. We hypothesized that ventilation according to the open lung concept (OLC) attenuates FRC reduction after extubation. DESIGN: A prospective, single-center, randomized, controlled clinical study. SETTING: Cardiothoracic operating room and intensive care unit of a university hospital. PATIENTS: Sixty-nine patients scheduled for elective coronary artery bypass graft and/or valve surgery with cardiopulmonary bypass. INTERVENTIONS: Before surgery, patients were randomly assigned to three groups: (1) conventional ventilation (CV); (2) OLC, started after arrival in the intensive care unit (late open lung); and (3) OLC, started directly after intubation (early open lung). In both OLC groups, recruitment maneuvers were applied until Pao2/Fio2 was >375 Torr (50 kPa). No recruitment maneuvers were applied in the CV group. MEASUREMENTS AND MAIN RESULTS: FRC was measured preoperatively and 1, 3, and 5 days after extubation. Peripheral hemoglobin saturation (Spo2) was measured daily till the third day after extubation while the patient was breathing room air. Hypoxemia was defined by an Spo2 value < or =90%. Averaged over the 5 postoperative days, FRC was significantly higher in the early open lung group and tended to be higher in the late open lung group, in comparison with the CV group (mean +/- sem: CV, 1.8 +/- 0.1; late open lung,1.9 +/- 0.1; and early open lung, 2.2 +/- 0.1l). In the CV group, 37% of the patients were hypoxic on the third day after extubation, compared with none of the patients in both OLC groups. CONCLUSIONS: After cardiac surgery, earlier application of OLC resulted in a significantly higher FRC and fewer episodes of hypoxemia than with CV after extubation.

Single-stage surgical repair of benign laryngotracheal stenosis in adults.

BACKGROUND: Benign laryngotracheal stenosis causes considerable morbidity. In a retrospective study, we describe the results of our surgical treatment. METHODS: Between June 1999 and June 2002, 14 adults with laryngotracheal stenosis were referred to our hospital. Stenosis resulted from mechanical ventilation in 11 patients, from Wegener's granulomatosis in 2 patients, and from strangulation in 1 patient. Eleven patients had a tracheotomy. One patient was found unfit for surgery. Nine patients underwent cricotracheal resection (CTR) with end-to-end anastomosis, and four patients underwent single-stage laryngotracheoplasty (SS-LTP) without stenting. RESULTS: There were no perioperative deaths. Patients were extubated after mean of 3 days (range, 0-10 days; CTR 2.3 days vs SS-LTP 3.5 days, p=.45). There were in-hospital complications in five patients. Mean hospital stay was 19 days (range, 8-53 days; after CTR 24 days vs SS-LTP 9 days, p=.015). With regard to airway patency and voice recovery, 10 patients (77%) had good results, including 1 patient with two readmissions, and 3 (23%) had satisfactory results, including 1 patient with 11 additional nonsurgical interventions. CONCLUSIONS: Benign laryngotracheal stenosis in the adult patient can be repaired successfully using a strategy of two single-stage surgical procedures. All patients had good or satisfactory functional results. A multidisciplinary approach was essential to achieve these good results.